Synthesis of carbobicyclic compounds via palladium-catalyzed cyclization/hydrosilylation: Evidence for reversible silylpalladation

Article abstract of DOI:10.1021/jo001438k

Cyclization/hydrosilylation of substituted 1-vinyl-1-(3-butenyl)cycloalkane's catalyzed by a 1:1 mixture of (phen)Pd(Me)Cl (1) and NaBAr₄ [phen = 1,10-phenanthroline; Ar = 3,5-C₆H₃(CF₃)₂] formed silylated spirocycles in high·yield with excellent regio and diastereoselectivity. Cyclization/ hydrosilylation of substituted 3-(3-butenyl)eyeloalkenes or 2,3-diallyl-5,6-dimethyl-1,4-hydroquinone diacetate (16) formed silylated fused bicyclic complexes in good yield. Reaction of substituted 1,6,11-nonatrienes with silane catalyzed by 1/NaBAr₄ led to cascade cyclization with hydrosilylation. This latter procedure was employed in the synthesis of silylated bicyclopentanes and a linear triquinane.

Full text of DOI:10.1021/jo001438k

J . Org. Chem. 2001, 66, 1755-1760
1755
Syn th esis of Ca r bobicyclic Com p ou n d s via P a lla d iu m -Ca ta lyzed
Cycliza tion /Hyd r osilyla tion : Evid en ce for Rever sible
Silylp a lla d a tion
Xiang Wang, Harinath Chakrapani, Carmine N. Stengone, and Ross A. Widenhoefer*
P. M. Gross Chemical Laboratory, Duke University, Durham, North Carolina 27708-0346
rwidenho@chem.duke.edu.
Received October 5, 2000
Cyclization/hydrosilylation of substituted 1-vinyl-1-(3-butenyl)cycloalkanes catalyzed by a 1:1
mixture of (phen)Pd(Me)Cl (1) and NaBAr4 [phen ) 1,10-phenanthroline; Ar ) 3,5-C6H3(CF3)2]
formed silylated spirocycles in high yield with excellent regio and diastereoselectivity. Cyclization/
hydrosilylation of substituted 3-(3-butenyl)cycloalkenes or 2,3-diallyl-5,6-dimethyl-1,4-hydroquinone
diacetate (16) formed silylated fused bicyclic complexes in good yield. Reaction of substituted
1,6,11-nonatrienes with silane catalyzed by 1/NaBAr4 led to cascade cyclization with hydrosilylation.
This latter procedure was employed in the synthesis of silylated bicyclopentanes and a linear
triquinane.
Sch em e 1
In tr od u ction
Many naturally occurring molecules possess a polycy-
clic core, typically heavily substituted and highly oxygen-
ated, and often containing one or more five-membered
rings.1 As a result, considerable effort has been directed
toward the development of efficient methods for the
synthesis of polycyclic organic compounds.2 We recently
reported several related procedures for the synthesis of
silylated five- and six-membered carbocycles via the
palladium-catalyzed cyclization/hydrosilylation of func-
tionalized 1,6- and 1,7-dienes, respectively.3-10 For ex-
ample, reaction of dimethyl diallylmalonate and dimeth-
ylphenylsilane catalyzed by a 1:1 mixture of (phen)-
Pd(Me)Cl (1) and NaBAr4 [phen ) 1,10-phenanthroline;
Ar ) 3,5-C6H3(CF3)2] formed the corresponding silylated
cyclopentane in 82% yield with high trans selectivity
(Scheme 1).6 The high activity and good selectivity
displayed in the formation of silylated carbocycles sug-
gested that this protocol might also be applicable in the
synthesis of carbobicyclic compounds. Here we report the
synthesis of spiro-, fused, and tethered bicyclic com-
pounds via palladium-catalyzed cyclization/hydrosilyl-
ation.
cyclization/hydrosilylation revealed several substitution
patterns which could potentially be exploited in the
synthesis of bicyclic compounds.6 For example, cycliza-
tion/hydrosilylation tolerated substitution at the allylic
positions of the diene, which suggested that 1-vinyl-1-
(3-butenyl) carbocycles would also undergo cyclization/
hydrosilylation to form functionalized spirocyclic deriva-
tives. To this end, cyclization/hydrosilylation of vinyl
cyclobutyl (2), cyclopentyl (3), and cyclohexyl derivatives
(4) gave the corresponding silylated spirocyclic com-
pounds 5-10 in good yield and with excellent regio- and
diastereoselectivity (Table 1, entries 1-6). We have
previously established the regiochemistry of cyclization/
hydrosilylation as that resulting from transfer of the
silane to the less hindered olefin along with trans
stereochemistry about the newly formed CsC bond.2,5
Because dimethylbenzylsilyl11 and pentamethylsiloxy9
derivatives can be oxidized in high yield under mild
conditions,12 spirocycles 6, 8, and 10 are direct precursors
to spirocyclic alcohols.
Resu lts a n d Discu ssion
Cycliza tion /Hyd r osilyla tion of Dien es. The syn-
thesis of monocyclic compounds via palladium-catalyzed
(1) (a) Hudlicky, T.; Price, J . D. Chem. Rev. 1989, 89, 1467. (b) Trost,
B. M. Chem. Soc. Rev. 1982, 11, 141.
(2) (a) Paquette L. A. Top. Curr. Chem. 1979, 79, 41. (b) Sannigrahi,
M. Tetrahedron 1999, 55, 9007.
(3) Widenhoefer, R. A.; DeCarli, M. A. J . Am. Chem. Soc. 1998, 120,
3805.
(4) Stengone, C. N.; Widenhoefer, R. A. Tetrahedron Lett. 1999, 40,
1451.
(5) Perch, N. S.; Widenhoefer, R. A. J . Am. Chem. Soc. 1999, 121,
6960.
(6) Widenhoefer, R. A.; Stengone, C. N. J . Org. Chem. 1999, 64, 8681.
(7) Perch, N. S.; Pei, T.; Widenhoefer, R. A. J . Org. Chem. 2000, 65,
3836.
