Cross-coupling reactions of hypervalent siloxane derivatives: An alternative to stille and Suzuki couplings

Article abstract of DOI:10.1021/jo982463h

Palladium-catalyzed cross-coupling of phenyl, vinyl, and allyl siloxane derivatives proceeded in good to excellent yield with aryl iodides, electron-deficient aryl bromides, and allylic benzoates. Methyl and 2,2,2-trifluoroethyl siloxane derivatives can be employed in the coupling reaction. Electron-donating and -withdrawing groups are tolerated on the aryl halide without affecting the coupling. The scope and limitations of this alternative to Stille and Suzuki couplings is outlined.

Full text of DOI:10.1021/jo982463h

1684
J . Org. Chem. 1999, 64, 1684-1688
Cr oss-Cou p lin g Rea ction s of Hyp er va len t Siloxa n e Der iva tives:
An Alter n a tive to Stille a n d Su zu k i Cou p lin gs†
Molly E. Mowery and Philip DeShong*
Department of Chemistry and Biochemistry, The University of Maryland, College Park, Maryland 20742
Received December 17, 1998
Palladium-catalyzed cross-coupling of phenyl, vinyl, and allyl siloxane derivatives proceeded in
good to excellent yield with aryl iodides, electron-deficient aryl bromides, and allylic benzoates.
Methyl and 2,2,2-trifluoroethyl siloxane derivatives can be employed in the coupling reaction.
Electron-donating and -withdrawing groups are tolerated on the aryl halide without affecting the
coupling. The scope and limitations of this alternative to Stille and Suzuki couplings is outlined.
Sch em e 1
In tr od u ction
Palladium-catalyzed cross-coupling reactions are ver-
satile methods for the synthesis of carbon-carbon bonds
in either a catalytic or a stoichiometric manner.1 The
Stille and Suzuki coupling protocols have achieved
prominence because of the high yields, tolerance for
functional groups, and excellent stereochemistry that is
observed (Scheme 1).1-3 However, there are serious
limitations associated with each of these processes. In
the Stille coupling, toxic tin(IV) substrates are used, and
multiple equivalents of the tin reagent are required.
Subsequently, the removal of tin byproducts poses a
problem.
Although the Stille methodology is powerful, it has
largely been supplanted by the Suzuki coupling technol-
ogy, in which tin reagents have been replaced by boronic
acid derivatives. As outlined in Scheme 1, Suzuki cou-
pling between an aryl iodide and a boronic acid in the
presence of Pd(0) results in formation of the cross-coupled
product in excellent yield. However, this methodology is
also limited by the availability of boronic acid deriva-
tives.4
We chose to employ silicon reagents in our cross-
coupling protocol for several reasons. One advantage of
this approach over the Stille methodology is that it
replaces the toxic tin reagents with environmentally
benign silicon compounds.5 Also, unlike the boronic acid
derivatives employed in Suzuki couplings, silicon re-
agents are readily prepared by a variety of methods and
are stable to many of the reaction conditions employed
in organic synthesis.5 The silicon activating group, unlike
a boronic acid functionality, can be carried through
several synthetic transformations prior to activation for
coupling. Hiyama and Hatanaka have developed Pd-
catalyzed, fluoride-promoted cross-coupling reactions of
organohalosilanes with alkenyl- and aryl-substituted
halides and triflates.6,7 Typically, the organohalosilanes
employed include alkenyl or aryl fluorosilanes. Although
some of the organohalosilanes are commercially avail-
able, most have to be prepared using several different
methodologies which often require multistep procedures
and/or employ the use of caustic reagents.6,7 Also, the
major limitation of the Hiyama/Hatanaka protocol is the
* To whom correspondence should be addressed. Phone: (301) 405-
1892. Fax: (301) 314-9121. E-mail: pd10@umail.umd.edu.
† This manuscript is dedicated to the memory of George H. Bu¨chi.
(1) (a) Trost, B. M.; Verhoeven, T. R. In Comprehensive Organome-
tallic Chemistry; Wilkinson, G., Stone, F. G. A., Eds.; Pergamon:
Oxford, 1982; Vol. 8, pp 799-938.(b) Tamao, K. Ibid. Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, pp 435-480. (c)
Knight, D. W. Ibid. Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1991; Vol. 3, pp 481-578. (d) Tsuji, T. Palladium Reagents and
Catalysis; J ohn Wiley & Sons: New York, 1985.
(2) (a) Stille, J . K.; Echavarren, A. M.; Williams, R. M.; Hendrix, J .
