Highly Regioselective Palladium-Catalyzed Internal Arylation of Allyltrimethylsilane with Aryl Triflates

Article abstract of DOI:10.1021/jo980249n

Highly regioselective ligand-controlled Heck-arylation reactions of allyltrimethylsilane, delivering branched β-products, were performed in moderate to good yields. The high preference for internal over terminal double-bond arylation suggests a contributi

Full text of DOI:10.1021/jo980249n

5076
J . Org. Chem. 1998, 63, 5076-5079
High ly Regioselective P a lla d iu m -Ca ta lyzed In ter n a l Ar yla tion of
Allyltr im eth ylsila n e w ith Ar yl Tr ifla tes
Kristofer Olofsson, Mats Larhed, and Anders Hallberg*
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Centre, Uppsala University,
Box 574, SE-751 23 Uppsala, Sweden
Received February 11, 1998
Highly regioselective ligand-controlled Heck-arylation reactions of allyltrimethylsilane, delivering
branched â-products, were performed in moderate to good yields. The high preference for internal
over terminal double-bond arylation suggests a contribution from the â-cation-stabilizing effect of
silicon. Microwave-promoted palladium-catalyzed coupling reactions proceeded with the same
regioselectivity in six entries out of eight with the reaction times cut sharply down to 5-10 min.
Ch a r t 1
In tr od u ction
Allylsilanes are important intermediates in organic
synthesis, and their utility is mainly attributed to the
high regioselectivity obtained in reactions with electro-
philes.1,2 Efficient synthetic methods for their prepara-
tion and functionalization are therefore desirable, and
we previously extended the Heck reaction3 to include
allylsilanes.4 Arylation of allyltrimethylsilane with iodo-
benzene under traditional Heck reaction conditions af-
forded 1 (Chart 1). We introduced silver additives as
potential halide abstractors since we at that time hoped
that the hyperconjugative stabilization of a cationic
center â to the silicon might promote formation of 3. The
silver additive suppressed desilylation and enhanced the
reaction rate considerably but was not preparatively
useful since adding silver salts promoted internal aryla-
tion only to a minor extent. Instead, the double-bond
isomer 2 was isolated as the major product.4 We have
now devised a convenient and highly regioselective
method for the preparation of a series of internally
arylated allylsilanes 3,5 which we suggest relies on the
â-cation-stabilizing properties of silicon6 in combination
with the bidentate ligand DPPF.7
Resu lts
Eight aryltriflates 4a -h were allowed to react with
allyltrimethylsilane in fresh acetonitrile under Heck
coupling conditions with palladium acetate and DPPF7
as the catalytic system and triethylamine or potassium
carbonate as base. An internal arylation of allyltrimeth-
ylsilane was achieved predominantly, generating inter-
nally arylated compounds 3a -h (eq 1). The correspond-
ing terminally arylated compounds 1 were detected in
small amounts in most, but not all, of the reactions. The
preparative results are summarized in Table 1.
The reaction proceeded with moderate to good yields
with one exception (Table 1, entry 7). The use of the
flexible bidentate ligand DPPF resulted in better selec-
tivities than with DPPP.7 In the entries where moderate
yields were isolated, the loss was mainly associated with
desilylation and reduction. Desilylation,8,9 producing the
(1) (a) Chan, T. H.; Flemming, I. Synthesis 1979, 761. (b) Weber,
W. P. Silicon Reagents for Organic Synthesis; Springer-Verlag: New
York 1983; p 173. (c) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845.
Allylsilanes similar to 2-aryl-3-(trimethylsilyl)-1-propenes have been
used for the synthesis of carbacephames and HIV-1 protease inhibitors;
see: (d) Oumoch, S.; Rousseau, G. Bioorg. Med. Chem. Lett. 1994, 4,
2841. (e) D’Aniello, F.; Taddei, M. J . Org. Chem. 1992, 57, 5247. Other
recent applications of allylsilanes include: (f) Tietze, L. F.; Schimpf,
R. Angew. Chem., Int. Ed. Engl. 1994, 33, 1089. (g) Singleton, D. A.;
Waller, S. C.; Zhang, Z.; Frantz, D. E.; Leung, S. W. J . Am. Chem.
