Enantioselective Imino-Ene Reaction of N-Sulfonyl Ketimines with Silyl Enol Ethers: Access to Chiral Benzosultams

Abstract

A highly efficient asymmetric imino-ene reaction of cyclic ketimines with silyl enol ethers was developed. Various chiral benzosultam derivatives were obtained in excellent yields (up to 99%), enantioselectivities (up to 99% ee), and diastereoselectivities (up to >19:1 dr) by utilizing a Ni­(BF4)2·6H2O/N,N′-dioxide complex as the catalyst. A possible transition state model was proposed to explain the stereoinduction. Furthermore, the synthetic utility of the protocol provided quick access to optically pure HIV-1 inhibitor.

NickelII-catalyzed asymmetric photoenolization/Mannich reaction of (2-alkylphenyl) ketones

“…Based on the experimental results, absolute configuration of the product C1 and our previous works, 20 a plausible transition state model was proposed (Scheme 3b). Under the UV irradiation, biradical Int-2 was obtained through 1,5-hydrogen atom transfer (HAT) of the triplet excited 2benzylbenzophenone Int 1.…”

Accessing unnatural α-amino acids with tetrasubstituted stereogenic centersviacatalytic enantioselective reactions of ketimine-type α-iminoesters/α-iminoamides

“…In 2020, Cao, Feng, and co-workers reported the enantioselective imino-ene reaction of cyclic sulfonyl ketimines 4 with silyl enol ethers (Scheme 8). 18 This reaction is catalyzed by the combination of a nickel salt and chiral N , N ′-dioxide ligand 20a to afford adducts 19 that are reacted at the allylic α-carbonyl position. The authors proposed a possible transition state for this reaction based on the stereochemistry of 19 , in which the carbonyl oxygen and imino nitrogen coordinate to a Ni( ii ) species.…”

“…In 2020, Cao, Feng, and co-workers reported the enantioselective imino-ene reaction of cyclic sulfonyl ketimines 4 with silyl enol ethers (Scheme 8). 18 This reaction is catalyzed by the combination of a nickel salt and chiral N,N 0 -dioxide ligand 20a to afford adducts 19 that are reacted at the allylic a-carbonyl In 2021, Hu, Xu, and co-workers used a unique gold organocatalysis to promote the tandem reaction involving the enantioselective imino-ene reaction of isatin-derived ketimines 21a (Scheme 9). 19 This reaction proceeds via the intramolecular cyclization of an N-propargylamide to form an alkylgold intermediate that acts as a nucleophile in the subsequent imino-ene reaction.…”

Recent Advances in Catalytic Synthesis of Benzosultams

“…They are also versatile building blocks for the assembly of a variety of diversely functionalized benzosultam derivatives and other heterocyclic systems. In this context, various transformations have been developed, such as dipolar cycloaddition [ 14 , 15 ], nucleophilic addition [ 16 , 17 , 18 , 19 , 20 , 21 ], transition metal-catalyzed C–H activation/annulation [ 22 , 23 , 24 , 25 ], Corey–Bakshi–Shibata reduction, and Aza-Darzens condensation [ 26 , 27 ] etc., which extensively expand their application range in the area of synthetic chemistry. Therefore, the development of convenient methods for the efficient preparation of benzosultams play important roles in drug discovery and asymmetric synthesis, which have attracted much attention from synthetic chemists.…”