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Mini-Reviews in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-193X
ISSN (Online): 1875-6298

Review Article

Advances in the Mitsunobu Reaction: An Excellent Organic Protocol with Versatile Applications

Author(s): Sharad Kumar Panday*

Volume 16, Issue 2, 2019

Page: [127 - 140] Pages: 14

DOI: 10.2174/1570193X15666180612090313

Price: $65

Abstract

The beginning of 1970’s may well be regarded as turning point in the area of organic synthesis when an efficient and straight forward strategy for the reaction of primary and/or secondary alcohols with variety of nucleophiles in the presence of triphenylphosphine and azodicarboxylate reagent was discovered by O. Mitsunobu and since then rapid progress has been made in understanding and applying the Mitsunobu reaction for various derivatization reactions. Due to versatile applications and mild reaction conditions associated with the said strategy, the Mitsunobu reaction has received much attention in the last almost fifty years and has been well reported. The basic objective of this review is to pay attention on the recent advances and applications of the Mitsunobu reaction particularly in last decade. The attention has also been paid to describe various modifications which have been explored in the traditional Mitsunobu reaction by substituting P (III) reagents or azodicarboxylate reagents with other suitable reagents or else using an organocatalyst with the objective to improve upon the traditional Mitsunobu reaction. In the present review we wish to report the major advancements achieved in last few years which are likely to be beneficial for the researchers across the globe.

Keywords: Mitsunobu reaction, macromolecules, immobilized reagents, azodicarboxylate reagent system, nucleophile, organic synthesis.