Soc. 1996, 118, 9986. (h) Akiyama, T. Synlett. 1996, 1095. (i) Mayr,
H.; Ofial, A. R. J . Org. Chem. 1996, 61, 5823. (j) Le Roux, C.; Dubac,
J . Organometallics 1996, 15, 4646. (k) Yoshikawa, E.; Gevorgyan, V.;
Asao, N.; Yamamoto, Y. J . Am. Chem. Soc. 1997, 119, 6781.
(2) For regio- and stereochemical aspects of the palladium-catalyzed
reactions of silanes, see: Horn, K. A. Chem. Rev. 1995, 95, 1317.
(3) (a) Heck, R. F. Org. React. 1982, 27, 345. (b) Heck, R. F. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 4, p 833. (c) de Meijere, A.; Meyer,
F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379. (d) Cabri, W.;
Candiani, I. Acc. Chem. Res. 1995, 28, 2. (e) Tsuji, J . Palladium
Reagents and Catalysts; J ohn Wiley & Sons: Chichester 1995; p 125.
(f) J effery, T. In Advances in Metal-Organic Chemistry; Liebeskind,
L. S., Ed.; J AI Press, Inc: Greenwich, 1996; Vol. 5, p 153.
(5) For the preparation of 3d by arylation of 1,3-bis(trimethylsilyl)-
1-propene, see ref 4. For a selection of other methods for the prepara-
tion of 3, see the following. Via organocerium: (a) Narayan, B. A.;
Bunnelle, W. H. Tetrahedron Lett. 1987, 28, 6261. Via dithioacetals:
(b) Ni, Z. J .; Luh, T. Y. J . Chem. Soc., Chem. Commun. 1988, 15, 1011.
(c) Wong, K. T.; Ni, Z. J .; Luh, T. Y. J . Chem. Soc., Perkin Trans. 1
1991, 3113. Via organomagnesium and -derivates: (d) Hayashi, T.;
Katsuro, Y.; Kumada, M. Tetrahedron Lett. 1980, 21, 3915. (e) Fleming,
I.; Pearce, A. J . Chem. Soc., Perkin Trans. 1 1981, 81, 251. (f) Hayashi,
T.; Fujiwa, T.; Okamoto, Y.; Katsuro, Y.; Kumada, M. Synthesis 1981,
12, 1001. (g) Barluenga, J .; Ferna´ndez-Simo´n, J . L.; Concellon, J . M.;
Yus, M. Tetrahedron Lett. 1989, 30, 5927. (h) Kang, K. T.; Kim, S. S.;
Lee, J . C. Tetrahedron Lett. 1991, 32, 4341. Via vinylboranes: (i)
Rivera, I.; Soderquist, J . A. Tetrahedron Lett. 1991, 32, 2311. For
another palladium catalyzed method of introducing residues internally,
see: (j) Hojo, M.; Murakami, C.; Aihara, H.; Komori, E. i.; Kohra, S.;
Tominaga, Y.; Hosomi, A. Bull. Soc. Chim. Fr. 1995, 132, 499.
(4) Karabelas, K.; Westerlund, C.; Hallberg, A. J . Org. Chem. 1985,
50, 3896.
S0022-3263(98)00249-7 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/03/1998

Pd-Catalyzed Arylation of Allyltrimethylsilane
J . Org. Chem., Vol. 63, No. 15, 1998 5077
Ta ble 1. In ter n a l Ar yla tion of Allyltr im eth ylsila n e*
1, entries 6-8). The substitution of triethylamine in
favor of an inorganic base11 resulted in a suppression of
reduction and a higher yield. The moderate yields
encountered in reactions with 4-methoxy and 4-tert-butyl
phenyl triflates (Table 1, entries 1 and 2) are partly due
to the exchange of metal and phosphine bound aryl
groups in the oxidative-addition complex,12 as suggested
by the formation of 3d as a side product.
We observed that the reactions performed at 80 °C
tended to result in improved regioselectivities as com-
pared to the corresponding reactions at 60 °C, a phe-
nomenon that prompted us to conduct the same coupling
reaction with microwave flash heating.13,14 The micro-
wave-promoted coupling reactions were completed in
minutes instead of hours and proceeded smoothly, but
an inferior regioselectivity was encountered with 4a and
4b as substrates, as compared with the standard thermal
coupling reaction (Table 2). Notably, the reaction with
the acetyl compound 4g that delivered a relatively low
regioselectivity with standard heating gave 3g exclusively
under microwave irradiation (Table 2, entry 7).
