Kinetic Resolution of Allylic Alcohol with Chiral BINOL-Based Alkoxides: A Combination of Experimental and Theoretical Studies

Abstract

The development and characterization of enantioselective catalytic kinetic resolution of allylic alcohols through asymmetric isomerization with chiral BINOL derivatives-based alkoxides as bifunctional Brønsted base catalysts were described in the study. A number of chiral BINOL derivatives-based alkoxides were synthesized, and their structure−enantioselectivity correlation study in asymmetric isomerization identified a promising chiral Brønsted base catalyst, which afforded various chiral secondary allylic alcohols (ee up to 99%, S factor up to >200). In the mechanistic study, alkoxide species were identified as active species and the phenol group of BINOL largely affected the high reactivity and enantioselectivity via hydrogen bonding between the chiral Brønsted base catalyst and substrates. The strategy is the first successful synthesis strategy of various chiral secondary allylic alcohols through enantioselective transitionmetal-free base-catalyzed isomerization. The applicability of the strategy had been demonstrated by the synthesis of the bioactive natural product (+)-veraguensin.

Enhancing the Regioselectivity of B(C6F5)3-Catalyzed Epoxide Alcoholysis Reactions Using Hydrogen-Bond Acceptors

“…These species have their own intrinsic activities and selectivities as catalysts. The influence of hydrogen bonding in catalysis has been extensively documented, − and the hydrogen-bonding ability of the BCF·H 2 O adduct has been previously studied, , and H-bound complexes have been implicated in other examples of BCF catalysis . Related Lewis acid·H 2 O catalysis has been described for other molecular systems , and is likely involved in solid-supported Lewis acids.…”

A Gallium-based Chiral Solvating Agent Enables the Use of 1H NMR Spectroscopy to Differentiate Chiral Alcohols

“…Chiral alcohols can be synthesized via (1) multistep transformations from a chiral pool such as terpenes, amino acids, and carbohydrates (Fan et al., 2019, Hung et al., 2019, Brill et al., 2017) or (2) kinetic resolution of racemic alcohols or their derivatives (Liu et al., 2019, Selier et al., 2019, Zhang and Ma, 2018). In addition, asymmetric synthesis such as reduction or nucleophilic addition of prochiral carbonyls recently has been developed (Neves-Garcia et al., 2018, Tsai et al., 2018; Bieszczad and Gilheany, 2017, Nakamura et al., 2017).…”

Catalytic Asymmetric Isomerization of (Homo)Allylic Alcohols: Recent Advances and Challenges

“…In 2019, the Yan group established a highly enantioselective kinetic resolution of secondary allylic alcohols 21 , through asymmetric isomerization catalyzed by a newly devised chiral bifunctional BINOL derivatives‐based alkoxide 22 (Scheme 9). [22] A series of γ‐hydroxy substituted enones 21 bearing different substituents proved to be suitable substrates under the action of 5 mol % of catalyst 22 , and delivered the corresponding ( S )‐ 21 in 41–50 % yields with 90–99 % ee, together with the formation of 1,4‐diketones 23 . By mechanistic studies, the authors proposed that the alkoxide moiety in the catalyst 22 was identified as active species, whilst the phenol groups of BINOL had a great influence on the high reactivity and enantioselectivity via H‐bonding interaction.…”