Silver Dependent Enantiodivergent Gold(I) Catalysed Asymmetric Intramolecular Hydroamination of Alkenes: A Theoretical Study

Abstract

We report a theoretical study of the first silver–dependent enantiodivergent gold-catalysed reaction. The combination of a single chiral binuclear gold(I) chloride complex and silver perchlorate catalyses the asymmetric intramolecular hydroamination of alkenes and affords both enantiomers of the products by applying a simple solvent change from toluene to methanol. A gold–silver chloride adduct that occurs only in methanol appears to control the enantioinversion. If one gold atom coordinates and activates the alkene moiety, the other gold is included in an adduct with silver chloride, which coordinates a methanol solvent molecule and further interacts with the amine function. If the use of toluene implies free anions and affords (S)–enantiomer, methanol allows a proximal interaction with the amine, leads to an opposite stereodifferentiation of the two diastereomeric intermediates during the final protodeauration step and results in the (R)–enantiomer.

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

“…In particular, successful asymmetric methods were reported in short time after initially reported non-asymmetric methods, specifically Kojima's tropos BIPHEP-gold(I)-catalyzed hydroamination of alkenylureas in 2012 [9]. Michon [5][6][7][8]10] and Widenhoefer continued to make advancements in asymmetric intra-and intermolecular variants, and unique solvent and anion dependencies continue to be examined from a theoretical standpoint.…”

“…Great successes in mechanistic analysis and synthetic methods have been achieved for allene and alkyne activation, while the activation of alkenes remains challenging. Advances in asymmetric catalysis [2][3][4][5][6][7][8][9][10], C-N [11][12][13][14][15][16][17] and C-C functionalization [18,19] reveal opportunities, but harsh conditions and limited substrate scope present problems. Intramolecular reactions almost invariably require geminal substitution or backbone heteroatoms, internal alkenes are often not tolerated, and intermolecular reactions require high temperatures which can lead to significant catalyst decomposition [20].…”