Discu ssion
Cabri et al. introduced the use of bidentate ligands for
electronically controlled internal arylations of some
selected electron-rich, acyclic olefins.15 This powerful
means of regiocontrol was rationalized by assuming an
involvement of a cationic organopalladium π-complex
governing the regiochemical outcome.15 We believe that
the high regioselectivity encountered with allyltrimeth-
ylsilane as substrate is influenced by a hyperconjugative
stabilization of an electron-deficient center that develops
â to the silicon atom during the course of the reaction16
(Scheme 1).
* Reactions were run on a 2.5 mmol scale in sealed Pyrex tubes
under nitrogen atmosphere with 1 equiv of 4a -h , 5 equiv of
allyltrimethylsilane, 0.03 equiv of Pd(OAc)2, 0.066 equiv of DPPF,
and 2 equiv of base (Et3N in entries 1-5, K2CO3 in entries 6-8)
in 10 mL of fresh acetonitrile. Entries 1, 2, and 4-6 were
conducted at 60 °C and entries 3, 7, and 8 at 80 °C. All reactions
(10) (a) Cabri, W.; DeBernardinis, S.; Francalanci, F.; Penco, S.;
Santi, R. J . Org. Chem. 1990, 55, 350. (b) J utand, A.; Mosleh, A. J .
Org. Chem. 1997, 62, 261.
(11) Cabri, W.; Candiani, I.; DeBernardinis, S.; Francalanci, F.;
Penco, S.; Santi, R. J . Org. Chem. 1991, 56, 5796.
a
b
were completed in 20 h. Determined by GC/MS. Only product
3 was detected by GC/MS.
(12) (a) Andersson, C.-M.; Hallberg, A. J . Org. Chem. 1987, 52, 3529.
(b) Kelkar, A. A.; Hanaoka, T.; Kubota, Y.; Sugi, Y. J . Mol. Catal. 1994,
88, L113. (c) Herrmann, W. A.; Brossmer, C.; O¨ fele, K.; Beller, M.;
Fischer, H. J . Organomet. Chem. 1995, 491, C1-C4. (d) Morita, D.
K.; Stille, J . K.; Norton, J . K. J . Am. Chem. Soc. 1995, 117, 8576 and
references therein. (e) Herrman, W. A.; Brossmer, C.; Reisinger, C.
P.; Riermeier, T. H.; O¨ fele, K.; Beller, M. Chem. Eur. J . 1997, 1357. (f)
Goodson, F. E.; Wallow, T. I.; Novak, B. M. J . Am. Chem. Soc. 1997,
119, 12441. For an alternative mechanism see: (g) Sakamoto, M.;
Shimizu, I.; Yamamoto, A. Chem. Lett. 1995, 1101.
(13) The microwave technique lends its efficiency mainly from the
fact that a polar, homogeneous reaction mixture will be heated faster
under microwave irradiation than under thermal heating. Apart from
this, the boiling point elevation due to pressure in a closed Pyrex tube
allows higher temperatures than are ordinarily feasable. (a) Ha´jek,
M. Collect. Czech. Chem. Commun. 1997, 62, 347. Acetonitrile is known
to be of sufficient polarity for efficient heating in microwave fields;
see: (b) Stone-Elander, S.; Elander, N. Appl. Radiat. Isot. 1991, 42,
885. For a theoretical discussion of microwave irradiation, see: (c)
Neas, E. D.; Collins, M. J . Introduction to Microwave Sample Prepara-
tion; Kingston, H. M., J assie, L. B., Eds.; American Chemical Society:
Washington, DC, 1988; p 7. For general references on microwave-
assisted organic synthesis, see: (d) Mingos, D. M. P.; Baghurst D. R.
Chem. Soc. Rev. 1991, 20, 1. (e) Caddick, S. Tetrahedron 1995, 51,
10403. (f) Strauss, C. R.; Trainor, R. W. Aust. J . Chem. 1995, 48, 1665.
(g) Galema, S. A. Chem. Soc. Rev. 1997, 26, 233. (h) Langa, F.; de la
Cruz, P.; de la Hoc, A.; D´ıaz Ortiz, A.; D´ıez Barra, E. Contemp. Org.