A. Org. Synth. 1992, 71, 97-106 and references therein. (b) Del Valle,
L.; Stille, J . K.; Hegedus, L. S. J . Org. Chem. 1990, 55, 3019-3023. (c)
Echavarren, A. M.; Stille, J . K. J . Am. Chem. Soc. 1987, 109, 5478-
5486. (d) Stille, J . K.; Groh, B. L. Ibid. 1987, 109, 813-817. (e) Stille,
J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524. (f) Scott, W. J .;
Stille, J . K. J . Am. Chem. Soc. 1986, 108, 3033-3040. (g) Stille, J . K.
Pure Appl. Chem. 1985, 57, 1771-1780.
(5) Siloxanes have been widely used industrially in the production
of fluids, resins, elastomers, rubbers, polymers, and miscellaneous
products. Because many siloxane polymers are readily prepared by
hydrolysis of functionalized siloxane monomers, the preparation of
these monomers is well-developed. For more information, see: (a)
Freeman, G. G. Silicones: An Introduction to Their Chemistry and
Applications; The Chapel River Press Ltd.: Andover, Hants, England,
1962; pp 1-21 and 105-110. (b) Mehrotra, R. C. In Chemistry and
Technology of Silicon and Tin; Kumar Das, V. G., Weng, N. G., Gielen,
M., Eds.; Oxford University Press: New York, 1992; pp 93-109. For
information regarding toxicology studies of silicone products, see: (c)
Freeman, G. G. Silicones: An Introduction to Their Chemistry and
Applications; The Chapel River Press Ltd.: Andover, Hants, England,
1962; pp 99-104. For information regarding toxicology studies of tin
reagents, see: (d) Arakawa, Y. In Chemistry of Tin, 2nd ed.; Smith, P.
J ., Ed.; Blackie Academic & Professional: London, 1998; pp 388-428.
(e) Smith, P. J . Ibid. Smith, P. J ., Ed.; Blackie Academic & Profes-
sional: London, 1998; pp 429-441. (f) Aldridge, W. N. In Chemistry
and Technology of Silicon and Tin; Kumar Das, V. G., Weng, N. G.,
Gielen, M., Eds.; Oxford University Press: New York, 1992; pp 78-
92.
(3) (a) Kalivretenos, A.; Stille, J . K.; Hegedus, L. S. J . Org. Chem.
1991, 56, 2883-2894 and references cited therein. (b) Gyorkos, A. C.;
Stille, J . K.; Hegedus, L. S. J . Am. Chem. Soc. 1990, 112, 8465-8472.
(c) Stille, J . K.; Sweet, M. P. Tetrahedron Lett. 1989, 30, 3645-3648.
(4) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
10.1021/jo982463h CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/05/1999

Reactions of Hypervalent Siloxane Derivatives
J . Org. Chem., Vol. 64, No. 5, 1999 1685
Sch em e 2
requirement for the use of hydrolytically unstable and
strongly Lewis acidic silyl fluoride derivatives.
In this paper, we report that siloxane derivatives such
as 1-4 are substrates for Pd(0)-catalyzed coupling reac-
tions with allylic alcohol and aryl derivatives affording
cross-coupling products in high yields. Our results comple-
ment those of Tamao8 and Shibata9 that have been
recently reported.
unsymmetrical biaryls in good to excellent yields.11 The
major limitation of the silicate methodology described
above is that only one of the three phenyl groups of TBAT
(5) is transferred under the coupling conditions.
In an effort to overcome this limitation, the use of
silicate derivatives generated in situ was investigated.
Treatment of phenyl trimethylsiloxane (1) with equimolar
amount of tetrabutylammonium fluoride (TBAF) pre-
sumably resulted in formation of hypervalent fluorosili-
cate anion 6 (Scheme 2).6,7 Silicate 6 coupled with
4-iodotoluene in the presence of a Pd(0) catalyst to afford
the unsymmetrical biphenyl 7 in high yield. A survey of
the coupling reaction with aryl halide derivatives is
summarized in Table 1, and these results indicate that
this approach is a viable alternative to the Stille and
Suzuki protocols for the synthesis of unsymmetrical
biaryls.
Control experiments with 4-iodotoluene and phenyl-
trimethylsilane (entries 1 and 2) demonstrated that
silanes would not participate in the coupling reaction.
Equimolar quantities of PhSiMe3 and TBAF yielded only
the homocoupled adduct (40%, entry 1).12 Changing from
a silane to siloxane derivative was postulated to favor
formation of the hypervalent silicate anion (i.e., 6) and
subsequent transmetalation to palladium would occur.13
The control experiment employing PhSi(OMe)3 and no
TBAF gave only starting material (entry 3). Adding an
equimolar amount of TBAF to siloxane 1, presumably
with formation of silicate anion 6 in situ, gave 90% of
the heterocoupled product (entry 4).
