Synthesis and configuration determination of enantiopure 4,10-bis-ortho-substituted Tröger’s base derivatives

Abstract

A practical and scalable method for synthesis and resolution of 4,10-di-substituted Tröger's base derivatives is described. By combination of circular dichroism (CD) spectra and X-ray diffraction (XRD) analysis method, the absolute configuration on two sterogenic nitrogen atoms of the crucial intermediate (-)-diastereomer is assigned as 5S,11S.

Facile access to imidazole and imidazolium substituted dibenzo-diazocines

“…13 4,10-Dihalo substituted methanodibenzo-diazocine analogues were synthesized in good yields even in the presence of halogens as additional groups (on the benzene ring) (see ESI, † Table S2). 14 Although the importance of the century old methanodibenzodiazocine skeleton has been a subject of focus in the last several decades, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] examples based on methanodibenzo-diazocine tethered heterocyclic ring systems are still rare. 18,19 The only report available to date is 2,8-diazolyl substituted Tro ¨ger's bases (Type A, Chart 1) by Pardo et al 19a Notably, the symmetric disubstituted type B-D are not known.…”

Tröger’s Base Twisted Amides: Endo Functionalization and Synthesis of an Inverted Crown Ether

“…These applications of the structural features of TB have elicited substantial synthetic efforts that include (1) a facile synthesis of halogenated TB analogues, − which allows its aromatic ring functionalization, , (2) N -mono and -dialkylations, and (3) replacement of the methylene bridge. , Although C-6 and C-12 functionalized TB analogues have been synthesized from substituted dibenzodiazocines, the preparation of such exo -monosubstituted ( 2 ) or exo , exo -disubstituted ( 3 ) derivatives from the readily available TB has been feasible only by the metalation strategy developed in our laboratories (Figure ) . We have previously reported on the use of exo -substituted analogues of TB in the catalytic asymmetric addition of diethylzinc to substituted benzaldehydes in up to 86% ee .…”