Synth. 1997, 373.
corresponding R-methylstyrenes, appeared in particular
at higher reaction temperatures and the reduction of the
aryl triflates, forming the analogous arenes, appeared
mainly with the electron-deficient reactants10 4f-h (Table
(6) (a) Wierschke, S. G.; Chandrasekhar, J .; J orgensen, W. L. J . Am.
Chem. Soc. 1985, 107, 1496. (b) Mayr, H.; Pock, R. Tetrahedron 1986,
42, 4211. (c) Lambert, J . B.; Wang, G. t.; Teramura, D. H. J . Org. Chem.
1988, 53, 5422. (d) Ibrahim, M. R.; J orgensen, W. L. J . Am. Chem.
Soc. 1989, 111, 819. (e) Lambert, J . B. Tetrahedron 1990, 46, 2677. (f)
Gabelica, V.; Kresge, A. J . J . Am. Chem. Soc. 1996, 118, 3838 and
references therein. (g) Chiavarino, B.; Crestoni, M. E.; Fornarini, S.
J . Am. Chem. Soc. 1998, 120, 1523. Some recent examples where the
â-effect has been utilized in organic synthesis: (h) Thorimbert, S.;
Malacria, M. Tetrahedron Lett. 1996, 37, 8483. (i) Alvisi, D.; Blart, E.;
Bonini, B. F.; Mazzanti, G.; Ricci, A.; Zani, P. J . Org. Chem. 1996, 61,
7139. (j) Miura, K.; Hondo, T.; Saito, H.; Ito, H.; Hosomi, A. J . Org.
Chem. 1997, 62, 8292.
(7) DPPF ) 1, 1′-bis(diphenylphosphino)ferrocene, DPPP ) 1,3-
bis(diphenylphosphino)propane. For a discussion of the properties of
DPPF, see: Gan, K. S.; Hor, T. S. A. In Ferrocenes; Togni, A., Hayashi,
T., Eds.; VCH: Weinheim, 1995; p 3.
(8) Initial screening experiments revealed that acetonitrile leads to
a smaller extent of desilylation and better regioselectivities than other
solvents (DMF, NMP, dioxane, and DMSO) for this particular reaction.
For
a
recent discussion of the palladium-mediated mechanism of
(14) We have previously reported on the application of microwave
irradiation in palladium-catalyzed synthesis. (a) Larhed, M.; Lindeberg,
G.; Hallberg, A.; Tetrahedron Lett. 1996, 37, 8219. (b) Larhed, M.;
Hallberg, A. J . Org. Chem. 1996, 61, 9582. (c) Larhed, M.; Hoshino,
M.; Hadida, S.; Curran, D. P.; Hallberg, A. J . Org. Chem. 1997, 62,
5583.
desilylation, see: LaPointe, A. M.; Rix, F. C.; Brookhart, M. J . Am.
Chem. Soc. 1997, 119, 906. See also ref 6h.
(9) As regards the desilylation process, a higher degree of desilyla-
tion takes place as the temperature rises but the desilylation is brought
about in the product-forming stage of the reaction and does not change
markedly thereafter, suggesting that the desilylation is palladium-
mediated. See also refs 4 and 6h.
(15) Cabri, W.; Candiani, I.; Bedeschi, A.; Santi, R. J . Org. Chem.
1992, 57, 3558.

5078 J . Org. Chem., Vol. 63, No. 15, 1998
Olofsson et al.
Ta ble 2. Micr ow a ve-P r om oted In ter n a l Ar yla tion a
1/1/1 ratio of reactants, revealing that allyltrimethylsi-
lane was more reactive than 4-methyl-1-pentene.
