Enantioselective Phosphine-Catalyzed Formal [4+4] Annulation of α,β-Unsaturated Imines and Allene Ketones: Construction of Eight-Membered Rings

Huanzhen Ni; Xiaodong Tang; Wenrui Zheng; Weijun Yao; Nisar Ullah; Yixin Lu

doi:10.1002/anie.201707183

Enantioselective Phosphine-Catalyzed Formal [4+4] Annulation of α,β-Unsaturated Imines and Allene Ketones: Construction of Eight-Membered Rings

Angew Chem Int Ed Engl. 2017 Nov 6;56(45):14222-14226. doi: 10.1002/anie.201707183. Epub 2017 Oct 10.

Authors

Huanzhen Ni^{1

2}, Xiaodong Tang^{2

3}, Wenrui Zheng^{2

3}, Weijun Yao⁴, Nisar Ullah⁵, Yixin Lu^{1

2

3}

Affiliations

¹ Graduate School for Integrative Sciences & Engineering (NGS), National University of Singapore, 28 Medical Drive, 117456, Singapore, Singapore.
² Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore, Singapore.
³ National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Suzhou, Jiangsu, 215123, P. R. China.
⁴ Department of chemistry, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, 310018, P. R. China.
⁵ Chemistry Department, King Fahd University of Petroleum and Materials, Dhahran, 31261, Saudi Arabia.

PMID: 28816392
DOI: 10.1002/anie.201707183

Abstract

The first highly enantioselective phosphine-catalyzed formal [4+4] annulation has been developed. In the presence of amino-acid-derived phosphines, the unprecedented [4+4] annulations between benzofuran/indole-derived α,β-unsaturated imines and allene ketones proceeded smoothly, thus affording azocines, bearing either a benzofuran or an indole moiety, in excellent yields and with nearly perfect enantioselectivities (≥98 % ee in most cases). This work marks the first efficient asymmetric construction of optically enriched eight-membered rings by phosphine catalysis.

Keywords: annulations; heterocycles; organocatalysis; phosphines; synthetic methods.

Publication types

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