The development of enantioselective alkyl-alkyl cross-couplings with coinstantaneous formation of a stereogenic center without the use of sensitive organometallic species is attractive yet challenging. Herein, we report the intermolecular regio-and enantioselective formal hydrofunctionalizations of acrylamides, forging a stereogenic center a-position to the newly formed C sp3 -C sp3 bond for the first time. The use of a newly developed chiral ligand enables the electronicallyreversed formal hydrofunctionalizations, including hydroalkylation, hydrobenzylation, and hydropropargylation, offering an efficient way to access diverse enantioenriched amides with a tertiary a-stereogenic carbon center which is facile to racemize. This operationally simple protocol allows for the anti-Markovnikov enantioselective hydroalkylation, and unprecedented hydrobenzylation, hydropropargylation under mild conditions with excellent functional group compatibility, delivering a wide range of amides with excellent levels of enantioselectivity.Scheme 1. Alkyl-alkyl cross-coupling strategies to construct stereogenic carbon center.

A series of tunable iminium ions, generated in situ by the condensation of 4-trifluoromethyl-p-quinols with cyclic amines, can lead to the divergent synthesis of trifluoromethylated arylamines in a single step via redox-neutral isomerization. The direct α- and β-functionalization of saturated amines can be achieved regioselectively under mild conditions.

A formal [4 + 2] cyclization of easily available ketene dithioacetals with acyl chlorides has been developed. Mediated by lithium bis(trimethylsilyl)amide, a series of γ-pyrones were obtained with a broad substrate scope. This unprecedented formal [4 + 2] cyclization provides a novel mode for ketene dithioacetals as versatile synthons. The synthesized γ-pyrones could be successfully transformed to 2-aryl/amino γ-pyrones and 2,3-dihydroimidazo[1,2-a]pyridin-7(1H)-ones mainly via the cleavage of the C−S bond. Article pubs.acs.org/joc

TheC À Cbond formation via C À Sbond activation( disclosed in 2000) has received increasing attention. However, stoichiometric amounts of exogenous thiophilic reagents are generally requireda s thiolate scavengers.H erein, an ew model for the synthesis of 4-aminoquinolines, the copper(II)-catalyzed aerobic oxidative desulfitative 6p cyclization of the readily available N-arylimino ketene N,S-acetals is described. Ther eactionc an proceed efficiently under mild conditions without any exogeneous thiolate scavengers (due to the formation of disulfide as the by-product) to affordd iverse 4-aminoquinolines, ap rivileged structure motif displaying antimalarial activity,w ith aw ide range of functional groups at the C-2 to C-8 positions.Scheme 3. Preparation of ketene N,S-acetals 2x-2z,4 -aminoquinolines 3x-3z,and carbodiimide 10.

The development of enantioselective alkyl-alkyl cross-couplings with coinstantaneous formation of a stereogenic center without the use of sensitive organometallic species is attractive yet challenging. Herein, we report the intermolecular regio-and enantioselective formal hydrofunctionalizations of acrylamides, forging a stereogenic center a-position to the newly formed C sp3 -C sp3 bond for the first time. The use of a newly developed chiral ligand enables the electronicallyreversed formal hydrofunctionalizations, including hydroalkylation, hydrobenzylation, and hydropropargylation, offering an efficient way to access diverse enantioenriched amides with a tertiary a-stereogenic carbon center which is facile to racemize. This operationally simple protocol allows for the anti-Markovnikov enantioselective hydroalkylation, and unprecedented hydrobenzylation, hydropropargylation under mild conditions with excellent functional group compatibility, delivering a wide range of amides with excellent levels of enantioselectivity.Scheme 1. Alkyl-alkyl cross-coupling strategies to construct stereogenic carbon center.