A Scalable Synthesis of (R,R)-2,6-Dimethyldihydro-2H-pyran-4(3H)-one

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2014-06-12 DOI:10.1021/op500135x

Ian S. Young*, Matthew W. Haley, Annie Tam, Steven A. Tymonko*, Zhongmin Xu, Ronald L. Hanson, Animesh Goswami

引用次数: 7

Abstract

A scalable synthesis of (R,R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one is reported. Key to this strategy is the Ti(OiPr)₄-catalyzed Kulinkovich cyclopropanation of silyl protected (R)-ethyl 3-hydroxybutanoate, and subsequent oxidative fragmentation of the cyclopropanol. The resulting vinyl ketone intermediate was then subjected to oxidative Heck cyclization to form the enone substrate required for conjugate addition. A diastereoselective copper-catalyzed Grignard addition procedure was implemented to install the requisite methyl group, with the inclusion of 1,3-bis(diphenylphosphino)propane and trimethylsilyl chloride greatly increasing the robustness of this process.

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(R,R)-2,6-二甲基二氢- 2h -吡喃-4(3H)- 1的规模化合成

报道了(R,R)-2,6-二甲基二氢- 2h -吡喃-4(3H)- 1的规模化合成。该策略的关键是Ti(OiPr)4催化硅基保护(R)- 3-羟基丁酸乙酯的Kulinkovich环丙烷化，以及随后的环丙醇氧化裂解。得到的乙烯基酮中间体然后进行氧化Heck环化，形成共轭加成所需的烯酮底物。采用非对映选择性铜催化的格氏加成法，加入1,3-双(二苯基膦)丙烷和三甲基硅氯大大提高了该工艺的稳健性。

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 Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.