Current Developments in Michael Addition‐Based Multicomponent Domino Reactions Involving 1,3‐Dicarbonyls and Derivatives

Abstract

The aim of this mini-review is to present an overview of the high synthetic potential of Multicomponent Reactions (MCRs) involving the specific reactivity of easily accessible 1,3-dicarbonyl derivatives. The present contribution only focuses on sequences in which the first step consists of a Michael addition. Recent developments of these new useful methodologies valuable for the selective construction of highly functionalized heterocycles of high synthetic value are surveyed.

Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

“…Hantzsch, Biginelli). [104][105][106] Variations on these themes have led to the discovery of many interesting MCRs. However, options for further expansion of this repertoire are limited.…”

1,3-Dicarbonyl compounds in stereoselective domino and multicomponent reactions

“…Although this addition with such substrates is an old, but still very powerfull and simple reaction, it came to be of interest for MCRs only recently, and has emerged as promising approach with a wide synthetic potential in heterocyclic synthesis. In this context, we will focus in this paragraph on recent selected examples of the application of Michael additionbased MCRs 65 to the synthesis of chiral polysubstituted heterocycles 66 in the five-to seven-membered series.…”

Expanding the Chemical Space in Practice: Diversity-Oriented Synthesis

“…Rodriguez and co-workers [45,46] reported that a difference in steric hindrance can affect the mode of cyclization towards different bicyclic structures in a Michael addition based 3CR involving a 1,3-dicarbonyl (11), an acrolein (12), and a primary amine (13) or (14) (Scheme 6). Applying the same reaction conditions, a less hindered amine (13) led to the 1,6-hydronaphthyridine (±)-(15), whereas a much more hindered amine (14) directed the cyclization towards the formation of the azabicyclo[3.3.1]nonanone (±)-(16) (dd skel = 2).…”

“…In the inverse electron demand [4+2] heterocycloaddition, the [(tBuBOX)Cu(OTf) 2 ] complex ((R)- (49) or (S)-(49)) proved to be a robust enantioselective catalyst that displays a broad substrate tolerance. By permuting the catalyst ((R)- (49) or (S)- (49)) and the support-bound vinyl ethers ((Z)- (47) or (E)- (48)) in the reaction with the , -unsaturated ketoester (46), each of the four possible combinations can selectively lead to a new stereoisomer (50), (50'), (51) or (51').…”