L-Proline: A Versatile Organo-Catalyst in Organic Chemistry

Bapu   R.   Thorat; Suraj   N.   Mali; Swati   S.   Wavhal; Devidas   S.   Bhagat; Ravikumar   M.   Borade; A.      Chapolikar; Ajaykumar      Gandhi; Pawan      Shinde
doi:10.2174/1386207325666220720105845
Abstract

Background: L-proline is a natural amino acid having secondary amine functionality and acts as a bifunctional catalyst (organo-catalyst). The amino-functional group acts as Lewis base type while carboxylic acids act as Brønsted acid type catalysts. It catalyzed different asymmetric syntheses, including known reactions such as Aldol condensation, Mannich reaction, Michael Addition, Knoevenagel condensation, Hantzsch synthesis, OXA-Michael Henry tandem, Ullmann reactions, Wieland-Miescher ketone synthesis, Robinson annulation, Biginelli reaction, α- amination. It is also an essential catalyst for synthesizing heterocyclic skeletons such as coumarin, spiro-oxindoles, imidazoles, benzimidazoles, quinoxalines, podophyllotoxin, benzothiazoles, isoxazolidines, phenothiazines, aziridine, indole, 1,5-benzodiazepines, pyridine, and quinazolines.
Objective: In this review, we had the objective to critically summarize the use of proline and proline derivatives as catalysts of multicomponent reactions performed in various media and leading to synthetically and biologically relevant heterocycles, a very important class of compounds that constitutes over 60% of drugs and agrochemicals.
Methods: All scholarly articles for L-Proline catalyzed reactions were retrieved from ScienceDirect, Google Scholar , PubMed, etc.
Results and Conclusion: Given the importance of L-Proline based reactions, it has been observed to have tremendous applications in organic chemistry. It can also act as a 'Green catalyst'.
Keywords: L-proline, organo-catalyst, amino acids, bifunctional catalyst, asymmetric synthesis.
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Graphical Abstract

[1]
a) Berkessel, A.; Gröger, H. Asymmetric organocatalysis; Wiley-VCH: New York, 2005. 
 [http://dx.doi.org/10.1002/3527604677]; 
b) New development of organocatalyst; Shibasaki, M., Ed.; CMC-Shuppan: Tokyo, 2006. ; 
c) Enantioselective organocatalysis; Dalko, P.I., Ed.; Wiley-VCH: New York, 2007. 
 [http://dx.doi.org/10.1002/9783527610945]; 
d) List, B. Asymmetric aminocatalysis. Synlett,  2001, 1675.
 [http://dx.doi.org/10.1055/s-2001-18074]; 
e) Dalko, P.I.; Moisan, L. Enantioselective organocatalysis. Angew. Chem. Int. Ed. Engl.,  2001, 40(20), 3726-3748.
 [http://dx.doi.org/10.1002/1521-3773(20011015)40:20<3726:AID-ANIE3726>3.0.CO;2-D] [PMID: 11668532]; 
f) Jarvo, E.R.; Miller, S.J. Amino acids and peptides as asymmetric organocatalysts. Tetrahedron,  2002, 58, 2481.
 [http://dx.doi.org/10.1016/S0040-4020(02)00122-9]; 
g) Mali, S.N.; Pandey, A. Balanced QSAR and molecular modeling
to identify structural requirements of imidazopyridine analogues
as anti-infective agents against trypanosomiases. J. Comput. Biophy. Chem.,  2022, 1-32.; 
h) List, B. Enamine catalysis is a powerful strategy for the catalytic generation and use of carbanion equivalents. Acc. Chem. Res.,  2004, 37(8), 548-557.
 [http://dx.doi.org/10.1021/ar0300571] [PMID: 15311954]; 
i) Miller, S.J. In search of peptide-based catalysts for asym-metric organic synthesis. Acc. Chem. Res.,  2004, 37(8), 601-610.
 [http://dx.doi.org/10.1021/ar030061c] [PMID: 15311959]; 
j) Forsyth, S.A.; Pringle, J.M.; MacFarlane, D.R. Ionic liq-uids-An overview. Aust. J. Chem.,  2004, 57(2), 113-119.
 [http://dx.doi.org/10.1071/CH03231]; 
k) Seayad, J.; List, B. Asymmetric organocatalysis. Org. Biomol. Chem.,  2005, 3(5), 719-724.
 [http://dx.doi.org/10.1039/b415217b] [PMID: 15731852]; 
l) Tanaka, F.; Barbas, C.F., III Organocatalytic asymmetric synthesis using proline and related molecules. Part 1. Yuki Gosei Kagaku Kyokai-shi,  2005, 63, 709.
 [http://dx.doi.org/10.5059/yukigoseikyokaishi.63.709]; 
m) Limbach, M. 5-(pyrrolidin-2-yl)-1H-tetrazole and 5-[(pyrrolidin-2-yl)methyl]-1H-tetrazole: Proline surrogates with increased potential in asymmetric catalysis. Chem. Biodivers.,  2006, 3(2), 119-133.
 [http://dx.doi.org/10.1002/cbdv.200690016] [PMID: 17193251]; 
n) Marques, M.M.B. Catalytic enantioselective cross-Mannich reaction of aldehydes. Angew. Chem. Int. Ed.,  2006, 45(3), 348-352.
 [http://dx.doi.org/10.1002/anie.200502630] [PMID: 16342308]; 
o) Guillena, G.; Nájera, C.; Ramón, D.J. Enantioselective direct aldol reaction: The blossoming of modern organocatalysis. Tetrahedron Asymmetry,  2007, 18, 2249.
 [http://dx.doi.org/10.1016/j.tetasy.2007.09.025]

[2]
a) Das, T.K.; Bhawal, P.; Ganguly, S.; Mondal, S.; Das, N.C. A facile green synthesis of amino acid boosted Ag decorated reduced graphene oxide nanocomposites and its catalytic activity towards 4-nitrophenol reduction. Surf. Interfaces,  2018, 13, 79-91.
 [http://dx.doi.org/10.1016/j.surfin.2018.08.004]; 
b) Kanti Das, T.; Ganguly, S.; Remanan, S.; Das, N.C. Temperature‐
Dependent Study of Catalytic Ag Nanoparticles Entrapped resin
nanocomposite towards reduction of 4‐nitrophenol. ChemistrySelect,  2019, 4(13), 3665-3671.
 [http://dx.doi.org/10.1002/slct.201900470]; 
c) Das, T.K.; Ganguly, S.; Remanan, S.; Ghosh, S.; Das, N.C. Mussel-inspired Ag/poly (norepinephrine)/MnO2 heterogene-ous nanocatalyst for efficient reduction of 4-nitrophenol and 4-nitroaniline: An alternative approach. Res. Chem. Intermed.,  2020, 46(7), 3629-3650.
 [http://dx.doi.org/10.1007/s11164-020-04165-0]; 
d) Das, T.K.; Das, N.C. Advances on catalytic reduction of 4-nitrophenol by nanostructured materials as benchmark reaction. Int. Nano Lett.,  2022, 1-20.
 [http://dx.doi.org/10.1007/s40089-021-00362-w]; 
e) Fache, F.; Piva, O. Synthesis and applications of the first polyfluorous proline derivative. Tetrahedron Asymmetry, 2003. 14,
139, 598.
 [http://dx.doi.org/10.1016/S0957-4166(02)00796-6]

[3]
Shen, Z.; Chen, W.; Jiang, H.; Ding, Y.; Luo, X.; Zhang, Y. Direct asymmetric aldol reactions catalyzed by (4R)-4-(β-Naphthalenyl) methoxy-(S)-proline. Chirality,  2005, 17(2), 119-120.
 [http://dx.doi.org/10.1002/chir.20107] [PMID: 15669082]

[4]
Bellis, E.; Kokotos, G. 4-Substituted prolines as organocatalysts for aldol reactions. Tetrahedron,  2005, 61, 8669.
 [http://dx.doi.org/10.1016/j.tet.2005.06.113]

[5]
Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.; Sumiya, T.; Shoji, M. Combined proline-surfactant organocatalyst for the highly diastereo-and enantioselective aqueous direct cross-aldol reaction of aldehydes. Angew. Chem. Int. Ed.,  2006, 45(33), 5527-5529.
 [http://dx.doi.org/10.1002/anie.200601156] [PMID: 16856197]

[6]
a) Inomata, K.; Barragué, M.; Paquette, L.A. Diastereoselectivities realized in the amino acid catalyzed aldol cyclizations of triketo acetonides of differing ring size. J. Org. Chem.,  2005, 70(2), 533-539.
 [http://dx.doi.org/10.1021/jo0486084] [PMID: 15651798]; 
b) Itagaki, N.; Kimura, M.; Sugahara, T.; Iwabuchi, Y. Organocatalytic entry to chiral bicyclo[3.n.1]alkanones via direct asymmetric intramolecular aldolization. Org. Lett.,  2005, 7(19), 4185-4188.
 [http://dx.doi.org/10.1021/ol051569d] [PMID: 16146383]; 
c) Hayashi, Y.; Sumiya, T.; Takahashi, J.; Gotoh, H.; Urushima, T.; Shoji, M. Highly diastereo-and enantioselective direct aldol reactions in water. Angew. Chem. Int. Ed.,  2006, 45(6), 958-961.
 [http://dx.doi.org/10.1002/anie.200502488] [PMID: 16385603]

[7]
a) Itagaki, N.; Sugahara, T.; Iwabuchi, Y. Expedient synthesis of potent cannabinoid receptor agonist (-)-CP55,940. Org. Lett.,  2005, 7(19), 4181-4183.
 [http://dx.doi.org/10.1021/ol051570c] [PMID: 16146382]; 
b) Itagaki, N.; Iwabuchi, Y. Enantio- and diastereo-controlled synthesis of (+)-juvabione employing organocatalytic desymmetrization and photoinduced fragmentation. Chem. Commun. (Camb.),,  2007, (11), 1175-1176.
 [http://dx.doi.org/10.1039/b616641e] [PMID: 17347730]

[8]
a) Wang, Y.; Shang, Z.C.; Wu, T.X.; Fan, J.C.; Chen, X. Synthetic and theoretical study on proline-catalyzed Knoevenagel condensation in ionic liquid. J. Mol. Catal. Chem.,  2006, 253, 212.
 [http://dx.doi.org/10.1016/j.molcata.2006.03.035]; 
b) Srinivasan, M.; Perumal, S.; Selvaraj, S. (L)-Proline catalysed efficient synthesis of 3-substituted 2, 6-diarylpiperidin-4-ones. ARKIVOC,  2005, xi, 201.
 [http://dx.doi.org/10.3998/ark.5550190.0006.b17]; 
c) Sabitha, G.; Fatima, N.; Reddy, E.V.; Yadav, J.S. First examples
of proline‐catalyzed domino knoevenagel/hetero‐dielsalder/
elimination reactions. Adv. Synth. Catal.,  2005, 347, 1353.
 [http://dx.doi.org/10.1002/adsc.200505144]; 
d) Dodda, R.; Zhao, C.G. L-proline-catalyzed one-pot three-component reaction for the synthesis of β-alkoxy ketones. Synthesis,  2006, 19, 3238.

