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.
Fleming
Fraser F
FF
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282-1530, USA. flemingf@duq.edu
Wei
Guoqing
G
Zhang
Zhiyu
Z
Steward
Omar W
OW
D000478:Alkylation; D001966:Bromine / Q000737:chemistry; D003500:Cyclization; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D013237:Stereoisomerism
D008670:Metals; D009570:Nitriles; D010100:Oxygen; D001966:Bromine