The asymmetric allylic alkylation (AAA), which features employing active allylic substrates, has historical significance in organic synthesis. The allylic C−H alkylation is principally more atom-and step-economic than the classical allylic functionalizations and thus can be considered a transformative variant. However, asymmetric allylic C−H alkylation reactions are still scarce and yet underdeveloped. Herein, we have found that Z/E-and regioselectivities in the Pd-catalyzed asymmetric allylic C−H alkylation of 1,4-dienes are highly dependent on the type of nucleophiles. A highly stereoselective allylic C−H alkylation of 1,4-dienes with azlactones has been established by palladium-chiral phosphoramidite catalysis. The protocol proceeds under mild conditions and can accommodate a wide scope of substrates, delivering structurally divergent α,αdisubstituted α-amino acid surrogates in high yields and excellent levels of diastereo-, Z/E-, regio-, and enantioselectivities. Notably, this method provides key chiral intermediates for an efficient synthesis of lepadiformine marine alkaloids. Experimental and computational studies on the reaction mechanism suggest a novel concerted proton and two-electron transfer process for the allylic C−H cleavage and reveal that the Z/E-and regioselectivities are governed by the geometry and coordination pattern of nucleophiles.
Transition-metal-catalyzed asymmetric C–H activation
reactions
generally rely on the design of ligands with sterically bulky groups
to create a chiral environment for enantioinduction through steric
repulsion. Here we describe an Ir(III)-catalyzed asymmetric C–H
activation enabled by noncovalent interactions. A broad range of sulfur-stereogenic
sulfoximines was prepared in high yields with excellent enantioselectivities via the asymmetric C–H activation/annulation of sulfoximines
with diazo compounds. Desymmetrization, kinetic resolution, and parallel
kinetic resolution are compatible with this protocol. Detailed DFT
calculations suggested that the N–H···O hydrogen
bonding interaction between sulfoximine and the chiral carboxylic
acid ligand was crucial for the high enantiocontrol. Moreover, chiral
iridacycle intermediates were isolated, characterized, and subjected
to stoichiometric reactions. Computational and experimental studies
suggested that the C–H cleavage step was the rate- and enantio-determining
step.
An asymmetric C-H functionalization strategy with L-pGlu-OH as chiral ligand has been developed for the atroposelective synthesis of styrene atropisomers with open-chained alkene. The strategy allows quick access to a wide range of enantioenriched axially chiral styrenes in high yields and enantioselectivities. The axially chiral styrene-derived chiral acids have been demonstrated to be an efficient type of chiral ligands in Co(III)-catalyzed enantioselective CÀH amidation reactions.
Atropisomeric anilides have received tremendous attention as a novel class of chiral compounds possessing restricted rotation around an N-aryl chiral axis. However, in sharp contrast to the well-studied synthesis of biaryl atropisomers, the catalytic asymmetric synthesis of chiral anilides remains a daunting challenge, largely due to the higher degree of rotational freedom compared to their biaryl counterparts. Here we describe a highly efficient catalytic asymmetric synthesis of atropisomeric anilides via Pd(II)-catalyzed atroposelective C−H olefination using readily available L-pyroglutamic acid as a chiral ligand. A broad range of atropisomeric anilides were prepared in high yields (up to 99% yield) and excellent stereoinduction (up to >99% ee) under mild conditions. Experimental studies indicated that the atropostability of those anilide atropisomers toward racemization relies on both steric and electronic effects. Experimental and computational studies were conducted to elucidate the reaction mechanism and rate-determining step. DFT calculations revealed that the amino acid ligand distortion is responsible for the enantioselectivity in the C−H bond activation step. The potent applications of the anilide atropisomers as a new type of chiral ligand in Rh(III)-catalyzed asymmetric conjugate addition and Lewis base catalysts in enantioselective allylation of aldehydes have been demonstrated. This strategy could provide a straightforward route to access atropisomeric anilides, one of the most challenging types of axially chiral compounds.
Enantioselective
hydroarylation of unactivated terminal akenes
constitutes a prominent challenge in organic chemistry. Herein, we
reported a Cp*Co(III)-catalyzed asymmetric hydroarylation of unactivated
aliphatic terminal alkenes assisted by a new type of tailor-made amino
acid ligands. Critical to the chiral induction was the engaging of
a novel noncovalent interaction (NCI), which has seldomly been disclosed
in the C–H activation area, arising from the molecular recognition
among the organocobalt(III) intermediate, the coordinated alkene,
and the well-designed chiral ligand. A broad range of C2-alkylated
indoles were obtained in high yields and excellent enantioselectivities.
DFT calculations revealed the reaction mechanism and elucidated the
origins of chiral induction in the stereodetermining alkene insertion
step.
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