Lithium 4,4’-Di-Tert-Butylbiphenylide: Characterization, Use in Spirocyclic Synthesis and Applications in Flow Reactors
Abstract
The first part of the dissertation describes the characterization of lithium 4,4’-di-tert-butylbiphenylide (LiDBB). The rates of formation and degradation of LiDBB were investigated and decomposition products identified. Stored LiDBB was found to give equivalent yields of a [4.5] spirocycle over 16 weeks.
The second part of the dissertation details the preparation of substituted spiropyrrolidines and spiropiperidines by double alkylation of α-aminonitriles, followed by stereoselective reductive lithiation and cyclization. In all cases, cyclization occurred with high diastereoselectivity.
The third part of the dissertation investigated the use of LiDBB in flow reactors. Direct ring opening of an epoxide, instead of its thiophenyl derivative, was examined. Non-cryogenic flow conditions substantially increased the yield of spiropyrrolidines and a spiropiperidine. A substituted [4.5] spirocycle also was formed in higher yield and diastereoselectivity as compared to batch conditions.