Modular Synthesis of Optically Active Tröger’s Base Analogues

Abstract

For the first time, enantioselective catalysis was applied for the preparation of Tröger’s base derivatives affording N‐stereogenic building blocks not only in excellent enantiomeric purity but also in an easily scalable fashion. Enzymatic kinetic resolution proved efficient to yield functionalized Tröger’s bases, which can be subsequently modified by various chemical methods without any erosion of stereogenic information. In concert with a preparatively convenient protocol for the synthesis of the racemic substrates from commercially available anilines, a highly practicable and flexible route towards a wide range of enantiopure Tröger’s base analogues is provided.

Enantiomerically Pure Tribenzotriquinacenes through Stereoselective Synthesis

“…Thep resent results demonstrate that the enzymes used here are able to differentiate the stereochemistry not only of the carbinol functionalities of the TBTQ-based secondary alcohols containing al arge,b owl-shaped hydrocarbon backbone, [29,30] but also that of the inherently chiral polycyclic framework itself. [31,32] Therefore,wewere curious to examine the suitability of the corresponding primary benzylic alcohols and benzyl acetates bearing the same TBTQ backbone for enzyme catalysis.Infact, the same strategy was successful for the synthesis of enantiomerically pure TBTQ-benzaldehydes (M)-6 and (P)-6 (Scheme 3).…”

Synthesis of enantiomerically pure Tröger's base derivatives via chiral disulfoxides

“…13 Recently, larger quantities of enantiomerically pure Tro ¨ger's base-derived benzylic alcohols were made accessible by enzymatic kinetic resolution. 14 Given our interest in ligand design based on Tro ¨ger's base scaffold, 15 we set out to develop a protocol, which would allow for the preparation of a large quantity of a common enantiopure Tro ¨ger's base intermediate, which can be easily transformed into a broad palette of analogues. Chiral sulfoxides 16 are often used as chiral auxiliaries for the resolution of racemic products.…”