Enantioselective C-H Arylation and Vinylation of Cyclobutyl Carboxylic Amides.

Chiral mono-N-protected aminomethyl oxazoline (MPAO) ligands are found to promote enantioselective C-H arylation and vinylation of the cyclobutyl carboxylic acid derivatives via Pd(II)/Pd(IV) redox catalysis. This ligand scaffold overcame two important limitations of the previous MPAHA (mono-N-protected α-amino-O-methylhydroxamic acid) ligands-enabled asymmetric C-H activation/C-C coupling reactions of cyclic carboxylic amides through Pd(II)/Pd(0) catalysis: substrates containing α-hydrogen atoms are not compatible; vinylation has not been developed. Sequential C-H arylation and vinylation of cyclobutanes are also accomplished to construct three consecutive chiral centers on the crowded cyclobutane rings, rendering this reaction highly versatile for the preparation of chiral cyclobutanes.