Multiplicative enhancement of stereoenrichment by a single catalyst for deracemization of alcohols

Abstract

Stereochemical enrichment of a racemic mixture by deracemization must overcome unfavorable entropic effects as well as the principle of microscopic reversibility; recently, photochemical reaction pathways unveiled by the energetic input of light have led to innovations toward this end, most often by ablation of a stereogenic C(sp 3 )–H bond. We report a photochemically driven deracemization protocol in which a single chiral catalyst effects two mechanistically different steps, C–C bond cleavage and C–C bond formation, to achieve multiplicative enhancement of stereoinduction, which leads to high levels of stereoselectivity. Ligand-to-metal charge transfer excitation of a titanium catalyst coordinated by a chiral phosphoric acid or bisoxazoline efficiently enriches racemic alcohols that feature adjacent and fully substituted stereogenic centers to enantiomeric ratios up to 99:1. Mechanistic investigations support a pathway of sequential radical-mediated bond scission and bond formation through a common prochiral intermediate and reveal that, although the overall stereoenrichment is high, the selectivity in each individual step is moderate.

Photoinduced Selective B–H Activation of nido-Carboranes

“…In recent years, photoredox catalysis has emerged as a powerful tool for the development of selective functional group-specific coupling protocols through the generation of open-shell radical intermediates . We have explored the photocatalytic reactions for the B–H functionalization of carboranes …”

Enantioconvergent synthesis of chiral fluorenols from racemic secondary alcohols via Pd(ii)/chiral norbornene cooperative catalysis

“…1,2 Therefore, the transformation of racemic secondary alcohols into value-added chiral compounds is an attractive approach in asymmetric synthesis. 1 a ,2–6 Considerable progress has been made in this area so far, culminating in the development of several elegant strategies, including deracemization, 3,4 enantioconvergent transformation, 1 a ,2,5 and kinetic resolution (KR). 6 For example, two common reaction modes, linear and cyclic redox deracemizations, have been established to prepare enantioenriched secondary alcohols from the corresponding racemates (Fig.…”

Chiral Flipping in Viedma Deracemization

“…Deracemization is the process of converting a racemic mixture, which contains equal amounts of two enantiomers made up of chiral or achiral molecules, into a single enantiomerically pure form. − This process is highly significant and has garnered considerable interest due to its critical role in the field of chiral chemistry. In the pharmaceutical industry, for instance, access to enantiomerically pure drugs is vital since the two enantiomers can exhibit contrasted biological activities and side effects. − Furthermore, in agriculture, the use of enantiomerically pure compounds can lead to more targeted and efficient pest control, thus minimizing environmental impacts. − The advancements in deracemization techniques also drive innovation in the development of asymmetric catalysis and the synthesis of novel optical materials and chemicals. − …”