An alcohol-directed, nickel-catalyzed
three-component umpolung
carboamination of unactivated alkenes with aryl/alkenylboronic esters
and electrophilic aminating reagents is reported. This transformation
is enabled by specifically tailored O-(2,6-dimethoxybenzoyl)hydroxylamine
electrophiles that suppress competitive processes, including undesired
β-hydride elimination and transesterification between the alcohol
substrate and electrophile. The reaction delivers the desired 1,2-carboaminated
products with generally high regio- and syn-diastereoselectivity
and exhibits a broad scope of coupling partners and alkenes, including
complex natural products. Various mechanistic experiments and analysis
of the stereochemical outcome with a cyclic alkene substrate, as confirmed
by X-ray crystallographic analysis, support alcohol-directed syn-insertion of an organonickel(I) species.
A nickel‐catalyzed conjunctive cross‐coupling of alkenyl carboxylic acids, aryl iodides, and aryl/alkenyl boronic esters is reported. The reaction delivers the desired 1,2‐diarylated and 1,2‐arylalkenylated products with excellent regiocontrol. To demonstrate the synthetic utility of the method, a representative product is prepared on gram scale and then diversified to eight 1,2,3‐trifunctionalized building blocks using two‐electron and one‐electron logic. Using this method, three routes toward bioactive molecules are improved in terms of yield and/or step count. This method represents the first example of catalytic 1,2‐diarylation of an alkene directed by a native carboxylate group.
Regioselective hydrofunctionalization of alkynes represents a straightforward route to access alkenyl boronate and silane building blocks. In previously reported catalytic systems, high selectivity is achieved with a limited scope of substrates and/or reagents, with general solutions lacking. Herein, we describe a selective copper-catalyzed Markovnikov hydrofunctionalization of terminal alkynes that is facilitated by strongly donating cyclic (alkyl)(amino)carbene (CAAC) ligands. Using this method, both alkyl-and aryl-substituted alkynes are coupled with a variety of boryl and silyl reagents with high α-selectivity. The reaction is scalable, and the products are versatile intermediates that can participate in various downstream transformations.Preliminary mechanistic experiments shed light on the role of CAAC ligands in this process. File list (2) download file view on ChemRxiv Manuscript.pdf (2.91 MiB) download file view on ChemRxiv Supporting Info.pdf (7.13 MiB)
An asymmetric 1,2-dicarbofunctionalization of unactivated
alkenes
with aryl iodides and aryl/alkenylboronic esters under nickel/bioxazoline
catalysis is disclosed. A wide array of aryl and alkenyl nucleophiles
are tolerated, furnishing the products in good yield and with high
enantioselectivity. In addition to terminal alkenes, 1,2-disubstituted
internal alkenes participate in the reaction, establishing two contiguous
stereocenters with high diastereoselectivity and moderate enantioselectivity.
A combination of experimental and computational techniques shed light
on the mechanism of the catalytic transformation, pointing to a closed-shell
pathway with an enantiodetermining migratory insertion step, where
stereoinduction arises from synergistic interactions between the sterically
bulky achiral sulfonamide directing group and the hemilabile bidentate
ligand.
A versatile
method to access differentially substituted 1,3- and
1,4-diamines via nickel-catalyzed three-component 1,2-carboamination
of alkenyl amines with aryl/alkenylboronic ester nucleophiles and
N–O electrophiles is reported. The reaction proceeds efficiently
with free primary and secondary amines without needing a directing
auxiliary or protecting group and is enabled by fine-tuning the leaving
group on the N–O reagent. The transformation is highly regioselective
and compatible with a wide range of coupling partners and alkenyl
amine substrates, all performed at room temperature. A series of kinetic
studies support a mechanism in which alkene coordination to the nickel
catalyst is turnover-limiting.
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