Graphical Abstract

[1]
Kumara Swamy, K.C.; Bhuvan Kumar, N.N.; Balaraman, E.; Pavan Kumar, K.V.P. Mitsunobu and related reactions: Advances and applications. Chem. Rev., 2009, 109, 2551-2651.
[2]
Mitsunobu, O.; Yamada, M. Preparation of esters of carboxylic and phosphoric acid via quaternary phosphonium salts. Bull. Chem. Soc. Jpn., 1967, 40, 2380-2382.
[3]
Mitsunobu, O.; Yamada, M.; Mukaiyama, T. Preparation of esters of phosphoric acid by the reaction of trivalent phosphorus compounds with diethyl azodicarboxylate in the presence of alcohols. Bull. Chem. Soc. Jpn., 1967, 40, 935-939.
[4]
Mitsunobu, O.; Kato, K.; Kakese, F.A. Novel method for the preparation of carbodiimides. Tetrahedron Lett., 1969, 10, 2473-2475.
[5]
Mitsunobu, O.; Kato, K.; Tomari, M. Preparation of carbodiimides by the reaction of thioureas with diethyl azodicarboxylate. Tetrahedron, 1970, 26, 5731-5736.
[6]
Kato, K.; Mitsunobu, O. Oxidation of mercaptans with diethyl azodicarboxylate and trivalent phosphorus compounds. J. Org. Chem., 1970, 35, 4227-4229.
[7]
Mitsunobu, O.; Eguchi, M. Preparation of carboxylic esters and phosphoric esters by the activation of alcohols. Bull. Chem. Soc. Jpn., 1971, 44, 3427-3430.
[8]
Mitsunobu, O.; Kato, K.; Wada, M. Formation of ketenimines by the reaction of thioamides with diethyl azodicarboxylate and triphenylphosphine. Bull. Chem. Soc. Jpn., 1971, 44, 1362-1364.
[9]
Mitsunobu, O.; Kimura, J.; Fujisawa, Y. Studies on nucleosides and nucleotides. II. Selective acylation of 5′-hydroxyl group of thymidine. Bull. Chem. Soc. Jpn., 1972, 45, 245-247.
[10]
Mitsunobu, O.; Wada, M.; Sano, T. Stereo specific and stereo selective reactions. I. Preparation of amines from alcohols. J. Am. Chem. Soc., 1972, 94, 697-698.
[11]
Wada, M.; Sano, T.; Mitsunobu, O. Stereospecific and stereo selective reactions. II. Preparation of esters of N-phthaloyl-α-amino acid from esters of α-hydroxy acid. Bull. Chem. Soc. Jpn., 1973, 46, 2833-2835.
[12]
Wada, M.; Mitsunobu, O. Intermolecular dehydration between alcohols and active hydrogen compounds by means of diethyl azodicarboxylate and triphenylphosphine. Tetrahedron Lett., 1972, 13, 1279-1282.
[13]
Kurihara, T.; Nakajima, Y.; Mitsunobu, O. Synthesis of lactones and cycloalkanes. Cyclization of ω-hydroxy acids and ethyl α-cyano-ω-hydroxycarboxylates. Tetrahedron Lett., 1976, 17, 2455-2458.
[14]
Mitsunobu, O.; Kimura, J.; Iiizumi, K.; Yanagida, N. Stereoselective and stereospecific reactions. III. Benzoylation, cyclization, and epimerization of diols. Bull. Chem. Soc. Jpn., 1976, 49, 510-513.
[15]
Kurihara, T.; Sugizaki, M.; Kime, I.; Wada, M.; Mitsunobu, O. Stereospecific and stereoselective reactions. V. Alkylation of active methylene compounds by the use of alcohols, diethyl azodicarboxylate, and triphenylphosphine. Bull. Chem. Soc. Jpn., 1981, 54, 2107-2112.
[16]
Mitsunobu, O. The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products. Synthesis, 1981, 1, 1-28.
[17]
Castro, B. Replacement of alcoholic hydroxy groups by halogens and other nucleophiles via oxyphosphonium intermediates. Org. React., 1983, 29, 1-162.
[18]
Mitsunobu, O. Comprehensive Organic Synthesis. Trost, B.M., Fleming, I., Eds.; Pergamon: New York, 1991, 6, pp. 65.
[19]
Hughes, D.L. The Mitsunobu Reaction. Org. React., 1992, 42, 335-656.
[20]
