Stereoselective Synthesis of trans-3-Amino-2,2,4,4-tetramethylcyclobutanol

IF 5 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2025-07-24 DOI:10.1021/acs.orglett.5c02505

Daniel Zell*, Guy Pillon, Hans Iding, Patrick Stocker, Johannes A. Burkhard, Lauren E. Sirois, Chong Han and Francis Gosselin,

引用次数: 0

Abstract

A highly trans-diastereoselective synthesis of the useful synthon tert-butyl(3-hydroxy-2,2,4,4-tetramethylcyclobutyl)carbamate was accomplished by ketoreductase (KRED) catalysis with ∼98:2 dr. Herein, we describe its development from inexpensive 2,2,4,4-tetramethylcyclobutane-1,3-dione, evolving from a poorly selective and stoichiometric oxime reduction to an efficient sequence of chemo- and biocatalytic reactions. The utility of this process, which also resulted in a 10-fold improvement in process mass intensity (PMI), was demonstrated on scale en route to a fragment of the investigational androgen receptor degrader GDC-2992.

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反式3-氨基-2,2,4,4-四甲基环丁醇的立体选择性合成。

通过酮还原酶（KRED）与~ 98:2博士催化，实现了有用的合成叔丁基（3-羟基-2,2,4,4-四甲基环丁基）氨基甲酸酯的高度反式非对对选择性合成。本文描述了它从廉价的2,2,4,4-四甲基环丁烷-1,3-二酮，从低选择性和化学计量肟还原到高效的化学和生物催化反应。这一过程的效用也导致过程质量强度（PMI）提高了10倍，并在研究中的雄激素受体降解剂GDC-2992片段的过程中进行了大规模演示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.