the synthesis of spirooxindoles has therefore evoked im-
mense interest from both synthetic and biological stand-
points. Various synthetic methods1,7 have been reported in
the literature, including oxidative rearrangement,8 Heck
reaction,9 intramolecular Mannich reaction,10 ring
expansion,11 and 1,3-dipolar cycloaddition.12 Although
the construction of spiro(pyrrolidine-3,30-oxindole) has
attracted many groups, including ours,13 there has been
no focus on devising a concise synthesis of spirooxindoles
fused with various ring systems. A unified strategy for the
synthesis of various spirooxindoles would be valuable
because it could be applied not only to natural products
synthesis but also to library synthesis in medicinal chem-
istry. In this paper, we report a new strategy for the
synthesis of spirooxindoles fused with tetrahydropyran,
piperidine, and a five-membered carbocycle, based on
palladium-catalyzed carbosilylation followed by a Sakur-
ai-type cyclization to construct three stereogenic centers.
Bismetalation of 1,3-dienes is a valuable process because
the reaction product contains two carbon-metal bonds;
these bonds could be used for further derivatization.14
Mori et al. reported nickel-catalyzed bismetallative cycli-
zation of 1,3-dienes bearing an aldehyde group.15 The
reaction with Me3SiSnBu3 gave a cyclized product con-
taining an allylstannyl group. Yu et al. successfully
extended this reaction for making two carbon-carbon
bonds by sequential allylic transfer in one pot.16 The
nickel-catalyzed cyclization of 1,3-dienes bearing an alde-
hyde group with an external aldehyde and a diboronyl
reagent proceeded diastereoselectively. Based on this bis-
metallative cyclization, we investigated carbosilylation for
the synthesis of spirooxindoles. As shown in Scheme 1,
Scheme 1. Synthetic Strategy
(7) For recent approchesto spirooxindoles, see: (a) Zhang, Y.; Panek,
J. S. Org. Lett. 2009, 11, 3366. (b) Shintani, R.; Hayashi, S.; Murakami,
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Neuville, L.; Zhu, J. Chem.;Eur. J. 2010, 16, 5863. (j) Chen, W.-B.; Wu,
Z.-J.; Pei, Q.-L.; Cun, L.-F.; Zhang, X.-M.; Yuan, W.-C. Org. Lett.
2010, 12, 3132. (k) Deppermann, N.; Thomanek, H.; Prenzel, A. H. G.
P.; Maison, W. J. Org. Chem. 2010, 75, 5994. (l) George, S. C.; John, J.;
Anas, S.; John, J.; Yamamoto, Y.; Suresh, E.; Radhakrishnan, K. V.
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Waldmann, H. Nature Chem. 2010, 2, 735. (n) Helan, V.; Mills, A.;
Drewry, D.; Grant, D. J. Org. Chem. 2010, 75, 6693. (o) Jaegli, S.;
Dufour, J.; Wei, H.-L.; Piou, T.; Duan, X.-H.; Vors, J.-P.; Neuville, L.;
Zhu, J. Org. Lett. 2010, 12, 4498. (p) Jiang, X.; Cao, Y.; Wang, Y.; Liu,
L.; Shen, F.; Wang, R. J. Am. Chem. Soc. 2010, 132, 15328. (q) Lu, C.;
Xiao, Q.; Floreancig, P. E. Org. Lett. 2010, 12, 5112. (r) Voituriez, A.;
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treatment of 1,3-diene I, bearing a carbamoyl chloride
unit, with a disilanyl reagent would give the π-allyl com-
plex II, which would be converted into the disubstituted
oxindole III by reaction with an internal carbamoyl chlor-
ide. By taking advantage of the allylic silanyl group in the
product, spirooxindole IV could be readily accessed by the
Sakurai-type reaction of a tethered electrophile (R00), with
control of three contiguous stereocenters. So far, carba-
moyl chloride and a 1,1-disubstituted diene have not been
employed in bismetallative cyclization. It should be noted
that the C1 position of the diene unit is converted to a
quaternary carbon center.
In an initial survey, we examined the carbosilylation of
1,3-diene 1a using hexamethyldisilane and 10 mol % of a
palladium or rhodium catalyst in xylene (Table 1).
Although Rh(PPh3)3Cl did not afford the cyclized product
2a, [Rh(cod)Cl]2 gave 2a in 43% yield as a mixture of (E)-
and (Z)-isomers (entries 1 and 2).17 Several palladium
catalysts afforded the desired product 2a in 22-75% yields
(entries 3-7).18 Addition of PPh3 was not effective (entries
8 and 9). Finally, we found that [Pd(η3-allyl)Cl]2 is an
efficient catalyst for this transformation, and the reaction
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