Preparation ofTröger Base Derivatives by Cross-Coupling Methodologies

Abstract

Derivatives of the Trˆger base are finding increasing application in supramolecular chemistry: they are introduced as rigid scaffolds into synthetic receptors and −molecular torsional balances× to quantify weak intermolecular interactions, and serve as efficient −covalent templates× in the tether-directed remote functionalization of fullerenes. This paper describes the facile synthesis of symmetrically (Schemes 1 and 2) and unsymmetrically (Schemes 4 and 5) substituted Trˆger base derivatives starting from the corresponding, readily available dihalo compounds. A variety of metal-catalyzed cross-coupling reactions, including Suzuki couplings, palladium-catalyzed cyanation and boronation, and copper-catalyzed amidations are used to achieve these transformations. . Recently, derivatives of the Trˆger base were introduced as chiral tethers for the regio-and stereoselective tether-directed remote functionalization of fullerenes [10] [11]. Many of these increasingly sophisticated scaffolds require intensive synthetic efforts, and, to this end, halogenated derivatives of the Trˆger base have recently been transformed by metal-catalyzed cross-coupling methodologies to provide a variety of acetylenic and biaryl derivatives [12] [13]. We report herein the application of metal-catalyzed cross-coupling methodologies to create two different classes of Trˆger base derivatives, one bearing identical substituents at the two aryl rings (see A) and the other featuring two different substituents at atoms C(2) and C(8) (see B) ( Fig.).

Synthesis, Resolution, and Absolute Configuration of Difunctionalized Tröger's Base Derivatives

“…[17] This prompted us and other groups to apply various cross-coupling methodologies for the construction of larger architectures with extended V-shaped cores. [18,19] Our group has succeeded in applying these disubstituted analogues of Trçgers base for the synthesis of racemic bis-A C H T U N G T R E N N U N G (catechol) ligands and the construction of triple-stranded complexes through coordination to titanium(IV) ions [20] and also for the preparation of racemic N-heterocyclic bis(bipyridine) and bis(2-pyridylmethanimine) ligands, which were demonstrated to form dinuclear double-and triple-stranded helicates in a (mostly) diastereoselective manner upon coordination to metal ions like Ag + , Cu + , Fe 2 + , and Zn 2 + .…”

Synthesis of Versatile Nonsymmetric Amine‐ and Boron‐Functionalized Tröger's Base Derivatives, Including a Tröger's Base Amino Acid

“…Conversion of this iodo substituent into a boronic acid equivalent would also allow it to function as the organoboron partner of a Suzuki reaction. [17] Reaction of the iodo group of 6 with bis(pinacolato)diboron (B 2 pin 2 , 7) and a palladium catalyst {[1,1Ј-bis(diphenylphosphanyl)ferrocene]dichloropalladium [Pd(dppf)Cl 2 ]}, led to boronic ester 8 in 84 % yield following column chromatography. The boronic ester was deprotected to form the boronic acid 9 upon treatment with sodium periodate in acetone and aqueous ammonium acetate in 92 % yield after isolation by extraction.…”

“…Wärnmark [16] and Sergeyev [17] and their co-workers demonstrated that a cross-coupling methodology could be used to generate desymmetrized Tröger's bases containing amino-and carbon-based functional groups from 2,8-diiodo-Tröger's base.…”

Halogenation of Tröger’s base analogues

“…[17][18][19][20] In the last few years halogenated Tröger's base analogues have been prepared from haloanilines [21][22][23][24] and proven to be extremely valuable in the synthesis of other analogues as the halogens act as "handles" for further functionalisation. [25][26][27][28] As part of a preliminary study aimed at alternate ways of accessing functionalised Tröger's base analogues, a methodology to brominate and chlorinate four Tröger's base compounds, as racemic mixtures, (Figure 1) was investigated. Numerous methods to halogenate aromatic compounds exist, [29][30][31][32][33][34] however, in terms of ease of handling and health issues, N-halosuccinimides are excellent reagents, especially if benzylic halogenation is suppressed.…”