Regio‐ and Enantioselective Synthesis of Sulfone‐Bearing Quaternary Carbon Stereocenters by Pd‐Catalyzed Allylic Substitution

Abstract

Chiral sulfones are of great importance in medicinal chemistry and chemical synthesis.E fficient methods for preparing enantiomerically enriched sulfone-containing molecules can therefore be of significant value;s uch methods, however,a re uncommon. Herein, we report the first general palladium-catalyzed sulfonylation of vinyl cyclic carbonates with sodium sulfinates.Aseries of enantiomerically enriched tertiary allylic sulfones were synthesized in good yields with excellent enantiomeric ratios.B oth aliphatic-and aryl-substituted vinyl cyclic carbonates are suitable reactants with excellent results.This reaction features broad substrates scope, readily available starting materials,e xcellent regio-and enantioselectivity,and synthesis of sulfone-bearing quaternary carbon stereocenters.T hrough the sulfonylation of geranyl derived cyclic carbonate 1h,w ea chieve the formal total synthesis of (+)-agelasidine A.

Ligand coordination- and dissociation-induced divergent allylic alkylations using alkynes

“…It is noteworthy that allylic substitution of these compounds using heteroatom-based nucleophiles including enantioselective variants has been well-established in recent years. [29][30][31][32][33][34] In contrast, the use of carbon-nucleophiles in this reaction remains rare in the literature. 35 The allylic alkynylation of 11a (R 0 = Ph) using 5a under the standard conditions from Figure 6A turned out to be very sluggish, leading to minimal formation of the desired 10a.…”

Mechanism of palladium-catalyzed allylic substitution of tertiary allylic carbonates with sodium sulfinates: unusual bifunctional nucleophile-enabled inner-sphere pathway and origin of regio- and enantioselectivities

“…[4][5][6] Thus, the development of efficient and practical methods for the synthesis of these compounds has attracted much interest. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] In this context, transition metal-catalyzed allylic sulfonylation, [8][9][10][11][12][13][14][15][16] hydrosulfonylation, [17][18][19][20] and hydrothiolation/oxidation [21][22][23][24] have been developed. For instance, Trost and co-workers reported early examples of palladium-catalyzed allylic sulfonylation reactions.…”

“…It should be mentioned that Zhao, Khan, and co-workers around the same time reported a similar approach using vinyl cyclic carbonates as allylic precursors to furnish tertiary allylic sulfones. 11 Given the significance of transition metal-catalyzed allylic substitution reactions, detailed mechanistic analysis has been performed both computationally [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] and experimentally. [41][42][43][44][45] In general, it is argued that palladium-catalyzed reactions preferentially take place via an outersphere pathway to give the linear allylic products in most cases with the process being under steric control.…”

Rh-Catalyzed Asymmetric Hydrogenation of α-Substituted Alkenyl Sulfones: Highly Chemo- and Enantioselective Access to Chiral Sulfones

“…Chiral sulfones are important structural motifs that are ubiquitous in biologically active natural products, medicinal chemistry, and functional materials, such as apremilast, remikiren renin inhibitor, inflammatory cytokines inhibitor, pomaglumetad methionil, and dorzolamide antiglaucoma drug (Figure ). In the past decades, many new synthesis methods for chiral sulfones have been developed, including addition reactions, cycloadditions, asymmetric sulfonylation reactions, direct substitutions, asymmetric hydrogenation, and other related examples . Among them, these methodologies mainly focus on β-substituted chiral sulfone compounds.…”