Palladium-catalyzed cyclization/hydrosilylation also
tolerated substitution at the terminal olefinic position,6
which pointed to the feasibility of forming fused bicyclic
(8) Widenhoefer, R. A.; Vadehra, A. Tetrahedron Lett. 1999, 40, 8499.
(9) Pei, T.; Widenhoefer, R. A. Org. Lett. 2000, 2, 1469.
(10) Pei, T.; Widenhoefer, R. A. Tetrahedron Lett. 2000, 41, 7597.
(11) Mirura, K.; Hondo, T.; Nakagawa, T.; Takahashi, T.; Hosomi,
A. Org. Lett. 2000, 2, 385.
(12) J ones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599.
10.1021/jo001438k CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/02/2001

1756 J . Org. Chem., Vol. 66, No. 5, 2001
Wang et al.
Ta ble 1. Cycliza tion /Hyd r osilyla tion of Dien es Ca ta lyzed by a 1:1 Mixtu r e of 1 a n d Na BAr 4 in DCE a t
Room Tem p er a tu r e Wh er e E ) CO2Me
a
b
Yield refers to isolated material of >95% purity. Diastereomeric ratio determined by GC analysis of the crude reaction mixture.
c Isolated material contained 6% of the silylated uncyclized isomer.
ring systems from the cyclization/hydrosilylation of 3-(3-
butenyl)cycloalkenes. For example, reaction of dimethyl
allyl(3-cyclopentenyl)malonate (11) with HSiEt3 or HSiMe2-
Bn catalyzed by 1/NaBAr4 gave the corresponding bicyclo-
[3.3.0]octanes 12 or 13, respectively, in good yield and
with excellent regio- and diastereoselectivity (Table 1,
entries 7 and 8). Similarly, cyclization/hydrosilylation of
the allylcyclohexenyl derivative 14 formed bicyclo[4.3.0]-
nonane 15 in 69% yield with good diastereoselectivity
(33:1) (Table 1, entry 9). Noteworthy was the selective
formation of three contiguous stereocenters on the more
substituted cyclopentane ring of compounds 12, 13, and
15. Cyclization/hydrosilylation of 2,3-diallyl-5,6-dimethyl-
1,4-hydroquinone diacetate (16) led to the isolation of the
silylated tetrahydronaphthalene derivatives 17-19 (Table
1, entries 10-13) in good yield with good diastereoselec-
tivity.
Mech a n istic In sigh ts. We have previously proposed
a mechanism for palladium-catalyzed cyclization/hydro-
silylation initiated by â-migratory insertion of an olefin
into the PdsSi bond of the palladium silyl intermediate
I to form palladium alkyl intermediate II (Scheme 2).6
Coordination and insertion of the pendant olefin of II into
the PdsC bond could then form the palladium methyl-
cyclopentyl intermediate III which could react with silane
to release the silylated carbocycle and regenerate I. Both
the formation of I from reaction of cationic palladium
alkyl complexes with silane and the insertion of unfunc-
tionalized olefins into the PdsSi bond of I have been
Sch em e 2
established.13 The proposed mechanism also accounts for
many of our experimental observations. In particular, the
transfer of the silane to the less hindered olefin of dienes
2-4, 11, and 14 is consistent with a mechanism initiated
by silylpalladation rather than hydropalladation.
Brookhart has reported that unfunctionalized alkenes
such as 1-hexene undergo rapid and reversible â-migra-
tory insertion into the PdsSi bond of I.13 In contrast, the
reversibility of silylpalladation in palladium-catalyzed
cyclization/hydrosilylation has not been established and
we have previously considered that coordination of the
(13) LaPoint, A. M.; Rix, F. C.; Brookhart, M. J . Am. Chem. Soc.
1997, 119, 906.

Evidence for Reversible Silylpalladation
J . Org. Chem., Vol. 66, No. 5, 2001 1757
Sch em e 3
Ca sca d e Cycliza tion /Hyd r osilyla tion of Tr ien es.
The fused- and spirobicyclic compounds shown in Table
1 were synthesized by closing a ring on an existing
monocyclic ring system. A more desirable approach to the
synthesis of bicyclic compounds would be through mul-
tiple cyclization of a suitably designed triene. Specifically,
if the initially formed palladium cyclopentylmethyl in-
termediate III could be trapped by a tethered olefin prior
to silylative cleavage, a bicyclic compound would be
formed (Scheme 2). To this end, reaction of 1,6-11-
undecatriene 22 with HSiEt3 or HSiMe2Bn catalyzed by
1/NaBAr4 led to formation of the tethered bicyclic deriva-
tives 23 or 24, respectively, in >80% isolated yield as a
1
single diastereomer by H and 13C NMR analysis (Table
2, entries 1 and 2). Noteworthy was the formation of four
contiguous stereocenters with high stereoselectivity in
these transformations. The absence of any silylated
monocyclized products in the conversion of 22 to either
23 or 24 indicates that â-migratory insertion of the
pendant olefin of intermediate III-D is significantly faster
than reaction of III-D with free silane.
Sch em e 4
pendant olefin of palladium alkyl complex II may render
silylpalladation irreversible by filling the coordination
site required for â-silyl elimination.7 However, the ex-
clusive (>97%) formation of the trans,cis diastereomer
of 12 (trans,cis-12) (or the formation of trans,cis-13 or
trans,cis-15) in the cyclization/hydrosilylation of 11
strongly suggests that silylpalladation is reversible under
these conditions. Silylpalladation of the unhindered olefin
of 11 could form two diastereomeric palladium alkyl
intermediates, III-A and III-B (Scheme 3). Of these two,
only III-A can cyclize to form trans,cis-12.14 The failure
to observe cis,cis-12 in the cyclization of 11 indicates that
intermediate III-B is either not formed under reaction
conditions or once formed, undergoes â-silyl elimination
to regenerate 11 and I.15
Reaction of tetrapivolate 25 with silane catalyzed by
1/NaBAr4 led to the isolation of a 10:1 mixture of silylated
bicyclopentane 26 along with the corresponding mono-
cyclized isomer (Table 2, entry 3). Cascade cyclization/
hydrosilylation tolerated the presence of allylic gem
dimethyl groups, and triene 27 cyclized to form bicyclo-
pentane 28 with excellent regio and diastereoselectivity
(Table 2, entry 4). In contrast, palladium-catalyzed
reaction of triene 29, which possessed substitution at one
of the terminal olefinic carbon atoms, with HSiEt3 led to
formation of a 2:1 mixture of the desired silylated
bicyclopentane 30 along with the monocyclized/silylated
product (Table 2, entry 5). Palladium-catalyzed cascade
cyclization/hydrosilylation was also employed in the
synthesis of a fused tricyclic system. For example,
reaction of 3,5-bis(3-butenyl)cyclopentane 31 with HSiEt3
catalyzed by 1/NaBAr4 led to the isolation of a silylated
linear triquinane 32 in 74% yield as a 20:1 mixture of
isomers (Table 2, entry 6).17 The selective conversion of
31 to 32 also presumably requires reversible silylpalla-
dation to achieve high selectivity.