[9]
a) Janey, J.M.; Hsiao, Y.; Armstrong, J.D. III Proline-catalyzed, asymmetric mannich reactions in the synthesis of a DPP-IV inhibitor. J. Org. Chem.,  2006, 71(1), 390-392.
 [http://dx.doi.org/10.1021/jo0519458] [PMID: 16388667]; 
b) Kantam, M.L.; Rajasekhar, C.V.; Gopikrishna, G.; Reddy, K.R.; Choudary, B.M. Proline catalyzed two-component, three-component and self-asymmetric Mannich reactions promoted by ultrasonic conditions. Tetrahedron Lett.,  2006, 47, 5965.
 [http://dx.doi.org/10.1016/j.tetlet.2006.06.042]; 
c) Hahn, B.T.; Fröhlich, R.; Harms, K.; Glorius, F. Proline-catalyzed highly enantioselective and anti-selective Mannich reaction of unactivated ketones: Synthesis of chiral α-amino acids. Angew. Chem. Int. Ed. Engl.,  2008, 47(51), 9985-9988.
 [http://dx.doi.org/10.1002/anie.200803515] [PMID: 19006133]

[10]
a) Notz, W.; Tanaka, F.; Barbas, C.F., III Enamine-based organocatalysis with proline and diamines: The development of direct catalytic asymmetric Aldol, Mannich, Michael, and Diels-alder reactions. Acc. Chem. Res.,  2004, 37(8), 580-591.
 [http://dx.doi.org/10.1021/ar0300468] [PMID: 15311957]; 
b) Dalko, P.I.; Moisan, L. In the golden age of organocatalysis. Angew. Chem. Int. Ed.,  2004, 43(39), 5138-5175.
 [http://dx.doi.org/10.1002/anie.200400650] [PMID: 15455437]; 
c) Lacoste, E. Proline: An essential amino acid as effective chiral
organocatalyst. Synlett,  2006, 12, 1973.
 [http://dx.doi.org/10.1055/s-2006-947332]; 
d) Alcaide, B.; Almendros, P.; Luna, A.; Torres, M.R. Proline-catalyzed diastereoselective direct aldol reaction between 4-oxoazetidine-2-carbaldehydes and ketones. J. Org. Chem.,  2006, 71(13), 4818-4822.
 [http://dx.doi.org/10.1021/jo0604235] [PMID: 16776507]; 
e) Zotova, N.; Franzke, A.; Armstrong, A.; Blackmond, D.G. Clarification of the role of water in proline-mediated aldol reactions. J. Am. Chem. Soc.,  2007, 129(49), 15100-15101.
 [http://dx.doi.org/10.1021/ja0738881] [PMID: 18001021]; 
f) Chandrasekhar, S.; Narsihmulu, C.; Reddy, R.N.; Sultan, S.S. Asymmetric aldol reactions in poly (ethylene glycol) catalyzed by L-proline. Tetrahedron Lett.,  2004, 45, 4581.
 [http://dx.doi.org/10.1016/j.tetlet.2004.03.116]; 
g) Kumar, I.; Rode, V.C. L-Proline catalyzed direct diastereoselective aldol reactions: Towards the synthesis of lyxo-(2S, 3S, 4S)-phytosphingosine. Tetrahedron Asymmetry,  2007, 18, 1975.
 [http://dx.doi.org/10.1016/j.tetasy.2007.08.018]; 
h) Bernard, A.M.; Frongia, A.; Guillot, R.; Piras, P.P.; Secci, F.; Spiga, M. L-Proline-catalyzed direct intermolecular asymmetric aldol reactions of 1-phenylthiocycloalkyl carboxaldehydes with ketones. Easy access to spiro- and fused-cyclobutyl tetrahydrofurans and cyclopentanones. Org. Lett.,  2007, 9(3), 541-544.
 [http://dx.doi.org/10.1021/ol063084a] [PMID: 17249807]; 
i) List, B.; Pojarliev, P.; Castello, C. Proline-catalyzed asymmetric aldol reactions between ketones and α-unsubstituted aldehydes. Org. Lett.,  2001, 3(4), 573-575.
 [http://dx.doi.org/10.1021/ol006976y] [PMID: 11178828]

[11]
a) Holbrey, J.D.; Seddon, K.R. Ionic liquids. Clean Prod. Process.,  1999, 1(4), 223-236.; 
b) Kotrusz, P.; Toma, S. L-Proline catalysed Michael additions of different active methylene compounds to α-enones in ionic liquid. ARKIVOC,  2006, 100.
 [http://dx.doi.org/10.3998/ark.5550190.0007.510]; 
c) Kotrusz, P.; Toma, S. L-proline catalyzed Michael additions of thiophenols to α,β-unsaturated compounds, particularly α-enones, in the ionic liquid [bmim]PF6. Molecules,  2006, 11(2), 197-205.
 [http://dx.doi.org/10.3390/11020197] [PMID: 17962790]; 
d) List, B.; Pojarliev, P.; Martin, H.J. Efficient proline-catalyzed Michael additions of unmodified ketones to nitro olefins. Org. Lett.,  2001, 3(16), 2423-2425.
 [http://dx.doi.org/10.1021/ol015799d] [PMID: 11483025]

[12]
a) Mali, S.N.; Pandey, A. molecular modeling studies on 2, 4-disubstituted imidazopyridines as anti-malarials: Atom-based 3D-QSAR, molecular docking, virtual screening, in-silico ADMET and theoretical analysis. J. Comput. Biophy. Chem.,  2021, 20(03), 267-282.
 [http://dx.doi.org/10.1142/S2737416521500125]; 
b) Xie, H.; Zu, L.; Oueis, H.R.; Li, H.; Wang, J.; Wang, W. Proline-catalyzed direct inverse electron demand diels-alder reactions of ketones with 1,2,4,5-tetrazines. Org. Lett.,  2008, 10(10), 1923-1926.
 [http://dx.doi.org/10.1021/ol800417q] [PMID: 18410125]

[13]
a) Hajos, Z.G.; Parrish, D.R. Asymmetric synthesis of bicyclic intermediates of natural product chemistry. J. Org. Chem.,  1974, 39, 1615.
 [http://dx.doi.org/10.1021/jo00925a003]; 
b) Eder, U.; Sauer, G.; Wiechert, R. New type of asymmetric cyclization to optically active steroid CD partial structures. Angew. Chem. Int. Ed. Engl.,  1971, 10, 496.
 [http://dx.doi.org/10.1002/anie.197104961]; 
c) Agami, C.; Platzer, N.; Sevestre, H. Enantioselective cyclizations of acyclic 1, 5-diketones. Bull. Soc. Chim. Fr.,  1987, 2, 358-360.

[14]
Bogevig, A.; Juhl, K.; Kumaragurubaran, N.; Zhuang, W.; Jorgensen, K.A. Direct organo-catalytic asymmetric amination of aldehydes-
a simple approach to optically active. Angew. Chem. Int. Ed.,  2002, 41, 1790.
 [http://dx.doi.org/10.1002/1521-3773(20020517)41:10<1790::AID-ANIE1790>3.0.CO;2-Y]

[15]
a) Yamada, S.; Hiroi, K.; Achiwa, K. Asymmetric synthesis with amino acid I asymmetric induction in the alkylation of keto-enamine. Tetrahedron Lett.,  1969, 10(48), 4233-4236.
 [http://dx.doi.org/10.1016/S0040-4039(01)88662-7]; 
b) Yamada, S.; Otani, G. Asymmetric synthesis with amino acid II asymmetric synthesis of optically active 4, 4-disubstituted-cyclohexenone. Tetrahedron Lett.,  1969, 10(48), 4237-4240.
 [http://dx.doi.org/10.1016/S0040-4039(01)88663-9]

[16]
Hossein, A.O.; Elham, R.; Majid, M.H. Solvent-free l-proline catalysed condensation of ethyl cyanoacetate with aldehydes. J. Chem. Res.,  2006, 246.

[17]
List, B.; Pojarliev, P.; Biller, W.T.; Martin, H.J. The proline-catalyzed direct asymmetric three-component Mannich reaction: Scope, optimization, and application to the highly enantioselective synthesis of 1,2-amino alcohols. J. Am. Chem. Soc.,  2002, 124(5), 827-833.
 [http://dx.doi.org/10.1021/ja0174231] [PMID: 11817958]

[18]
a) Yadav, J.S.; Kumar, S.P.; Kondaji, G.; Rao, R.S.; Nagaiah, K. A novel L-proline catalyzed biginelli reaction: One-pot synthesis of 3,4-Dihydropyrimidin-2 (1H)-ones under solvent-free conditions. Chem. Lett.,  2004, 33, 1168.
 [http://dx.doi.org/10.1246/cl.2004.1168]; 
b) Mabry, J.; Ganem, B. Studies on the Biginelli reaction: A mild and selective route to 3, 4-dihydropyrimidin-2 (1H)-ones via enamine intermediates. Tetrahedron Lett.,  2006, 47, 55.
 [http://dx.doi.org/10.1016/j.tetlet.2005.10.124]

[19]
Thorat, B.R.; Mali, S.N.; Rani, D.; Yamgar, R.S. Synthesis, in
silico and in vitro analysis of hydrazones as potential antituberculosis
agents. Curr. Computeraided Drug Des.,  2021, 17(2), 294-306.
 [http://dx.doi.org/10.2174/1573409916666200302120942] [PMID: 32141422]

[20]
a) List, B. Proline-catalyzed asymmetric reactions. Tetrahedron,  2002, 58, 5573-5590.
 [http://dx.doi.org/10.1016/S0040-4020(02)00516-1]; 
b) Shen, Z.; Li, B.; Wang, L.; Zhang, Y. Proline-catalyzed aldol reactions of acyl cyanides with acetone: An efficient and convenient synthesis of 1, 3-diketones. Tetrahedron Lett.,  2005, 46, 8785-8788.
 [http://dx.doi.org/10.1016/j.tetlet.2005.10.036]

[21]
a) Ramachary, D.B.; Kishor, M.; Reddy, G.B. Development of drug intermediates by using direct organocatalytic multi-component reactions. Org. Biomol. Chem.,  2006, 4(9), 1641-1646.
 [http://dx.doi.org/10.1039/b602696f] [PMID: 16633553]; 
b) Ramachary, D.B.; Reddy, G.B. Towards organo-click reactions: Development of pharmaceutical ingredients by using direct organocatalytic bio-mimetic reductions. Org. Biomol. Chem.,  2006, 4(24), 4463-4468.
 [http://dx.doi.org/10.1039/b612611a] [PMID: 17268640]; 
c) Ramachary, D.B.; Kishor, M. Organocatalytic sequential one-pot double cascade asymmetric synthesis of Wieland-Miescher ketone analogues from a Knoevenagel/hydrogenation/Robinson annulation sequence: Scope and applications of organocatalytic biomimetic reductions. J. Org. Chem.,  2007, 72(14), 5056-5068.
 [http://dx.doi.org/10.1021/jo070277i] [PMID: 17552564]; 
d) Ramachary, D.B.; Ramakumar, K.; Narayana, V.V. Organocatalytic cascade reactions based on push-pull dienamine platform: Synthesis of highly substituted anilines. J. Org. Chem.,  2007, 72(4), 1458-1463.
 [http://dx.doi.org/10.1021/jo0623639] [PMID: 17288390]; 
e) Ramachary, D.B.; Kishore, M.; Reddy, Y.V. Development of pharmaceutical drugs, drug intermediates and ingredients by using direct organo-click reactions. Eur. J. Org. Chem.,  2008, 6, 975-993.
 [http://dx.doi.org/10.1002/ejoc.200701014]; 
f) Ramachary, D.B.; Kishor, M. Direct amino acid-catalyzed cascade biomimetic reductive alkylations: Application to the asymmetric synthesis of Hajos-Parrish ketone analogues. Org. Biomol. Chem.,  2008, 6(22), 4176-4187.
 [http://dx.doi.org/10.1039/b807999d] [PMID: 18972048]; 
g) Ramachary, D.B.; Reddy, Y.V.; Kishor, M. Multi-catalysis reactions: Direct organocatalytic sequential one-pot synthesis of highly functionalized cyclopenta[b]chromen-1-ones. Org. Biomol. Chem.,  2008, 6(22), 4188-4197.
 [http://dx.doi.org/10.1039/b812551a] [PMID: 18972049]; 
h) Ramachary, D.B.; Kishore, M.; Ramakumar, K. A novel and green protocol for two-carbon homologation: A direct amino acid/K2CO3-catalyzed four-component reaction of aldehydes, active methylenes, Hantzsch, esters and alkyl halides. Tetrahedron Lett.,  2006, 47, 651.
 [http://dx.doi.org/10.1016/j.tetlet.2005.11.128]

