Abstract
Background: The hetero-Diels-Alder (HDA) reaction is an important method for the construction of heterocyclic six-membered rings. The HDA reaction involving the carbonyl functionality as a dienophile or as a heterodiene makes dihydropyran ring accessible, which is present in many biologically active compounds. However, reactivity of the carbonyl group as a dienophile or as heterodiene is much less and for successful completion of the reaction, usually a catalyst is required. In view of this, there are always attempts afoot to devise more effective and specific catalysts for this purpose.
Methods: The catalysts used for these reactions are generally of two types, namely the Lewis acid (LA) catalysts and organocatalysts. A large number of LA catalysts used in these reactions belong to the main group metals. However, some of these catalysts are the derivatives of the hard transition metals and a few lanthanide elements with a variety of ligands. Besides, in recent years a variety of organocatalysts based on different principles, such as enamine formation and hydrogen-bonding have been developed. Results: The use of a catalyst results in lowering of the activation energy barrier thus facilitating occurrence of the HDA reaction. Depending on the nature of the diene and the catalyst, the reaction may occur through a concerted or a stepwise mechanism. There are a few reports about the theoretical investigation of the mechanism. The catalysts have been used both homogeneously and heterogeneously grafted on polymers. The latter technique makes it possible to recycle the catalyst several times without losing its activity. The use of chiral catalysts makes it possible to obtain the cycloadducts in high enantiomeric excess (ee). In some cases, it has been possible to increase enantioselectivities by tuning the coordination sphere of the metallic ion. The use of organocatalysts has also been successful. The present article overviews the use of both types of the catalysts for the HDA reactions of the carbonyl compounds during the last 15 years. Conclusion: It is possible to accomplish HDA reactions with the carbonyl functionality successfully by the use of an appropriate catalyst, Lewis acid based catalyst or organocatalyst. By the use of chiral catalysts, asymmetric HDA reactions can be accomplished affording the products with high enantio- or diastereoselectivitiesKeywords: Hetero-Diels-Alder reactions, asymmetric Hetero-Diels-Alder reactions, carbonyl compounds, chiral catalysts, organocatalysts.
Graphical Abstract
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