Published on Web 10/13/2010
Catalytic Asymmetric Synthesis of Chiral Allylic Esters
Jeffrey S. Cannon, Stefan F. Kirsch,† and Larry E. Overman*
Department of Chemistry, 1102 Natural Sciences II, UniVersity of California, IrVine,
California 92697-2025
Received August 1, 2010; E-mail: leoverma@uci.edu
Abstract: A broadly useful catalytic enantioselective synthesis of branched allylic esters from prochiral
(Z)-2-alkene-1-ols has been developed. The starting allylic alcohol is converted to its trichloroacetimidate
intermediate by reaction with trichloroacetonitrile, either in situ or in a separate step, and this intermediate
undergoes clean enantioselective SN2′ substitution with a variety of carboxylic acids in the presence of the
palladium(II) catalyst (Rp,S)-di-µ-acetatobis[(η5-2-(2′-(4′-methylethyl)oxazolinyl)cyclopentadienyl-1-C,3′-N)(η4-
tetraphenylcyclobutadiene)cobalt]dipalladium, (Rp,S)-[COP-OAc]2, or its enantiomer. The scope and
limitations of this useful catalytic asymmetric allylic esterification are defined.
Ru(II)14 catalysts have been described.15 Of these, the iridium-
catalyzed methods are of particular importance because irid-
Introduction
Branched allylic alcohols (1-alken-3-ols) are versatile inter-
mediates for the synthesis of a wide variety of organic
compounds.1,2 When chiral, these alcohols are often accessed
in enantioenriched form by kinetic resolution,3,4 although their
synthesis using enantioselective chemical catalysts is becoming
increasingly important. For example, they can be assembled
enantioselectively by forming allylic C-H or C-C bonds by
catalytic asymmetric reduction of enones5 or catalytic asym-
metric addition of vinyl nucleophiles to aldehydes.6,7 Alterna-
tively, branched allylic alcohols can be prepared in enantiose-
lective fashion by formation of the allylic C-O bond. Numerous
catalytic asymmetric allylic alkylations of alkoxides, phenoxides,
or carboxylates with Pd(0),8-10 Ir(I),11 Rh(III),12 Cu(II),13 and
ium(I) η3-allyl intermediates react preferentially with nucleo-
philes at the more-substituted end of the allyl fragment.16 Using
phosphoramidite ligands, Hartwig has shown that Ir-catalyzed
allylation of phenoxides and alkoxides can generate the corre-
sponding allylic ethers in high enantiomeric purity and up to
99:1 branched to linear selectivity. In principle, this method
could deliver branched allylic alcohols in high enantiomeric
purity; however, conversion of an allylic benzyl ether or related
intermediate to the parent allylic alcohol is complicated by the
presence of the CdC π-bond.
With Ir-phosphoramidite catalysts, Carreira recently reported
the two-step conversion of allylic carbonates to enantioenriched
(7) A novel catalytic asymmetric approach involving Cu-catalyzed catalytic
asymmetric allylic alkylation was described recently: (a) Geurts, K.;
Fletcher, S. P.; van Zijl, A. W.; Minnaard, A. J.; Feringa, B. L. Pure
Appl. Chem. 2008, 80, 1025–1037. (b) Harutyunyan, S. R.; den Hartog,
T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. ReV. 2008, 108,
2824–2852.
† Current address: Department Chemie, Technische Universita¨t Mu¨nchen,
Lichtenbergstrasse 4, 85747 Garching, Germany.
(1) Enantioenriched allylic esters are ubiquitous intermediates in the
synthesis of complex molecules. Selected recent examples include the
following: (a) Shimizu, Y.; Shi, S.-L.; Usuda, H.; Kanai, M.; Shibasaki,
M. Angew. Chem., Int. Ed. 2010, 49, 1103–1106. (b) Crimmins, M. T.;
Jacobs, D. L. Org. Lett. 2009, 11, 2695–2698. (c) Stivala, C. E.;
Zakarian, A. J. Am. Chem. Soc. 2008, 130, 3774–3776.
(8) Trost, B. M.; Organ, M. G. J. Am. Chem. Soc. 1994, 116, 10320–
10321.
(9) For comprehensive reviews see: (a) Trost, B. M. J. Org. Chem. 2004,
69, 5813–5837. (b) Trost, B. M.; Crawley, M. L. Chem. ReV. 2003,
103, 2921–2943.
(2) For a comprehensive review of the synthesis of allylic alcohols, see:
Hodgson, D. M.; Humphreys, P. G. In Science of Synthesis: Houben-
Weyl Methods of Molecular Transformations; Clayden, J. P., Ed.;
Thieme: Stuttgart, 2007; Vol. 36, pp 583-665.
(3) Enzymatic kinetic resolution: (a) Garc´ıa-Urdiales, E.; Alfonso, I.;
Gotor, V. Chem. ReV. 2005, 105, 313–354. (b) Carrea, G.; Riva, S.
Angew. Chem., Int. Ed. 2000, 39, 2226–2254. (c) Enzyme Catalysis
in Organic Synthesis; Drauz, K., Waldmann, H., Eds.; VCH: Wein-
heim, Germany, 1995. (d) Faber, K. Biotransformations in Organic
Chemistry, 3rd ed.; Springer: Berlin, 1997; pp 201-205.
(10) Direct palladium-catalyzed allylic C-H oxidation to provide 3-acy-
loxy-1-alkenes in modest enantioselectivity has been reported by the
White group: Covell, D. J.; White, M. C. Angew. Chem., Int. Ed. 2008,
47, 6448–6451.
(11) (a) Stanley, L. M.; Bai, C.; Ueda, M.; Hartwig, J. F. J. Am. Chem.
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J. T.; Ferreira, E. M.; McFadden, R. M.; Caspi, D. D.; Trend, R. M.;
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(15) For a recent review of enantioselective allylation reactions, see: Lu,
Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258–297.
(16) For a recent review, see: Helmchen, G.; Dahnz, A.; Du¨bon, P.;
Schelwies, M.; Weihofen, R. Chem. Commun. 2007, 675–691.
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10.1021/ja106685w 2010 American Chemical Society
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