Use of Tröger's Base as a Scaffold for New Chiral Molecular Tweezers: Synthesis of Trimeric, Fused Tröger's Bases

Abstract

Dedicated to Professor Rolf Huisgen on the occasion of his 85th birthday Four novel molecular tweezers, 6 ± 9, have been synthesized having, for the first time, three fused Trögers bases. The compounds differ in the relative configuration of the three fused methylene bridges and have been unambiguously characterized by NMR.Introduction. ± Trögers base (1) [1] is a concave chiral molecule, the chirality of which results from the blocked configuration of its stereogenic N-atoms. Trögers base and its derivatives have been described as fascinating molecules [2]. They provide relatively rigid chiral frameworks for the construction of chelating and biomimetic systems, which were essentially developed by Wilcox and co-workers, and elaborated by others [3]. Trögers bases show a perpendicular arrangement of the two aromatic rings [3c], as in Kagans ether, which was used by Harmata and co-workers for the synthesis of molecular tweezers [4]. In this context, we have utilized the Trögers base skeleton as a scaffold for the construction of the molecular clips 2 [5], 3 [6], and 4 [7].In this paper, we report the synthesis of chiral molecular tweezers with a trimeric, fused Trögers base skeleton. During the course of the present work, Klärner et al. [8] have described the synthesis of another family of molecular tweezers of type 5, with three methylene bridges, achiral carbocylic analogues of the compounds described in this paper.

Oligo Tröger's bases—new molecular scaffolds

“…no isomerization of the starting bisTB subunits was observed. 18 Similarly, the troegeration of anti-12 (HMTA, TFA, rt, 48 h) gave only anti,anti-7ah (in 33% yield) and anti,syn-7ah (in 19% yield). 18 Total regioselectivity, usual for troegeration in general, was observed in all these cases, i.e., no UZ-trisTB was isolated.…”

“…The troegeration with HMTA in TFA (rt, 24 h) gave no bisTB 2ah, 31 which is surprising in comparison with preparation of 7ah (vide supra). 18 In contrast, the troegeration by 35% formalin in ethanol with conc. hydrochloric acid (50 1C, 24 h) gave a 10% yield of anti-2ah, while at 90 1C gave a 12% yield of anti-2ah and a 10% yield of syn-2ah.…”

“…16 The estimation based on 1 H NMR was even supported by quantum chemical calculations, and was also successful in the case of Z-bisTB, 11 and partially validated for U-trisTB. 11,17,18 Scheme 1 General structure of TB derivatives, enantiomers of Tro¨ger's base (1a), and Reed's naphthalene TB 1b. Scheme 2 General structure of bisTB, and diastereoisomers of U-bisTB 2c.…”

“…of HCl, ethanol, 80 1C, 36 h) gave diastereoisomers anti,anti-7ah, anti,syn-7ah, syn,anti-7ah and syn,syn-7ah in a ratio of 1 : 2 : 2 : 2. 18 Their NMR spectra were solved in detail. 14 2.1.3.…”

Synthesis of Symmetric Dinitro‐Functionalised Tröger's Base Analogues

“…In addition, we have synthesised the first example of a tetranitro Tröger's base analogue. We expect that these molecules will become useful building blocks, via conversion to the corresponding diamines, in the synthesis of more highly functionalised compounds such as bis-, [22][23][24][25] tris- [26][27][28] or higher-order fused Tröger's base analogues and in the synthesis of new double-stranded helicates. [10,29] …”