[22]
Guo, S.R.; Yuan, Y-Q. CuI/L-proline-catalyzed synthesis of vinyl sulfides in 95% alcohol. Synth. Commun.,  2008, 38, 2722.
 [http://dx.doi.org/10.1080/00397910802222746]

[23]
a) Varala, R.; Ramu, E.; Sreelatha, N.; Adapa, S.R. Catalytic aldol-type reaction of aldehydes with ethyl diazoacetate using quarternary ammonium hydroxide as the base. Tetrahedron Lett.,  2006, 47(6), 877-880.
 [http://dx.doi.org/10.1016/j.tetlet.2005.12.005]; 
b) Varala, R.; Adapa, S.R. A practical and efficient synthesis of thalidomide via Na/Liquid NH3 Methodology. Org. Process Res. Dev.,  2005, 9, 853.
 [http://dx.doi.org/10.1021/op050129z]; 
c) An, Z.; Zhang, W.; Shi, H.; He, J. An effective heterogeneous L-proline catalyst for the asymmetric aldol reaction using anionic clays as intercalated support. J. Catal.,  2006, 241, 319-327.
 [http://dx.doi.org/10.1016/j.jcat.2006.04.035]; 
d) Karade, N.N.; Budhewar, V.H.; Shinde, S.V.; Jadhav, W.N. L-proline as an efficient organo-catalyst for the synthesis of polyhydroquinoline via multicomponent Hantzsch reaction. Lett. Org. Chem.,  2007, 4, 16.
 [http://dx.doi.org/10.2174/157017807780037405]; 
e) Shi, C.L.; Shi, D.Q.; Kim, S.H.; Huang, Z.B.; Ji, S.J.; Ji, M. A novel and efficient one-pot synthesis of furo [3'; 4'; 5, 6] pyrido [2, 3-c] pyrazole derivatives using organocatalysts. Tetrahedron,  2008, 64, 2425-2432.
 [http://dx.doi.org/10.1016/j.tet.2007.12.053]; 
f) Shi, C.L.; Shi, D.Q.; Kim, S.H.; Huang, Z.B.; Ji, M. A novel and efficient synthesis of 3, 3'-Benzylidenebis (4-hydroxy-6-methylpyridin-2 (1H)-one) derivatives through a multi-component reaction catalyzed by l-prolin. Aust. J. Chem.,  2008, 61, 547-551.
 [http://dx.doi.org/10.1071/CH08113]; 
g) Li, Y.; Chen, H.; Shi, C.; Shi, D.; Ji, S. Efficient one-pot synthesis of spirooxindole derivatives catalyzed by L-proline in aqueous medium. J. Comb. Chem.,  2010, 12(2), 231-237.
 [http://dx.doi.org/10.1021/cc9001185] [PMID: 20085353]

[24]
Rajesh, S.M.; Bala, B.D.; Perumal, S.; Men’endez, J.M. L-Proline-catalysed sequential four-component “on water” protocol for the synthesis of structurally complex heterocyclic ortho-quinones. Green Chem.,  2011, 13, 3248-3254.
 [http://dx.doi.org/10.1039/c1gc15794a]

[25]
a) Elnagdi, N.M.H.; Al-Hokbany, N.S. Organocatalysis in synthesis: L-proline as an enantioselective catalyst in the synthesis of pyrans and thiopyrans. Molecules,  2012, 17(4), 4300-4312.
 [http://dx.doi.org/10.3390/molecules17044300] [PMID: 22491679]; 
b) Bora, P.P.; Bihani, M.; Bez, G. Beyond enzymatic promiscuity: Asymmetric induction by l-proline on lipase catalyzed synthesis of polyfunctionalized 4 H-pyrans. RSC Advances,  2015, 5, 50597-50603.
 [http://dx.doi.org/10.1039/C5RA08785F]

[26]
a) Janardhan, B.; Ravibabu, V.; Crooks, P.A.; Rajitha, B. L-proline catalyzed an efficient multicomponent one-pot synthesis of poly substituted pyridines. Org. Commun,  2012, 5, 186-195.; 
b) Mukhopadhyay, C.; Tapaswi, P.K.; Butcher, R.J. L-Proline-catalyzed one-pot expeditious synthesis of highly substituted pyridines at room temperature. Tetrahedron Lett.,  2010, 51, 1797-1802.
 [http://dx.doi.org/10.1016/j.tetlet.2010.01.106]

[27]
Md, R.P.; Heravi, P.; Mohammadi, A. L-Proline-catalysed one-pot synthesis of tetrahydrobenzo [c] acridin-8 (7H)-ones at room temperature. C. R. Chim.,  2012, 15, 448-453.
 [http://dx.doi.org/10.1016/j.crci.2011.12.001]

[28]
Karamthulla, S.; Pal, S.; Parvin, T.; Choudhury, L.H. L-proline catalyzed multicomponent reactions: Facile access to 2 H-benzo [g] pyrazolo [3, 4-b] quinoline-5, 10 (4 H, 11 H)-dione derivatives. RSC Advances,  2014, 4, 15319-15324.
 [http://dx.doi.org/10.1039/C4RA00876F]

[29]
a) Borah, B.M.; Das, G. A one-pot synthesis and self-assembled superstructure of organic salts of a 1, 5-benzodiazepine derivative. Tetrahedron Lett.,  2006, 47, 3135.
 [http://dx.doi.org/10.1016/j.tetlet.2006.02.137]; 
b) Li, G.L.; Zhao, G. Efficient allylation of aldehydes promoted by carboxylic acids. J. Org. Chem.,  2005, 70(11), 4272-4278.
 [http://dx.doi.org/10.1021/jo050186q] [PMID: 15903300]; 
c) Yanagisawa, A.; Nakamura, Y.; Arai, T. α-Amino acid-promoted asymmetric allylation of aldehydes with allylstannanes. Tetrahedron Asymmetry,  2004, 15, 1909.
 [http://dx.doi.org/10.1016/j.tetasy.2004.04.036]

[30]
Mecadon, H.; Rohman, Md. R.; Kharbangar, I.; Laloo, B.M.; Kharkongor, I.; Rajbangshi, M.; Myrboh, B. L-Proline as an efficicent catalyst for the multi-component synthesis of 6-amino-4-alkyl/aryl-3-methyl-2, 4-dihydropyrano [2, 3-c] pyrazole-5-carbonitriles in water. Tetrahedron Lett.,  2011, 52, 3228-3231.
 [http://dx.doi.org/10.1016/j.tetlet.2011.04.048]

[31]
a) Ramachary, D.B.; Chowdari, N.S.; Barbas, C.F. III Organocatalytic asymmetric domino knoevenagel/diels-alder reactions: A bioorganic approach to the diastereospecific and enantioselective construction of highly substituted spiro[5,5]undecane-1,5,9-triones. Angew. Chem. Int. Ed.,  2003, 42(35), 4233-4237.
 [http://dx.doi.org/10.1002/anie.200351916] [PMID: 14502744]; 
b) Ramachary, D.B.; Chowdari, N.S.; Barbas, C.F., III The first organocatalytic hetero-domino knoevenagel-diels-alder-epimerization reactions: Diastereoselective synthesis of highly substituted Spiro[cyclohexane-1,2'-indan]-1'3'4-trione. Synlett, 2003.; 
c) Ramachary, D.B.; Anebouselvy, K.; Chowdari, N.S.; Barbas, C.F., III Direct organocatalytic asymmetric hetero-domino reactions: The Knoevenagel/Diels-Alder/epimerization sequence for the highly diastereoselective synthesis of symmetrical and nonsymmetrical synthons of benzoannelated centropolyquinanes. J. Org. Chem.,  2004, 69(18), 5838-5849.
 [http://dx.doi.org/10.1021/jo049581r] [PMID: 15373469]; 
d) Ramachary, D.B.; Barbas, C.F., III Direct amino acid-catalyzed asymmetric desymmetrization of meso-compounds: Tandem aminoxylation/O-N bond heterolysis reactions. Org. Lett.,  2005, 7(8), 1577-1580.
 [http://dx.doi.org/10.1021/ol050246e] [PMID: 15816756]; 
e) Ramachary, D.B.; Reddy, Y.V.; Prakash, B.V. Double cascade reactions based on the barbas dienamine platform: Highly stereoselective synthesis of functionalized cyclohexanes for cardiovascular agents. Org. Biomol. Chem.,  2008, 6(4), 719-726.
 [http://dx.doi.org/10.1039/b718122a] [PMID: 18264572]

[32]
a) Gruttadauria, M.; Giacalone, F.; Marculescu, A.M.; Noto, R. Novel prolinamide-supported polystyrene as highly stereoselective and recyclable organocatalyst for the aldol reaction. Adv. Synth. Catal.,  2008, 350, 1397.
 [http://dx.doi.org/10.1002/adsc.200800090]; 
b) Gruttadauria, M.; Salvo, A.M.P.; Giacalone, F.; Agrigento, P.; Noto, R. Enhanced activity and stereoselectivity of polystyrene-supported proline-based organic catalysts for direct asymmetric aldol reaction in water. Eur. J. Org. Chem.,  2009, 31, 5437.
 [http://dx.doi.org/10.1002/ejoc.200900829]

[33]
a) Zhong, G. A facile and rapid route to highly enantiopure 1,2-diols by novel catalytic asymmetric α-aminoxylation of aldehydes. Angew. Chem. Int. Ed.,  2003, 42(35), 4247-4250.
 [http://dx.doi.org/10.1002/anie.200352097] [PMID: 14502748]; 
b) Calogero, S. Supported l-proline on zirconium phosphates methyl and/or phenyl phosphonates as heterogeneous organocatalysts for direct asymmetric aldol addition. J. Catal.,  2011, 282, 112.
 [http://dx.doi.org/10.1016/j.jcat.2011.06.004]; 
c) Doyagüez, E.G.; Calderón, F.; Sanchez, F.; Fernandez-Mayoralas, A. Asymmetric aldol reaction catalyzed by a heterogenized proline on a mesoporous support. The role of the nature of solvents. J. Org. Chem.,  2007, 72(24), 9353-9356.
 [http://dx.doi.org/10.1021/jo070992s] [PMID: 17958368]

[34]
Vachan, B.S.; Karuppasamy, M.; Vinoth, P.; Kumar, S.V.; Perumal, S.; Vellaisamy, S.; Menéndez, J.C. Proline and its derivatives as organocatalysts for multi-component reactions in aqueous media: Synergic pathways to the green synthesis of heterocycles. Adv. Synth. Catal.,  2020, 362(1), 2020.
 [http://dx.doi.org/10.1002/adsc.201900558]

[35]
List, B.; Lerner, R.A.; Barbas, C.F., III Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc.,  2000, 122, 2395.
 [http://dx.doi.org/10.1021/ja994280y]

[36]
Hoang, L.; Bahmanyar, S.; Houk, K.N.; List, B. Kinetic and stereochemical evidence for the involvement of only one proline molecule in the transition states of proline-catalyzed intra- and intermolecular aldol reactions. J. Am. Chem. Soc.,  2003, 125(1), 16-17.
 [http://dx.doi.org/10.1021/ja028634o] [PMID: 12515489]

[37]
Ramachary, D.B.; Kishor, M. Direct catalytic asymmetric synthesis of highly functionalized tetronic acids/tetrahydro-isobenzofuran-1,5-diones via combination of cascade three-component reductive alkylations and Michael-aldol reactions. Org. Biomol. Chem.,  2010, 8(12), 2859-2867.
 [http://dx.doi.org/10.1039/c003588b] [PMID: 20454721]

[38]
Jimeno, C. Water in asymmetric organocatalytic systems: A global perspective. Org. Biomol. Chem.,  2016, 14(26), 6147-6164.
 [http://dx.doi.org/10.1039/C6OB00783J] [PMID: 27215302]

[39]
Pidathala, C.; Hoang, L.; Vignola, N.; List, B. Direct catalytic asymmetric enolexo aldolizations. Angew. Chem. Int. Ed.,  2003, 42(24), 2785-2788.
 [http://dx.doi.org/10.1002/anie.200351266] [PMID: 12820268]

[40]
Sekiguchi, Y.; Sasaoka, A.; Shimomoto, A.; Fujioka, S.; Kotsuki, H. High-pressure-promoted asymmetric aldol reactions of ketones with aldehydes catalyzed by L-proline. Synlett,  2003, 1655.

