trans-Selective sp³ C-H Bond Arylation of Pyrrolidines and Piperidines

Significance

Pyrrolidine and piperidine substrates can be selectively arylated at the α-position in the presence of Ru₃(CO)₁₂, an arylboronic ester and a sacrificial ketone via an amidine-directed C-H activation-ketone reduction-transmetallation-C-C bond-formation sequence. This process was also extended to the use of pyridine- and pyrimidine-directing groups. High regioselectivity was observed in all cases giving the 2,5-di­substituted products in good yields, with a preference for formation of the trans isomer, albeit with poor diastereoselectivity in most cases. Control experiments found that in some products, isomerization occurs faster than arylation, and hence it is difficult to improve the selectivity.