Tamao and co-workers have reported that alkenyl
alkoxysilanes serve as effective transmetalation reagents
with alkenyl and aryl halides.8 Interestingly, it was noted
that alkenyl trialkoxysilanes were much more reactive
than the corresponding alkenyl trifluorosilanes.8 Shibata
investigated the Pd-catalyzed, fluoride promoted cross-
coupling of various aryl trimethoxysilanes with aryl
bromides for the synthesis of liquid crystalline biaryl
derivatives.9
Resu lts a n d Discu ssion
Recently, studies in our laboratory demonstrated that
silicate anions such tetrabutylammonium triphenyldi-
fluorosilicate (TBAT, 5) underwent condensation with
allylic benzoates in the presence of Pd(0) catalysts to
afford coupling products.10 Subsequently, we have also
shown that TBAT (5) underwent Pd(0)-catalyzed coupling
with aryl iodides, bromides, and triflates, affording
The cross-coupling reaction of siloxanes appears to be
insensitive to the reaction conditions. Changing the
catalyst from (Pd(dba)2) to allyl palladium chloride dimer
(APC) gave a marginally lower yield (85%, entry 5).
Similarly, replacing dimethylformamide (DMF) with
tetrahydrofuran (THF) (entry 6) gave a higher yield (94%
vs 90%) of the cross-coupling product, but 6% of the
homocoupled product, which was not observed in the
reactions performed in DMF, was also obtained in the
(6) For recent reviews on organosilicon compounds and cross-
coupling reactions, see: (a) Hiyama, T. In Metal-catalyzed Cross-
coupling Reactions; Diederich, F., Stang, P. J ., Eds.; Wiley-VCH:
Weinhein, Germany, 1998; pp 421-452. (b) Horn, K. A. Chem. Rev.
1995, 95, 1317-1350. (c) Hiyama, T.; Hatanaka, Y. Pure Appl. Chem.
1994, 66, 1417-1478. (d) Chuit, C.; Corriu, R. J . P.; Reye, C.; Young,
J . C. Chem. Rev. 1993, 93, 1317-1448. (e) Hatanaka, Y.; Hiyama, T.
Synlett 1991, 845-853.
(7) For information about Pd-catalyzed, fluoride promoted cross-
coupling reactions of reactions of organohalosilanes with aryl and
alkenyl-halides see: (a) Gouda, K.; Hagiwara, E.; Hatanaka, Y.;
Hiyama, T. J . Org. Chem. 1996, 61, 7232-7233. (b) Hatanaka, Y.;
Goda, K.; Okahara, Y.; Hiyama, T. Tetrahedron 1994, 50, 8301-8316.
(c) Hatanaka, Y.; Fukushima, S.; Hiyama, T. Heterocycles 1990, 30,
303-306. (d) Hatanaka, Y.; Fukushima, S.; Hiyama, T. Chem. Lett.
1989, 1711-1714. For information about alkylation of aryl halides with
alkyltrifluorosilanes, see: (e) Matsuhashi, H.; Asai, S.; Hirabayashi,
K.; Hatanaka, Y.; Mori, A. Hiyama, T. Bull. Chem. Soc. J pn. 1997,
70, 437-444. (f) Matsuhashi, H.; Kuroboshi, M.; Hatanaka, Y.; Hiyama,
T. Tetrahedron Lett. 1994, 35, 6507-6510. For information about Pd-
catalyzed, NaOH-promoted reactions of organochlorosilanes with aryl
chlorides, see: (g) Hagiwara, E.; Gouda, K.; Hatanaka, Y.; Hiyama,
T. Tetrahedron Lett. 1997, 38, 439- 442.
(10) Brescia, M.-R.; DeShong, P. J . Org. Chem. 1998, 63, 3156-
3157. See also ref 7. For other papers relating to the application of
hypervalent silicates as reagents, see: (a) Pilcher, A. S.; DeShong, P.
J . Org. Chem. 1996, 61, 6901-6905. (b) Pilcher, A. S.; Ammon, H. L.;
DeShong, P. J . Am. Chem. Soc. 1995, 117, 5166-5167. (c) Pilcher, A.
S.; DeShong, P. J . Org. Chem. 1993, 58, 5130-5134. (d) Pilcher, A. S.;
Hill, D. K.; Waltermire, R. E.; Shimshock, S. J .; DeShong, P. J . Org.
Chem. 1992, 57, 2492-2495.
(11) Mowery, M. E.; DeShong, P. Submitted for publication in J .
Org. Chem.
(12) The mechanism of this remarkable fluoride-induced homo-
coupling of aryl iodides by Pd is under investigation.
