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

5 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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10.1002/chem.202000747

Cite this

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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. 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. Publisher Copyright: {\textcopyright} 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

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. 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. Publisher Copyright: © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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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JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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CCDC 1973184: Experimental Crystal Structure Determination

Cite this

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Datasets

CCDC 1973184: Experimental Crystal Structure Determination

Cite this