C O M M U N I C A T I O N S
(I)-catalyzed reactions of alkynes. Further studies on the mechanism
and scope of gold(I)-catalyzed cyclopropanation as well as ap-
plication of chiral phosphinegold(I) complexes to enantioselective
catalysis are ongoing and will be reported in due course.
encouraged to find that 22 was generated with 22% ee in the
BINAP-gold(I)-catalyzed reaction (eq 5).9,10 Further ligand opti-
mization identified DTBM-SEGPHOS-gold(I) as the catalyst of
choice for the enantioselective olefin cyclopropanation reaction.11
Alteration of the steric size of the propargyl ester led to the
observation that sterically more demanding esters, such as pivaloate,
produced cyclopropanes with higher enantiomeric excess (eq 6).12
Notably, in all cases the gold(I)-catalyzed reaction afforded the cis-
isomer with high diastereoselectively.
Acknowledgment. We gratefully acknowledge the University
of California, Berkeley, NIHGMS (R01 GM073932-01) Merck
Research Laboratories, Bristol-Myers Squibb, Amgen Inc., DuPont,
GlaxoSmithKline, Eli Lilly & Co., Pfizer, AstraZeneca. M.J.J.
thanks the Swedish Foundation for Strategic Research for financial
support. We thank Takasago International Corporation for their
generous donation of SEGPHOS ligands and Dr. X. Shi for
performing the chirality transfer experiment.
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
References
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Mamane, V.; Gress, T.; Krause, H.; Fu¨rstner, A. J. Am. Chem. Soc. 2004,
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With these conditions in hand, we examined the effects of styrene
aromatic ring substitution on the enantioselective cyclopropanation.
As with the propargyl esters, there is a clear correlation between
the steric size of the aryl substituent and enantioselectivity. For
example, the enantioselectivity of the gold(I)-catalyzed cyclopro-
panation reaction improved from 81% ee with styrene to 87% ee
with o-methylstyrene, and further to 94% ee in the synthesis of
cyclopropane 26 (eq 7). Halogenated styrenes also participate in
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(III)-catalyzed intramolecular cyclopropanation, see: (c) Fu¨rstner, A.;
Hannen, P. Chem. Commun. 2004, 2546.
(5) Shi, X.; Gorin, D. J.; Toste F. D. J. Am. Chem. Soc. 2005, 127, 5802.
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(9) BINAP(AuCl)2-catalyzed reaction in other solvents produced 21 in lower
enantiomeric excess and/or lower yield. THF 30%, 0% ee; CH3CN 28%,
27% ee; DCE 85%, 4% ee; toluene 62%, 12% ee.
(10) 5% MOP-AuCl/5% AgSbF6 produced 22 in 44% yield and only 5% ee.
(11) Other SEGPHOS derivatives gave 23 with lower selectivities: SEGPHOS
43%, 35% ee, DM-SEGPHOS 58%, 61% ee.
(12) The 2,4,6-tri-iso-propylbenzoyl ester afforded the cyclopropane in 86%
ee but only 24% yield. Other esters (i-Pr, 74% ee; diphenylacetyl 70%
ee) gave lower enantioselectivity.
(13) For gold(I)-catalyzed olefin cyclopropanation of styrene using ethyldi-
azoacetate as a carbene precursor, see: Fructos, M. R.; Belderrain, T. R.;
de Fre´mont, P.; Scott, N. M.; Nolan, S. P.; Diaz-Requejo, N. M.; Pe´rez,
P. J. Angew. Chem., Int. Ed. 2005, 44, 5284.
(14) The absolute stereochemistry of 4 was assigned by comparison of the
optical rotation of 33 (-17° (c ) 0.4, CHCl3)) with that reported in Elling,
G. R.; Hahn, R. C.; Schwab, G. J. Am. Chem. Soc. 1973, 96, 5659. The
stereochemistry of the remaining cyclopropanes was assigned by analogy.
the cyclopropanation reaction. For example, 4-fluorostyrene af-
forded cyclopropane 29 in 85% yield and 82% ee. Gold(I)-catalyzed
reaction of propargyl pivaloate 1 with 1-vinylnaphthylene produced
cis-cyclopropane 30 in 79% yield and 85% ee. Notably, the
enantioselective cyclopropanation is not limited to aryl olefins;
silylmethylcyclopropane 31 is produced as a 5:1 mixture of cis:
trans isomers with 78% and 65% ee, respectively (eq 8).
In conclusion, we have developed a triphenylphosphinegold(I)-
catalyzed cyclopropanation of olefins using propargyl esters as gold-
(I)-carbene precursors.13 This reaction provided the basis for the
application of chiral phosphinegold(I) complexes in the enantiose-
lective preparation of vinyl cyclopropanes with high cis-selectivity.
Subsequent oxidative cleavage of the olefin provides cis-cyclopro-
pylcarboxylic acid 32 (eq 9),14 and therefore complements the trans-
selectivity often observed in enantioselective olefin cyclopropana-
tions using R-diazoacetates.7 Moreover, the results reported herein
lend further support to the intermediacy of carbene species in gold-
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