Enantiospecific Synthesis of ortho-Substituted 1,1-Diarylalkanes by a 1,2-Metalate Rearrangement/anti-SN 2' Elimination/Rearomatizing Allylic Suzuki-Miyaura Reaction Sequence

Belén Rubial; Beatrice S L Collins; Raphael Bigler; Stefan Aichhorn; Adam Noble; Varinder K Aggarwal

doi:10.1002/anie.201811343

Enantiospecific Synthesis of ortho-Substituted 1,1-Diarylalkanes by a 1,2-Metalate Rearrangement/anti-S_N 2' Elimination/Rearomatizing Allylic Suzuki-Miyaura Reaction Sequence

Angew Chem Int Ed Engl. 2019 Jan 28;58(5):1366-1370. doi: 10.1002/anie.201811343. Epub 2018 Dec 21.

Authors

Belén Rubial¹, Beatrice S L Collins¹, Raphael Bigler¹, Stefan Aichhorn¹, Adam Noble¹, Varinder K Aggarwal¹

Affiliation

¹ School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.

Abstract

The one-pot sequential coupling of benzylamines, boronic esters, and aryl iodides has been investigated. In the presence of an N-activator, the boronate complex formed from an ortho-lithiated benzylamine and a boronic ester undergoes stereospecific 1,2-metalate rearrangement/anti-S_N 2' elimination to form a dearomatized tertiary boronic ester. Treatment with an aryl iodide under palladium catalysis leads to rearomatizing γ-selective allylic Suzuki-Miyaura cross-coupling to generate 1,1-diarylalkanes. When enantioenriched α-substituted benzylamines are employed, the corresponding 1,1-diarylalkanes are formed with high stereospecificity.

Keywords: 1,1-diarylalkane; boronic ester; cross-coupling; one-pot; stereospecific.

Publication types

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

Abstract

Publication types

Grants and funding