We have previously observed that cyclization/hydro-
silylation of 4,4-dicarbomethoxy-3-methyl-1,6-heptadiene
(20) forms 1,1-dicarbomethoxy-2,3-dimethyl-4-triethyl-
silylmethylcyclopentene (21) as a 1:1 mixture of the
diastereomers (Scheme 4).6 This observation is consistent
with the initial, nonselective silylpalladation of the less
hindered olefin of 20 and formation of palladium alkyl
intermediate III-C as a 1:1 mixture of diastereomers
(Scheme 4). Therefore, it appears unlikely that interme-
diate III-A is formed selectively in the cyclization/
hydrosilylation of 11 and strongly suggests that silylpal-
ladation of 11 by I is rapid and reversible. Furthermore,
the failure to observe significant amounts (<2%) of
dimethyl 2-cyclopentenyl-3-(triethylsilyl)butylmalonate
(resulting from hydrosilylation of 11 without cyclization)
indicates that â-silyl elimination from III-B is fast
relative to reaction of III-B with free silane.16
The radical-mediated or transition metal-catalyzed
cascade cyclization of polyolefins and polyenynes has
been an area of considerable interest.18 The majority of
transition-metal-catalyzed procedures are initiated by
oxidative addition of an (sp2)C-X (X ) Br, I, OTf) bond
to Pd(0).19,20 Alternative pathways for initiation of cascade
cyclization include the hydro-,21 silyl-,22 or carbometala-
(14) Cyclization of III-B would be disfavored because it would lead
either to a highly strained trans-fused bicyclo[3.3.0]octane ring struc-
ture or to a cis arrangement of the triethylsilyl and methylene group
about the newly formed CsC bond (the origin of the stereoselectivity
of ring closure is not understood).
(15) This requires both â-silyl elimination and olefin dissociation.
(16) The conversion of 11 to 12 or 13 and also the conversion of 14
to 15 and 31 to 32 may be a special cases, and we cannot conclude
that all cyclization/hydrosilylation occurs via reversible silylpallada-
tion. Nevertheless, these experiments establish reversible silylpalla-
dation as a viable pathway in palladium-catalyzed diene cyclization/
hydrosilylation.
(17) Attempts to extend the cascade cyclization/hydrosilylation to
the cyclization of tetraenes led to the formation of inseparable mixtures
of di- and tricyclized isomers.
(18) Malacria, M. Chem. Rev. 1996, 96, 289.
(19) Negishi, E.; Coperet, C.; Ma, S.; Liou, S. Y.; Lium F. Chem.
Rev. 1996, 96, 365.

1758 J . Org. Chem., Vol. 66, No. 5, 2001
Wang et al.
Ta ble 2. Ca sca d e Cycliza tion /Hyd r osilya tion of Tr ien es Ca ta lyzed by a 1:1 Mixtu r e of 1 a n d Na BAr 4 (10 m ol %) in DCE
a t Room Tem p er a tu r e
a
b
Yield refers to isolated material of >95% purity. Isomer ratio determined by GC analysis of the isolated material. c Minor isomer
d
was the monocyclization/hydrosilylation product. Reaction run at 40 °C.
tion23 of an alkyne. The palladium-catalyzed cascade
cyclization/hydrosilylation reactions reported here are
unusual as these transformations are initiated by si-
lylpalladation of an unactivated olefin. Previous examples
of cascade cyclization initiated by olefin metalation are
limited to the titanium-catalyzed cascade carboalumina-
tion of dienes and trienes24 and the yttrium-catalyzed
cascade cyclization/hydrosilylation of trienes.25 However,
due to the extreme Lewis acidity of both the organoalu-
minum reagent and group IV catalyst in the former case
and the yttrocene catalyst in the latter case, these
procedures are restricted primarily to the cyclization of
unfunctionalized substrates.
Con clu sion s
Several types of spiro- and fused bicyclic ring systems
were constructed via palladium-catalyzed cyclization/
hydrosilylation of carbocyclic dienes. Similarly, several
silylated bicyclopentanes and a linear triquinane deriva-
tive were formed via the palladium-catalyzed cascade
cyclization/hydrosilylation of functionalized trienes. The
selective conversion of 11 to 12 or 13 and also the
selective conversion of 14 to 15 and 31 to 32 was
consistent with a mechanism initiated by rapid and
reversible silylpalladation.
Exp er im en ta l Section
(20) (a) Abelman, M. M.; Overman, L. E. J . Am. Chem. Soc. 1988,
110, 2328. (b) Zhang, Y.; Negishi, E. J . Am. Chem. Soc. 1989, 111,
3454. (c) Wu, G.; Lamaty, F.; Negishi, E. J . Org. Chem. 1989, 54, 2507.
(d) Ashimori, A.; Overman, L. E. J . Org. Chem. 1992, 57, 4571. (e)
Sugihara, T.; Coperet, C.; Owczarczyk, Z.; Harring, L. S.; Negishi, E.
J . Am. Chem. Soc. 1994, 116, 7923. (f) Burns, B.; Grigg, R.; Sridharan,
V.; Stevenson, P.; Sukirthalingam, S.; Worakun, T. Tetrahedron Lett.
1989, 30, 1135. (g) Zhang, Y.; Wu, G.; Agnel, G.; Negishi, E. I. J . Am.
