α-Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane

Tadafumi Matsunaga; Junichiro Kanazawa; Tomohiro Ichikawa; Mei Harada; Yusuke Nishiyama; Nghia Tuan Duong; Takashi Matsumoto; Kazunori Miyamoto; Masanobu Uchiyama

doi:10.1002/anie.202014997

α-Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane

Angew Chem Int Ed Engl. 2021 Feb 1;60(5):2578-2582. doi: 10.1002/anie.202014997. Epub 2021 Jan 4.

Authors

Affiliations

¹ Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
² RIKEN-JEOL Collaboration Center and SPring-8 Center, RIKEN, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
³ JEOL RESONANCE Inc., 3-1-2 Musashino, Akishima, Tokyo, 196-8558, Japan.
⁴ Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima, Tokyo, 196-8666, Japan.
⁵ Cluster for Pioneering Research (CPR), RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.
⁶ Research Initiative for Supra-Materials (RISM), Shinshu University, 3-15-1 Tokida, Ueda, Nagano, 386-8567, Japan.

PMID: 33205884
DOI: 10.1002/anie.202014997

Abstract

The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α-cyclodextrin (α-CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3-diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non-polar solvents. The combination of these methodologies enables simple, on-demand preparation of [1.1.1]propellane in various solvents under mild conditions from α-CD capsules containing 1,3-diiodo BCP.

Keywords: [1.1.1]propellane; bicyclo[1.1.1]pentane; deiodination; on-demand preparation; α-cyclodextrin.

Publication types

Research Support, Non-U.S. Gov't