The higher reactivity of allyltrimethylsilane compared
to 4-methyl-1-pentene might be consistent with a reduced
energy barrier mediated by the â-effect of silicon in a
rate-determining insertion step.18 The preference for
internal products to form even with the sterically hin-
dered triflates 4c and 4e is compatible with the hypoth-
esis that in the reactions proceeding via a cationic
π-complex electronic factors predominate over steric.15
Tin is expected to exhibit a substantially more pro-
nounced â-stabilizing effect than silicon.6c Therefore, an
even higher selectivity was expected with phenyl triflate
(4d ) and allyltrimethylstannane. A series of experiments
with these reactants was performed, but we were unfor-
tunately unable to trace any arylated allyltrimethylstan-
nane from the reaction mixture. However, the predomi-
nant formation of R-methyl styrene in favor of the
unbranched allyl compound suggests that internal aryla-
tion is predominant.19
reaction
time (min)/
microwave selectivityc yield (%)d
entry triflate product power (W)b
3/1
3 + 1
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
3a
3b
3c
3d
3e
3f
5/50
5/50
5/50
5/50
5/50
7/50
7/60
10/50
78/22e
88/12f
93/7e
92/8
34
69
66
62
66
54
48
28
97/3
97/3
4g
4h
3g
3h
100/0g
100/0g
a
Reactions were run on a 1.0 mmol scale in sealed Pyrex tubes
with septa under nitrogen atmosphere and heated by means of
microwave irradiation. Reactions were performed in 1.5 mL of
fresh acetonitrile with 1 equiv of 4a -h , 2.5 equiv of allyltrimeth-
ylsilane, 0.03 equiv of Pd(OAc)2, 0.066 equiv of DPPF, and 2 equiv
of Et3N in entries 1-5 and 1.5 equiv of K2CO3 in entries 6-8.
Continuous irradiation (2450 MHz). c Determined by GC/MS.
b
GC/MS yield. e Three isomeric products detected by GC/MS.
d
f Four isomeric products detected by GC/MS. g Only product 3 was
detected by GC/MS.
Con clu sion
Sch em e 1
The palladium-catalyzed, DPPF-controlled, internal
arylation of allyltrimethylsilane constitutes an effective
method for the preparation of 2-aryl-3-(trimethylsilyl)-
1-propenes 3. The method compares advantageously
with other methods reported previously.5 We suggest
that the superior regiocontrol as well as the faster rate
of insertion of allyltrimethylsilane compared to 4-methyl-
1-pentene is attributed to the â-effect of silicon. With
microwave irradiation, the reaction times were reduced
from up to 20 h to 5-10 min without seriously affecting
the regiochemical control. Furthermore, we have now
demonstrated that selective synthesis of three isomers
(1-3) can be accomplished simply by modifying the
original Heck reaction procedure.
Exp er im en ta l Section
P r oced u r es. 1H and 13C NMR spectra were recorded in
CDCl3 at 270 and 67.8 MHz, respectively. Chemical shifts
were reported as δ values (ppm) indirectly referenced to TMS
by the solvent signal (CHCl3) δ 7.26 and (CDCl3) δ 77.0. Low-
resolution mass spectra were recorded on a GC/MS instrument
equipped with a HP-1 capillary column (25 m × 0.22 mm)
operating at an ionization potential of 70 eV. The oven
temperature was 70-305 °C (gradient 20 °C/min). Isomers 1
and 3 were assumed to have identical GC/MS response factors.
Elemental analyses were performed by Mikro Kemi AB,
Uppsala, Sweden.
Sch em e 2. Regioselectivity in th e
DP P F -Con tr olled Heck Rea ction w ith P h en yl
Tr ifla te (4d )
Microwave heating was carried out with a MicroWell 10
single-mode microwave cavity20 from Labwell AB, Sweden,
producing continuous irradiation at 2450 MHz. The microwave-
assisted reactions were performed under nitrogen in oven-
dried, heavy-walled Pyrex tubes21 (8 mL, l ) 150 mm) sealed
with a silicon septum. If overpressurization occurs this septum
will burst.
To assess the role of the â-effect, we conducted experi-
ments where phenyl triflate (4d ) was used as an arylat-
ing agent with 4-methyl-1-pentene, a compound chosen
for its steric similarity to allyltrimethylsilane. An internal/
terminal regioselectivity of 86/14 was observed,17 which
is inferior as compared to the selectivity obtained with
allyltrimethylsilane (Scheme 2).
Furthermore, a competitive experiment was conducted
with allyltrimethylsilane (1 equiv), 4-methyl-1-pentene
(1 equiv), and phenyl triflate (4d ) (1 equiv). By 1H NMR,
we could detect 5.5 times more of arylated allyltrimeth-
ylsilane than arylated 4-methyl-1-pentene, despite the
(18) Cabri, W.; Candiani, I.; Bedeschi, A.; Penco, S.; Santi, R. J . Org.
Chem. 1992, 57, 1481.
