Cyclic Oxonitriles: Stereodivergent Grignard Addition−Alkylations

Sequential carbonyl addition−conjugate addition of Grignard reagents to cyclic 5−7-membered
oxoalkenenitriles efficiently generates cyclic magnesiated nitriles. Alkylations of these magnesiated nitriles
exhibit diastereoselectivities that depend intimately on the size of the carbocyclic ring:  5-membered
oxonitriles generate magnesiated nitriles whose alkylations are controlled by steric constraints whereas
6- and 7-membered oxonitriles generate internally coordinated, C-magnesiated nitriles whose alkylations
are controlled by stereoelectronic effects. Reversing the alkylation selectivity of 6-membered C-magnesiated
nitriles is achieved by conversion to an N-metalated nitrile in which steric, rather than electronic, effects
direct the electrophile trajectory. Collectively, the conjugate addition−alkylation generates highly
substituted, cyclic 5−7-membered nitriles containing three new stereocenters with selective access to
diastereomers at the quaternary nitrile-bearing carbon.