(13) The presumed mechanism for these types of cross-coupling
reactions is as follows: formation of the hypervalent organosilane,
oxidative addition of Pd(0) to the aryl or alkyl halide, followed by
transmetalation of the hypervalent organosilane to the organopalla-
dium(II) complex. Reductive elimination then occurs, giving the cross-
coupled adduct, Pd(0), and a tetravalent organosilane. The transmet-
alation adduct using Hiyama-type conditions was recently isolated. For
more information, see: Mateo, C.; Fernandez-Rivas, C.; Echavarren,
A. M.; Cardenas, D. J . Organometallics 1997, 16, 1997-1999.
(8) Tamao, K.; Kobayashi, K.; Ito, Y. Tetrahedron Lett. 1989, 30,
6051-6064 and references cited therein.
(9) Shibata, K.; Miyazawa, K.; Goto, Y. Chem. Commun. 1997,
1309-1310.

1686 J . Org. Chem., Vol. 64, No. 5, 1999
Ta ble 1. Resu lts of Cr oss Cou p lin g Rea ction s Usin g Siloxa n es
Mowery and DeShong
yielda (%)
entry
R
X
siloxane (equiv)
TBAF (equiv)
solvent
hetero
homo
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
4-Me
4-Me
4-Me
4-Me
4-Med
4-Me
4-Me
4-Ac
4-OMe
Cl
4-Ac
4-Me
4-OMef
4-Ac
4-Me
4-Ac
I
I
I
I
I
I
I
I
PhSi(Me)3 (2.0)
PhSi(Me)3 (2.2)
2.0
0
0
DMF
DMF
DMF
DMF
DMF
THF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
0
0b
0c
40
0
0
trace
0
6
0
0
0
21
0
0
34
0
0
16
0
PhSi(OMe)3 (2.1)
PhSi(OMe)3 (2.0)
PhSi(OMe)3 (2.2)
PhSi(OMe)3 (2.0)
PhSi(OMe)3 (1.2)
PhSi(OMe)3 (2.0)
PhSi(OMe)3 (2.5)
PhSi(OMe)3 (2.2)
PhSi(OMe)3 (1.8)
PhSi(OMe)3 (2.0)
PhSi(OMe)3 (2.0)
PhSi(OMe)3 (2.0)
PhSi(OCH2CF3)3 (2.0)
PhSi(OCH2CF3)3 (2.3)
PhSi(OCH2CF3)3 (2.0)
PhSi(OCH2CF3)3 (1.9)
1.9
2.2
1.9
1.0
2.0
3.6
2.2
1.8
2.0
2.0
2.0
2.0
2.3
1.9
1.9
90
85
94
80e
58
54
78
78
0
0
0
97
78
77
56
I
I
Br
Br
Br
Cl
I
I
I
Br
4-OMe
4-Acg
0
a
Calculations are corrected for 2 equiv of starting material consumed to make the homocoupled product. Reaction times were not
optimized, and most reactions were complete within 1 h or less. Isolated starting material only. c 96% of starting material recovered.
b
18 mol % allyl Pd chloride dimer used. e 20% starting material recovered. f GC yield; 66% of starting material recovered. g 26% of starting
d
material recovered.
Sch em e 3
THF reactions. Finally, if siloxane 1 and TBAF were used
in equimolar concentration with the iodide (entry 7), the
yield of unsymmetrical biaryl decreased to 80%, with 20%
of the starting material recovered.
4-bromoacetophenone underwent coupling with the si-
loxane to give the unsymmetrical biaryl even more
efficiently than the iodo analog (entry 11). On the other
hand, neither 4-bromotoluene nor 4-bromoanisole gave
heterocoupled adducts in the reaction with siloxane 1
(entries 12 and 13, respectively). Last, 4-chloroacetophe-
none failed to react with siloxane 1 (entry 14) to give the
desired heterocoupled adduct, and none of the homo-
coupled adduct was isolated.
The electronic characteristics of the aromatic substitu-
ent on the ring do not have a significant impact on the
cross-coupling reactions with siloxane derivatives. As
noted in entries 8-10, siloxane 1 underwent Pd-catalyzed
coupling with aryl iodide derivatives bearing strongly
electron-withdrawing and electron-donating substituents
in yields of 58, 54, and 78%, respectively. The major
difference noted in this series of reactions was that a
significant quantity of the homocoupled product was
obtained with the chloro analog (entry 10). A rationaliza-
tion for this result is not apparent at this time but is
under investigation.12
Having demonstrated that phenyl trimethylsiloxane (1)
serves as the aryl donor for cross-coupling reactions, we
chose to determine whether the ether substituent of the
siloxane could be employed to modulate the reaction. On
the basis of the presumed intermediacy of hypervalent
species 6, an electron-withdrawing substituent was an-
ticipated to facilitate formation of the hypervalent inter-
mediate. Accordingly, coupling reactions of phenyl tris-
(2,2,2-trifluoroethyl)siloxane (PhSi(OCH2CF3)3, 2) were
investigated. Fluoride-induced coupling of siloxane 2 with
Aryl bromides and chlorides were less reactive than
iodides in the coupling, in analogy with trends generally
observed with Stille and Suzuki coupling.1-4 Surprisingly,

Reactions of Hypervalent Siloxane Derivatives
J . Org. Chem., Vol. 64, No. 5, 1999 1687
zoyl chloride (BzCl), (R)-(-)-carvone, cerium chloride heptahy-
drate (CeCl3‚7H2O), sodium borohydride (NaBH4), all aryl
iodides, all aryl bromides, and all aryl chlorides were pur-
chased from Aldrich and used as received. Bis(dibenzylidene-
acetone)palladium (Pd(dba)2) was purchased from Acros. Tet-
rabutylammonium fluoride (TBAF) was used as a 1.0 M
solution in THF and is commercially available from Acros and
Aldrich. Phenyl tris(trifluoroethoxy)silane (2) was prepared
according to the literature procedure.14 All compounds were
determined to be >95% pure by GC and 1H NMR unless
otherwise noted.