[41]
a) Hayashi, Y.; Tsuboi, W.; Shoji, M.; Suzuki, N. Application of high pressure, induced by water freezing, to the direct asymmetric aldol reaction. Tetrahedron Lett.,  2004, 45, 4353.
 [http://dx.doi.org/10.1016/j.tetlet.2004.03.190]; 
b) Mossé, S.; Alexakis, A. Organocatalyzed asymmetric reactions via microwave activation. Org. Lett.,  2006, 8(16), 3577-3580.
 [http://dx.doi.org/10.1021/ol0614727] [PMID: 16869664]

[42]
Zimmerman, H.E.; Traxler, M.D. The stereochemistry of the ivanov and reformatsky reactions. J. Am. Chem. Soc.,  1957, 79, 1920.
 [http://dx.doi.org/10.1021/ja01565a041]

[43]
a) Bahmanyar, S.; Houk, K.N. Transition states of amine-catalyzed aldol reactions involving enamine intermediates: Theoretical studies of mechanism, reactivity, and stereoselectivity. J. Am. Chem. Soc.,  2001, 123(45), 11273-11283.
 [http://dx.doi.org/10.1021/ja011403h] [PMID: 11697970]; 
b) Bahmanyar, S.; Houk, K.N. The origin of stereoselectivity in proline-catalyzed intramolecular aldol reactions. J. Am. Chem. Soc.,  2001, 123(51), 12911-12912.
 [http://dx.doi.org/10.1021/ja011714s] [PMID: 11749554]; 
c) Bahmanyar, S.; Houk, K.N.; Martin, H.J.; List, B. Quantum mechanical predictions of the stereoselectivities of proline-catalyzed asymmetric intermolecular aldol reactions. J. Am. Chem. Soc.,  2003, 125(2475); 
d) Bahmanyar, S.; Houk, K.N. Origins of opposite absolute stereoselectivities in proline-catalyzed direct Mannich and aldol reactions. Org. Lett.,  2003, 5, 1249.; 
e) Clemente, F.R.; Houk, K.N. Computational evidence for the enamine mechanism of intramolecular aldol reactions catalyzed by proline. Angew. Chem. Int. Ed.,  2004, 43, 5765.; 
f) Cheong, P.H-Y.; Warrier, J.S.; Hanessian, S. Catalysis of the Hajos—Parrish—Eder—Sauer—Wiechert reaction by cis- and trans-4,5-Methanoprolines: Sensitivity of proline catalysis to pyrrolidine ring. Adv. Synth. Catal.,  2004, 346, 1111.; 
g) Cheong, P.H-Y.; Houk, K.N. Origins and predictions of stereoselectivity in intramolecular aldol reactions catalyzed by proline derivatives. Synthesis,  2005, 9, 1533.; 
h) Clemente, F.R.; Houk, K.N. Theoretical studies of stereoselectivities of intramolecular aldol cyclizations catalyzed by amino acids. J. Am. Chem. Soc.,  2005, 12711294.; 
i) Arnó, M.; Domingo, K.R. Density functional theory study of the mechanism of the proline-catalyzed intermolecular aldol reaction. Theor. Chem. Acc.,  2002, 108, 232.; 
j) Rankin, K.N.; Gauld, J.W.; Boyd, R.J. Density functional study of the proline-catalyzed direct aldol reaction. J. Phys. Chem. A,  2002, 106, 5155.; 
k) List, B.; Hoang, L.; Martin, H.J. New mechanistic studies on the proline-catalyzed aldol reaction. Proc. Natl. Acad. Sci.,  2004, 101, 5839.; 
l) Marquez, C.; Metzger, J.O. ESI-MS study on the aldol reaction catalyzed by L-proline. Chem. Commun. (Camb.),  2006, 14, 1539-1541.

[44]
Chowdari, N.S. Proline-catalyzed asymmetric assembly reactions: Enzyme-like assembly of carbohydrates and polyketides from three aldehyde substrates. Tetrahedron Lett.,  2002, 43, 9591-9595.
 [http://dx.doi.org/10.1016/S0040-4039(02)02412-7]

[45]
Gröger, H.; Wilken, J. The application of L-proline as an enzyme mimic and further new asymmetric syntheses using small organic molecules as chiral catalysts. Angew. Chem. Int. Ed. Engl.,  2001, 40(3), 529-532.
 [http://dx.doi.org/10.1002/1521-3773(20010202)40:3<529:AID-ANIE529>3.0.CO;2-X] [PMID: 11180360]

[46]
Mase, N.; Tanaka, F.; Barbas, C.F. III Synthesis of β-hydroxyaldehydes with stereogenic quaternary carbon centers by direct organocatalytic asymmetric aldol reactions. Angew. Chem. Int. Ed.,  2004, 43(18), 2420-2423.
 [http://dx.doi.org/10.1002/anie.200353546] [PMID: 15114579]

[47]
a) Seebach, D.; Boes, M.; Naef, R.; Schweizer, W.B. Alkylation of amino acids without loss of the optical activity: Preparation of. alpha.-substituted proline derivatives. A case of self-reproduction of chirality. J. Am. Chem. Soc.,  1983, 105, 5390-5398.
 [http://dx.doi.org/10.1021/ja00354a034]; 
b) Orsini, F.; Pelizzoni, F.; Forte, M.; Sisti, M.; Bombieri, G.; Benetollo, F. Behaviour of aminoacids and aliphatic aldehydes in dipolar aprotic solvents: Formation of oxazolidinones-behaviour of aminoacids and aliphatic aldehydes in dipolar aprotic solvents. J. Heterocycl. Chem.,  1989, 26, 837-841.
 [http://dx.doi.org/10.1002/jhet.5570260360]; 
c) Szöllosi, G.; London, G.; Baláspiri, L.; Somlai, C.; Bartók, M. Enantioselective direct aldol addition of acetone to aliphatic aldehydes. Chirality,  2003, 15(Suppl.), S90-S96.
 [http://dx.doi.org/10.1002/chir.10267] [PMID: 12884379]

[48]
Notz, W.; List, B. Catalytic asymmetric synthesis of anti-1,2-Diols. J. Am. Chem. Soc.,  2000, 122, 7386.
 [http://dx.doi.org/10.1021/ja001460v]

[49]
Liu, H.; Peng, L.; Zhang, T.; Li, Y. L-Proline catalyzed asymmetric aldol reactions of protected hydroxyacetone. New J. Chem.,  2003, 27, 1159.
 [http://dx.doi.org/10.1039/b304019b]

[50]
Thayumanavan, R.; Tanaka, F.; Barbas, C.F. III Direct organocatalytic asymmetric aldol reactions of α-amino aldehydes: Expedient syntheses of highly enantiomerically enriched anti-β-hydroxy-α-amino acids. Org. Lett.,  2004, 6(20), 3541-3544.
 [http://dx.doi.org/10.1021/ol0485417] [PMID: 15387543]

[51]
Källström, S.; Erkkilä, A.; Pihko, P.M.; Sjöholm, R.; Sillan-pää, R.; Leino, R. Consecutive proline-catalyzed aldol reactions and metal-mediated allylations: Rapid entries to poly-propionates. Synlett,  2005, 751.

[52]
Northrup, A.B.; MacMillan, D.W. The first direct and enantioselective cross-aldol reaction of aldehydes. J. Am. Chem. Soc.,  2002, 124(24), 6798-6799.
 [http://dx.doi.org/10.1021/ja0262378] [PMID: 12059180]

[53]
a) Pan, Q.; Zou, B.; Wang, Y.; Ma, D. Diastereoselective aldol reaction of N,N-dibenzyl-α-amino aldehydes with ketones catalyzed by proline. Org. Lett.,  2004, 6(6), 1009-1012.
 [http://dx.doi.org/10.1021/ol049927k] [PMID: 15012087]; 
b) Kumar, I.; Rode, C.V. Stereoselective synthesis of 2-amino-1, 3, 5-hexane triols using l-proline catalyzed aldol reaction. Tetrahedron Asymmetry,  2006, 17, 763.
 [http://dx.doi.org/10.1016/j.tetasy.2006.02.013]

[54]
Casas, J.; Sundén, H.; Córdova, A. Direct organocatalytic asymmetric α-hydroxymethylation of ketones and aldehydes. Tetrahedron Lett.,  2004, 45, 6117.
 [http://dx.doi.org/10.1016/j.tetlet.2004.06.062]

[55]
a) Ward, D.E.; Jheengut, V. Proline-catalyzed asymmetric aldol reactions of tetrahydro-4H-thiopyran-4-one with aldehydes. Tetrahedron Lett.,  2004, 45, 8347.
 [http://dx.doi.org/10.1016/j.tetlet.2004.09.061]; 
b) Ward, D.E.; Jheengut, V.; Akinnusi, O.T. Enantioselective direct intermolecular aldol reactions with enantiotopic group selectivity and dynamic kinetic resolution. Org. Lett.,  2005, 7(6), 1181-1184.
 [http://dx.doi.org/10.1021/ol050195l] [PMID: 15760169]

[56]
Majewski, M.; Niewczas, I.; Palyam, N. Acids as proline co-catalysts in the aldol reaction of 1, 3-dioxan-5-ones. Synlett,  2006, 2387.
 [http://dx.doi.org/10.1055/s-2006-950421]

[57]
a) Zhou, Y.; Shan, Z. (R)-or (S)-Bi-2-naphthol assisted, l-proline catalyzed direct aldol reaction. Tetrahedron Asymmetry,  2006, 17, 1671.
 [http://dx.doi.org/10.1016/j.tetasy.2006.06.022]; 
b) Zhou, Y.; Shan, Z. Chiral diols: A new class of additives for direct aldol reaction catalyzed by L-proline. J. Org. Chem.,  2006, 71(25), 9510-9512.
 [http://dx.doi.org/10.1021/jo060802y] [PMID: 17137384]

[58]
a) Chandrasekhar, S.; Vijeender, K.; Reddy, K.V. New synthesis of flavanones catalyzed by L-proline. Tetrahedron Lett.,  2005, 46, 6991.
 [http://dx.doi.org/10.1016/j.tetlet.2005.08.066]; 
b) Baker-Glenn, C.; Ancliff, R.; Gouverneur, V. A bio-catalytic route to enantioenriched, sulfanyl aldol products. Tetrahedron,  2004, 60, 7607.
 [http://dx.doi.org/10.1016/j.tet.2004.06.033]; 
c) Edin, M.; Bäckvall, J-E.; Córdova, A. Tandem enantioselective organo-and biocatalysis: A direct entry for the synthesis of enantiomerically pure aldols. Tetrahedron Lett.,  2004, 45, 7697.
 [http://dx.doi.org/10.1016/j.tetlet.2004.08.079]

[59]
Chan, V.; Kim, J.G.; Jimeno, C.; Carroll, P.J.; Walsh, P.J. Dynamic kinetic resolution of atropisomeric amides. Org. Lett.,  2004, 6(12), 2051-2053.
 [http://dx.doi.org/10.1021/ol0492952] [PMID: 15176816]

[60]
Tokuda, O.; Kano, T.; Gao, W-G.; Ikemoto, T.; Maruoka, K. A practical synthesis of (S)-2-cyclohexyl-2-phenylglycolic acid via organocatalytic asymmetric construction of a tetrasubstituted carbon center. Org. Lett.,  2005, 7(22), 5103-5105.
 [http://dx.doi.org/10.1021/ol052164w] [PMID: 16235968]

[61]
Funabiki, K.; Yamamoto, H.; Nagaya, H.; Matsui, M. Proline-catalyzed direct asymmetric aldol reaction of trifluoroacetaldehyde ethyl hemiacetal with ketones. Tetrahedron Lett.,  2006, 47, 5507.
 [http://dx.doi.org/10.1016/j.tetlet.2006.05.165]

