Synthesis of new derivatives from a Tröger base via exchange of the methano bridge with carbonyl compounds

A simple one-pot method has been developed for the preparation of new Tröger base derivatives by an exchange reaction with the methano bridge of rac-Tröger base derivatives with carbonyl compounds in the presence of TiCl4 or POCl3. The use of chiral (S,S)-N,N-bis(α-methylbenzyl)formamide as a carbonyl compound gave the corresponding methano Tröger base derivatives with the diastereomeric ratios of up to 77:23.

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(5R,11R)-13-(S,S)bis(1-Phenylethylamino)-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocineC31H31N3dr = 100%[α]D25=-189.4±1 (c 0.32, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (5R,11R)

(5R,11R)-1,3,7,9-Tetramethyl-13-(S,S)-bis(1-phenylethylamino)-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocineC35H39N3dr = 100%[α]D25=-264±2 (c 0.10, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (5R,11R)