Asymmetric Allylation by Chiral Organocatalyst‐Promoted Formal Hetero‐Ene Reactions of Alkylgold Intermediates

Abstract

An unprecedented catalytic asymmetric allylation of isatins and isatin-derived ketimines is reported enabled by agold and chiral organocatalyst cooperative catalysis strategy. This method offers expeditious access to chiral 2,5-disubsituted alkylideneoxazolines containing vicinal stereogenic centers, mainly in optically pure form, and which are otherwise impossible to access.Mechanistic evidence reveals the presence of an alkylgold intermediate,and an X-raycrystal structure of the allylgold species illuminates its unique stability and reactivity.A na symmetric formal hetero-ene reaction of this gold intermediate,i nvolving ad earomatization process,i s enabled with assistance of aq uinine-derived squaramide catalyst. This novel discovery extends the synthetic applications of gold complexes and the versatility of gold catalysis. Scheme 1. Gold-catalyzed transformations of N-propargylamides.

Asymmetric Allylation by Chiral Organocatalyst‐Promoted Formal Hetero‐Ene Reactions of Alkylgold Intermediates

“…Chemie Forschungsartikel confirmed by X-ray crystallography (Scheme 2c;S upporting Information). [36] Ther ed bond length of intermediate 10 is 1.351 ,w hich is shorter than the single bond reported by Ahn (1.502 ) [12c] and is closer to the data of C À Cd ouble bond. Based on these observations,analkylgold structure 10 with allylgold reactivity,r ather than the vinylgold species,i s assigned in this reaction.…”

“…Considering the cost of the catalysts, Me 4 tBuXPhosAuNTf 2 and 3c were chosen as the optimal combination for the subsequent asymmetric allylation reaction (entry 4). Theabsolute configuration of this product was confirmed by single-crystal X-ray diffraction analysis of its chloro-derivative 4ah, [36] and other products were tentatively assigned by analogy.…”

“…According to the X-ray crystal structure of the catalyst, as well as the absolute configuration of the product, [36] apossible transition state is proposed (Scheme 3, in dashed box) to elucidate the source of stereoselectivity of this reaction. The squaramide hydrogens of the bifunctional catalyst activates…”

“…According to the X-ray crystal structure of the catalyst, as well as the absolute configuration of the product, [36] apossible transition state is proposed (Scheme 3, in dashed box) to elucidate the source of stereoselectivity of this reaction. The squaramide hydrogens of the bifunctional catalyst activates the ketimine via double hydrogen bonding; [35] whereas,t he N-atom on the quinoline part of the organocatalyst might interact with the gold catalyst.…”

Asymmetric Catalytic Ketimine Mannich Reactions and Related Transformations

“…In 2021, Hu, Xu, and coworkers developed a gold and chiral organocatalyst cooperative catalysis strategy for the allylation of isatin-derived ketimines with readily available N-propargylamides 52 (Scheme 43) [129]. Their method tolerated various Scheme 42.…”