Catalytic Enantioconvergent Allenylation of Aldehydes with Propargyl Halides

• Published in: Angewandte Chemie International Edition Vol. 61; no. 10; pp. e202117114 - n/a
• Main Authors: Zhang, Feng‐Hua, Guo, Xiaochong, Zeng, Xianrong, Wang, Zhaobin
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.03.2022; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Aldehydes; Asymmetric synthesis; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Chirality; Chromium Catalysis; Enantioconvergent Coupling; Enantiomers; Halides; Physical Sciences; Radicals; Science & Technology; Stereoisomerism; Stereoisomers; Substrates; α-Allenol; NOZAKI-HIYAMA ALLYLATION; ALKYNYL OXIRANES; KISHI REACTION; ASYMMETRIC-SYNTHESIS; ENANTIOSELECTIVE SYNTHESIS; Chromium Catalysis; Enantioconvergent Coupling; Radicals; CROSS-COUPLINGS; ALDOL REACTION; ADDITION-REACTIONS; alpha-Allenol; STEREOSELECTIVE-SYNTHESIS; ALPHA-ALLENOLS; α-Allenol
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202117114

α‐Allenol is a versatile synthon in organic synthesis. The catalytic asymmetric synthesis of α‐allenols from readily available starting materials remains a prominent challenge, especially when simultaneous control over axial and central chirality is required. Herein, we describe the Cr‐catalyzed enantioconvergent allenylation of aldehydes with racemic propargyl halides to rapidly access a wide range of chiral α‐allenols with adjacent axial and central chiralities. This method features excellent regio‐, diastereo‐ and enantioselectivity control with broad substrate scope, and provides facile access to all four stereoisomers when allied with a Mitsunobu reaction. Preliminary mechanistic studies support radical‐based reaction pathways. The synthetic utility is demonstrated by the application in late‐stage functionalization and the formal total synthesis of (+)‐varitriol. A Cr‐catalyzed enantioconvergent allenylation reaction of aldehydes with racemic propargyl halides has been developed. This robust method employs simple and readily accessible materials, exhibits exceptional functional group tolerance and broad substrate scope, and provides facile access to a wide range of valuable optically enriched α‐allenols with two or three continuous chiral centers, including both central and axial chirality.