Chem. Soc. 1990, 112, 8590. (h) Meyer, F. E.; Parsons, P. J .; de Meijere,
A. J . Org. Chem. 1991, 56, 6487. (i) Overman, L. E.; Ableman, M. M.;
Kucera, D. J .; Tran, V. D.; Ricca, D. J . Pure Appl. Chem. 1992, 64,
1813.
(21) (a) Trost, B. M.; Shi, Y. J . Am. Chem. Soc. 1993, 115, 9421. (b)
Trost, B. M.; Shi, Y. J . Am. Chem. Soc. 1991, 113, 701. (c) Trost, B.
M.; Shi, Y. J . Am. Chem. Soc. 1992, 114, 791. (d) Trost, B. M.; Lee, D.
C. J . Am. Chem. Soc. 1988, 110, 7255.
(22) Ojima, I.; McCullagh, J . V.; Shay, W. R. J . Organomet. Chem.
1996, 521, 421.
Gen er a l Meth od s. All reactions were performed under an
atmosphere of nitrogen employing standard Schlenk tech-
niques. NMR spectra were obtained at 400 MHz for 1H and
100 MHz for 13C in CDCl3 unless otherwise noted. Gas
chromatography was performed on a Hewlett-Packard 5890
gas chromatograph equipped with a 25 m poly(dimethylsilox-
ane) capillary column. Flash chromatography was performed
employing 200-400 mesh silica gel (EM). Elemental analyses
were performed by E+R Microanalytical Laboratories (Par-
sippany, NJ ). Methylene chloride and 1,2-dichloroethane
(DCE) were distilled from CaH2 under nitrogen. Triethylsilane
(Aldrich), benzyldimethylsilane (Petrarch), and pentamethyl-
disiloxane (Gelest) were used as received. Precatalysts (phen)-
PdMeCl26 (1) and NaBAr4 were prepared employing known
27
(23) Chatani, N.; Kataoka, K.; Murai, S.; Furukawa, N.; Seki, Y. J .
Am. Chem. Soc. 1998, 120, 9104.
(24) (a) Kondakov, D. Y.; Wang, S.; Negishi, E. Tetrahedron Lett.
1996, 37, 3803. (b) Negishi, E.; J ensen, M. D.; Kondakov, D. Y.; Wang,
S.; J . Am. Chem. Soc. 1994, 116, 8404.
(26) De Delice, V.; Albano, B. G.; Castellari, C.; Cucciolito, M. E.;
De Renzi, A. J . Organomet. Chem. 1991, 403, 269.
(27) Brookhart, M.; Grant, B.; Volpe, A. F. Organometallics 1992,
11, 3920.
(25) Molander, G. A.; Retsch, W. H. J . Org. Chem. 1998, 63, 5507.

Evidence for Reversible Silylpalladation
J . Org. Chem., Vol. 66, No. 5, 2001 1759
procedures. The synthesis of the dienes and trienes employed
in this study are described in the Supporting Information.
2874, 1733, 1432, 1242, 1207. Anal. Calcd (found) for C22H40O4-
Si: H, 10.16 (9.99); C, 66.62 (66.58).
Dim eth yl 3-[Dim eth yl(tr im eth ylsiloxy)silyl]m eth yl-4-
m eth yl-sp ir o[4.5] d eca n e-1,1-d ica r boxyla te (10). 1H NMR:
δ 3.71 (s, 3 H), 3.65 (s, 3 H), 2.21 (dd, J ) 7.2, 13.6 Hz, 1 H),
2.23 (d, J ) 11.6, 13.6 Hz, 1 H), 2.06 (dd, J ) 11.6, 13.6 Hz, 1
H), 1.54-1.76 (m, 6 H), 1.29-1.43 (m, 3 H), 1.18 (dd, J ) 3.6,
12.4 Hz, 1 H), 1.13 (d, J ) 7.2 Hz, 3 H), 1.07 (td, J ) 7.2, 12.8
Hz, 1 H), 0.89 (dd, J ) 4.4, 14.8 Hz, 1 H), 0.5 (dd, J ) 10.4,
14.8 Hz, 1 H), 0.60 (s, 9 H), 0.47 (s, 6 H). 13C{1H} NMR: δ
171.9, 171.7, 69.6, 52.1, 49.9, 49.8, 40.9, 40.6, 36.5, 27.4, 26.5,
25.6, 24.0, 22.5, 17.0, 2.1, 1.4, 1.3. IR (neat, cm-1): 2951, 2859,
1730, 1451, 1433, 1252, 1056. Anal. Calcd (found) for C21H40O2-
Si2: H, 9.40 (9.61); C, 58.83 (58.57).
Gen er a l P r oced u r e for Cycliza t ion /Hyd r osilyla t ion .
Silane (1.5 mmol) was added via syringe to a solution of (phen)-
PdMeCl (1) (9 mg, 0.027 mmol), NaBAr4 (30 mg, 0.034 mmol),
and diene (0.50 mmol) or triene (0.25 mmol) in 5 mL DCE at
0 °C, warmed to room temperature (or 40 °C in the case of
30), and stirred for the time indicated in Tables 1 and 2. The
solvent was evaporated and the residue was chromatographed
on silica gel to give the silylated carbocycles as colorless oils.
The stereochemistry of the silylated carbocycles was as-
signed based on the previously established trans selectivity
of cyclization/hydrosilylation. In addition, the stereochemistry
of the diquinane 12 and linear triquinane 32 were unambigu-
ously determined through combined COSY and NOE analysis
(see Supporting Information).
