Catalytic Asymmetric Reactions of Ketimines and Alkenes via [2 + 2] Cycloaddition: Chemical Reactivity Controlled by Switching a Heteroatom

• Published in: Journal of the American Chemical Society Vol. 146; no. 46; pp. 32088 - 32097
• Main Authors: Zhao, Qun, Li, Yao, Ren, Zhiyuan, Shao, Ying-Bo, Chen, Li, Li, Xin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.11.2024; Amer Chemical Soc
• Subjects: alkenes; Chemistry; Chemistry, Multidisciplinary; cycloaddition reactions; density functional theory; enantioselectivity; ketimines; Physical Sciences; Science & Technology; selenides; sulfur; PHOTOCHEMICAL REACTIVITY; ACID CATALYSTS; DESIGN; KETO IMINO ETHERS; PHOTOCYCLOADDITION; AZETIDINES; ALLENOATES; DIELS-ALDER REACTION; NITROGEN DOUBLE-BOND; THIOACETALIZATION
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.4c13302

Azetidine units are commonly found in natural products and biologically active drugs. The [2 + 2] cycloaddition of imines and alkenes has been extensively used in the synthesis of such structures, while enantioselective approaches remain elusive. Herein, an efficient B­(C6F5)3/chiral phosphoric acid-catalyzed asymmetric [2 + 2] cycloaddition of ketimines and aryl vinyl selenides was presented, delivering valuable chiral azetidines with excellent stereoselectivities (>20:1 dr and up to 96:4 er). What’s even more interesting was that when a “Se” atom was switched to an “S” atom, the reaction proceeded through a [2 + 2] cycloaddition/ring-opening cascade process, affording a range of chiral thioacetals with high enantioselectivities (up to 98:2 er), which were also important organic sulfur compounds. Mechanistic experiments, coupled with density functional theory (DFT) calculations, shed light on a mechanism involving stepwise [2 + 2] cycloaddition and ring-opening processes, with the initial alkenylation step identified as crucial for achieving stereoselective control.