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Synthesis 2024; 56(04): 527-538
DOI: 10.1055/a-2088-5000
special topic
Synthetic Development of Key Intermediates and Active Pharmaceutical Ingredients (APIs)

Transition-Metal-Free Cross-Coupling of Acetals and Grignard Reagents To Form Diarylmethyl Alkyl Ethers and Triarylmethanes

Yang Qin
a   College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610066, P. R. of China
b   State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China
,
Sheng Liu
b   State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China
,
Shi-Liang Shi  ∗
a   College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610066, P. R. of China
b   State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China
› Author AffiliationsThe authors are grateful for financial support from the National Key Research and Development Program of China (2022YFA1503702), the National Natural Science Foundation of China (22171280, 21821002), and the Program of Shanghai Academic Research Leader (22XD1424900).
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Abstract

We herein report a transition-metal-free cross-coupling reaction of acetals and Grignard reagents. The method provides a modular preparation of diarylmethyl alkyl ethers, triarylmethanes, and 1,1-diarylalkanes that constitute the core structures of many bioactive molecules and synthetic motifs. A series of readily accessible acetals bearing aryl, alkenyl, and alkyl substituents efficiently coupled with commercially available aryl, alkyl, and allylic magnesium bromides to give the products in high yields. In addition to acyclic and cyclic acetals, ketal and orthoester also serve as viable substrates to afford sterically hindered tertiary ether and ketal respectively. A sequential difunctionalization of acetals led to the rapid synthesis of triarylmethanes and diarylalkanes.

Key words

transition-metal-free - cross-coupling - acetals - Grignard reagents - diarylmethyl alkyl ethers - triarylmethanes

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2088-5000.
  • Supporting Information


Publication History

Received: 27 March 2023

Accepted after revision: 08 May 2023

Accepted Manuscript online:
08 May 2023

Article published online:
30 May 2023

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