Dim eth yl 3-Tr ieth ylsilylm eth yl-h exa h yd r op en ta len e-
1
1,1-d ica r boxyla te (12). H NMR (600 MHz, CDCl3): δ 3.72
(s, 3 H), 3.68 (s, 3 H), 3.24 (q, J ) 8.8 Hz, 1 H), 2.70 (dd, J )
6.9, 13.4 Hz, 1 H), 2.11 (dq, J ) 4.1, 8.8 Hz, 1 H), 1.74-1.83
(m, 2 H), 1.62-1.69 (m, 2 H), 1.50-1.55 (m, 1 H), 1.51 (dd,
J ) 9.6, 13.0 Hz, 1 H), 1.32-1.38 (m, 1 H), 1.16-1.21 (m, 1
H), 0.93 (t, J ) 8.1 Hz, 9 H), 0.76 (dd, J ) 4.1, 14.6 Hz, 1 H),
0.54 (dq, J ) 1.3, 7.8 Hz, 6 H), 0.35 (dd, J ) 9.9, 14.6 Hz, 1
H). 13C{1H} NMR: δ 173.7, 172.2, 63.1, 54.9, 52.7, 52.2, 49.9,
44.5, 42.1, 30.9, 29.74, 26.9, 16.9, 7.7, 4.0. Anal. Calcd (found)
for C19H34O4Si: C, 64.36 (64.44); H, 9.67 (9.78).
Dim et h yl 7-Tr iet h ylsilylm et h yl-8-m et h yl-sp ir o[3.4]-
octa n e-5,5-d ica r boxla te (5). H NMR: δ 3.77 (s, 3 H), 3.66
1
(s, 3 H), 2.69 (dd, J ) 9.2, 14.0 Hz, 1 H), 2.50-2.56 (m, 1 H),
1.97-2.04 (m, 1 H), 1.84-1.90 (m, 1 H), 1.59-1.78 (m, 4 H),
1.50 (dd, J ) 8.4, 14.0 Hz, 1 H), 1.35-1.43 (m, 1 H), 1.11 (d,
J ) 6.8 Hz, 3 H), 0.91 (t, J ) 8.0 Hz, 9 H), 0.81 (dd, J ) 2.0,
14.4 Hz, 1 H), 0.50 (q, J ) 8.0 Hz, 6 H), 0.26 (dd, J ) 11.6,
14.4 Hz, 1 H). 13C{1H} NMR: δ 172.7, 171.9, 65.9, 53.2, 52.4,
52.2, 51.1, 40.0, 37.8, 28.4, 25.3, 16.3, 16.0, 12,5, 7.6, 4.0. Anal.
Calcd (found) for C20H36O4Si: H, 9.84 (9.76); C, 65.17 (65.08).
Dim et h yl 3-Dim et h ylb en zylsilylm et h yl-h exa h yd r o-
1
p en ta len e-1,1-d ica r boxyla te (13). H NMR: δ 7.20 (t, J )
Dim eth yl 7-Ben zyldim eth ylsilylm eth yl-8-m eth yl-spir o-
7.2 Hz, 2 H), 7.06 (t, J ) 7.2 Hz, 1 H), 6.99 (d, J ) 7.2 Hz, 2
H), 3.70 (s, 3 H), 3.69 (s, 3 H), 3.23 (q, J ) 8.8 Hz, 1 H), 2.69
(dd, J ) 6.8, 13.2 Hz, 1 H), 2.09 (s, 2 H), 2.06-2.14 (overlapping
region, 1 H), 1.64-1.85 (m, 4 H), 1.46-1.56 (m, 2 H), 1.27-
1.35 (m, 4 H), 1.14-1.22 (m, 1 H), 0.76 (dd, J ) 4.8, 14.4 Hz,
1 H), 0.37 (dd, J ) 10.0, 14.4 Hz, 1 H), 0.00 (s, 3 H), -0.01 (s,
3 H). 13C{1H} NMR: δ 173.7, 172.1, 140.4, 128.4, 124.1, 54.6,
49.9, 44.3, 42.0, 31.0, 29.7, 26.9, 26.3, 20.6, -2.5, -2.7. IR
(neat, cm-1): 3023, 2951, 2867, 1737, 1731, 1493, 1453, 1434.
Anal. Calcd (found) for C22H32O4Si: H, 8.30 (8.20); C, 68.00
(68.18).
1
[3.4]octa n e-5,5-d ica r boxyla te (6). H NMR: δ 7.20 (t, J )
7.6 Hz, 2 H), 7.06 (t, J ) 7.6 Hz, 1 H), 6.98 (d, J ) 7.2 Hz, 2
H), 3.76 (s, 3 H), 3.70 (s, 3 H), 2.71 (dd, J ) 8.8, 13.6 Hz, 1 H),
2.56 (td, J ) 8.8, 11.2 Hz, 1 H), 2.08 (s, 2 H), 1.98-2.05 (m, 1
H), 1.58-1.89 (m, 6 H), 1.49 (dd, J ) 8.8, 13.6 Hz), 1.34-1.44
(m, 1 H), 1.58-1.89 (m, 6 H), 1.49 (dd, J ) 8.8, 13.6 Hz), 1.34-
1.44 (m, 1 H), 1.09 (d, J ) 6.8 Hz, 3 H), 0.84 (dd, J ) 2.4, 14.8
Hz, 1 H), 0.28 (dd, J ) 11.6, 14.8 Hz, 1 H), -0.01 (s, 3 H),
-0.02 (s, 3 H). 13C{1H} NMR: δ 172.6, 171.9, 140.4, 128.3,
124.1, 65.9, 53.1, 52.6, 52.3, 50.8, 40.0, 37.7, 28.2, 26.3, 25.3,
19.9, 16.0, 12.4, -2.3, -2.6. IR (neat, cm-1): 3023, 2951, 2894,
1737, 1730, 1493, 1453. Anal. Calcd (found) for C21H40O5Si2:
H, 8.51 (8.76); C, 68.62 (68.53).
5,8-Dia cetoxy-2-tr ieth ylsilylm eth yl-3,6,7-tr im eth yl-1,4-
d ih yd r on a p h th a len e (17). 1H NMR: δ 2.3-2.6 (m, 2 H), 2.08
(s, 3 H), 2.06 (s, 3 H), 1.78 (s, 6 H), 1.22 (m, 4 H), 0.76 (d, J )
6.0 Hz, 3 H), 0.69 (t, J ) 8.0 Hz, 9 H), 0.29 (q, J ) 8.0 Hz, 6
H), 0.19-0.00 (m, 1 H). One Et3SiCH2 proton obscured. 13C-
{1H} NMR: δ 169.3, 145.3, 127.9, 127.2, 35.5, 32.6, 20.9, 20.8,
20.1, 15.9, 13.2, 7.9, 7.8, 7.7, 4.5, 3.6, 3.5. IR (CCl4, cm-1): 3053,
2408, 2350, 1755, 1714, 1681, 1650, 1556, 1538, 1504, 1265,
1200, 1077, 896, 738, 705. Anal. Calcd (found) for C24H38SiO4:
H, 9.17 (9.28); C, 69.04 (68.80).
