ORGANIC
LETTERS
2012
Vol. 14, No. 1
194–197
Enantioselective Carbenoid Insertion into
Phenolic OꢀH Bonds with a Chiral
Copper(I) Imidazoindolephosphine
Complex
Takao Osako,† Duanghathai Panichakul,† and Yasuhiro Uozumi*,†,‡
Institute for Molecular Science (IMS), Myodaiji, Okazaki 444-8787, Japan, and
RIKEN, Wako 351-0198, Japan
Received November 4, 2011
ABSTRACT
The enantioselective OꢀH carbenoid insertion reaction with a new chiral copper(I) imidazoindolephosphine complex has been developed.
The chiral copper(I) complex catalyzed the insertion of carbenoids derived from R-diazopropionates into the OꢀH bonds of various phenol
derivatives to give the corresponding R-aryloxypropionates with up to 91% ee.
The transition-metal-catalyzed insertion of carbenoid
species derived from R-diazocarbonyl compounds into
XꢀH bonds (X = C, O, N, S, Si, etc.) has been widely
recognized as a direct and efficient method for the con-
struction of carbonꢀcarbon and carbonꢀheteroatom
bonds.1,2 In particular, the enantioselective catalytic
OꢀH insertion reaction provides chiral R-alkyloxy or R-
aryloxy carbonyl compounds, which are useful synthetic
intermediates for the construction of natural products and
biologically active molecules.3 Although various chiral
rhodium complexes have been developed to catalyze
the carbenoid insertion into CꢀH bonds with high
enantioselectivity,4 highly enantioselective OꢀH inser-
tions using chiral transition metal catalysts were not
achieved until 2006.5 In 2006, Fu reported the first example
of the highly enantioselective carbenoid insertion into an
OꢀH bond with a chiral copper catalyst. A copper com-
plex of the chiral bisazaferrocene A (Figure 1) efficiently
catalyzed the highly enantioselective insertion of R-diazo-
R-arylacetates into the OꢀH bonds of alcohols to give the
corresponding R-alkyloxy esters with up to 98% ee.6 Zhou
(5) For an example of the application of a chiral Rh catalyst to an
enantioselective OꢀH insertion, see: (a) Bulugahapitiya, P.; Landais, Y.;
Parra-Rapado, L.; Planchenault, D.; Weber, V. J. Org. Chem. 1997, 62,
1630–1641. For examples of early efforts for diastereoselective OꢀH
insertion, see:(b) Aller, E.; Cox, G. G.; Miller, D. J.; Moody, C. J.
Tetrahedron Lett. 1994, 35, 5949–5952. (c) Aller, E.; Brown, D. S.; Cox,
G. G.; Miller, D. J.; Moody, C. J. J. Org. Chem. 1995, 60, 4449–4460.
(d) Miller, D. J.; Moody, C. J.; Morfitt, C. N. Aust. J. Chem. 1999, 52,
97–108. (e) Jiang, N.; Wang, J.; Chan, A. S. C. Tetrahedron Lett. 2001,
42, 8511–8513.
(6) Maier, T. C.; Fu, G. C. J. Am. Chem. Soc. 2006, 128, 4594–4595.
(7) Asymmetric OꢀH insertion with a copper complex: (a) Chen, C.;
Zhu, S.-F.; Liu, B.; Wang, L.-X.; Zhou, Q.-L. J. Am. Chem. Soc. 2007,
129, 12616–12617. (b) Zhu, S.-F.; Chen, C.; Cai, Y.; Zhou, Q.-L. Angew.
Chem., Int. Ed. 2008, 47, 932–934. (c) Zhu, S.-F.; Chen, W.-Q.; Zhang,
Q.-Q.; Mao, H.-X.; Zhou, Q.-L. Synlett 2011, 919–922. (d) Zhu, S.-F.;
Song, X.-G.; Li, Y.; Cai, Y.; Zhou, Q.-L J. Am. Chem. Soc. 2010
132, 16374–16376. Asymmetric OꢀH insertion with an iron complex:
(e) Zhu, S.-F.; Cai, Y.; Mao, H.-X.; Xie, J.-H.; Zhou, Q.-L. Nat. Chem.
2010, 2, 546–551.
† Institute for Molecular Science.
‡ RIKEN.
(1) For general reviews of the reaction of R-diazocarbonyl com-
pounds, see: (a) Doyle, M. P.; Mckervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; Wiley: New York,
1998. (b) Zhang, Z; Wang, J Tetrahedron 2008, 64, 6577–6605.
(2) (a) For a review of catalytic OꢀH insertion, see: Miller, D. J.;
Moody, C. J. Tetrahedron 1995, 51, 10811–10843. (b) For a review of
catalytic NꢀH insertion, see: Moody, C. J. Angew. Chem., Int. Ed. 2007,
46, 9148–9150.
(3) For a recent example, see: Chimichi, S.; Boccalini, M.; Cravotto,
G.; Rosati, O. Tetrahedron Lett. 2006, 47, 2405–2408.
(4) (a) Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhou, L. Chem. Rev.
2010, 110, 704–724. (b) Davies, H. M. L.; Manning, J. R. Nature 2008,
451, 417–424. (c) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003,
103, 2861–2903.
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10.1021/ol202977j
Published on Web 12/05/2011
2011 American Chemical Society