A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ-Lactones

Mark A. Maskeri; Malte L. Schrader; Karl A. Scheidt

doi:10.1002/chem.202000747

A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ-Lactones

Mark A. Maskeri, Malte L. Schrader, Karl A. Scheidt^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Combining biological and small-molecule catalysts under a chemoenzymatic manifold presents a series of significant advantages to the synthetic community. We report herein the successful development of a two-step/single flask synthesis of γ-lactones through the merger of Umpolung catalysis with a ketoreductase-catalyzed dynamic kinetic resolution, reduction, and cyclization. This combined approach delivers highly enantio- and diastereoenriched heterocycles and demonstrates the feasibility of integrating NHC catalysis with enzymatic processes.

Original language	English (US)
Pages (from-to)	5794-5798
Number of pages	5
Journal	Chemistry - A European Journal
Volume	26
Issue number	26
DOIs	https://doi.org/10.1002/chem.202000747
State	Published - May 7 2020

Keywords

N-heterocyclic carbene catalysis
chemoenzymatic catalysis
ketoreductase enzyme
photoredox catalysis
sequential catalysis

ASJC Scopus subject areas

Catalysis
Organic Chemistry

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title = "A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ-Lactones",

abstract = "Combining biological and small-molecule catalysts under a chemoenzymatic manifold presents a series of significant advantages to the synthetic community. We report herein the successful development of a two-step/single flask synthesis of γ-lactones through the merger of Umpolung catalysis with a ketoreductase-catalyzed dynamic kinetic resolution, reduction, and cyclization. This combined approach delivers highly enantio- and diastereoenriched heterocycles and demonstrates the feasibility of integrating NHC catalysis with enzymatic processes.",

keywords = "N-heterocyclic carbene catalysis, chemoenzymatic catalysis, ketoreductase enzyme, photoredox catalysis, sequential catalysis",

author = "Maskeri, {Mark A.} and Schrader, {Malte L.} and Scheidt, {Karl A.}",

note = "Funding Information: We thank Northwestern and the National Institute of General Medical Sciences (GM073072 and GM131431) for support of this work. The authors thank Keegan Fitzpatrick and Charlotte Stern (NU) for X-ray crystallography assistance, Ada Kwong (NU) for high-resolution mass spectrometry assistance, and Dr. Adam Csakai for helpful early discussions.",

year = "2020",

month = may,

day = "7",

doi = "10.1002/chem.202000747",

language = "English (US)",

volume = "26",

pages = "5794--5798",

journal = "Chemistry - A European Journal",

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T1 - A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ-Lactones

AU - Maskeri, Mark A.

AU - Schrader, Malte L.

AU - Scheidt, Karl A.

N1 - Funding Information: We thank Northwestern and the National Institute of General Medical Sciences (GM073072 and GM131431) for support of this work. The authors thank Keegan Fitzpatrick and Charlotte Stern (NU) for X-ray crystallography assistance, Ada Kwong (NU) for high-resolution mass spectrometry assistance, and Dr. Adam Csakai for helpful early discussions.

PY - 2020/5/7

Y1 - 2020/5/7

N2 - Combining biological and small-molecule catalysts under a chemoenzymatic manifold presents a series of significant advantages to the synthetic community. We report herein the successful development of a two-step/single flask synthesis of γ-lactones through the merger of Umpolung catalysis with a ketoreductase-catalyzed dynamic kinetic resolution, reduction, and cyclization. This combined approach delivers highly enantio- and diastereoenriched heterocycles and demonstrates the feasibility of integrating NHC catalysis with enzymatic processes.

AB - Combining biological and small-molecule catalysts under a chemoenzymatic manifold presents a series of significant advantages to the synthetic community. We report herein the successful development of a two-step/single flask synthesis of γ-lactones through the merger of Umpolung catalysis with a ketoreductase-catalyzed dynamic kinetic resolution, reduction, and cyclization. This combined approach delivers highly enantio- and diastereoenriched heterocycles and demonstrates the feasibility of integrating NHC catalysis with enzymatic processes.

KW - N-heterocyclic carbene catalysis

KW - chemoenzymatic catalysis

KW - ketoreductase enzyme

KW - photoredox catalysis

KW - sequential catalysis

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