Sch em e 4
P r ep a r a tion of P h en yl Tr is(tr iflu or oeth oxy)sila n e (2).
The siloxane was prepared according to the procedure of
Swamy et al.:14 bp 112-116.5 °C/20 mmHg; IR (CCl4) 3078
(m), 3057 (m), 2957 (s), 2896 (m), 1594 (s), 1574 (s), 1533 (s),
1
1151 (s), 867 (s), 808 (s); H NMR (CDCl3) δ 4.52 (q, J ) 8.1,
1
6H), 7.40-7.65 (m, 5H). The H NMR matched spectral data
found in ref 14. 19F NMR and elemental analysis results are
also available in ref 14.
4-iodotoluene increased the yield of the heterocoupled
adduct to 97% (entry 15). Similar to the results noted
above, a variety of substituents on the aryl ring were
tolerated by the fluorosiloxane reagent, and good to
excellent yields of unsymmetrical biphenyls were ob-
tained as summarized in entries 16-18.
The in situ generation of silicate anion (i.e., 6) is not
limited to aryl transfer. Under these conditions, vinyl
trimethylsiloxane (3) gave 63% of the heterocoupled
adduct, 4-methylstyrene (8), on treatment with 4-iodo-
toluene (Scheme 3). Also, allyl trimethylsiloxane (4) and
4-iodotoluene coupled to afford allyl adduct 9 in good
yield.
This methodology has been extended to cross-coupling
reactions between siloxanes and allylic alcohol deriva-
tives as outlined in Scheme 4. Coupling of benzoate 10
gave a quantitative yield of 3-phenylcyclohexene (11)
when treated with PhSi(OMe)3 (1) and TBAF. Substitut-
ing fluorosiloxane 2 gave an equally high yield of adduct
11. Finally, when (R,R)-cis-carveol benzoate (12) was
coupled with PhSi(OMe)3 and TBAF, 81% of phenylated
adduct 13 was obtained (Scheme 4). As was observed with
preformed silicate derivatives,10 the cross-coupling reac-
tion occurred with complete inversion of configuration.
Gen er a l P r oced u r e for th e Cr oss-Cou p lin g Rea ction s
Utilizin g Ar yl Iod id es, Br om id es, a n d Ch lor id es. En tr y
1. To a solution of 0.104 g (0.477 mmol) of 4-iodotoluene and
0.159 g (1.058 mmol) of phenyl trimethylsilane in 10 mL of
DMF was added 25 mg (0.043 mmol) of Pd(dba)2. Then 1.10
mL (1.10 mmol) of TBAF was added to the reaction mixture
via syringe. The reaction mixture was degassed to remove
oxygen via one freeze-pump-thaw cycle. The brown reaction
was heated at 95 °C for 2 h. The resulting brown mixture was
quenched by the addition of 50 mL of water; the aqueous layer
was then extracted with 4 × 50 mL of Et2O, and the combined
organic layers were dried over MgSO4 and concentrated in
vacuo. Purification of the residue by flash chromatography (30
mm, 16 cm, pentane) gave 17 mg (40%) of 4,4′-dimethylbi-
phenyl. This matched an authentic sample (purchased from
Aldrich) by GC and TLC.
En tr y 4. 4-Meth ylbip h en yl (7): TLC Rf ) 0.47 (10% Et2O/
pentane); mp 44.5-46.5 °C (lit.15 mp 49 °C (EtOH)); IR (CCl4)
3081 (w), 3063 (w), 3038 (w), 2925 (w), 2863 (w), 1556 (s), 1531
1
(s); H NMR (CDCl3) δ 2.38 (s, 3H), 7.23 (m, 2H), 7.30 (t, J )
7.6, 1H), 7.41 (t, J ) 7.6, 2H), 7.48 (d, J ) 8.1, 2H), 7.58 (d, J
) 7.3, 2H); 13C NMR (CDCl3) δ 21.1, 127.0, 128.7, 129.5, 137.0,
138.4, 141.2; LRMS (EI) 169 ((M + 1), 19), 168 ((M+), 100),
167 (63), 90 (21); HRMS (EI) calcd for C13H12 168.0939 (M+),
found 168.0945. The IR and 1H NMR matched spectral data
found in ref 15.
