Catalytic Asymmetric Hydrocarboxylation and Hydrohydroxymethylation. A Two-Step Approach to the Enantioselective Functionalization of Vinylarenes
摘要:
A method for the catalytic asymmetric hydrocarboxylation and hydrohydroxymethylation of vinylarenes is reported. By separating the step in which asymmetry is installed from the one where carbon-carbon bond formation takes place, a highly enantioselective and regioselective synthesis of Ibuprofen and its analogs is achieved. Stereochemistry is installed via an enantioselective hydroboration reaction, catalyzed by cationic rhodium BINAP complexes, and the homologation is carried out with halomethyllithium reagents. If CH2Cl2/n-BuLi is used as the homologating reagent, carboxylic acids are produced after oxidation. On the other hand, if CH2ClBr is used in combination with n-BuLi, the corresponding primary alcohol is produced. This latter transformation represents a previously unknown asymmetric hydrohydroxymethylation reaction. In both cases, complete retention of stereochemistry is observed, yielding products in up to 97% ee. Superior results are obtained if the initially formed catecholate is converted into a pinacolate prior to homologation.
Catalytic Asymmetric Hydrocarboxylation and Hydrohydroxymethylation. A Two-Step Approach to the Enantioselective Functionalization of Vinylarenes
摘要:
A method for the catalytic asymmetric hydrocarboxylation and hydrohydroxymethylation of vinylarenes is reported. By separating the step in which asymmetry is installed from the one where carbon-carbon bond formation takes place, a highly enantioselective and regioselective synthesis of Ibuprofen and its analogs is achieved. Stereochemistry is installed via an enantioselective hydroboration reaction, catalyzed by cationic rhodium BINAP complexes, and the homologation is carried out with halomethyllithium reagents. If CH2Cl2/n-BuLi is used as the homologating reagent, carboxylic acids are produced after oxidation. On the other hand, if CH2ClBr is used in combination with n-BuLi, the corresponding primary alcohol is produced. This latter transformation represents a previously unknown asymmetric hydrohydroxymethylation reaction. In both cases, complete retention of stereochemistry is observed, yielding products in up to 97% ee. Superior results are obtained if the initially formed catecholate is converted into a pinacolate prior to homologation.
An existing challenge is the development of efficient regioselective catalytic systems that are compatible with stable hydroboration reagents and can be rendered enantioselective by the use of nonracemic ligands. Copper(I) complexes with chelating phosphines catalyzed the regio‐ and enantioselective hydroboration of styrenes with pinacolborane (PinBH) at room temperature to afford the corresponding
to the application of several alkyl organometallic nucleophiles (e.g., alkyl-zinc, boron, and magnesium) in asymmetric cross-couplings, more easily accessible alkylzirconocene reagents have received much less attention. Herein, we report a visible-light-induced, Ni-catalyzed, asymmetric cross-coupling of gem-borazirconocene alkenes with aryl and unactivated alkylhalides, furnishing a diverse series
Enantioselective Hydroboration of Styrenes with Markovnikov Selectivity Catalyzed by a Rhodium(I)-NHC Complex
作者:Kartick Dey、Zeqing Chen、Natalia Fridman、Graham de Ruiter
DOI:10.1021/acs.organomet.4c00002
日期:2024.4.22
developing field where N-heterocycliccarbenes (NHCs) are making increasingly more impact. Herein, we report the synthesis and characterization of carbene-oxazoline containing proligands that exhibit two chiral centers. The corresponding rhodium(I) complexes show excellent activity toward the asymmetric hydroboration of styrenes, which occurs with good regio– and enantioselectivity (up to 96% ee). The