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. 2020 Jan 23;362(2):295-301.
doi: 10.1002/adsc.201900816. Epub 2019 Sep 6.

Enantioselective Kinetic Resolution/Desymmetrization of Para-Quinols: A Case Study in Boronic-Acid-Directed Phosphoric Acid Catalysis

Banruo Huang  1 , Ying He  1 , Mark D Levin  1 , Jaime A S Coelho  1   2 , Robert G Bergman  1 , F Dean Toste  1
Affiliations

Enantioselective Kinetic Resolution/Desymmetrization of Para-Quinols: A Case Study in Boronic-Acid-Directed Phosphoric Acid Catalysis

Banruo Huang et al. Adv Synth Catal. .

Abstract

A chiral phosphoric acid-catalyzed kinetic resolution and desymmetrization of para-quinols operating via oxa-Michael addition was developed and subsequently subjected to mechanistic study. Good to excellent s-factors/enantioselectivities were obtained over a broad range of substrates. Kinetic studies were performed, and DFT studies favor a hydrogen bonding activation mode. The mechanistic studies provide insights to previously reported chiral anion phase transfer reactions involving chiral phosphate catalysts in combination with boronic acids.

Keywords: asymmetric catalysis; chiral phosphoric acid; directed reactivity; kinetics; oxa-Michael addition; reaction mechanisms.

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Figures

Figure 1.
Figure 1.
A) Boronic acid monoester as an in stiu directing group for CAPT enantioselective fluorination of allylic alcohols (CPA=chiral phosphoric acid); B) Oxa-Michael addition of boronic acid monoester promoted by push/pull-type catalyst; C) Kinetic resolution of para-quinols via complexation of in situ directing group and phosphate.
Figure 2.
Figure 2.. A)
Initial rate-(R)-TRIP catalyst loading plot; B) Reaction plot of [4a] under saturation of 3e.
Scheme 1.
Scheme 1.
Separate-pot kinetic isotope effect.
Scheme 2.
Scheme 2.
Proposed mechanism with calculated transition state.
See this image and copyright information in PMC

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