Visible Light Activation of Boronic Esters Enables Efficient Photoredox C(sp2 )-C(sp3 ) Cross-Couplings in Flow

Fabio Lima; Mikhail A Kabeshov; Duc N Tran; Claudio Battilocchio; Joerg Sedelmeier; Gottfried Sedelmeier; Berthold Schenkel; Steven V Ley

doi:10.1002/anie.201605548

Visible Light Activation of Boronic Esters Enables Efficient Photoredox C(sp² )-C(sp³ ) Cross-Couplings in Flow

Angew Chem Int Ed Engl. 2016 Nov 2;55(45):14085-14089. doi: 10.1002/anie.201605548. Epub 2016 Oct 6.

Authors

Fabio Lima¹, Mikhail A Kabeshov¹, Duc N Tran¹, Claudio Battilocchio¹, Joerg Sedelmeier², Gottfried Sedelmeier², Berthold Schenkel², Steven V Ley³

Affiliations

¹ Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
² Novartis Pharma AG, Novartis Campus, 4002, Basel, Switzerland.
³ Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. svl1000@cam.ac.uk.

Abstract

We report herein a new method for the photoredox activation of boronic esters. Using these reagents, an efficient and high-throughput continuous flow process was developed to perform a dual iridium- and nickel-catalyzed C(sp² )-C(sp³ ) coupling by circumventing solubility issues associated with potassium trifluoroborate salts. Formation of an adduct with a pyridine-derived Lewis base was found to be essential for the photoredox activation of the boronic esters. Based on these results we were able to develop a further simplified visible light mediated C(sp² )-C(sp³ ) coupling method using boronic esters and cyano heteroarenes under flow conditions.

Keywords: boronic esters; cross-coupling; flow chemistry; photoredox catalysis; synthetic methods.

Publication types

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