Complex-Induced Proximity Effects. Temperature-Dependent Regiochemical Diversity in Lithiation-Electrophilic Substitution Reactions of N-BOC-2-Azabicyclo[2.1.1]hexane. 2,4- and 3,5-Methanoprolines

Abstract

(Matrix Presented) Azabicycle 4 and sec-butyllithium/TMEDA afford the C1 bridgehead α-lithio anion at 0°C. Anion quenching with carbon dioxide, methyl chloroformate, or DMF provide the bridgehead acid 8a (N-BOC-2,4-methanoproline), ester 8b, or aldehyde 8c, respectively. By contrast, at -78 °C these same reagents give a mixture of regioisomeric methylene and bridgehead anions whose quenching leads to mixtures of regioisomeric methylene and bridgehead acids 6a/8a, esters 6b/8b, or aldehydes 6c/8c, respectively. The previously unknown 3,5-methanoproline was prepared as its N-BOC methyl ester 6b.