A desilylative approach to alkyl substituted C(1)-ammonium enolates : application in enantioselective [2+2] cycloadditions

Funding: The research leading to these results has received funding from the CSC-St Andrews PhD Scholarship Scheme (Y.W.), the Newton Fellowship Programme (H.L.) and the Engineering and Physical Sciences Research Council, University of St Andrews, and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) for financial support [Ph.D. studentship to W. H.; Grant code: EP/L016419/1].The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96% yield and >99:1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75% yield and >99:1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (±)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.Publisher PDFPeer reviewe