(19) The fact that minute amounts of the unbranched 3-aryl-1-
propene, possibly derived from a concomitant Stille reaction, was
observed by NMR made an accurate determination of the regiocontrol
difficult. The heavier elements in the group (Sn and Pb) have been
reported to be more easily displaced than the lighter elements (Si and
Ge). For a discussion of this phenomenon, see ref 6c. Internally arylated
allylstannane compounds are unstable; see: Desponds, O.; Schlosser,
M. J . Organomet. Chem. 1991, 93.
(20) Stone-Elander, S. A.; Elander, N.; Thorell, J . O.; Solås, C.;
Svennebrink, J . J . Label. Cmpds. Radiopharm. 1994, 34, 949.
(21) Pyrex tubes are recommended for microwave-assisted organic
synthesis. Baghurst, D. R.; Mingos, D. M. P. J . Chem. Soc., Dalton
Trans. 1 1992, 1151.
(16) A similar â-stabilized cation complex has been suggested by
Hosomi et al.; see ref 5j.
(17) According to GC/MS analyses, four compounds were formed.
Hydrogenation, delivering two compounds, allowed determination of
the regioselectivity ratio. See Phenylation of 4-Methyl-1-pentene in the
Experimental Section.

Pd-Catalyzed Arylation of Allyltrimethylsilane
J . Org. Chem., Vol. 63, No. 15, 1998 5079
Ma ter ia ls. Silica gel 60 (0.040-0.063 mm, E. Merck no
9385) and alumina gel 90 (0.063-0.200 mm, E. Merck no
101097, deactivated with 60 mL of water to 1000 g of
aluminum gel) were used for chromatography. DPPF was
purchased from Fluka and Pd(OAc)2 from E. Merck. Allyltri-
methylsilane and 4-methyl-1-pentene were obtained from
Fluka and Aldrich, respectively. Acetonitrile (p.a.) was of
commercial quality and taken from recently opened bottles.22
All other reagents were purchased from commercial suppliers
and used without further purification. The aryl triflates were
prepared from the corresponding phenols by a standard
procedure using 2,4,6-collidine as base.23 Products 1d ,24 3a ,5c
3d ,5c 3e,5c and 525 were previously characterized.
spectral data,25 and the minor unsaturated products were
taken as cis and trans isomers of the 1-phenyl-4-methyl-1-
pentene and 1-phenyl-4-methyl-2-pentene isomers.
Com p etitive P h en yla tion of Allyltr im eth ylsila n e a n d
4-Meth yl-1-p en ten e. The competitive experiment was per-
formed with 1.00 mmol (0.226 g) of 4d , 1.00 mmol (0.114 g) of
allyltrimethylsilane, 1.00 mmol (0.0840 g) of 4-methyl-1-
pentene, 0.030 mmol (0.00670 g) of Pd(OAc)2, 0.132 mmol
(0.0732 g) of DPPF, and 2.0 mmol (0.20 g) of Et3N in 4 mL of
acetonitrile. The reaction was performed at 60 °C. Workup
was performed as described in the general procedure. The
ratio of arylated allyltrimethylsilane in reference to arylated
1
4-methyl-1-pentene (5.5/1) was determined by H NMR.
Gen er a l P r oced u r e for Th er m a l Ar yla tion Rea ction s
of Allyltr im eth ylsila n e (Ta ble 1, Eq 1). A mixture of 2.50
mmol of aryl triflate 4a -h , 0.0750 mmol (0.0168 g) of
Pd(OAc)2, 0.330 mmol (0.183 g) of DPPF, 12.5 mmol (1.43 g)
of allyltrimethylsilane, 5.0 mmol (0.51 g) of triethylamine with
triflates 4a -e, and 3.75 mmol (0.518 g) of potassium carbonate
with triflates 4f-h and 10 mL of acetonitrile22 was heated
under nitrogen in oven-dried, heavy-walled, and thin-necked
Deviations from the aforementioned reaction conditions will
be given, when such deviations occur, in each description.
2-(2,4-Dich lor oph en yl)-3-(tr im eth ylsilyl)-1-pr open e (3f).