[62]
Bøgevig, A.; Kumaragurubaran, N.; Jørgensen, K.A. Direct catalytic asymmetric aldol reactions of aldehydes. Chem. Commun. (Camb.),  2002, (6), 620-621.
 [http://dx.doi.org/10.1039/b200681b] [PMID: 12120152]

[63]
Samanta, S.; Zhao, C-G. Asymmetric direct aldol reaction of 1, 2-diketones and ketones mediated by proline derivatives. Tetrahedron Lett.,  2006, 47, 3383.
 [http://dx.doi.org/10.1016/j.tetlet.2006.03.085]

[64]
Samanta, S.; Zhao, C-G. Organocatalytic enantioselective synthesis of α-hydroxy phosphonates. J. Am. Chem. Soc.,  2006, 128(23), 7442-7443.
 [http://dx.doi.org/10.1021/ja062091r] [PMID: 16756289]

[65]
Chen, G.; Wang, Y.; He, H.; Gao, S.; Yang, X.; Hao, X. L-proline-catalyzed asymmetric aldol condensation of N-substituted isatins with acetone. Heterocycles,  2006, 68, 2327.
 [http://dx.doi.org/10.3987/COM-06-10856]

[66]
a) Brogan, A.P.; Dickerson, T.J.; Janda, K.D. Enamine-based aldol organocatalysis in water: Are they really “all wet”? Angew. Chem. Int. Ed.,  2006, 45(48), 8100-8102.
 [http://dx.doi.org/10.1002/anie.200601392] [PMID: 17001595]; 
b) Hayashi, Y. In water or in the presence of water? Angew. Chem. Int. Ed.,  2006, 45, 8103.; 
c) Blackmond, D.G.; Armstrong, A.; Coombe, V.; Wells, A. Water in organocatalytic processes: Debunking the myths. Angew. Chem. Int. Ed.,  2007, 46, 3798.; 
d) Córdova, A.; Notz, W.; Barbas, C.F. Direct organocata-lytic aldol reactions in buffered aqueous media. Chem. Commun.,  2002, 3024.; 
e) Peng, Y-Y.; Ding, Q-P.; Li, Z.; Wang, P.G.; Cheng, J-P. Proline catalyzed aldol reactions in aqueous micelles: An environmentally friendly reaction system. Tetrahedron Lett.,  2003, 44, 3871.; 
f) Nyberg, A. I.; Usano, A.; Pihko, P.M Proline-catalyzed ketone-aldehyde aldol reactions are accelerated by water. Synlett.,  2004, 1891; 
g) Wu, Y-S.; Chen, Y.; Deng, D-S.; Cai, J. Proline-catalyzed asymmetric direct aldol reaction assisted by D-camphorsulfonic acid in aqueous media. Synlett,  2005, 1627.; 
h) Balalaie, S.; Bararjanian, M.; Amani, A.M.; Movas-sagh, B. (S)-Proline as a neutral and efficient catalyst for the one-pot synthesis of tetrahydrobenzo [b] pyran derivatives in aqueous media. Synlett,  2006, 263.

[67]
a) Darbre, T.; Machuqueiro, M. Zinc-proline catalyzed pathway for the formation of sugars. Chem. Commun. (Camb.),  2004, 13, 1540-1541.
 [http://dx.doi.org/10.1039/b301117h] [PMID: 12772917]; 
b) Wu, Y-S.; Shao, W-Y.; Zheng, C-Q.; Huang, Z-L.; Cai, J.; Deng, Q-Y. Studies on direct stereoselective aldol reactions in aqueous media. Helv. Chim. Acta,  2004, 87, 1377.
 [http://dx.doi.org/10.1002/hlca.200490125]; 
c) Fernandez-Lopez, R.; Kofoed, J.; Machuqueiro, M.; Darbre, T. A selective direct aldol reaction in aqueous media catalyzed byzinc-proline. Eur. J. Org. Chem.,  2005, 24, 5268-5276.
 [http://dx.doi.org/10.1002/ejoc.200500352]; 
d) Kofoed, J.; Darbre, T.; Reymond, J-L. Dual mechanism of zinc-proline catalyzed aldol reactions in water. Chem. Commun. (Camb.),  2006, (14), 1482-1484.
 [http://dx.doi.org/10.1039/b600703a] [PMID: 16575434]

[68]
Chandrasekhar, S.; Reddy, N.R.; Sultana, S.S.; Narsihmulu, Ch.; Reddy, K.V. L-Proline catalysed asymmetric aldol reactions in PEG-400 as recyclable medium and transfer aldol reactions. Tetrahedron,  2006, 62, 338.
 [http://dx.doi.org/10.1016/j.tet.2005.09.122]

[69]
a) Loh, T-P.; Feng, L-C.; Yang, H-Y.; Yang, J-Y. L-Proline in an ionic liquid as an efficient and reusable catalyst for direct asymmetric aldol reactions. Tetrahedron Lett.,  2002, 43, 8741.
 [http://dx.doi.org/10.1016/S0040-4039(02)02104-4]; 
b) Kotrusz, P.; Kmentová, I.; Gotov, B.; Toma, Š.; Solčániová, E. Proline-catalysed asymmetric aldol reaction in the room temperature ionic liquid [bmim] PF6. Chem. Commun. (Camb.),  2002, 21, 2510.
 [http://dx.doi.org/10.1039/B206911C]; 
c) Kitazume, T.; Jiang, Z.; Kasai, K.; Mihara, Y.; Suzuki, M. Synthesis of fluorinated materials catalyzed by proline or antibody 38C2 in ionic liquid. J. Fluor. Chem.,  2003, 121, 205.
 [http://dx.doi.org/10.1016/S0022-1139(03)00032-0]; 
d) Chowdari, N.S.; Ramachary, D.B.; Barbas, C.F., III Organocatalysis in ionic liquids: Highly efficient L-proline-catalyzed direct asymmetric Mannich reactions involving ketone and aldehyde nucleophiles. Synlett,  2003, 35(12), 1906-1909.; 
e) Gruttadauria, M.; Riela, S.; Lo Meo, P.; D’Anna, F.; Noto, R. Supported ionic liquid asymmetric catalysis. A new method for chiral catalysts recycling. The case of proline-catalyzed aldol reaction. Tetrahedron Lett.,  2004, 45, 6113.
 [http://dx.doi.org/10.1016/j.tetlet.2004.06.066]

[70]
a) Kellogg, R.M. The crystallization behavior of proline and its role in asymmetric organocatalysis. Angew. Chem. Int. Ed.,  2007, 46(4), 494-497.
 [http://dx.doi.org/10.1002/anie.200603028] [PMID: 17183591]; 
b) Zhong, L.; Xiao, J.; Li, C. An unexpected inversion of enantioselectivity in direct asymmetric aldol reactions on a unique L-proline/γ-Al2O3 catalyst. J. Catal.,  2006, 243, 442.
 [http://dx.doi.org/10.1016/j.jcat.2006.07.025]; 
c) Hayashi, Y.; Matsuzawa, M.; Yamaguchi, J.; Yonehara, S.; Matsumoto, Y.; Shoji, M.; Hashizume, D.; Koshino, H. Large nonlinear effect observed in the enantiomeric excess of proline in solution and that in the solid state. Angew. Chem. Int. Ed.,  2006, 45(28), 4593-4597.
 [http://dx.doi.org/10.1002/anie.200601506] [PMID: 16819754]; 
d) Rodríguez, B.; Rantanen, T.; Bolm, C. Solvent-free asymmetric organocatalysis in a ball mill. Angew. Chem. Int. Ed.,  2006, 45(41), 6924-6926.
 [http://dx.doi.org/10.1002/anie.200602820] [PMID: 17001709]

[71]
a) Bøgevig, A.; Gothelf, K.V.; Jørgensen, K.A. Nucleophilic
addition of nitrones to ketones: Development of a new catalytic
asymmetric nitrone-aldol reaction. Chemistry,  2002, 8(24), 5652-5661.
 [http://dx.doi.org/10.1002/1521-3765(20021216)8:24<5652::AID-CHEM5652>3.0.CO;2-J] [PMID: 12693046]; 
b) Bøgevig, A.; Poulsen, T.B.; Zhuang, W.; Jørgensen, K.A. Formation of optically active functionalized β-hydroxy nitrones using a proline catalyzed aldol reaction of aldehydes with carbonyl compounds and hydroxylamines. Synlett,  2003, 35(12), 1915-1918.; 
c) Arnó, M.; Zaragozá, R.J.; Domingo, L.R. The nucleo-philic addition of nitrones to carbonyl compounds: Insights on the nature of the mechanism of the l-proline induced asymmetric reaction from a DFT analysis. Tetrahedron Asymmetry,  2004, 15, 1541.
 [http://dx.doi.org/10.1016/j.tetasy.2004.03.031]

[72]
a) Sigman, M.S.; Jacobsen, E.N. Enantioselective addition of
hydrogen cyanide to imines catalyzed by a chiral (salen) Al (III)
complex. J. Am. Chem. Soc.,  1998, 120, 5315.
 [http://dx.doi.org/10.1021/ja980299+]; 
b) Sigman, M.S.; Vachal, P.; Jacobsen, E.N. A general catalyst for the asymmetric strecker reaction this work was supported by the NIH (GM-43214). A postdoctoral fellow-ship to M.S.S. (NIH), and a predoctoral fellowship to P.V. sponsored by Alfred Bader are gratefully acknowledged. Angew. Chem. Int. Ed. Engl.,  2000, 39(7), 1279-1281.
 [http://dx.doi.org/10.1002/(SICI)1521-3773(20000403)39:7<1279:AID-ANIE1279>3.0.CO;2-U] [PMID: 10767031]; 
c) Sigman, M.S.; Jacobsen, E.N. Schiff base catalysts for the asymmetric Strecker reaction identified and optimized from parallel synthetic libraries. J. Am. Chem. Soc.,  1998, 120, 4901.
 [http://dx.doi.org/10.1021/ja980139y]; 
d) Krueger, C.A.; Kuntz, K.W.; Dzierba, C.D.; Wirschun, W.G.; Gleason, J.D.; Snapper, M.L.; Hoveyda, A.H. Ti-catalyzed enantioselective addition of cyanide to imines. A practical synthesis of optically pure α-amino acids. J. Am. Chem. Soc.,  1999, 121, 4284.
 [http://dx.doi.org/10.1021/ja9840605]

[73]
a) Yamasaki, S.; Iida, T.; Shibasaki, M. Direct catalytic asymmetric Mannich reaction of unmodified ketones: Cooperative catalysis of an AlLibis (binaphthoxide) complex and La (OTf) 3· nH2O. Tetrahedron,  1999, 55, 8857.
 [http://dx.doi.org/10.1016/S0040-4020(99)00449-4]; 
b) Desale, V.J.; Mali, S.N.; Thorat, B.R.; Yamgar, R.S. Synthesis,
admetSAR Predictions, DPPH Radical Scavenging Activity, and
Potent Anti-mycobacterial Studies of Hydrazones of Substituted 4-
(anilino methyl) benzohydrazides (Part 2). Curr. Computeraided Drug Des.,  2021, 17(4), 493-503.
 [http://dx.doi.org/10.2174/1573409916666200615141047] [PMID: 32538732]; 
c) Juhl, K.; Gathergood, N.; Jørgensen, K.A. Catalytic asymmetric
direct mannich reactions of carbonyl compounds with α-Imino Esters. Angew. Chem. Int. Ed.,  2001, 40(16), 2995-2997.
 [http://dx.doi.org/10.1002/1521-3773(20010817)40:16<2995::AID-ANIE2995>3.0.CO;2-M] [PMID: 12203627]; 
d) Córdova, A.; Notz, W.; Zhong, G.; Betancort, J.M.; Barbas, C.F. III A highly enantioselective amino acid-catalyzed route to functionalized α-amino acids. J. Am. Chem. Soc.,  2002, 124(9), 1842-1843.
 [http://dx.doi.org/10.1021/ja017270h] [PMID: 11866583]; 
e) Córdova, A.; Watanabe, S.; Tanaka, F.; Notz, W.; Barbas, C.F. III A highly enantioselective route to either enantiomer of both α- and β-amino acid derivatives. J. Am. Chem. Soc.,  2002, 124(9), 1866-1867.
 [http://dx.doi.org/10.1021/ja017833p] [PMID: 11866595]