5,8-Dia cet oxy-3,6,7-t r im et h yl-2-d im et h ylp h en ylsilyl-
m eth yl-1,4-d ih yd r on a p h th a len e (18). 1H NMR: δ 7.53-
7.51 (m, 2 H), 7.36-7.26 (m, 3 H), 2.80-2.60 (m, 2 H), 2.33 (s,
6 H), 2.15 (d, J ) 3.6 Hz, 3 H), 2.02 (s, 6 H), 1.54-1.51 (m, 4
H), 0.91-0.86 (m, 1 H), 0.32 (s, 3 H), 0.30 (s, 3 H), 0.25-0.24
(m, 1 H). 13C{1H} NMR: δ 169.0, 144.7, 139.5, 133.4, 133.3,
128.7, 127.7, 127.6, 127.5, 126.6, 57.8, 34.0, 20.3, 20.2, 20.1,
20.0, 19.5, 18.0, 13.0, 12.6, -2.3, -3.4. IR (neat, cm-1): 3054,
2956, 2408, 2350, 1757, 1556, 1427, 1369, 1265, 1247, 1198,
1112, 1079, 1013, 894, 834, 738, 703. Anal. Calcd (found) for
Dim eth yl 3-(Tr ieth ylsilylm eth yl)-4-m eth yl-sp ir o[4.4]-
n on a n e-1,1-d ica r boxyla te (7). 1H NMR: δ 3.70 (s, 3 H), 3.63
(s, 3 H), 2.17 (dd, J ) 6.8, 13.6 Hz, 1 H), 2.13 (d, J ) 15.6 Hz,
1 H), 2.02 (dd, J ) 11.6, 13.6 Hz, 1 H), 1.53-1.65 (m, 6 H),
1.30-1.43 (m, 3 H), 1.19 (dd, J ) 3.6, 12.4 Hz, 1 H), 1.13 (d,
J ) 6.8 Hz, 3 H), 1.06 (td, J ) 3.6, 12.8 Hz, 1 H), 0.92 (t, J )
8.0 Hz, 9 H), 0.49 (q, J ) 8.0 Hz, 6 H), 0.46-0.53 (m, 1 H).
13C{1H} NMR: δ 171.9, 171.7, 69.9, 52.1, 50.8, 49.6, 41.4, 40.6,
36.6, 27.3, 25.6, 24.0, 22.5, 19.4, 17.0, 7.6, 4.0. IR (neat, cm-1):
2950, 2874, 1732, 1432, 1242, 756, 721. Anal. Calcd (found)
for C22H40O4Si: H, 10.16 (9.99); C, 66.62 (66.58).
Dim eth yl 3-Ben zyldim eth ylsilylm eth yl-4-m eth yl-spir o-
1
[4.4]n on a n e-1,1-d ica r boxyla te (8). H NMR: δ 7.20 (t, J )
7.2 Hz, 2 H), 7.06 (t, J ) 7.2 Hz, 1 H), 6.98 (d, J ) 8.0 Hz, 2
H), 3.69 (s, 3 H), 3.67 (s, 3 H), 2.68 (dd, J ) 10.0, 14.4 Hz, 1
H), 2.06-2.15 (m, 1 H), 2.08 (s, 2 H), 1.95 (qd, J ) 6.8, 10.4
Hz, 1 H), 1.68 (dd, J ) 7.2, 10.4 Hz, 1 H), 1.43-1.67 (m, 7 H),
1.21-1.26 (m, 1 H), 0.85 (d, J ) 7.2 Hz, 3 H), 0.82 (dd, J )
2.4, 14.8 Hz, 1 H), 0.38 (dd, J ) 12.0, 14.8 Hz, 1 H), -0.01 (s,
3 H), -0.02 (s, 3 H). 13C{1H} NMR: δ 173.2, 172.0, 140.4, 128.3,
124.1, 67.3, 57.9, 52.4, 52.2, 40.7, 38.4, 34.8, 30.1, 26.7, 26.3,
20.6, 13.0, -2.3, -2.6. IR (neat, cm-1): 3023, 2950, 2871, 1731,
1492, 1451, 1432, 1247, 1206. Anal. Calcd (found) for C24H36O4-
Si: H, 8.71 (8.79); C, 69.19 (68.83).
C
26H34SiO4: H, 7.81 (8.17); C, 71.19 (71.37).
5,8-Dia cet oxy-3,6,7-t r im et h yl-2-d im et h ylb en zylsilyl-
m eth yl-1,4-d ih yd r on a p h th a len e (19). 1H NMR: δ 7.20-
6.96 (m, 5 H), 2.85-2.45 (m, 2 H), 2.31 (s, 3 H), 2.28 (s, 3 H),
2.08 (s, 2 H), 2.02 (s, 6 H), 1.62-1.39 (m, 2 H), 1.30-1.21 (m,
2 H), 0.95 (d, J ) 6.4 Hz, 3 H), 0.40-0.30 (m, 1 H), 0.00 (s, 3
H), -0.02 (s, 3 H). One BnMe2SiCH2 proton partially obscured.
13C{1H} NMR: δ 170.1, 170.0, 146.0, 141.3, 141.2, 129.3, 129.2,
128.5, 128.1, 128.0, 125.1, 125.0, 36.5, 35.2, 33.2, 27.4, 23.4,
21.59, 21.55, 20.7, 20.4, 15.1, 14.0, -1.0, -1.6. Anal. Calcd
(found) for C27H36SiO4: H, 8.02 (8.29); C, 71.64 (71.89).
