Stereoselective Aza-Diels-Alder Reactions

Abstract

The Diels-Alder reaction is one of the most useful and often studied transformations in organic chemistry. The reaction has been employed, often as the key step, in the total synthesis of a wide range of biologically-active natural products. The utility of the reaction is based upon its ability to form six-membered cyclic systems with up to four contiguous stereocenters as well as the reactions ability to incorporate heteroatoms into the cycloadduct. The use of imines as the dienophile has been studied in great detail over the last fifteen years. The development of stereoselective variants of the reaction has been at the forefront of these studies. The use of chiral auxiliaries and chiral catalyst to control the stereochemistry of the product has seen much success over this period of time. The purpose of this review is to give a detailed discussion of the recent advances in Diels-Alder methodology involving a carbon-nitrogen double bond. The review is divided into two major sections. The first discusses the development of Diastereoselective aza-Diels-Alder reactions, while the second part discusses Enantioselective variants of the reaction.

Syntheses of chromenes and chromanes via o‐quinone methide intermediates

“…A very important variation of the typical Diels‐Alder reaction is the hetero‐Diels‐Alder reaction. In this variation, heteroatoms, such as a carbonyl group, replace a carbon–carbon double bond in either the diene or dienophile [159–162].…”

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

“…In general, aza‐DARs are classified as normal and inverse electron demand types. A normal electron demand aza‐Diels‐Alder reaction (NED aza‐DAR) [7] is characterized by the involvement of electron‐rich 1,3‐dienes and electron‐deficient dienophiles such as imines, hydrazones, diazene or nitroso derivatives and rarely alkenes bearing an electron‐withdrawing group (Scheme 1). An inverse electron demand aza‐Diels‐Alder reaction (IED aza‐DAR) [8–10] features interaction between electron‐deficient 1,3‐dienes (generally, 1‐ or 2‐aza‐1,3‐dienes) and electron‐rich dienophiles (olefins, enols, enamines, and ketenes).…”

Oxidative Asymmetric Formal Aza-Diels–Alder Reactions of Tetrahydro-β-carboline with Enones in the Synthesis of Indoloquinolizidine-2-ones

“…Aza-Diels–Alder reaction is one of the most efficient and direct approaches for the synthesis of six-membered N -heterocycles, especially in the syntheses of biologically active natural products and pharmaceutical compounds [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Despite all these advantages, aza-Diels–Alder reaction has been rarely applied in the synthesis of indoloquinolizidine derivatives [ 10 , 11 , 12 ].…”