En tr y 8. 4-Acetylbip h en yl: TLC Rf ) 0.29 (10% EtOAc/
hexane); mp 119-119.5 °C (lit.2c mp 119-120 °C (EtOH)); IR
(CCl4) 3081 (w), 3038 (w), 3000 (w), 2931 (m), 2850 (w), 1691
(m), 1569 (s), 1538 (s); 1H NMR (CDCl3) δ 2.63 (s, 3H), 7.38 (t,
J ) 7.3, 1H), 7.46 (t, J ) 7.4, 2H), 7.61 (d, J ) 7.2, 2H), 7.67
Con clu sion
These results summarized above conclusively demon-
strate that siloxane derivatives such as 1-4 are versatile
transmetalation reagents for Pd(0)-catalyzed cross-
coupling reactions using aryl halides and allylic alcohol
derivatives in moderate to excellent yield. In addition,
the reaction conditions are compatible with a variety of
functional groups. The scope and limitations of this
methodology for the synthesis of natural products will
be reported in due course.
(A of AB quartet, J AB ) 8.4, 2H), 8.02 (B of AB quartet, J AB
)
8.4, 2H); 13C NMR (CDCl3) δ 26.6, 127.2, 128.9, 135.9, 139.0,
145.8, 197.7; LRMS (EI) 197 ((M + 1), 10), 196 ((M+), 59), 181
(100), 153 (35); HRMS (EI) calcd for C14H12O 196.0888 (M+),
found 196.0883. The IR and 1H NMR matched spectral data
found in ref 2c.
En tr y 9. 4-Meth oxybip h en yl: TLC Rf ) 0.46 (10% EtOAc/
hexane); mp 83.5-85.5 °C (lit.16 mp 90 °C (EtOH)); IR (CCl4)
3081 (w), 3047 (w), 3006 (w), 2931 (w), 2856 (w), 2838 (w),
1563 (s), 1512 (s), 1250 (s), 1006 (m); 1H NMR (CDCl3) δ 3.83
(s, 3H), 6.95-6.97 (m, 2H), 7.40 (t, J ) 7.7, 2H), 7.50-7.54
(m, 5H); 13C NMR (CDCl3) δ 55.4, 114.2, 126.6, 126.7, 128.2,
128.7, 135.2; LRMS (EI) 185 ((M + 1), 15), 184 ((M+), 100),
169 (39); HRMS (EI) calculated for C13H12O 184.0888 (M+),
found 184.0885. The IR and 1H NMR matched spectral data
found in ref 17.
Exp er im en ta l Section
Gen er a l Meth od s. All 1H and 13C NMR spectra were
recorded on a 400 MHz instrument in CDCl3 unless otherwise
indicated. Coupling constants (J ) are given in Hz. Tetrahy-
drofuran (THF) was distilled from sodium/benzophenone ketyl.
Pyridine and methylene chloride (CH2Cl2) were distilled from
calcium hydride. Dimethyl formamide (DMF) was distilled
from molecular sieves. Methanol (MeOH) was dried and stored
over molecular sieves. Glassware used in the reactions was
dried overnight in an oven at 120 °C. All reactions were
performed under an atmosphere of nitrogen unless noted
otherwise.
En tr y 10. 4-Ch lor obip h en yl: TLC Rf ) 0.56 (pentane);
(14) Swamy, K. C. K.; Holmes, J . M.; Day, R. O.; Holmes, R. R. J .
Am. Chem. Soc. 1990, 112, 2341-2348.
(15) Rao, M. S. C.; Rao, G. S. K. Synthesis 1987, 231-233.
(16) Neeman, M.; Caserio, M. C.; Roberts, J . D.; J ohnson, W. S.
Tetrahedron 1959, 6, 36-47.
Allyl palladium chloride dimer, allyl trimethoxysilane (4),
phenyl trimethoxysilane (1), vinyl trimethoxysilane (3), ben-
(17) Lipshutz, B. H.; Siegmann, K.; Garcia, E.; Kayser, F. J . Am.
Chem. Soc. 1993, 115, 9276- 9282.

