pubs.acs.org/joc
Transition-metal-catalyzed nitrene insertions into C-H
Copper-Catalyzed Amination of Primary Benzylic
C-H Bonds with Primary and Secondary
Sulfonamides
bonds remain the most widely developed and impactful direct
amination procedure,2-4 although mechanistically distinct
C-H amination strategies continue to be investigated.5-8
Despite significant progress within the C-H amination
field, challenges remain. For example, methodologies for the
amination of primary benzylic C-H bonds are relatively
scarce.4e,9 Primary benzylic hydrocarbons such as toluene
typically afford unacceptably low yields under previously
developed amination conditions, including our own
(eq 1).5b,10 Notable exceptions include recently described
copper- and rhodium-catalyzed nitrene-based amina-
tions,4b,c,k,8b in particular procedures utilizing only a single
equivalent of hydrocarbon substrate.4e,h While clearly pro-
mising, these aminations procedures described few primary
benzylic hydrocarbon substrates (typically only toluene) and
utilize an optimized primary sulfonamide-based nucleophile.
In addition, these methodologies, as a consequence of the
David A. Powell* and Hope Fan
Merck Frosst Centre for Therapeutic Research, 16711 Trans
ꢀ
Canada Highway, Kirkland, Quebec H9H 3L1, Canada
Received February 4, 2010
(4) Representative intermolecular metal-nitrene based aminations: (a)
Lu, H.; Subbarayan, V.; Tao, J.; Zhang, X. P. Organometallics 2010, 29, 389–
393. (b) Badiei, Y. M.; Dinescu, A.; Dai, X.; Palomino, R. M.; Heinemann,
F. W.; Cundari, T. R.; Warren, T. H. Angew. Chem., Int. Ed. 2008, 47, 9961–
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Kalita, B.; Lamar, A. A.; Nicholas, K. M. Chem. Commun. 2008, 4291–4293.
A room-temperature, copper-catalyzed amination of pri-
mary benzylic C-H bonds with primary and secondary
sulfonamides is described. The reaction is applicable to
the coupling of a range of primary and secondary benzylic
hydrocarbons with a diverse set of sulfonamides and is
tolerant of substitution on both coupling partners. Fac-
tors which influence the selectivity of C-H functionaliza-
tion between primary and secondary sites are examined.
€
(e) Liang, C.; Collet, F.; Robert-Peillard, F.; Muller, P.; Dodd, R. H.;
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(9) Some of the increased challenge associated with oxidations of primary
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(10) The amination of toluene with a variety of transition metal catalysts
are reported to proceed in 9-30% yields even when toluene is used in large
excess as the solvent. See Supporting Information for further details.
€
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2726 J. Org. Chem. 2010, 75, 2726–2729
Published on Web 03/19/2010
DOI: 10.1021/jo100197r
r
2010 American Chemical Society