Studies on the synthesis, resolution, applications of Tröger base derivatives and mechanism of the osmium catalyzed asymmetric dihydroxylation of Alkenes

Abstract

It comprises of three chapters. 1) Introduction, 2) Results and Discussion and 3) Experimental Section. The work described in this thesis is exploratory in nature. The first chapter describes a brief review of literature on the synthetic methods, resolution and various applications of Tröger base and its derivatives. The second chapter deals with the results and discussion on the studies undertaken on the synthesis, resolution of Tröger base derivatives and their applications in chiral recognition, asymmetric aziridination, osmium catalyzed dihydroxylation, reductions, and hydroboration studies. A convenient method to readily access racemic Tröger base and its derivatives by Lewis acid catalysis was developed. Among all the Lewis acids screened, AlCl3 gave the best yields (Scheme 1). A new method has been devised for the resolution of racemic Tröger base 3 by using readily available and recoverable dibenzoyl-L-tartaric acid 7 as resolving agent (Scheme 2). The configurations of the N-chiral centres of (-)-3 were assigned as 5R,11R by the single crystal X-ray analysis of the precipitated diastereomeric complex. Scheme 2 Similarly, the racemic methoxy Tröger base 4 was also resolved using dibenzoyl-L-tartaric acid 7 and the (-)-4 enantiomer was obtained with gt98% ee from the precipitate fraction. Figure 1 The 5,11-substituted Tröger base derivatives 8 were prepared in a single step by the reaction of Tröger base 3 with carbonyl compounds in the presence of TiCl4 (Scheme 3). Further, these derivatives were also prepared by the reaction in the presence of POCl3 (Scheme 3). The structure of the spiro compound obtained in the reaction with cyclopentanone was further confirmed by single crystal X-ray analysis. Attempts on the resolution of 5,11-endobenzylidine derivative of Tröger base 8a (R = Ph) using different chiral acids were not successful. However, the enantiomers of 5,11-endosubstituted derivatives of Tröger base 8 were readily separated in analytical scale using HPLC on Chiralcel- OJ-H column using ethanol...