Jenkins, I.D.; Mitsunobu, O. Encyclopedia of Reagents for Organic Synthesis; Paquette, L.A., Ed.; Wiley: New York, 1995. 8, 5379- 5390.
[21]
Hughes, D.L. Progress in the Mitsunobu reaction. A Review. Org. Prep. Proced. Int., 1996, 28, 127-164.
[22]
Dodge, J.A.; Jones, S.A. Advances in the Mitsunobu reaction for the stereochemical inversion of hindered secondary alcohols. Recent Res. Dev. Org. Chem., 1997, 1, 273-283.
[23]
Simon, C.; Hosztafi, S.; Makleit, S. Application of the Mitsunobu reaction in the field of alkaloids. J. Heterocycl. Chem., 1997, 34, 349-365.
[24]
Wisniewski, K.; Kołdziejczyk, A.S.; Falkiewicz, B. Applications of the Mitsunobu reaction in peptide chemistry. J. Pept. Sci., 1998, 4, 1-14.
[25]
Wisniewski, K.; Kolodziejczyk, A.S.; Falkiewiez, B. Uses of Mitsunobu reaction in amino acid chemistry. Wiad. Chem., 1998, 52, 243-267.
[26]
Herr, R.J. A whirlwind tour of current Mitsunobu chemistry. Technical Report. Albany Molecular Research. Inc., 1999, 3, 1-36.
[27]
Ito, S. Development of new synthetic reagents in Mitsunobu-type reaction. Yakugaku Zasshi, 2001, 121, 567-583.
[28]
Janzi, K.A. Mitsunobu reaction; Wikipedia, 2001.
[29]
Jenkins, I.D.; Mitsunobu, O. Electronic Encyclopedia of Reagents for Organic Synthesis; Paquette, L.A., Ed.; John Wiley & Sons, Ltd.: New York, 2001.
[30]
Lawrence, S. The Mitsunobu reaction. Pharma Chem., 2002, 1, 12-14.
[31]
Paul, N.M.; Gabriel, C.J.; Parquette, J.R. Developments in fluorous Mitsunobu chemistry. Chemtracts, 2002, 15, 617-622.
[32]
Valentine, D.H., Jr; Hillhouse, J.H. Alkyl phosphines as reagents and catalysts in organic synthesis. Synthesis, 2003, 317-334.
[33]
Nam, N-H.; Sardari, S.; Parang, K. Reactions of solid-supported reagents and solid supports with alcohols and phenols through their hydroxyl functional group. J. Comb. Chem., 2003, 5, 479-546.
[34]
Nune, S.K. Mitsunobu reagent [triphenyl-phosphine (TPP) and diethyl azodi-carboxylate (DEAD)/diisopropyl azodicarboxylate (DIAD)]. Synlett., 2003, 1221-1222.
[35]
Dembinski, R. Recent advances in the Mitsunobu reaction: Modified reagents and the quest for chromatography‐free separation. Eur. J. Org. Chem., 2004, 2763-2772.
[36]
Tsunoda, T.; Kaku, H.; Ito, S. New Mitsunobu reagents. TCIMAIL, 2004, 123, 2.
[37]
Dandapani, S.; Curran, D.P. Separation‐friendly Mitsunobu reactions: A microcosm of recent developments in separation strategies. Chem. Euro. J, 2004, 10, 3130-3138.
[38]
Ren, X-F.; Xu, J-L.; Chen, S-H. Recent progress of Mitsunobu reaction. Chin. J. Org. Chem., 2006, 26, 454-461.
[39]
Parenty, A.; Moreau, X.; Campagne, J-M. Macrolactonizations in the total synthesis of natural products. Chem. Rev., 2006, 106, 911-939.
[40]
But, T.Y.S.; Toy, P.H. The Mitsunobu reaction: Origin, mechanism, improvements, and applications. Chem. Asian J., 2007, 2, 1340-1355.
[41]
Otera, J.; Nishikido, J. Reaction of alcohols with carboxylic acids and their derivatives in esterification: Methods, reactions, and applications, second edition, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany , 2009.
[42]
Fletcher, S. The Mitsunobu reaction in the 21st century. Org. Chem. Front., 2015, 2, 739-752.
[43]
Reynolds, A.J.; Kassiou, M. Recent advances in the Mitsunobu reaction: Modifications and applications to biologically active molecules. Curr. Org. Chem., 2009, 13(16), 1610-1632.
[44]