Tetr a m eth yl 2-Tr ieth ylsilylm eth yl-2′-m eth yl-bicyclo-
p en tyl-4,4,4′,4′-tetr a ca r boxyla te (23). 1H NMR: δ 3.65-
3.67 (s, 12 H), 2.50-2.54 (m, 2 H), 2.44 (dd, J ) 6.4, 12.6 Hz,
2 H), 2.13-2.22 (m, 2 H), 1.48-1.87 (m, 7 H), 0.86-0.92 (m,
12 H), 0.48 (q, J ) 8.0 Hz, 6 H), 0.19 (dd, J ) 10.8, 14.8 Hz, 1
H). 13C{1H} NMR: δ 173.6, 173.5, 58.3, 58.2, 53.1, 48.1, 45.8,
Dim et h yl 3-Tr iet h ylsilylm et h yl-4-m et h yl-sp ir o[4.5]-
d eca n e-1,1-d ica r boxyla te (9). 1H NMR: δ 3.70 (s, 3 H), 3.64
(s, 3 H), 2.17 (dd, J ) 6.8, 13.2 Hz, 1 H), 2.13 (d, J ) 15.6 Hz,
1 H), 2.02 (dd, J ) 11.6, 13.6 Hz, 1 H), 1.53-1.69 (m, 6 H),
1.31-1.43 (m, 3 H), 1.19 (dd, J ) 3.6, 12.4 Hz, 1 H), 1.12 (d,
J ) 6.8 Hz, 3 H), 1.07 (td, J ) 3.2, 12.8 Hz, 1 H), 0.92 (t, J )
8.0 Hz, 9 H), 0.85-0.89 (overlapping region, 1 H), 0.50 (q, J )
8.0 Hz, 6 H), 0.44-0.50 (overlapping region, 1 H). 13C{1H}
NMR: δ 171.9, 171.7, 69.7, 52.1, 50.8, 49.6, 41.4, 40.6, 36.6,
27.3, 25.6, 23.9, 22.5, 19.4, 17.0, 7.6, 4.0. IR (neat, cm-1): 2949,

1760 J . Org. Chem., Vol. 66, No. 5, 2001
Wang et al.
43.2, 39.8, 38.1, 34.4, 33.7, 17.5, 14.9, 7.8, 4.2. IR (neat, cm-1):
3732, 3646, 3626, 2952, 2874, 1734, 1653, 1558, 1457, 1253,
1196, 1164, 1144, 1104, 1016, 960, 861, 759, 727. Anal. Calcd
(found) for C26H44O8Si: C, 60.91 (60.43); H, 8.65 (8.64).
Tetr a m eth yl 2-Ben zyld im eth ylsilylm eth yl-2′-m eth yl-
ethylsilylmethyl)cyclopentane (33) (145 mg, 84%). The mixture
was analyzed by IR spectroscopy and elemental analysis and
then rechromatographed to give samples of pure 30 (39 mg,
23%) and 33 (24 mg, 14%) which were analyzed by NMR
spectroscopy. IR (neat, cm-1): 3695, 3634, 2952, 2874, 1734,
1459, 1437, 1252, 1196, 1165, 1017. Anal. Calcd (found) for
C27 H46O8Si: C, 61.57 (61.36); H, 8.80 (8.93).
1
bicyclop en tyl-4,4,4′,4′-tetr a ca r boxyla te (24). H NMR: δ
7.15 (m, 2 H), 7.00-7.05 (m, 1 H), 6.95-6.98 (m, 2 H), 3.68-
3.70 (s, 12 H), 2.54 (d, J ) 6.4 Hz, 1 H), 2.45-2.51 (m, 1 H),
2.23 (dd, J ) 6.8 Hz, 13.4 Hz, 1 H), 2.16 (dd, J ) 6.8 Hz, 13.4
Hz, 1 H), 2.07 (s, 2 H), 1.79-1.91 (m, 2 H), 1.54-1.72 (m, 6
H), 0.92 (d, J ) 5.6 Hz, 3 H), 0.84-0.86 (m, 1 H), 0.25 (dd,
J ) 10.4, 14.6 Hz, 1 H), -0.03 (s, 3 H), -0.04 (s, 3 H). 13C{1H}
NMR: δ 173.5, 173.4, 140.3, 128.5, 128.4, 124.2, 58.2, 58.1,
52.9, 45.7, 43.1,4 3.0, 39.7, 38.0, 34.3, 33.7, 26.3, 18.6, 17.5,
-2.3, -2.5. IR (neat, cm-1): 2977, 2935, 2869, 2804, 1737,
1683, 1653, 1636, 1559, 1457, 1490, 1444, 1382, 1350, 1297,
1254, 1120, 1076, 1043, 1024, 934, 845, 794. Anal. Calcd
(found) for C29H43O8Si: C, 63.71 (63.65); H, 7.74 (8.09).
2-Tr iet h ylsilylm et h yl-2′-m et h yl-4,4,4′,4′-t et r a k is(t r i-
F or 30. 1H NMR: δ 3.66-3.69 (s, 12 H) 2.53-2.58 (m, 1
H), 2.48 (dd, J ) 7.0, 13.4 Hz, 1 H), 2.23 (dd, J ) 6.0, 13.6 Hz,
1 H), 2.17 (dd, J ) 7.4, 13.0 Hz, 1 H), 1.71-1.89 (m, 5 H),
1.48-1.67 (m, 3 H), 1.38-1.43 (m, 1 H), 1.23-1.31 (m, 1 H),
0.99-1.15 (m, 1 H), 0.79-0.92 (m, 12 H), 0.47-0.53 (m, 6 H),
0.20 (dd, J ) 10.8, 14.8 Hz, 1 H). 13C{1H} NMR: δ 173.6, 173.5,
58.2, 58.1. 53.0, 48.3, 44.8, 44.0, 43.1, 40.4, 39.7, 34.9, 33.9,
25.9, 14.9, 12.6, 7.9, 4.1.
1
F or 33. H NMR: δ 5.00 (m, 2 H), 3.65 (m, 12 H), 2.97 (d,
J ) 17.6 Hz, 1 H), 2.82 (d, J ) 17.2 Hz, 1 H), 2.60-2.40 (m, 3
H), 2.20 (m, 1 H), 1.92-1.53 (m, 4 H), 1.33-1.15 (m, 3 H), 1.10
(m, 2 H), 0.90 (t, J ) 8.0 Hz, 9 H), 0.80 (d, J ) 6.4 Hz, 3 H),
0.49 (q, J ) 8.0 Hz, 6 H), 0.36 (dd, J ) 10.8, 14.8 Hz, 1 H).
