Modular Synthesis of Chiral NHC Precursors and Their Silver and Gold Complexes

Abstract

The stereoselective synthesis of chiral heterocyclic carbene precursors and the structural features of their silver and gold complexes were investigated. The prepared compounds are all based on the imidazolidine scaffold and bear the bulky tert-butyl substituent on the backbone in a stereocontrolled manner. The majority of the synthesized carbene precursors carry an additional element of central chirality in the side chain, and for some of them on formation of their silver or gold complexes a third element of asymmetry, axial chirality through hindered rotation of the aromatic substituent, is also present. The systematic study of the stereoselective formation of the NHC precursors led to scalable routes without the need for chiral chromatography. The NHC precursors were transformed efficiently into their silver and gold complexes, whose structural features were studied in detail both in solution and in the solid phase.

Synthesis and Vibrational Circular Dichroism Analysis of N-Heterocyclic Carbene Precursors Containing Remote Chirality Centers

“…The synthesis of optically active NHC precursors 1–2a,b , 4–5a,b and 15a,b , as well as their conversion to gold(I) NHC complexes was reported earlier [ 34 ]. These procedures utilized the optically active diamines ( S )- 19a and ( R )- 19b as key intermediates ( Scheme 1 ), which were obtained previously from ( S )- 18a and ( R )- 18b in three steps with an overall yield of 53% using 1-(4-methoxyphenyl)methanamine as an ammonia surrogate [ 34 ].…”

“…The synthesis of optically active NHC precursors 1–2a,b , 4–5a,b and 15a,b , as well as their conversion to gold(I) NHC complexes was reported earlier [ 34 ]. These procedures utilized the optically active diamines ( S )- 19a and ( R )- 19b as key intermediates ( Scheme 1 ), which were obtained previously from ( S )- 18a and ( R )- 18b in three steps with an overall yield of 53% using 1-(4-methoxyphenyl)methanamine as an ammonia surrogate [ 34 ]. For the synthesis of NHC precursors 6–16a,b having different substitution of the C-1′ chirality center, we simplified and improved the transformation of 18 to 19 by employing hydroxylamine and reduction of the oxime intermediate without isolation.…”

“…Herein, we report the stereoselective synthesis of NHC stereoisomers 6–17a , b and the chiroptical analysis of 1–17a,b containing remote chirality centers at C-5 of the imidazolium core and C-1′ of the side chain, the relative configuration of which could not be determined by NMR experiments ( Figure 1 ). The absolute configuration (AC) had been determined for some of these NHC precursors such as (5 R ,1′ R )- 5a and (5 R ,1′ S )- 5b , retrospectively, on the basis of single-crystal X-ray diffraction analysis of their gold(I) complexes [ 34 ]. However, chiroptical data (electronic and vibrational circular dichroism (ECD, VCD), optical rotation) of the NHC precursors were not measured and correlated with the stereochemistry, which would have enabled direct configurational assignment of the synthetic samples.…”

N-Heterocyclic carbenes as privileged ligands for nickel-catalysed alkene functionalisation

“…The key features of NHC ligands include their strong σ-donating capacity and their large buried volume (% V bur ) because of their steric bulkiness. Modular synthesis of structurally diverse NHC precursors 149 allows for convenient tuning of electronic and steric properties, which can considerably impact the efficiency, as well as the chemo-, regio- and stereo-selectivity of a reaction. The multifaceted design of NHC scaffolds permits the incorporation of stereogenicity at different positions of the NHCs, leading to the emergence of chiral NHC ligands employed in numerous enantioselective transformations facilitated with transition-metal catalysts.…”