Zhirov, A.M.; Aksenov, A.V. Azodicarboxylates: Synthesis and functionalization of organic compounds. Russ. Chem. Rev., 2014, 83, 502-522.
[45]
Kitahara, K.; Toma, T.; Shimokawa, J.; Fukuyama, T.O-T.B.S. -N-tosylhydroxylamine: A reagent for facile conversion of alcohols to oximes. Org. Lett., 2008, 10, 2259-2261.
[46]
Keith, J.M.; Gomez, L. Exploration of the Mitsunobu reaction with tosyl- and Boc- hydrazones as nucleophilic agents. J. Org. Chem., 2006, 71, 7113-7116.
[47]
Myers, A.G.; Movassaghi, M.; Zheng, B. Single-step process for the reductive deoxygenation of unhindered alcohols. J. Am. Chem. Soc., 1997, 119, 8572-8573.
[48]
Sen, S.E.; Roach, S.L. A convenient two-step procedure for the synthesis of substituted allylic amines from allylic alcohols. Synthesis, 1995, 756-758.
[49]
Green, J.E.; Bender, D.M.; Jackson, S.; O’Donell, M.J.; McCarthy, J.R. Mitsunobu approach to the synthesis of optically α, α-disubstituted amino acids. Org. Lett., 2009, 11, 807-810.
[50]
Fletcher, S.; Shahani, V.M.; Gunning, P.T. Facile and efficient access to 2, 6, 9-tri-substituted purines through sequential N9, N2 Mitsunobu reactions. Tetrahedron Lett., 2009, 50, 4258-4261.
[51]
Dai, L-Y.; Shi, Q-L.; Zhang, J.; Wang, X-Z.; Chen, Y-Q. Accelerated effect on Mitsunobu reaction via bis-N-tert-butoxy-carbonylation protection of 2-amino-6-chloropurine and its application in a novel synthesis of penciclovir. J. Zhejiang Univ. Sci. A, 2013, 14(10), 760-766.
[52]
Fletcher, S. Regioselective alkylation of the exocyclic nitrogen of adenine and adenosine by the Mitsunobu reaction. Tetrahedron Lett., 2010, 51, 2948-2950.
[53]
Quezada, E.; Vina, D.; Delogu, G.; Borges, F.; Santana, L.; Uriarte, E. Synthesis of carbocyclic pyrimidine nucleosides using the Mitsunobu reaction: O2-vs. N1-alkylation. Helv. Chim. Acta, 2010, 93, 309-313.
[54]
Panday, S.K.; Pathak, M.B.; Prasad, J. An efficient and straight forward strategy for the synthesis of enantiomerically pure (S)-1-benzyl-5(alkyl/aryl amino) methyl- pyrrolidin-2-ones. Indian J. Chem., 2015, 54B, 936-939.
[55]
Panday, S.K.; Prasad, J.; Pathak, M.B. Straightforward and facile approach toward the n-derivatization of pyroglutamates through Mitsunobu reaction: Synthesis of N-alkyl/N-acyl pyroglutamates. Synth. Commun., 2011, 41, 3654-3661.
[56]
Bates, R.W.; Lim, C.J. Synthesis of two nuphar alkaloids by allenic hydroxylamine cyclisation. Synlett, 2010, 866-868.
[57]
Lepore, S.D.; He, Y. Use of sonication for the coupling of sterically hindered substrates in the phenolic Mitsunobu reaction. J. Org. Chem., 2003, 68, 8261-8263.
[58]
Wang, G.; Ella-Menya, J-R.; Martin, M.S.; Yang, H.; Williams, K. Regioselective esterification of vicinal diols on monosaccharide derivatives via Mitsunobu reaction. Org. Lett., 2008, 10, 4203-4206.
[59]
Camp, D.; Harvey, P.J.; Jenkins, I.D. The effect of polarity on the rate of the Mitsunobu esterification reaction. Tetrahedron, 2015, 71, 3932-3938.
[60]
Huang, G.; Schramm, S.; Heilmann, J.; Biedermann, D.; Kren, V.; Decker, M. Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins. Beilstein J. Org. Chem., 2016, 12, 662-669.
[61]
Mahdi, K.M.; Abdul-Reda, N.A.; Al-Masoudi, N.A. Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study. Eur. J. Chem., 2015, 6, 1-7.
[62]
