nucleophilic reagents for allylic substitution, the high
toxicity of these compounds as well as their atom inef-
ficiency makes them less attractive for use in total
synthesis. As another potential alternative, in situ pre-
pared, nontoxic organoindium reagents are able to par-
ticipate in highly atom-economical cross-coupling reac-
tions with aryl and vinyl (pseudo)halides, even in the
presence of protic solvents.10
Efficien t P a lla d iu m -Ca ta lyzed Nu cleop h ilic
Ad d ition of Tr ior ga n oin d iu m Rea gen ts to
Ca r bocyclic Der iva tives
Lucas Baker and Thomas Minehan*
Department of Chemistry, Harvey Mudd College,
Claremont, California 91711
tom_minehan@hmc.edu
Sarandeses has recently disclosed that acyclic allylic
halides and phosphates undergo nucleophilic substitution
reactions with triorganoindium compounds at low tem-
peratures in the presence of a copper catalyst.11 In this
study, we report that substoichiometric amounts of
trivinyl- and triarylindiums participate in palladium-
catalyzed nucleophilic substitution reactions not only
with acyclic allylic acetates but also with a variety of
cyclohex-2-enyl esters in good yield.
Received November 21, 2003
Abstr a ct: Palladium (0)-catalyzed allylic substitution reac-
tions employing triorganoindium reagents have been inves-
tigated. In situ generated vinyl- and arylindiums react with
substituted and unsubstituted cyclohex-2-enyl esters in the
presence of 1-3 mol % Pd2(dba)3 to produce vinyl- or
arylcyclohexenes in moderate to excellent yields. The ste-
reoselectivity of this process was also examined, and evi-
dence is presented that the reaction proceeds with inversion
of stereochemical configuration.
To assess the reactivity of indium reagents with allylic
esters, we undertook our investigations by treating
commercially available trans-cinnamyl acetate I (Scheme
1) with 0.5 equiv of Ph3In 2a in THF (0.1 M) at 55 °C in
the presence or absence of palladium catalyst. After 1.5
h, a 19% yield of the expected substitution product II was
observed by GC-MS analysis of the uncatalyzed reaction
mixture, with ∼80% of the starting material still present.
In contrast, the catalyzed reaction (1 mol % Pd2dba3/4
mol % PPh3) gave a 95% yield of II after the same amount
of time at 55 °C. Gratifyingly, this reactivity extended
to more difficult substitutions on cyclic templates: while
stirring cyclohex-2-enyl acetate 1a 12 with 2a for 3 h at
55 °C in the absence of catalyst resulted in only an 11%
conversion to the expected product 3-phenylcyclohexene
3a a by GC-MS analysis,13 the same reaction performed
in the presence of 1 mol % Pd2dba3/4 mol % PPh3 gave
an 85% yield of 3a a , with the only other compounds
evident in the crude 1HNMR being 1a (∼10%) and
biphenyl.14 By comparison, the corresponding catalyzed
and uncatalyzed substitution reactions of 1a with Ph-
MgBr at either room temperature or 55 °C led to low
Transition-metal-promoted allylic substitution reac-
tions have emerged as a powerful methodology in organic
synthesis.1 The palladium-catalyzed version of this reac-
tion is an efficient and highly stereoselective method for
the formation of carbon-carbon bonds.2 Numerous stud-
ies have shown that allylations with stabilized (“soft”)
carbon nucleophiles proceed with retention of configura-
tion, while reactions with unstabilized (“hard”) nucleo-
philes proceed with inversion of configuration.3
Grignard reagents have traditionally been employed
as unstabilized nucleophiles for allylic substitutions.
However, the inability of organomagnesium (or organo-
lithium and organoaluminum4) reagents to tolerate reac-
tive functional groups on the allylic substrate limits the
functionality that can be brought into the coupled
product.5 Reagents containing boron,6 silicon,7 zirconium,
zinc,8 and tin9 avoid such reactivity and/or moisture-
sensitivity issues; of these, perhaps the most commonly
employed compounds for this purpose are the organo-
stannanes. Although organotin species are stable, reliable
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4, pp 109-168.
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Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483. (c) Hegedus,
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Scott, W. J . Organic Reactions; J ohn Wiley & Sons: New York, 1997;
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(3) (a) Trost, B. M. Tetrahedron 1977, 33, 2615-2649. (b) Trost, B.
M. Pure Appl. Chem. 1979, 51, 787-800. (c) Trost, B. M. Acc. Chem.
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Chem Soc., Chem Commun. 1984, 107-111.
(4) Flemming, S.; Kabbara, J .; Nickisch, K.; Westermann, J .; Mohr,
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(10) (a) Perez, I.; Sestelo, J . P.; Sarandeses, L. A. J . Am. Chem. Soc.
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(12) Cylohexen-1-yl acetate was prepared from cyclohexen-2-one by
DIBAH reduction (1 h, 0 °C, Et2O) followed by acylation (Ac2O/pyridine,
rt, 14 h). See the Supporting Information for experimental details.
(13) Stirring the uncatalyzed reaction (1a , 0.5 equiv of 2a , THF,
0.1 M, 55 °C) for 24 h in the presence of 1 equiv of InCl3 as a Lewis
acid promoter gave only unidentifiable decomposition products.
10.1021/jo0357162 CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/30/2004
J . Org. Chem. 2004, 69, 3957-3960
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