[74]
Kumaragurubaran, N.; Juhl, K.; Zhuang, W.; Bøgevig, A.; Jørgensen, K.A. Direct L-proline-catalyzed asymmetric α-amination of ketones. J. Am. Chem. Soc.,  2002, 124(22), 6254-6255.
 [http://dx.doi.org/10.1021/ja026412k] [PMID: 12033850]

[75]
Feng, X.; Jena, H.S.; Leus, K.; Wang, G.; Ouwehand, J.; Van Der Voort, P. l-proline modulated zirconium metal organic frameworks: Simple chiral catalysts for the aldol addition reaction. J. Catal.,  2018, 365, 36-42.
 [http://dx.doi.org/10.1016/j.jcat.2018.06.013]

[76]
Guillena, G.; Marı’a del Carmen, H.; Na’jera, .; C, . Organocatalyzed direct aldol condensation using L-proline and BINAM-prolinamides: Regio-, diastereo-, and enantioselective controlled synthesis of 1, 2-diols. Tetrahedron Asymmetry,  2006, 17, 1027-1031.
 [http://dx.doi.org/10.1016/j.tetasy.2006.03.023]

[77]
Ibrahem, I.; Zou, W.; Casas, J.; Sundén, H.; Córdova, A. Direct organocatalytic enantioselective α-aminomethylation of ketones. Tetrahedron,  2006, 62, 357.
 [http://dx.doi.org/10.1016/j.tet.2005.08.113]

[78]
Yang, J.W.; Chandler, C.; Stadler, M.; Kampen, D.; List, B. Proline-catalysed Mannich reactions of acetaldehyde. Nature,  2008, 452(7186), 453-455.
 [http://dx.doi.org/10.1038/nature06740] [PMID: 18288105]

[79]
Indumathi, S.; Perumal, S.; Menéndez, J.C. l-Proline-catalysed three-component domino reactions for the diastereoselective synthesis of 5, 6-disubstituted 3-thiomorpholinones. Tetrahedron,  2011, 67, 7101.
 [http://dx.doi.org/10.1016/j.tet.2011.06.107]

[80]
Schulz, K.; Ratjen, L.; Martens, J. Homo-and heterogeneous organocatalysis: Enantioselective Mannich addition of ketones to endocyclic carbon-nitrogen double bonds. Tetrahedron,  2011, 67, 546.
 [http://dx.doi.org/10.1016/j.tet.2010.10.079]

[81]
Indumathi, S.; Perumal, S.; Banerjee, D.; Yogeeswari, P.; Sriram, D. L-proline-catalysed facile green protocol for the synthesis and antimycobacterial evaluation of [1,4]-thiazines. Eur. J. Med. Chem.,  2009, 44(12), 4978-4984.
 [http://dx.doi.org/10.1016/j.ejmech.2009.09.001] [PMID: 19781824]

[82]
Veverková, E.; Štrasserová, J.; Šebesta, R.; Toma, Š. Asymmetric Mannich reaction catalyzed by N-arylsulfonyl-L-proline amides. Tetrahedron Asymmetry,  2010, 21, 58.
 [http://dx.doi.org/10.1016/j.tetasy.2009.12.013]

[83]
Gnanamani, E.; Yan, X.; Zare, R.N. Chemoselective N-alkylation of indoles in aqueous microdroplets. Angew. Chem. Int. Ed. Engl.,  2020, 59(8), 3069-3072.
 [http://dx.doi.org/10.1002/anie.201913069] [PMID: 31837281]

[84]
List, B. The direct catalytic asymmetric three-component Mannich reaction. J. Am. Chem. Soc.,  2000, 122, 9336.
 [http://dx.doi.org/10.1021/ja001923x]

[85]
He, Y-H.; Cao, J-F.; Li, R.; Xiang, Y.; Yang, D-C.; Guan, Z. L-Proline-catalyzed multicomponent synthesis of 3-indole derivatives. Tetrahedron,  2015, 71, 9299-9306.
 [http://dx.doi.org/10.1016/j.tet.2015.10.027]

[86]
Kumar, A.; Gupta, M.K.; Kumar, M. L-Proline catalysed multicomponent synthesis of 3-amino alkylated indoles via a Mannich-type reaction under solvent-free conditions. Green Chem.,  2012, 14, 290.
 [http://dx.doi.org/10.1039/C1GC16297G]

[87]
Ghosh, P.P.; Das, A.R. Nano crystalline ZnO: A competent and reusable catalyst for one pot synthesis of novel benzylamino coumarin derivatives in aqueous media. Tetrahedron Lett.,  2012, 53, 3140-3143.
 [http://dx.doi.org/10.1016/j.tetlet.2012.04.033]

[88]
Srinivas, N.; Bhandari, K. Proline-catalyzed facile access to Mannich adducts using unsubstituted azoles. Tetrahedron Lett.,  2008, 49, 7070-7073.
 [http://dx.doi.org/10.1016/j.tetlet.2008.09.155]

[89]
Srinivas, N.; Marrapu, V.K.; Bhandari, K. A mild and efficient bisaldolization of ketones and its application towards spirocyclic 1, 3-dioxanes and novel 1, 3, 5-trioxocanes. Synlett,  2009, 1346-1350.

[90]
Dongare, S.B.; Chavan, H.V.; Bhale, P.S.; Mule, Y.B.; Kotmale, A.S.; Bandgar, B.P. A catalyst-and solvent-free multicomponent synthesis of 7-azagramine analogues via a Mannich type reaction. Chin. Chem. Lett.,  2016, 27, 99-103.
 [http://dx.doi.org/10.1016/j.cclet.2015.07.029]

[91]
Jafari, A.A.; Moradgholi, F.; Tamaddon, F. A highly efficient michael addition of indoles to α β-unsaturated electron-deficient compounds in acidic SDS micellar media. J. Iran. Chem. Soc,  2009, 6, 588-593.
 [http://dx.doi.org/10.1007/BF03246538]

[92]
Bandi, M.; Reddy, C.V.R. Water mediated, eco-friendly enantioselective synthesis of indole substituted N-heterocyclic compounds via Friedel-Crafts alkylation. Lett. Org. Chem.,  2017, 14, 372-380.

[93]
Rasalkar, M.S.; Potdar, M.K.; Mohile, S.S.; Salunkhe, M.M. An ionic liquid influenced L-proline catalysed asymmetric Michael addition of ketones to nitrostyrene. J. Mol. Catal. Chem.,  2005, 235, 267.
 [http://dx.doi.org/10.1016/j.molcata.2005.03.024]

[94]
a) Zhao, H.; Yang, Z.; Yue, Y.; Li, H.; Song, X.; Sheng, Z.; Meng, W.; Guo, X. Asymmetric direct Michael reactions of cyclohexanone with aromatic nitroolefins in water catalyzed by novel axially unfixed biaryl-based bifunctional organocatalysts. Synlett,  2014, 25, 293.
 [http://dx.doi.org/10.1055/s-0033-1340289]; 
b) Bhanja, C.; Jena, S.; Nayak, S.; Mohapatra, S. Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines. Beilstein J. Org. Chem.,  2012, 8, 1668-1694.
 [http://dx.doi.org/10.3762/bjoc.8.191] [PMID: 23209500]; 
c) Xu, D.; Wang, Y.; Luo, S.; Zhang, S.; Zhong, A.; Chen, H.; Xu, Z. A novel enantioselective catalytic Tandem Oxa-Michael-Henry reaction: One-pot organocatalytic asymmetric synthesis of 3-Nitro-2H-chromenes. Adv. Synth. Catal.,  2008, 350, 2610.
 [http://dx.doi.org/10.1002/adsc.200800535]; 
d) Karthikeyan, T.; Sankararaman, S. New pyrrolidine-triazole-based C2 symmetric organocatalysts and their utility in the asymmetric Michael reaction of β-nitrostyrenes and the synthesis of nitrochromenes. Tetrahedron Asymmetry,  2008, 19, 2741.
 [http://dx.doi.org/10.1016/j.tetasy.2008.12.007]; 
e) Das, B.C.; Mohapatra, S.; Campbell, P.D.; Nayak, S.; Mahalingam, S.M.; Evans, T. Synthesis of function-oriented 2-phenyl-2H-chromene derivatives using L-pipecolinic acid and substituted guanidine organocatalysts. Tetrahedron Lett.,  2010, 51(19), 2567-2570.
 [http://dx.doi.org/10.1016/j.tetlet.2010.02.143] [PMID: 21785516]; 
f) Zhang, Z.; Jakab, G.; Schreiner, P.R. Enantioselective synthesis of 2-aryl-3-nitro-2H-chromenes catalyzed by a bi-functional thiourea. Synlett,  2011, 9, 1262.; 
g) Yin, G.; Zhang, R.; Li, L.; Tian, J.; Chen, L. One-pot enantioselective synthesis of 3-Nitro-2H-chromenes catalyzed by a Simple 4-Hydroxyprolinamide with 4-Nitrophenol as Cocatalyst. J. Org. Chem.,  2013, 24, 5431.

[95]
do Carmo, L.F.; Silva, S.C.; Machado, M.V. The role of L-Proline and co-catalysts in the enantioselectivity of OXA-Michael-Henry reactions. J. Braz. Chem. Soc.,  2019, 30(5), 893-903.

[96]
Cai, Q.; Zhang, H.; Zou, B.; Xie, X.; Zhu, W.; He, G.; Wang, J.; Pan, X.; Chen, Y.; Yuan, Q.; Liu, F.; Lu, B.; Ma, D. Amino acid-promoted Ullmann-type coupling reactions and their applications in organic synthesis. Pure Appl. Chem.,  2009, 81(2), 227-234.
 [http://dx.doi.org/10.1351/PAC-CON-08-08-19]

[97]
Zhu, W.; Ma, D. Synthesis of aryl sulfones viaL-proline-promoted CuI-catalyzed coupling reaction of aryl halides with sulfinic acid salts. J. Org. Chem.,  2005, 70(7), 2696-2700.
 [http://dx.doi.org/10.1021/jo047758b] [PMID: 15787561]

[98]
Kumar, A.; Maurya, R.M. Organocatalysed three-component domino synthesis of 1, 4-dihydropyridines under solvent free conditions. Tetrahedron,  2008, 64, 3477-3482.
 [http://dx.doi.org/10.1016/j.tet.2008.02.022]

[99]
Sivamurugan, V.; Suresh kumar, R.; Palanichamy, M.; Murugesan, V. Synthesis of hantzsch 1,4-dihydropyridines under solvent-free condition using zn[ (L)proline]2 as lewis acid catalys. J. Heterocycl. Chem.,  2005, 42, 969.
 [http://dx.doi.org/10.1002/jhet.5570420534]

[100]
Tamaddon, F.; Razmi, Z.; Jafari, A.A. Synthesis of 3, 4-dihydropyrimidin-2(1H)-ones and 1, 4-dihydropyridines using ammonium carbonate in water. Tetrahedron Lett.,  2010, 51, 1187.
 [http://dx.doi.org/10.1016/j.tetlet.2009.12.098]

[101]
Srivastava, V. Recyclable L-proline organocatalyst for Wie-land-Miescher ketone synthesis. J. Chem. Sci.,  2013, 125(6), 1523-1527.
 [http://dx.doi.org/10.1007/s12039-013-0527-2]

[102]
Ramamurthi, N.; Swaminathan, S. Proline-catalysed asymmetric annelations: A novel observation. Indian J. Chem.,  1990, 29B, 401-404.

