Asymmetric trapping of zwitterionic intermediates by sulphur ylides in a palladium-catalysed decarboxylation-cycloaddition sequence

Abstract

Through nearly 50 years of development, sulphur ylides have been established as versatile and powerful reagents for the construction of carbocycles and heterocycles. Despite advances, two important and yet elusive bottlenecks continue to inhibit the advancement of this chemistry: a limited number of reagents with polar groups to react with sulphur ylides, and the wide utilization of chiral auxiliaries or substrates to achieve asymmetric cycloaddition processes in the majority of known reports. Herein, we apply an asymmetric palladium catalysis strategy to the chemistry of sulphur ylides to address these two fundamental problems. We thus achieve an unprecedented decarboxylation-cycloaddition sequence of cyclic allylic esters with sulphur ylides through the enantioselective trapping of Pd-stabilized zwitterionic intermediates by the ylides. As a result, a series of biologically and synthetically important 3-vinyl indolines are rapidly assembled with a high reaction efficiency and stereoselectivity.

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

“…In 2014, the group of Xiao reported a palladium-catalyzed decarboxylation/cycloaddition sequence with vinyl carbamates 587 as 1,4-dipole precursors. 341 This transformation allows the synthesis of a wide range of trans -2-acyl-3-vinylindolines ( 590 ) with excellent diastereo- and enantioselectivity (Scheme 101). This was the first time the enantioselective capture of Pd-stabilized allylic zwitterionic intermediates by sulfur ylides was achieved.…”

Synergetic iridium and amine catalysis enables asymmetric [4+2] cycloadditions of vinyl aminoalcohols with carbonyls

“…Among existing methods for synthesizing chiral hydroquinolines, catalytic asymmetric [4+2] cycloadditions stand out as one of the most streamlined approaches 45–49 . As part of our ongoing studies on the synthesis of heterocycles via TM-catalyzed cycloadditions 15,50–55 , in this work, we plan to develop reaction methodologies that utilize readily available reagents and feature good selectivity and high synthetic efficiency. A detailed description of a possible mechanism is outlined in Fig.…”

“…1a, path b: inverse electron-demand cycloaddition) 13,14 . In the few known examples, some additional interaction (i.e., electrostatic interactions or hydrogen bonding interactions) between the Pd-containing dipole and nucleophilic dipolarophile was required to induce branched selectivity in the Pd-catalyzed intermolecular AA processes 15–19 . For this reason, the exploitation of alternative catalyst systems is required to develop general dipolar cycloadditions and efficiently utilize the synthetic potential of TM catalysis in the synthesis of heterocycles.

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Sulfur-Based Ylides in Transition-Metal-Catalysed Processes

“…In this framework, stabilised sulfonium ylides have displayed a remarkable tolerance toward a range of catalytic systems. In 2014, Xiao and co-workers reported a palladium-catalysed decarboxylation/cycloaddition sequence with vinyl benzoxazinanones as 1,4-dipole precursors [ 17 ]. Using this methodology, the authors obtained several trans 2-acyl-3-vinyl indolines with excellent diastereo- and enantioselectivity (Scheme 4 ).…”