Chaturvedi, D.; Mishra, N.; Mishra, V. An efficient, one-pot synthesis of S-alkyl thiocarbamates from the corresponding thiols using the Mitsunobu reagent. Synthesis, 2008, 355-357.
[63]
Iranpoor, N.; Firouzabadi, H.; Akhlaghinia, B.; Azadi, R. Conversion of alcohols, thiols, carboxylic acids, trimethylsilyl ethers, and carboxylates to thiocyanates with triphenylphosphine/diethylazo-dicarboxylate/NH4SCN. Synthesis, 2004, 92-96.
[64]
Takacs, J.M.; Xu, Z.; Jiang, X-T.; Leonov, A.P.; Theriot, G.C. Carbon nucleophiles in the Mitsunobu reaction. Mono and dialkylation of bis (2, 2, 2-trifluorethyl) malonates. Org. Lett., 2002, 4, 3843-3845.
[65]
Krohn, K.; Ahmed, I.; John, M.; Letzel, M.C.; Kuck, D. Stereoselective synthesis of benzylated prodelphinidins and their diastereomers with use of the Mitsunobu reaction in the preparation of their gallocatechin precursors. Eur. J. Org. Chem., 2010, 2010, 2544-2554.
[66]
Xu, S.; Shang, J.; Zhang, J.; Tang, Y. Regioselective SN2′ Mitsunobu reaction of Morita-Baylis-Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives. Beilstein J. Org. Chem., 2014, 10, 990-995.
[67]
Petit, S.; Azzouz, R.; Fruit, C.; Bischoff, L.; Marsais, F. An efficient protocol for the preparation of pyridinium and imidazolium salts based on the Mitsunobu reaction. Tetrahedron Lett., 2008, 49, 3663-3665.
[68]
Prasad, J.; Pathak, M.B.; Panday, S.K. An efficient and straight forward synthesis of (5S)-1-benzyl-5-(1H-imidazol-1-ylmethyl)-2-pyrrolidinone (MM1): A novel antihypertensive agent. Med. Chem. Res., 2012, 21, 321-324.
[69]
Hagiya, K.; Muramoto, N.; Misaki, T.; Sugimura, T. DMEAD: A new dialkyl azodicarboxylate for the Mitsunobu reaction. Tetrahedron, 2009, 65, 6109-6114.
[70]
Muramoto, N.; Yoshino, K.; Misaki, T.; Sugimura, T. Mitsunobu reaction with 4-(diphenylphosphino) benzoic acid: A separation-friendly bifunctional reagent that serves as both a reductant and a pronucleophile. Synthesis, 2013, 45, 931-935.
[71]
Iranpoor, N.; Firouzabadi, H.; Khalili, D.; Motevalli, S. Easily prepared azopyridines as potent and recyclable reagents for facile esterification reactions. An efficient modified Mitsunobu reaction. J. Org. Chem., 2008, 73, 4882-4887.
[72]
Lipshutz, B.H.; Chung, D.W.; Rich, B.; Corral, R. Simplification of the Mitsunobu Reaction. Di-p-chlorobenzyl azodicarboxylate: A new azodicarboxylate. Org. Lett., 2006, 73, 5069-5072.
[73]
Tsunoda, T.; Yamamiya, Y.; Ito, S. 1,1′-(azodicarbonyl)di-piperidine-tributylphosphine, a new reagent system for Mitsunobu reaction. Tetrahedron Lett., 1993, 34, 1639-1642.
[74]
Yang, J.; Dai, L.; Wang, X.; Di Chen, Y. -p-nitrobenzyl azodicarboxylate (DNAD): An alternative azo-reagent for the Mitsunobu reaction. Tetrahedron, 2011, 67, 1456-1462.
[75]
Iranpoor, N.; Firouzabadi, H.; Khalili, D. 5,5′-Dimethyl-3,3′-azoisoxazole as a new heterogeneous azo reagent for esterification of phenols and selective esterification of benzylic alcohols under Mitsunobu conditions. Org. Biomol. Chem., 2010, 8, 4436-4443.
[76]
Dandapani, S.; Curran, D.P. Fluorous Mitsunobu reagents and reactions. Tetrahedron, 2002, 58, 3855-3864.
[77]
But, T.Y.S.; Toy, P.H. Organocatalytic Mitsunobu reaction. J. Am. Chem. Soc., 2006, 128, 9636-9637.
[78]
Hirose, D.; Gazvoda, M.; Kosmrlj, J.; Taniguchi, T. Advances and mechanistic insight on the catalytic Mitsunobu reaction using recyclable azo reagents. Chem. Sci., 2016, 7, 5148-5159.
[79]
