Enantioselective Organocatalytic Michael Addition of Cyclobutanones to Nitroalkenes

Abstract

International audienceSynthetic applications of cyclobutanones other than ring expansion and fragmentation reactions are rare. Herein, highly efficient diastereo- and enantioselective organocatalytic Michael additions of 2-substituted cyclobutanone derivatives to nitroalkenes are reported allowing the stereocontrolled creation of " all-carbon " quaternary centers. The approach relies on both the use of Brønsted base/hydrogen-bond donor bifunctional organocatalysts, and importantly, the specific stabilization and activation of cyclobutanone with a secondary amide moiety. The reaction was found to nicely accommodate a broad scope of substrates, allowing the control of up to three contiguous stereogenic centers. This work has opened new synthetic opportunities

Synthesis of Cyclobutanones via Gold‐Catalyzed Oxidative Rearrangement of Homopropargylic Ethers

“…[1] A number of successful synthetic strategies including ring expansion [2] or ring contraction, [3] formal [4+2] cycloaddition, [4] aldol reaction [5] and ring fission [6] have been realized in recent years. Literature protocols for the synthesis of substituted cyclobutanones include [2+2] cycloaddition of ketenes or ketiminium salts with olefins, [7] ring enlargement of cyclopropane derivatives, [8] C À H insertion or rearrangement of diazo componds [9] etc.…”

α,β‐Unsaturated Acyl Cyanides as New Bis‐Electrophiles for Enantioselective Organocatalyzed Formal [3+3]Spiroannulation

“…To the best of our knowledge, there is no report of direct enantioselective synthesis of glutarimide derivatives, [11] which is an important structural motif found in many natural products. [14] Based on our experience in enantioselective domino transformations, [15] we started our investigations using b-ketoamide 6 a as the bis-nucleophilic partner, which was reacted with cinnamoyl cyanide (5 a) under hydrogen-bonding catalysis (Table 1). The overall cascade forms one CÀC and one CÀN bond, [13] and produces ring systems bearing two adjacent stereogenic centers including a tetrasubstituted one.…”

“…[12] Moreover, the domino sequence involves the dual reactivity of acyl cyanides as new C/C bis-electrophiles allowing a one-pot enantioselective organocatalytic Michael addition-intramolecular acylation with simple b-ketoamides as C/N bis-nucleophiles. [14] Based on our experience in enantioselective domino transformations, [15] we started our investigations using b-ketoamide 6 a as the bis-nucleophilic partner, which was reacted with cinnamoyl cyanide (5 a) under hydrogen-bonding catalysis ( Table 1). [14] Based on our experience in enantioselective domino transformations, [15] we started our investigations using b-ketoamide 6 a as the bis-nucleophilic partner, which was reacted with cinnamoyl cyanide (5 a) under hydrogen-bonding catalysis ( Table 1).…”

Recent Advances in Organocatalytic Methods for Asymmetric CC Bond Formation

“…The best results were achieved with a cinchona derived catalyst 104 bearing α‐ N ‐benzylsquaramide unit. The corresponding reaction products were isolated in moderate to good yields, varying enantioselectivity and very high diastereoselectivity 95…”