37 research outputs found
Nickel-Catalyzed Carbon–Carbon Bond-Forming Reactions of Unactivated Tertiary Alkyl Halides: Suzuki Arylations
The first Suzuki cross-couplings of unactivated tertiary alkyl electrophiles are described. The method employs a readily accessible catalyst (NiBr[subscript 2]·diglyme/4,4′-di-tert-butyl-2,2′-bipyridine, both commercially available) and represents the initial example of the use of a group 10 catalyst to cross-couple unactivated tertiary electrophiles to form C–C bonds. This approach to the synthesis of all-carbon quaternary carbon centers does not suffer from isomerization of the alkyl group, in contrast with the umpolung strategy for this bond construction (cross-coupling of a tertiary alkylmetal with an aryl electrophile). Preliminary mechanistic studies are consistent with the generation of a radical intermediate along the reaction pathway.National Institute of General Medical Sciences (U.S.) (R01-GM62871)Merck Research Laboratories (Summer Fellowship
Catalytic Enantioselective Cross-Couplings of Secondary Alkyl Electrophiles with Secondary Alkylmetal Nucleophiles: Negishi Reactions of Racemic Benzylic Bromides with Achiral Alkylzinc Reagents
We have developed a nickel-catalyzed method for the asymmetric cross-coupling of secondary electrophiles with secondary nucleophiles, specifically, stereoconvergent Negishi reactions of racemic benzylic bromides with achiral cycloalkylzinc reagents. In contrast to most previous studies of enantioselective Negishi cross-couplings, tridentate pybox ligands are ineffective in this process; however, a new, readily available bidentate isoquinoline–oxazoline ligand furnishes excellent ee’s and good yields. The use of acyclic alkylzinc reagents as coupling partners led to the discovery of a highly unusual isomerization that generates a significant quantity of a branched cross-coupling product from an unbranched nucleophile
Feedstocks to Pharmacophores: Cu-Catalyzed Oxidative Arylation of Inexpensive Alkylarenes Enabling Direct Access to Diarylalkanes
A Cu-catalyzed method
has been identified for selective oxidative
arylÂation of benzylic C–H bonds with arylboronic esters.
The resulting 1,1-diarylÂalkanes are accessed directly from inexpensive
alkylÂarenes containing primary and secondary benzylic C–H
bonds, such as toluene or ethylÂbenzene. All catalyst components
are commercially available at low cost, and the arylÂboronic
esters are either commercially available or easily accessible from
the commercially available boronic acids. The potential utility of
these methods in medicinal chemistry applications is highlighted
Practical Synthesis of Amides via Copper/ABNO-Catalyzed Aerobic Oxidative Coupling of Alcohols and Amines
A modular
Cu/ABNO catalyst system has been identified that enables
efficient aerobic oxidative coupling of alcohols and amines to amides.
All four permutations of benzylic/aliphatic alcohols and primary/secondary
amines are viable in this reaction, enabling broad access to secondary
and tertiary amides. The reactions exhibit excellent functional group
compatibility and are complete within 30 min–3 h at rt. All
components of the catalyst system are commercially available
Catalytic Asymmetric Îł-Alkylation of Carbonyl Compounds via Stereoconvergent Suzuki Cross-Couplings
Nickel-Catalyzed Enantioselective Cross-Couplings of Racemic Secondary Electrophiles That Bear an Oxygen Leaving Group
To date, effective nickel-catalyzed enantioselective cross-couplings of alkyl electrophiles that bear oxygen leaving groups have been limited to reactions of allylic alcohol derivatives with Grignard reagents. In this Communication, we establish that, in the presence of a nickel/pybox catalyst, a variety of racemic propargylic carbonates are suitable partners for asymmetric couplings with organozinc reagents. The method is compatible with an array of functional groups and utilizes commercially available catalyst components. The development of a versatile nickel-catalyzed enantioselective cross-coupling process for electrophiles that bear a leaving group other than a halide adds a significant new dimension to the scope of these reactions.National Institute of General Medical Sciences (U.S.) (Grant R01-GM62871