Hirose, D.; Taniguchi, T.; Ishibashi, H. Recyclable Mitsunobu Reagents: Catalytic Mitsunobu reactions with an iron catalyst and atmospheric oxygen. Angew. Chem. Int. Ed., 2013, 52, 4613-4617.
[80]
Hirose, D.; Gazvoda, M.; Kosmrlj, J.; Taniguchi, T. The “fully catalytic system” in Mitsunobu reaction has not been realized yet. Org. Lett., 2016, 18(16), 4036-4039.
[81]
Shimotori, Y.; Aoyama, M.; Miyakoshi, T. Enantioselective synthesis of δ-lactones with lipase-catalyzed resolution and Mitsunobu reaction. Synth. Commun., 2012, 42, 694-704.
[82]
Figlus, M.; Wellaway, N.; Cooper, A.W.J.; Sollis, S.L.; Hartley, R.C. Synthesis of arrays using low molecular weight MPEG-assisted Mitsunobu reaction. ACS Comb. Sci., 2011, 13(3), 280-285.
[83]
Maity, P.K.; Rolfe, A.; Samarakoon, T.B.; Faisal, S.; Kurtz, R.D.; Long, T.R.; Schatz, A.; Flynn, D.L.; Grass, R.N.; Stark, W.J.; Reiser, O.; Hanson, P.R. Monomer-on-Monomer (MoM) Mitsunobu reaction: Facile purification utilizing surface-initiated sequestration. Org. Lett., 2011, 13(1), 8-10.
[84]
Valeur, E.; Roche, D. Efficient, mild, parallel and purification-free synthesis of aryl ethers via the Mitsunobu reaction. Tetrahedron Lett., 2008, 49, 4182-4185.
[85]
Panday, S.K.; Langlois, N. Enantioselective synthesis of (S)-5-aminopiperidin-2-one from (S)-pyroglutaminol. Tetrahedron Lett., 1995, 36, 8205-8208.
[86]
Olofsson, B.; Wijtmans, R.; Somfai, P. Olofsson, B.; Wijtmans, R.; Somfai, P.; Synthesis of N-H vinylaziridines: A comparative study. Tetrahedron, 2002, 58, 5979-5982.
[87]
Samanta, K.; Srivastava, N.; Saha, S.; Panda, G. Inter- and intramolecular Mitsunobu reaction and metal complexation study: Synthesis of S-amino acids derived chiral 1, 2, 3, 4-tetrahydroquinoxaline, benzo-annulated [9]-N3 peraza, [12]-N4 peraza-macrocycles. Org. Biomol. Chem., 2012, 10, 1553-1564.
[88]
Pierrat, P.; Rethore, C.; Muller, T.; Brase, S. Di‐ and dodeca‐Mitsunobu reactions on C60 derivatives: Post‐functionalization of fullerene mono‐ and hexakis‐adducts. Chem. Eur. J., 2009, 15, 11458-11460.
[89]
Tang, X.; Chapman, C.; Whiting, M.; Denton, R. Development of a redox-free Mitsunobu reaction exploiting phosphine oxides as precursors to dioxyphosphoranes. Chem. Commun., 2014, 50, 7340-7343.
[90]
Martin, S.F.; Dodge, J.A. Efficacious modification of the Mitsunobu reaction for inversions of sterically hindered secondary alcohols. Tetrahedron Lett., 1991, 32, 3017-3020.
[91]
Azzouz, R.; Fruit, C.; Bischoff, L.; Marsais, F. A concise synthesis of lentiginosine derivatives using a pyridinium formation via the Mitsunobu reaction. J. Org. Chem., 2008, 73, 1154-1157.
[92]
Berree, F.; Gernigon, N.; Hercouet, A.; Lin, C.H.; Carboni, B.S. N2′ boron‐mediated Mitsunobu reactions - A new one‐pot three‐component synthesis of substituted enamides and enol benzoates. Eur. J. Org. Chem., 2009, 2009, 329-333.
[93]
Hoffman, J.A.; Miller, J.N.; Gardner, M.E.; LePar, D.R.; Pongdee, R. Synthesis of N, N-diethylbenzamides via a nonclassical Mitsunobu reaction. Synth. Commun., 2014, 44(7), 976-980.
[94]
Cassani, C.; Martin-Rapun, R.; Arceo, E.; Bravo, F.; Melchiorre, P. Synthesis of 9-amino(9-deoxy)epi cinchona alkaloids, general chiral organocatalysts for the stereoselective functionalization of carbonyl compounds. Nat. Protoc., 2013, 8, 325-344.

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