Induction of Planar Chirality Using Asymmetric Click Chemistry by a Novel Desymmetrisation of 1,3‐Bisalkynyl Ferrocenes

Adam J Wright,David L Hughes,Phillip C Bulman Page,G Richard Stephenson

doi:10.1002/ejoc.201901192

Abstract

The new asymmetric click CuAAC reaction is used for the first time to induce asymmetry in planar chiral compounds. There are only three classes of stereogenicity (atom‐centred, axial and planar), and these results are therefore of fundamental importance as well as practical significance, providing access to chiral ferrocenes at near enantiopurity. Here, we report asymmetric induction (AI) and kinetic resolution (KR) studies on a novel library of prochiral 1,2,3‐trisubstituted bis‐alkynylferrocenes, obtained by diiodination, derivatisation (including reduction and etherification), double Sonogashira coupling and finally transesterification, azidation or silylation. Desymmetrisation using chiral ligands to modify the CuAAC reaction proceeds in up to 60 % yield and >99.5 % ee, yielding planar chiral ferrocenes. The absolute configuration of two of the preferred products was proved by chemical correlation and related to the entire series by circular dichroism spectroscopy (CD).

Highlights

Thousands of papers have been published on the copper-catalysed azide-alkyne cycloaddition (CuAAC) click reactions,[1] but only eleven[2], report examples of asymmetric “click” chemistry in which a chiral ligand is used to influence the stereochemistry of desymmetrisation reactions of prochiral diazides[2b] and dialkynes[2a,2c–2f,2i,2h] or in kinetic resolutions.[2g,2j,2k] We provide the first example of a novel induction of planar chirality, achieving ees as high as 99.5 %
Mic substituted ferrocenes in the literature, most rely on classic directing groups such as oxazolines,[7a] acetals[7b] and Ugi's amine.[7c]. Examples of desymmetrisation approaches are far rarer, but include a series of asymmetric C-H activation reactions,[8a–8d] a lithiation using a chiral amine base[8e] and a twostep asymmetric esterification process.[8f]. Our work, reported here, adds a novel alternative to the range of methods that can be employed to access enantiopure planar chiral compounds
Because of the ready availability of the starting material, our work on the asymmetric click chemistry of prochiral ferrocenes began with a study of 1,2-diethynylferrocene,[9] but this gave almost entirely the achiral bis-triazole product, and only very low yields of the required mono-triazole

Summary

Introduction

Thousands of papers have been published on the copper-catalysed azide-alkyne cycloaddition (CuAAC) click reactions,[1] but only eleven[2] (one of them ours[2a]), report examples of asymmetric “click” chemistry in which a chiral ligand is used to influence the stereochemistry of desymmetrisation reactions of prochiral diazides[2b] and dialkynes[2a,2c–2f,2i,2h] or in kinetic resolutions.[2g,2j,2k] We provide the first example of a novel induction of planar chirality, achieving ees as high as 99.5 %. Mic substituted ferrocenes in the literature, most rely on classic directing groups such as oxazolines,[7a] acetals[7b] and Ugi's amine.[7c] Examples of desymmetrisation approaches are far rarer, but include a series of asymmetric C-H activation reactions,[8a–8d] a lithiation using a chiral amine base[8e] and a twostep asymmetric esterification process.[8f] Our work, reported here, adds a novel alternative to the range of methods that can be employed to access enantiopure planar chiral compounds

Methods

Results

Conclusion