1688 J . Org. Chem., Vol. 64, No. 5, 1999
Mowery and DeShong
mp 75-77 °C (lit.18 mp 77-77.5 °C (MeOH/H2O)); IR (CCl4)
3112 (w), 3089 (w), 3032 (w), 1584 (s), 1526 (s), 1479 (s), 836
(s); 1H NMR (CDCl3) δ 7.33-7.56 (m, 9H); 13C NMR (CDCl3) δ
127.0, 127.6, 128.4, 128.9, 139.7, 140.0; LRMS (EI) 190 ((M +
2), 32), 189 ((M + 1), 13), 188 ((M+), 100), 152 (28); HRMS
(EI) calcd for C12H9Cl 188.0393 (M+), found 188.0386. The IR
and LRMS matched spectral data found in ref 18.
the addition of 200 mL of H2O; the aqueous layer was washed
with 4 × 250 mL of Et2O, and the combined organics were
washed with 3 × 200 mL of saturated NaCl and 1 × 200 mL
of H2O. The reaction was dried over MgSO4 and concentrated
in vacuo. The crude product was >95% pure by GC and
indicated a 32.9:1 ratio of cis/trans alcohols was present. The
1
yield was 6.16 g (87%) of a clear oil. The H NMR (200 MHz)
4-Meth ylstyr en e (8): TLC Rf ) 0.70 (pentane); IR (CCl4)
matched spectral data in ref 22, so further characterization
was not performed. IR and elemental analysis results are
located in ref 22.
3089 (m), 3048 (m), 3009 (s), 2962 (s), 2926 (s), 2855 (s), 1628
1
(m), 1570 (s), 1513 (s); H NMR (200 MHz, CDCl3) δ 2.32 (s,
3H), 2.59 (d, J ) 10.9, 1H), 2.56 (d, J ) 17.6, 1H), 6.67 (dd, J
) 17.5, 10.9, 1H), 7.12 (d, J ) 8.0, 2H), 7.29 (d, J ) 8.1, 2H);
13C NMR (CDCl3) δ 21.2, 112.8, 126.1, 129.2, 134.8, 136.7,
137.6; LRMS (EI) 119 ((M + 1), 11), 118 ((M+), 100), 117 (68),
91 (42); HRMS (EI) calcd for C9H10 118.0783 (M+), found
118.0777. The IR and 1H NMR matched spectral data found
in ref 19.
4-Allyltolu en e (9): TLC Rf ) 0.55 (pentane); IR (CCl4) 3126
(w), 3082 (m), 3049 (s), 3005 (s), 2980 (s), 2923 (s), 2853 (m),
1639 (s), 1576 (s), 1514 (s); 1H NMR (200 MHz, CDCl3) δ 2.31
(s, 3H), 3.34 (d, J ) 6.7, 2H), 5.01 (t, J ) 1.4, 1H), 5.06-5.10
(m, 1H), 5.88-6.02 (m, 1H), 7.04-7.20 (m, 4H); 13C NMR
(CDCl3) δ 21.0, 39.8, 115.5, 126.8, 128.4, 129.1, 135.5, 137.8;
LRMS (EI) 132 ((M+), 12), 131 (13), 117 (81), 91 (100); HRMS
(EI) calcd for C10H12 132.0939 (M+), found 132.0940. The 1H
NMR matched spectral data found in ref 20.
P r ep a r a tion of Allylic Alcoh ol Der iva tives. 3-Ben zoyl-
cycloh exen e (10). To a solution of 0.320 g (3.26 mmol) of
2-cyclohexen-1-ol and 0.76 mL (9.40 mmol) of pyridine in 20
mL of CH2Cl2 was added 1.04 mL (8.96 mmol) of benzoyl
chloride via syringe. The reaction mixture was yellow with a
white precipitate. The reaction was stirred at room tempera-
ture for 17 h. The reaction was quenched by the addition of
50 mL of H2O; the aqueous layer was washed with 4 × 50 mL
of Et2O, and the combined organic layers were dried over
MgSO4 and concentrated in vacuo. Purification of the residue
by flash chromatography (35 mm, 20 cm, 10% CH2Cl2/hexane)
gave 0.635 g (99%) of 3-benzoylcyclohexene as a pale yellow
oil: TLC Rf ) 0.35 (10% CH2Cl2/hexane); IR (CCl4) 3100 (w),
3081 (w), 3038 (w), 2931 (s), 1725 (s), 1550 (s); 1H NMR (CDCl3)
δ 1.66-2.12 (m, 6H), 5.49 (bs, 1H), 5.79-5.83 (m, 1H), 5.97-
6.01 (m, 1H), 7.41 (t, J ) 7.7, 2H), 7.52 (t, J ) 7.4, 1H), 8.02-
8.04 (m, 2H); 13C NMR (CDCl3) δ 19.0, 25.0, 28.4, 68.6, 125.8,
128.3, 129.6, 130.9, 132.7, 132.8, 166.2; LRMS (EI) 203 ((M +
1), 3), 202 ((M+), 20), 105 (100); HRMS (EI) calcd for C13H14O2
202.0994 (M+), found 202.1003. The IR, 1H NMR, and 13C NMR
matched spectral data found in ref 21.
