Organotitanium Nucleophiles in Asymmetric Cross-Coupling Reaction: Stereoconvergent Synthesis of Chiral α-CF₃ Thioethers

Ligand‐Promoted, Enantioconvergent Synthesis of Aliphatic Alkanes Bearing Trifluoromethylated Stereocenters via Hydrotrifluoroalkylation of Unactivated Alkenes

“…[ 3 ] However, while drug chirality has seen its importance and thus emerged as one major theme in drug research and development in the past decades, the utility of chiral fluorine‐containing compounds featuring a trifluoromethylated stereogenic carbon center is still underdeveloped due to lack of feasible methods for enantioselective syntheses of such chiral molecules. Moreover, the precedented protocols for asymmetric construction of trifluoromethylated stereogenic carbon centers usually relies on skeletal divergence at bond‐ forming site, resulting in positioning of this CF 3 ‐substituted carbon at specific spots [ 8,13 ] like benzyl, [ 4,6,11 ] allylic, [ 12 ] or ɑ‐position of heteroatoms, [ 5,9‐10 ] etc . [ 7 ] A general, highly efficient and enantioselective strategy for diverse synthesis of enantiopure alkanes featuring trifluoromethyl‐substituted stereocenters remains elusive but extremely desired.…”

Synthesis of (Enantioenriched) Dibenzyl Thioethers and Disulfides via SN2 Nucleophilic Substitution of Quaternary Ammonium Salts

“…In the past decades, there are many methods for the preparation of thioethers, [11–12] but there are only a few approaches that prepare chiral thioethers from amine derivatives [13–14] via C−N cleavages. In particular, the exploration of organosulfur reagents for the construction of carbon‐sulfur bonds is of widespread interest [15,16] . Tian and co‐workers reported that stereospecifific nucleophilic substitution of higher reactive enantioenriched quaternary ammonium salts with a N‐phenyl group from enantioenriched tertiary benzylic amines via in situ activation with benzyne (Scheme 1, eqn.…”

“…In particular, the exploration of organosulfur reagents for the construction of carbon-sulfur bonds is of widespread interest. [15,16] Tian and co-workers reported that stereospecifific nucleophilic substitution of higher reactive enantioenriched quaternary ammonium salts with a Nphenyl group from enantioenriched tertiary benzylic amines via in situ activation with benzyne (Scheme 1, eqn. (a)); [17] it is no reaction for less reactive benzylic quaternary ammonium salts with a N,N,N-trimethyl group.…”

Recent Advances in Synthesis of Chiral Thioethers

“…In 2019, Gandelman's group developed a method to achieve catalytically asymmetric synthesis of CF 3 ‐substituted chiral benzylic thioethers 26 (Scheme 9). [18] In this method, organotitanium 25 used as a nucleophile react with halogenated alkanes 24 via Ni‐catalyzed asymmetric cross‐coupling reaction. Initially, this group tried organosilicon nucleophiles to provide the chiral thioethers with α‐CF 3 by the Hiyama reaction.…”