Enantioselective Indole Insertion Reactions of α-Carbonyl Sulfoxonium Ylides

Abstract

The first example of organocatalytic enantioselective C–H insertion reactions of indoles and sulfoxonium ylides is reported. Under the influence of phosphoric acid catalysis, levels of enantiocontrol in the range of 20–93% ee and moderate yields (up to 50%) were achieved for 29 examples in formal C–H insertion reactions of free indoles and α-carbonyl sulfoxonium ylides. No nitrogen protection on the indole is necessary.

Sulfoxonium Ylides in Aminocatalysis: An Enantioselective Entry to Cyclopropane-Fused Chromanol Structures

“…The latter group of reactions is generally performed with Jørgensen–Hayashi type catalysts, whose simplest congener proved to be effective in our case too (Scheme b). This reaction represents the first example of utilization of sulfoxonium ylides in asymmetric aminocatalysis and affords the tricyclic ring-fused derivatives 3 with very good stereocontrol. Importantly, the connectivity and relative stereochemistry of these compounds match the core of GP40 agonist III (Scheme a).…”

“…Disclosing the first utilization of sulfoxonium ylides under aminocatalytic conditions, these results add an important piece to the still poorly disclosed puzzle of asymmetric organocatalysis with sulfoxonium ylide substrates. 8b , 12 …”

Asymmetric transformations from sulfoxonium ylides

“…Very recently, the first example of organocatalytic enantioselective formal C-H insertion between sulfoxonium ylide and indoles (C3 position) was disclosed (Scheme 15E), by Burtoloso's and Mattson's groups, in collaboration. 143 Using chiral phosphoric acid ((S)-TRIP, 124) catalysis, the authors were able to obtain 29 formal C-H insertion products (125) with enantioselectivities in the range of 20-93% ee and low to Please do not adjust margins Please do not adjust margins Please do not adjust margins Please do not adjust margins moderate yields (15-50%). The reactions proceeded without need for nitrogen protection in the indole.…”

Organocatalytic asymmetric azidation of sulfoxonium ylides: mild synthesis of enantioenriched α-azido ketones bearing a labile tertiary stereocenter

“…Recently, α -carbonyl sulfur ylides have been developed as powerful surrogates to α -diazocarbonyl compounds, participating in a range of asymmetric cycloaddition and H–X bond insertion reactions, with the latter still in its infancy. 15–17 The amenability of this chemistry to mild metal-free organocatalytic conditions, combined with our continued interests in this topic, 17 led us to envision that an asymmetric formal H–N 3 insertion of α -carbonyl sulfoxonium ylides could be possibly achieved. 18 If successful, it would not only eliminate the drawback of the already powerful diazo-based carbene insertion chemistry, but also serve as an important alternative solution to the above challenge in the synthesis of enantioenriched α -azido carbonyl compounds (Scheme 1d).…”