Overcoming Regioselectivity Issues Inherent in Bis-Tröger's Base Preparation

Abstract

[structure: see text] Bis-Tröger's base derivatives are a new family of molecular tweezers. A major drawback to their study is a lack of commercially available precursors, ortho-nitrocarboxylic acids. A reverse synthetic strategy starting from known dinitrodicarboxylic acids, which circumvents this problem, is presented. Via this methodology regioisomeric bis-TB derivatives can be prepared selectively, using only common aromatic amines that are typically commercially available.

Recent Developments in Synthetic Chemistry, Chiral Separations, and Applications of Tröger's Base Analogues

“…Various synthetic methodologies have been developed to overcome regio-an diastereoselectivity issues, which are becoming increasingly complex when the number of fused methanodibenzodiazocine cores grows. This subject was extensively covered by the excellent review of Dolenský et al [10] (see also the most recent works from some of the authors of this review [69]). The recently published synthesis of a linear tris-Trçgers base (Scheme 11) may serve as an illustrative example of an efficient approach towards selective construction of a single regioisomer [70].…”

Oligo Tröger's bases—new molecular scaffolds

“…Formation of the corresponding imide by intramolecular reaction is the first serious complication for this protocol. 40 The second complication is connected with the following reduction step. If the arylamine is larger than aniline then the corresponding tetraamines are unstable in the reduction environment, thus the yields of the reduction is very low or nil.…”

Determination of relative configuration of symmetrical bis-Tröger’s base derivatives

“…The preparations of studied compounds were described in our previous works: syn/anti-1a [4,5], syn/anti-1b [5], syn/anti-1c [5], syn/anti-2a [6,7], syn/anti-2b [6,7], syn/anti-2c [8], 3a [4], 3b [9], 3c [9]. The structures of both syn-1a and anti-1a were already proofed via single-crystal X-ray diffraction [4], and can be obtained from the Cambridge Crystallographic Data Centre (CCDC 297485 syn-1a and CCDC 297484 for anti-1a).…”