13C{1H} NMR: δ 172.4, 172.2, 148.7, 114.4, 58.4, 57.8, 52.9,
52.5, 42.5, 39.4, 37.1, 32.7, 32.5, 26.5, 23.1, 15.5, 14.0, 12.4,
7.6, 7.0, 6.5, 4.1.
1
m eth yla cetoxym eth yl) Bicyclop en ta n e (26). H NMR: δ
3.85-4.07 (s, 8 H), 2.06 (d, J ) 5.6 Hz, 1 H), 1.77 (dd, J ) 6.8,
12.8 Hz, 2 H), 1.56-1.71 (m, 2 H), 1.40-1.53 (m, 4 H), 1.18-
1.20 (s, 34 H), 0.88-1.07 (m, 12 H), 0.53 (q, J ) 8.0 Hz, 6 H),
0.50 (q, J ) 8.0 Hz, 6 H), 0.19 (dd, J ) 11.6 Hz, 14.8 Hz, 1 H).
13C{1H} NMR: δ 178.8, 68.8, 68.6, 41.5, 40.8, 39.3, 39.1, 37.4,
35.5, 34.5, 32.0, 31.4, 27.5, 17.7, 16.4, 15.2, 15.0, 7.8, 4.2. IR
(neat, cm-1): 3691, 3630, 3584, 2957, 1733, 1654, 1480, 1459,
1397, 1364, 1282, 1146, 1034. HRMS (EI) calcd (found) for
Tetr a m eth yl 4-Tr ieth ylsilylm eth yl-3-m eth yl-octa h y-
dr o cyclopen ta[r]pen talen e-1,1,6,6-tetr acar boxylate (32).
1H NMR (600 MHz): δ 3.71 (s, 3 H), 3.65 (s, 3 H), 3.23-3.35
(m, 2 H), 2.78 (dd, J ) 7.8, 14.0 Hz, 1 H), 2.76 (dd, J ) 7.5,
13.8 Hz, 1 H), 2.37 (q, J ) 8.7 Hz, 1 H), 2.31 (q, J ) 8.7 Hz, 1
H), 2.12-2.24 (m, 2 H), 1.65 (dd, J ) 7.8, 13.7 Hz, 1 H), 1.58
(dd, J ) 9.0, 13.3 Hz, 1 H), 1.50 (td, J ) 6.8, 13.0 Hz, 1 H),
0.98 (d, J ) 6.8 Hz, 3 H), 0.94 (t, J ) 8.0 Hz, 9 H), 0.82 (q,
J ) 12.1 Hz, 1 H), 0.77 (dd, J ) 3.1, 14.9 Hz, 1 H), 0.54 (q,
J ) 8.0 Hz, 6 H), 0.37 (dd, J ) 11.2, 14.6 Hz, 1 H). 13C{1H}
NMR: δ 133.4, 173.3, 171.6, 171.4, 62.0, 61.3, 56.5, 53.5, 52.8,
52.2, 51.9, 44.4, 43.5, 36.2, 34.0, 31.2, 21.7, 19.1, 7.6, 4.0. Anal.
Calcd (found) for C27H44O8Si: C, 61.80 (61.59); H, 8.45 (8.64).
C
40H71O8Si (M+ - C2H5): 707.4918 (707.4951).
Tetr a m eth yl 2′-Tr ieth ylsilylm eth yl-2,3,3-tr im eth yl-bi-
1
cyclop en ta n e-4,4,4′,4′-tetr a ca r boxyla te (28). H NMR: δ
3.64-3.69 (s, 12 H), 2.43-2.55 (m, 2 H), 2.06-2.19 (m, 2 H),
1.81-1.91 (m, 2 H), 1.45-1.71 (m, 4 H), 1.17 (s, 3 H), 0.89 (t,
J ) 7.8 Hz, 9 H), 0.78 (d, J ) 6.8 Hz, 3 H), 0.76 (d, J ) 2.4 Hz,
3 H), 0.70 (s, 3 H), 0.48 (q, J ) 8.0 Hz, 6 H), 0.21 (dd, J ) 6.0,
11.4 Hz, 1 H). 13C{1H} NMR: δ 173.7, 173.5, 172.7, 171.9, 66.7,
58.3, 52.9, 52.3, 48.9, 48.1, 45.6, 43.2, 41.5, 39.3, 34.1, 31.9,
22.1, 19.4, 14.8, 12.3, 7.8, 4.1. IR (neat, cm-1): 2952, 2904,
2875, 1654, 1636, 1559, 1458, 1426, 1261, 1197, 1166, 1094,
1048, 1016, 958. Anal. Calcd (found) for C28H48O8Si: C, 62.25
(62.19); H, 8.95 (8.91).
Ack n ow led gm en t is made to the National Institutes
of Health (GM59830-01) for support of this research.
R.W. thanks the Camille and Henry Dreyfus Foundation
and DuPont for young faculty awards and the Alfred P.
Sloan Foundation for a Research Fellowship. We thank
Dr. Anthony Ribeiro for assistance with COSY and
NOESY analysis of compounds 12 and 32.
Cyclization /Hydr osilylation of 4,4,9,9-Tetr acar bom eth -
oxy-1,6,11-tr id eca tr ien e (29). Triethylsilane (1.5 mmol) was
added via syringe to a solution of (phen)PdMeCl (1) (9 mg,
0.027 mmol), NaBAr4 (30 mg, 0.034 mmol), and triene 29 (135
mg, 0.33 mmol) in 5 mL of DCE at 0 °C, warmed to room
temperature, and stirred for 12 h. Solvent was evaporated, and
the residue was chromatographed (SiO2; hexanes-EtOAc )
12:1) to give a 2:1 mixture of tetramethyl 2′-ethyl-2-triethyl-
silylmethyl-bicyclopentyl-4,4,4′,4′-tetracarboxylate (30) and
1,1-dicarbomethoxy-4-(5,5-carbomethoxy-(E)-2-heptenyl)-3-(tri-
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectroscopic and analytical data for relevant
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O001438K