To a solution of 1.859 g (12.21 mmol) of carveol and 3.98
mL (32.26 mmol) of pyridine in 145 mL of CH2Cl2 was added
4.60 mL (37.00 mmol) of benzoyl chloride via syringe. The
yellow reaction was stirred at room temperature for 24 h. The
reaction was quenched by the addition of 200 mL of H2O; the
aqueous layer was washed with 1 × 100 mL of each of the
following: 10% HCl, 10% NaHCO3, saturated NaCl, and H2O,
and the extracts were dried with MgSO4 and concentrated in
vacuo. Purification of a 1.004 g portion of the crude material
by flash chromatography (50 mm, 17 cm, 10% EtOAc/hexane)
gave 0.441 g (44%) of pure (+)-(R,R)-cis-carveolbenzoate: TLC
Rf ) 0.43; [R]27 ) +17.0 (c ) 3.70, EtOH) (lit.23b [R]22 ) 13.3
D
D
1
(c ) 1.25, EtOH)). The IR and H NMR spectra were identical
to spectral data located in ref 23, so further characterization
was not performed.
Cr oss-Cou p lin g Rea ction s Utilizin g Allylic Alcoh ol
Der iva tives. 3-P h en ylcycloh exen e (11): TLC Rf ) 0.67
(10% CH2Cl2/hexane); IR (CCl4) 3088 (m), 3063 (m), 3025 (s),
1
2938 (s), 2863 (s), 2838 (s), 1656 (w), 1606 (m), 1543 (m); H
NMR (CDCl3) δ 0.85-2.09 (m, 6H), 3.38 (bs, 1H), 5.70 (dd, J
) 10.0, 2.1, 1H), 5.86-5.88 (m, 1H), 7.16-7.30 (m, 5H); 13C
NMR (CDCl3) δ 21.2, 22.7, 32.6, 41.8, 125.9, 127.7, 128.2, 128.3,
130.2, 146.6; LRMS (EI) 159 ((M + 1), 15), 158 ((M+), 100),
143 (43), 129 (79); HRMS (EI) calcd for C12H14 158.1096 (M+),
found 158.1098. The IR, 1H NMR, 13C NMR, and MS matched
spectral data found in ref 24.
(R,S)-tr a n s-2-Met h yl-3-p h en yl-5-isop r op en yl-1-cyclo-
h exen e (13): TLC Rf ) 0.43 (10% CH2Cl2/hexane). The 1H
NMR spectrum (200 MHz) matched spectral data from com-
pounds made previously in the DeShong laborabory and the
data are published as part of the Supporting Information in
ref 10 so further characterization was not necessary.
Ack n ow led gm en t. We thank Dr. Yui-Fai Lam and
Ms. Caroline Ladd for their assistance in obtaining
NMR and mass spectral data. P.D. and M.M. thank the
University of Maryland for financial support. In addi-
tion, M.M. thanks the Organic Division of the American
Chemical Society for a Graduate Fellowship (sponsored
by Pfizer, Inc.).
(+)-(R,R)-cis-Ca r veolben zoa te (12). To a solution of (R)-
(-)-carvone and 19.269 g (51.72 mmol) of CeCl3‚7H2O in 97
mL of anhydrous MeOH was added 2.026 g (53.56 mmol) of
NaBH4 via a solid addition funnel. The NaBH4 was slowly
added over a period of 10 min. The reaction was stirred at
room temperature for 1.5 h. The reaction was quenched by
J O982463H
(18) Chikasawa, K.; Uyeta, M. Chem. Pharm. Bull. 1980, 28, 57-
61.
(22) Nonoshita, K.; Marvoka, K.; Yamamoto, H. Bull. Chem. Soc.
J pn. 1988, 61, 2241-2243.
(19) Hollywood, F.; Suschitzsky, H. Synthesis 1982, 662-665.
(20) Fueno, T.; Kajimoto, O.; Izawa, K.; Masago, M. Bull. Chem. Soc.
J pn. 1973, 46, 1418-1421.
(21) Akermark, B.; Larsson, E. M.; Oslob, J . D. J . Org. Chem. 1994,
59, 5729-5733.
(23) (a) Ravindranath, B.; Srinivas, P. Ind. J . Chem. 1984, 23B,
666-667. (b) Utagawa, A.; Hirota, H.; Ohno, S.; Takahashi, T. Bull.
Chem. Soc. J pn. 1988, 61, 1207-212.
(24) Arnold, D. R.; Mines, S. A. Can. J . Chem. 1989, 67, 689-698.