[103]
a) Ragagopal, D.; Narayanan, R.; Swaminathan, S. Asymmetric one-pot Robinson annulations. Tetrahedron Lett.,  2001, 42, 4887.; 
b) Enantioselective solvent-free Robinson annulation reactions Proc. Indian Acad. Sci. Chem. Sci.,  2001, 113, 197.

[104]
Przezdziecka, A.; Stepanenko, W. Wicha, Catalytic enantioselective annulation using phenylsulfanylmethyl vinyl ketone. An approach to trans-hydrindane building blocks for ent-vitamin D3 synthesis. J. Tetrahedron Asymmetry,  1999, 10, 1589.
 [http://dx.doi.org/10.1016/S0957-4166(99)00142-1]

[105]
Bui, T.; Barbas, C.F. A proline-catalyzed asymmetric Robinson annulation reaction. Tetrahedron Lett.,  2000, 42, 4887.

[106]
Bararjanian, M.; Balalaie, S.; Movassagh, B.; Amani, A.M. One-pot synthesis of pyrano [2, 3-d] pyrimidinone derivatives catalyzed by L-proline in aqueous media. J. Iran. Chem. Soc.,  2009, 6(2), 436-442.
 [http://dx.doi.org/10.1007/BF03245854]

[107]
a) Enders, D.; Hüttl, M.R.M.; Grondal, C.; Raabe, G. Control of four stereocentres in a triple cascade organocatalytic reaction. Nature,  2006, 441(7095), 861-863.
 [http://dx.doi.org/10.1038/nature04820] [PMID: 16778886]; 
b) Berkessel, A.; Groeger, H. Asymmetric Organocatlysis; 

[108]
Dam, B.; Saha, M.; Pal, A.K. Magnetically recyclable nano-FDP: A novel, efficient nano-organocatalyst for the one-pot multi-component synthesis of pyran derivatives in water under ultrasound irradiation. Catal. Lett.,  2015, 145, 1808-1816.
 [http://dx.doi.org/10.1007/s10562-015-1586-4]

[109]
Prasanna, P.; Perumal, S.; Menéndez, J.C. Chemodivergent, multicomponent domino reactions in aqueous media: L-proline-catalyzed assembly of densely functionalized 4H-pyrano[2,3-c]pyrazoles and bispyrazolyl propanoates from simple, acyclic starting materials. Green Chem.,  2013, 15, 1292-1299.
 [http://dx.doi.org/10.1039/c3gc37128j]

[110]
Muramulla, S.; Zhao, C. A new catalytic mode of the modularly designed organocatalysts (MDOs): Enantioselective synthesis of dihydropyrano [2, 3-c] pyrazoles. Tetrahedron Lett.,  2011, 52, 3905-3908.
 [http://dx.doi.org/10.1016/j.tetlet.2011.05.092]

[111]
Gou, S. Wang, S.; Li, J.D. L-Proline-catalyzed one-pot synthesis of pyrans and pyrano[2,3-c]pyrazole derivatives by a grinding method under solvent-free conditions. Synth. Commun.,  2007, 37, 2111-2120.
 [http://dx.doi.org/10.1080/00397910701396906]

[112]
a) Yan, S.; Jiang, X.; Wang, Z.; He, S.; Zhang, W. Zinc-proline complex as a novel and efficient catalyst for the green synthesis of 1H-pyrazolo [1, 2-b] phthalazine-5, 10-diones. Res. Chem. Intermed.,  2022, 1-15.
 [http://dx.doi.org/10.1007/s11164-022-04728-3]; 
b) Behbahani, F.K.; Alipour, F. One-pot synthesis of 2-amino-4H-pyrans and 2-amino-tetrahydro-4H-chromenes using L-proline, GU. J. Sci.,  2015, 28, 387-393.

[113]
Mofakham, H.; Ghadari, R.; Shaabani, A.; Pedarpour, M.; Ghasemi, S. “On-water” organic synthesis: L-proline catalyzed synthesis of pyrimidine-2, 4-dione-, benzo [g]-and dihydropyrano [2, 3-g] chromene derivatives in aqueous media. J. Iran. Chem. Soc,  2013, 10, 307-317.
 [http://dx.doi.org/10.1007/s13738-012-0160-x]

[114]
Gohil, J.D.; Patel, H.B.; Patel, M.P. Comparative study on the use of conventional, microwave and ultrasound-irradiation for the synthesis of pyrano [3, 2-c] chromene and benzopyrano [4, 3-b] chromene derivatives in water. Heterocyclic Lett,  2016, 6, 123-132.

[115]
Li, M.; Zhang, B.; Gu, Y. Facile construction of densely functionalized 4 H-chromenes via three-component reactions catalyzed by l-proline. Green Chem., 2012.
 [http://dx.doi.org/10.1039/c2gc35668f]

[116]
Li, J.; Lu, L.; Su, W. A new strategy for the synthesis of benzoxanthenes catalyzed by proline triflate in water. Tetrahedron Lett.,  2010, 51, 2434-2437.
 [http://dx.doi.org/10.1016/j.tetlet.2010.02.149]

[117]
a) Seebach, D.; Grošelj, U.; Badine, D.M.; Schweizer, W.B.; Beck, A.K. Isolation and X-Ray Structures of Reactive Intermediates of Organocatalysis with Diphenylprolinol Ethers and with Imidazolidinones Helv. Chim. Acta.,  2008, 91, 1999-2034.; 
b) Grošelj, U.; Schweizer, W.B.; Ebert, M.O.; Seebach, D. 5-Benzyl-3-methylimidazolidin-4-one-derived reactive intermediates of Organocatalysis-A Comforting Resemblance of X-Ray, NMR, and DFT solid-phase, liquid-phase, and gas-phase structures. Helv. Chim. Acta,  2009, 92, 1-13.

[118]
Abdolmohammadi, S.; Balalaie, S. Novel and efficient catalysts for the one-pot synthesis of 3, 4-dihydropyrano [c] chromene derivatives in aqueous media. Tetrahedron Lett.,  2007, 48, 3299-3303.
 [http://dx.doi.org/10.1016/j.tetlet.2007.02.135]

[119]
Nagalapalli, R.; Jaggavarapu, S.R.; Jalli, V.P.; Kamalakaran, A.S.; Gaddamanugu, G. Ultrasound promoted green and facile one-pot multicomponent synthesis of 3, 4-dihydropyrano [c] chromene derivatives. J. Chem.,  2013, 593803.
 [http://dx.doi.org/10.1155/2013/593803]

[120]
Shanthi, G.; Perumal, P.T.; Rao, U.; Sehgal, P.K. Synthesis and antioxidant activity of indolyl chromenes. Indian J. Chem.,  2009, 48B, 1319-1323.

[121]
Ganguly, N.C.; Roy, S.; Mondal, P.; Saha, R. An efficient one-pot organocatalytic synthesis of 9-(1H-indol-3-yl)-xanthen-4- (9H)-ones under mild aqueous micellar conditions. Tetrahedron Lett.,  2012, 53, 7067-7071.
 [http://dx.doi.org/10.1016/j.tetlet.2012.10.055]

[122]
Zhu, S.; Wang, J.; Xu, Z.; Li, J. An efficient one-pot synthesis of pyrano[3,2-c]quinolin-2,5-dione derivatives catalyzed by L-proline. Molecules,  2012, 17(12), 13856-13863.
 [http://dx.doi.org/10.3390/molecules171213856] [PMID: 23174901]

[123]
Indumathi, S.; Perumal, S.; Anbananthan, N. A facile eco-friendly three-component protocol for the regio-and stereoselective synthesis of functionalized trans-dihydrofuro [3, 2-c]-quinolin-4 (2 H)-ones. Green Chem.,  2012, 14, 3361-3367.
 [http://dx.doi.org/10.1039/c2gc36040c]

[124]
Liu, X-H.; Fan, J-C.; Liu, Y.; Shang, Z-C. L-Proline as an efficient and reusable promoter for the synthesis of coumarins in ionic liquid. J. Zhejiang Univ. Sci. B,  2008, 9(12), 990-995.
 [http://dx.doi.org/10.1631/jzus.B0820079] [PMID: 19067468]

[125]
Jiang, L.; Lu, X.; Zhang, H.; Jiang, Y.; Ma, D. CuI/4-hydro-L-proline as a more effective catalytic system for coupling of aryl bromides with N-boc hydrazine and aqueous ammonia. J. Org. Chem.,  2009, 74(12), 4542-4546.
 [http://dx.doi.org/10.1021/jo9006738] [PMID: 19432437]

[126]
Santos, M.M.M. Recent advances in the synthesis of biologically active spirooxindoles. Tetrahedron,  2014, 70, 9735-9757.
 [http://dx.doi.org/10.1016/j.tet.2014.08.005]

[127]
Jamatia, R.; Gupta, A.; Pal, A.K. Nano-FGT: A green and sustainable catalyst for the synthesis of spirooxindoles in aqueous medium. RSC Advances,  2016, 6, 20994-21000.
 [http://dx.doi.org/10.1039/C5RA27552K]

[128]
Khalafi-Nezhad, S.; Sarikhani, F.P. A new silica-supported organocatalyst based on L-proline: An efficient heterogeneous catalyst for one-pot synthesis of spiroindolones in water. J. Mol. Catal. Chem.,  2013, 379, 1-8.
 [http://dx.doi.org/10.1016/j.molcata.2013.07.009]

[129]
Dabiri, M.; Tisseh, Z.N.; Nobahar, M.; Bazgir, A. Organic reaction in water: A highly efficient and environmentally friendly synthesis of spiro compounds catalyzed by L‐Proline. Helv. Chim. Acta,  2011, 94, 824-830.
 [http://dx.doi.org/10.1002/hlca.201000307]

[130]
Rai, P.; Srivastava, M.; Singh, J.; Singh, J. An eco-efficient, domino synthesis of highly functionalized spiro-oxindole derivatives catalyzed by an organocatalyst in an aqueous medium. RSC Advances,  2013, 3, 18775-18782.
 [http://dx.doi.org/10.1039/c3ra43023e]

[131]
Yu, J.; Zhou, Y.; Shen, T.; Mao, W.; Chen, K.; Song, Q. Novel and efficient one-pot synthesis of spiro [Indoline-3, 4'-Pyrano [2, 3-c] pyrazole] derivatives catalysed by l-proline in aqueous medium. J. Chem. Res.,  2013, 37, 365-368.
 [http://dx.doi.org/10.3184/174751913X13687116634925]

[132]
Kalita, S.J.; Das, B.; Deka, D.C. l-Proline-catalysed one-pot regio-and diastereoselective synthesis of Spiro [pyrido [2, 3-d] pyrimidin-2-amine-6, 5'-pyrimidines] in water. SynOpen,  2017, 1, 45-49.
 [http://dx.doi.org/10.1055/s-0036-1588456]

[133]
Dommaraju, Y.; Borthakura, S.; Prajapati, D. L-proline-catalysed one-pot aza-diels-alder reaction in water: Regioselective synthesis of spiro (isoxazolo [5, 4-b] pyridine-5, 5'-pyrimidine) derivatives. Synlett,  2018, 29, 1195-1198.
 [http://dx.doi.org/10.1055/s-0036-1591949]

[134]
Arya, K.; Rajesh, U.C.; Rawat, D.W. Proline confined FAU zeolite: Heterogeneous hybrid catalyst for the synthesis of spiroheterocycles via a Mannich type reaction. Green Chem.,  2012, 14, 3344-3351.
 [http://dx.doi.org/10.1039/c2gc35822k]

[135]
Shitole, N.V.; Shelke, K.F.; Sonar, S.S.; Sadaphal, S.A.; Shingate, B.B.; Shingare, M.S. Bull. Korean Chem. Soc.,  2009, 30(9), 1963.
 [http://dx.doi.org/10.5012/bkcs.2009.30.9.1963]

[136]
Samai, S.; Nandi, G.C.; Singh, P.M.S. Singh, L-Proline: An efficient catalyst for the one-pot synthesis of 2, 4, 5-trisubstituted and 1, 2, 4, 5-tetrasubstituted imidazoles. Tetrahedron,  2009, 65, 10155-10161.
 [http://dx.doi.org/10.1016/j.tet.2009.10.019]

[137]
Damavandi, S. Facile three-component synthesis of imidazo [4, 5-b] indoles. J. Chem. Pharm. Res.,  2011, 3(6), 1157-1162.

