||Stereochemical Course of Deprotonation-Acylation of N-Boc- and N-Carbamoyl-2-cyano-6-methylpiperidines
Kotomori, Yuri ,
Sasaki, Michiko ,
Kawahata, Masatoshi ,
Yamaguchi, KentaroTakeda, Kei
The Journal of Organic Chemistry
11020 , 2015-11-06 , American Chemical Society
The stereochemical course of electrophilic substitution of α-nitrile metallocarbanions generated by deprotonation from N-Boc- and N-carbamoyl-2-cyano-6-methylpiperidines was investigated. Deprotonation in the presence of an electrophile taking advantage of the high acidity of α-nitrile protons allowed examination of the effects of a chelating group on the nitrogen atom, a countercation, and the reactivity of an electrophile on the steric course. Analyses of reactions using aroyl chlorides and methyl iodide revealed the following: (1) the substitution reactions basically proceed with retention of configuration, (2) the extent of an inversion product increases with decreasing chelating ability of the N-substituent and with increasing leaving ability (ionic character) of a countercation (Li, Na, K) of the anionic species, and (3) the use of a more reactive electrophile results in an increase of the retention product.
This research was partially supported by a Grant-in-Aid for Scientific Research (C) 25460015 (M.S.) a Grant-in-Aid for Scientific Research (B) 22390001 (K.T.), a Grant-in-Aid for Challenging Exploratory Research 23659007 (K.T.) and 15K14929 (K.T.) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Hoansha Foundation (M.S.), the Takeda Science Foundation (M.S.) and the Naito Foundation Natural Science Scholarship (M.S.).