The solid copper-mediated C-N cross-coupling of phenylboronic acids under continuous flow conditions

• Jennifer Bao ^a
• Geoffrey K. Tranmer ^a,b

• ^a College of Pharmacy, Faculty of Health Science, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
• ^b Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada

We have developed two general methods for the C–N cross-coupling of phenylboronic acids with amines using solid copper flow reactors, in combination with an oxidant. We have developed one method for a C–N arylation reaction which employs a solid copper coil reactor, in combination with tert-butyl peroxybenzoate, to give products in moderate isolated yields. We have also developed a general method for the C–N cross coupling of phenylboronic acids using a column packed with solid copper powder, in combination with acetic acid and TEMPO, to give products in isolated yields in excess of 75+%. We have also applied our general copper powder method to generate a library of products which highlights the utility of solid copper flow reactors for C–N cross coupling reactions, generating 16 examples in good yields. Mechanistic implications and future directions are also discussed.

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