[138]
Damavandi, S.; Sandaroos, R. L-Proline-catalyzed three-component synthesis of condensed imidazoles. Arab. J. Chem.,  2016, 9, S1138-S1143.
 [http://dx.doi.org/10.1016/j.arabjc.2011.12.004]

[139]
Maity, S.; Pathak, S.; Pramanik, A. Microwave assisted synthesis of 2,3-diaryl-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles through direct condensation of aryl 1,2-diketones and L-proline under solvent-free condition. Tetrahedron Lett.,  2013, 54, 2528-2532.
 [http://dx.doi.org/10.1016/j.tetlet.2013.03.017]

[140]
Varala, R.; Nasreen, A.; Enugala, R.; Adapa, S.R. l-Proline catalyzed selective synthesis of 2-aryl-1-arylmethyl-1H-benzimidazoles. Tetrahedron Lett.,  2007, 48, 69-72.
 [http://dx.doi.org/10.1016/j.tetlet.2006.11.010]

[141]
Kamal, A.; Babu, K.S.; Faazil, S.; Ali Hussaini, S.M.; Basha Shaik, A. L-Proline mediated synthesis of quinoxalines; Evaluation of cytotoxic and antimicrobial activity. RSC Advances,  2014, 4, 46369.
 [http://dx.doi.org/10.1039/C4RA08615E]

[142]
Heravi, M.M.; Tehrani, M.H.; Bakhtiari, K.; Oskooie, H.A. Zn [(L) proline]: A powerful catalyst for the very fast synthesis of quinoxaline derivatives at room temperature. Catal. Commun.,  2007, 8, 1341-1344.
 [http://dx.doi.org/10.1016/j.catcom.2006.11.026]

[143]
Shi, C.; Wang, J.; Chen, H.; Shi, D. Regioselective synthesis and in vitro anticancer activity of 4-aza-podophyllotoxin derivatives catalyzed by L-proline. J. Comb. Chem.,  2010, 12(4), 430-434.
 [http://dx.doi.org/10.1021/cc100003c] [PMID: 20503973]

[144]
Yuan, L.; Adam, S.; Hui, C.C.; Ting, C.Y.; Lung, C.P. L-proline catalyzed condensation reaction of aldehyde or carboxylic acid with 2-aminothiophenol under solvent-free and microwave irradiation. J. Appl. Sci. Eng.,  2012, 15(3), 311-315.

[145]
Tan, B.; Zhu, D.; Zhang, L.; Chua, P.J.; Zeng, X.; Zhong, G. Water--more than just a green solvent: A stereoselective one-pot access to all-chiral tetrahydronaphthalenes in aqueous media. Chemistry,  2010, 16(12), 3842-3848.
 [http://dx.doi.org/10.1002/chem.200902932] [PMID: 20151437]

[146]
Ma, D.; Geng, Q.; Zhang, H.; Jiang, Y. Assembly of substituted phenothiazines by a sequentially controlled CuI/L-proline-catalyzed cascade C-S and C-N bond formation. Angew. Chem. Int. Ed. Engl.,  2010, 49(7), 1291-1294.
 [http://dx.doi.org/10.1002/anie.200905646] [PMID: 20058286]

[147]
a) Zhang, H.; Cai, Q.; Ma, D. Amino acid promoted CuI-catalyzed C-N bond formation between aryl halides and amines or N-containing heterocycles. J. Org. Chem.,  2005, 70, 5164.; 
b) Zhang, H. Cai, Q.; Ma, D. L -Proline-promoted cui-catalyzed C-S bond formation between aryl iodides and thi-ols. Synth. Commun.,  2007, 37, 25.
 [http://dx.doi.org/10.1080/00397910600977533]

[148]
a) Deng, W.; Zou, Y.; Wang, Y-F.; Liu, L.; Guo, Q-X. CuI-catalyzed coupling reactions of aryl iodides and bromides with thiols promoted by amino acid ligands. Synlett,  2004, 2004(4), 1254-1258.; 
b) Ma, D.; Cai, Q. Copper/amino acid catalyzed cross-couplings of aryl and vinyl halides with nucleophiles. Acc. Chem. Res.,  2008, 41, 1450.; 
c) Evano, G.; Toumi, M. Coste, Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis. Chem. Rev.,  2008, 108(8), 3054-3131.; 
d) Evano, G.; Blanchard, N.; Toumi, M. Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis. Chem. Rev.,  2008, 108, 3054.; 
e) Monnier, F.; Taillefer, M. Catalytic C-C, C-N, and C-O ullmann-type coupling reactions. Angew. Chem. Int. Ed.,  2009, 48, 6954.

[149]
Wang, H.; Li, L.; Lin, W.; Xu, P.; Huang, Z.; Shi, D. An efficient synthesis of pyrrolo[2,3,4-kl]acridin-1-one derivatives catalyzed by L-proline. Org. Lett.,  2012, 14(17), 4598-4601.
 [http://dx.doi.org/10.1021/ol302058g] [PMID: 22920713]

[150]
Kamalraja, J.; Sowndarya, R.; Perumal, P.T. A greener approach for the regioselective synthesis of multifunctionalized indolylpyrrole and indolyltriazolylpyrrole hybrids via michael addition of α-azido ketones. Synlett,  2014, 25, 2208-2212.
 [http://dx.doi.org/10.1055/s-0034-1378523]

[151]
Zhang, F.; Li, C.; Qi, C. An efficient and mild synthesis of tetrahydro-4H-indol-4-one derivatives via a domino reaction in water. Synthesis,  2013, 45, 3007-3017.
 [http://dx.doi.org/10.1055/s-0033-1338526]

[152]
Sivamurugan, V.; Deepa, K.; Palanichamy, M.; Murugesan, V. [ (L)Proline]2Zn catalysed synthesis of 1,5-Benzodiazepine derivatives under solvent-free condition. An Inter. J. Rapid Commun. Synthetic Organic Chem.,  2004, 34(21), 3833-3846.
 [http://dx.doi.org/10.1081/SCC-200034752]

[153]
Bhattacharjee, D.; Kshiar, B.; Myrboh, B. L-Proline as an efficient enantioinduction organo-catalyst in the solvent-free synthesis of pyrazolo [3, 4-b] quinoline derivatives via one-pot multi-component reaction. RSC Advances, 2016.
 [http://dx.doi.org/10.1039/C6RA22429F]

[154]
Jung, Y.; Marcus, R.A. On the nature of organic catalysis “on water”. J. Am. Chem. Soc.,  2007, 129(17), 5492-5502.
 [http://dx.doi.org/10.1021/ja068120f] [PMID: 17388592]

[155]
Maleki, A.; Firouzi-Haji, R. L-Proline functionalized magnetic nanoparticles: A novel magnetically reusable nanocatalyst for one-pot synthesis of 2,4,6-triarylpyridines. Sci. Rep.,  2018, 8(1), 17303.
 [http://dx.doi.org/10.1038/s41598-018-35676-x] [PMID: 30470821]

[156]
Gunasekaran, P.; Prasanna, P.; Perumal, S. L-Proline-catalyzed three-component domino reactions for the synthesis of highly functionalized pyrazolo [3, 4-b] pyridines. Tetrahedron Lett.,  2014, 55, 329-332.
 [http://dx.doi.org/10.1016/j.tetlet.2013.11.016]

[157]
Zare, L.; Nikpassand, M. Multicomponent synthesis of dihydropyridines catalyzed by L-proline. Chin. Chem. Lett.,  2011, 22, 531-534.
 [http://dx.doi.org/10.1016/j.cclet.2010.12.012]

[158]
Venkatesan, K.; Pujari, S.S.; Srinivasan, K.V. Proline-catalyzed simple and efficient synthesis of 1, 8-dioxo-decahydroacridines in aqueous ethanol medium. Synth. Commun.,  2009, 39, 228-241.
 [http://dx.doi.org/10.1080/00397910802044306]

[159]
Bhagat, D.S.; Tekale, S.U.; Dhas, A.K.; Deshmukh, S.U.; Pawar, R.P.; Kendrekar, P.S. A rapid and convenient synthesis of acridine derivatives using camphor sulfonic acid catalyst. Org. Prep. Proced. Int.,  2019, 51, 96-101.
 [http://dx.doi.org/10.1080/00304948.2018.1549907]

[160]
Kumar, A.; Maurya, R.A. Synthesis of polyhydroquinoline derivatives through unsymmetric Hantzsch reaction using organocatalysts. Tetrahedron,  2007, 63, 1946-1952.
 [http://dx.doi.org/10.1016/j.tet.2006.12.074]

[161]
Behbahani, F.K.; Alaei, H.S. L-proline-catalysed synthesis of functionalized unsymmetrical dihydro-1H-indeno [1, 2-b] pyridines. J. Chem. Sci.,  2013, 125, 623-626.
 [http://dx.doi.org/10.1007/s12039-013-0419-5]

[162]
Xiong, X.; Yi, C.; Liao, X.; Lai, S. An effective one-pot ac-cess to 2-Amino-4H-benzo[b]pyrans and 1,4-Dihydropyridines viaγ-Cyclodextrin-catalyzed multi-component tandem reactions in deep eutectic solvent. Catal. Lett.,  2019, 149, 1690-1700.
 [http://dx.doi.org/10.1007/s10562-019-02767-x]

[163]
Khalafi-Nezhad, S.; Sarikhani, E.S.; Shahidzadeh, F. P L-Proline-promoted three-component reaction of anilines, aldehydes and barbituric acids/malononitrile: Regioselective synthesis of 5-arylpyrimido[4,5-b]quinoline-diones and 2-amino-4-arylquinoline-3-carbonitriles in water. Green Chem.,  2012, 14, 2876-2884.
 [http://dx.doi.org/10.1039/c2gc35765h]

[164]
Tabassum, S.; Govindaraju, S.; Khan, R.R.; Pasha, M.A. Ultrasound mediated, green innovation for the synthesis of polysubstituted 1,4-dihydropyridines. RSC Advances,  2016, 6, 29802-29810.
 [http://dx.doi.org/10.1039/C6RA05441B]

[165]
a) Ehteshami, M.; Scarth, B.J.; Tchesnokov, E.P.; Dash, C.; Le Grice, S.F.J.; Hallenberger, S.; Jochmans, D.; Götte, M. Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against nucleotide-competing reverse transcriptase inhibitors. J. Biol. Chem.,  2008, 283, 29904-29911.; 
b) Ehteshami, M.; Nijhuis, M.; Bernatchez, J.A.; Ablenas, C.J.; McCormick, S.; Jong, D.D.; Jochmans, D.; Götte, M. Formation of a quaternary complex of HIV-1 reverse transcriptase with a nucleotide-competing inhibitor and its ATP enhancer. J. Biol. Chem.,  2013, 28, 17336-17346.; 
c) Bai, D.L.; Tang, X.C.; He, X.C.; Huperzine, A. A potential therapeutic agent for treatment of alzheimer’s disease. Curr. Med. Chem.,  2000, 7, 355-374.

[166]
Sarkar, R.; Mukhopadhyay, C. L-Proline catalyzed expeditious multicomponent protocol for the synthesis of fused N-substituted-2-pyridone derivatives in aqueous medium. Tetrahedron Lett.,  2014, 55, 2618-2624.
 [http://dx.doi.org/10.1016/j.tetlet.2014.02.123]

[167]
Kumari, K.; Raghuvanshi, D.S.; Singh, K.N. Microwave assisted eco-friendly protocol for one pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones in water. Indian J. Chem.,  2012, 51B, 860-865.
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DOI https://dx.doi.org/10.2174/1386207325666220720105845	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402
Combinatorial Chemistry & High Throughput Screening

L-Proline: A Versatile Organo-Catalyst in Organic Chemistry

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