Asymmetric conjugate additions of 2-substituted benzofuran-3(2H)-ones to α,β-unsaturated ketones catalyzed by chiral copper complexes

2017 ◽  
Vol 15 (19) ◽  
pp. 4191-4198 ◽  
Author(s):  
Haojiang Wang ◽  
Yifeng Wang ◽  
Cheng Zhang ◽  
Yidong Jiang ◽  
Mingming Chu ◽  
...  
Keyword(s):  
Copper Complexes ◽  
Conjugate Addition ◽  
Conjugate Additions ◽  
Unsaturated Ketones

A highly enantioselective conjugate addition of 2-substituted benzofuran-3(2H)-ones to α,β-unsaturated ketones promoted by chiral copper complexes has been developed.

scholarly journals Retooling Asymmetric Conjugate Additions for Sterically Demanding Substrates with an Iterative Data-Driven Approach

2019 ◽  
Author(s):  
Alexandre Brethomé ◽  
Robert Paton ◽  
Stephen P. Fletcher
Keyword(s):  
Functional Groups ◽  
Conjugate Addition ◽  
Data Driven ◽  
Quantitative Structure ◽  
Conjugate Additions ◽  
Unsaturated Ketones ◽  
Alkyl Chains ◽  
Reaction Optimization ◽  
Sterically Demanding ◽  
Data Driven Approach

The development of new catalytic enantioselective methods is routinely carried out using easily accessible and prototypical substrates. This approach to reaction development often yields asymmetric methods that perform poorly using substrates sterically or electronically dissimilar to those used during the reaction optimization campaign. Consequently, expanding the scope of previously optimized catalytic asymmetric reactions to include new substrates is decidedly non-trivial. Here we address this challenge through the development of a systematic workflow to broaden the applicability and reliability of asymmetric conjugate additions to substrates conventionally regarded as sterically and electronically challenging. The copper-catalyzed asymmetric conjugate addition of alkylzirconium nucleophiles to form tertiary centers, although successful for linear alkyl chains, fails for more sterically demanding linear α,β-unsaturated ketones. Key to adapting this method to obtain high enantioselectivity was the discovery of new phosphoramidite ligands, designed using quantitative structure-selectivity relationships (QSSR). Iterative rounds of model construction and ligand synthesis were executed in parallel to evaluate the performance of twenty chiral ligands. The copper-catalyzed asymmetric addition is now more broadly applicable, even tolerating linear enones bearing tert-butyl β-substituents. The presence of common functional groups is tolerated in both nucleophiles and electrophiles, giving up to 99% yield and 95% ee across twenty examples.

scholarly journals Retooling Asymmetric Conjugate Additions for Sterically Demanding Substrates with an Iterative Data-Driven Approach

2019 ◽  
Author(s):  
Alexandre Brethomé ◽  
Robert Paton ◽  
Stephen P. Fletcher
Keyword(s):  
Functional Groups ◽  
Conjugate Addition ◽  
Data Driven ◽  
Quantitative Structure ◽  
Conjugate Additions ◽  
Unsaturated Ketones ◽  
Alkyl Chains ◽  
Reaction Optimization ◽  
Sterically Demanding ◽  
Data Driven Approach

The development of new catalytic enantioselective methods is routinely carried out using easily accessible and prototypical substrates. This approach to reaction development often yields asymmetric methods that perform poorly using substrates sterically or electronically dissimilar to those used during the reaction optimization campaign. Consequently, expanding the scope of previously optimized catalytic asymmetric reactions to include new substrates is decidedly non-trivial. Here we address this challenge through the development of a systematic workflow to broaden the applicability and reliability of asymmetric conjugate additions to substrates conventionally regarded as sterically and electronically challenging. The copper-catalyzed asymmetric conjugate addition of alkylzirconium nucleophiles to form tertiary centers, although successful for linear alkyl chains, fails for more sterically demanding linear α,β-unsaturated ketones. Key to adapting this method to obtain high enantioselectivity was the discovery of new phosphoramidite ligands, designed using quantitative structure-selectivity relationships (QSSR). Iterative rounds of model construction and ligand synthesis were executed in parallel to evaluate the performance of twenty chiral ligands. The copper-catalyzed asymmetric addition is now more broadly applicable, even tolerating linear enones bearing tert-butyl β-substituents. The presence of common functional groups is tolerated in both nucleophiles and electrophiles, giving up to 99% yield and 95% ee across twenty examples.

Nickel-catalyzed conjugate addition of alkynyl groups to .alpha.,.beta.-unsaturated ketones

1980 ◽  
Vol 45 (15) ◽  
pp. 3053-3061 ◽  
Author(s):  
Jeffrey Schwartz ◽  
Denise B. Carr ◽  
Robert T. Hansen ◽  
Fabian M. Dayrit
Keyword(s):  
Conjugate Addition ◽  
Unsaturated Ketones ◽  
Alpha Beta
Sign in / Sign up

Export Citation Format

Share Document