Compound 3f + 1f (ratio 98/2) was obtained in 85% yield at
60 °C. The eluent was isohexane, and the products were
further purified by bulb-to-bulb distillation (∼110 °C at 10
mmHg): 1H NMR (270 MHz, CDCl3) δ 7.36 (d, J ) 2.0 Hz, 1
H), 7.17 (d, J ) 2.0 Hz, 1H), 7.15 (s, 1 H), 5.07 (m, 1 H), 4.88
(d, J ) 1.7 Hz, 1 H), 2.01 (d, J ) 1.0 Hz, 2 H), -0.09 (s, 9 H);
Pyrex tubes, sealed with
a Teflon stopcock on oil bath,
4a ,b,d -f at 60 °C and 4c,g,h at 80 °C. Samples were
periodically taken and partitioned between diethyl ether and
water. The ethereal layers were dried over potassium carbon-
ate before analysis by GC/MS. All reactions were completed
after 20 h (>99% conversion of the aryl triflate). The reaction
mixture was allowed to cool, diluted with water and extracted
with diethyl ether. The combined organic layers were there-
after washed with brine and concentrated under reduced
pressure. Products were subjected to purification by rapid
silica column chromatography followed by bulb-to-bulb distil-
lation under reduced pressure to give clear, sometimes slightly
yellowish oils with a >95% purity of internally and terminally
arylated products based on GC/MS analyses. The relatively
low isolated yields connected with 3a ,b,h are partly due to
the difficulty in getting pure fractions in the bulb-to-bulb
distillation. The γ-products 1 were never produced in such
yields that would make an isolation feasible. The true identity
of 1d was confirmed by comparison of spectroscopic data24 and
a GC/MS co-injection of a sample prepared by the Karabelas-
Hallberg methodology.4
P h en yla tion of 4-Meth yl-1-p en ten e (Sch em e 2). The
coupling of 4d with 4-methyl-1-pentene was performed with
2.50 mmol (0.565 g) of 4d , 12.5 mmol (1.05 g) of 4-methyl-1-
pentene, 0.0750 mmol (0.0168 g) of Pd(OAc)2, 0.330 mmol
(0.183 g) of DPPF, and 5.0 mmol (0.51 g) of triethylamine
dissolved in 10 mL of acetonitrile for 48 h at 60 °C. The
workup was performed as described in the general procedure
and purified on silica with isohexane as eluent. The isolated
yield of phenylated products was 56%. A GC/MS analysis of
the mixture of phenylated products revealed four compounds,
which were reduced to two after hydrogenation over palladium
in ethanol at atmospheric pressure.26 The reported regiose-
lectivity refers to the two isomers obtained after hydrogena-
tion. The identity of the major unsaturated product proved
to be 2-phenyl-4-methyl-1-pentene (5) by comparison with
13
C NMR (67.8 MHz, CDCl3) δ 145.1, 141.7, 133.0, 132.6,
131.0, 129.2, 126.7, 114.5, 27.8, -1.9; MS m/z (relative
intensity 70 eV) 258 (M+, 9), 243 (7), 73 (100). Anal. Calcd
for C12H16Cl2Si: C, 55.6; H, 6.2. Found: C, 55.7; H, 6.3.
Gen er a l P r oced u r e for Micr ow a ve-P r om oted Ar yla -
tion Rea ction s (Ta ble 2). A mixture of 1.00 mmol of aryl
triflate 4a -h , 0.030 mmol (0.00670 g) of Pd(OAc)2, 0.132 mmol
(0.0732 g) of DPPF, 2.50 mmol (0.286 g) of allyltrimethylsilane,
0.150 g of internal standard (2,3-dimethylnaphthalene), 2.0
mmol (0.20 g) of triethylamine in entries 1-5 and 1.5 mmol
potassium carbonate (0.17 g) in entries 6-8, and 1.5 mL of
fresh acetonitrile was irradiated by microwaves in a Pyrex tube
under nitrogen. For details, see Table 2. The reaction volume
filled not more than one-fifth of the total volume of the tube,
thereby allowing headspace for pressure to build up during
the microwave treatment. All couplings with microwave
irradiation were performed without stirring. The reaction
mixtures were allowed to cool before the tubes were carefully
opened in a fume cupboard. Small samples were removed,
partitioned between diethyl ether and water, and dried by
potassium carbonate before the organic phase was analyzed
by GC/MS. The yield was determined by a GC/MS mean value
of three injections after calibration curves made from pure
3a -h and 2,3-dimethylnaphthalene as internal standard. In
entries 1-3, where three or four arylated isomers were
detected by GC/MS, the regioselectivities were calculated by
dividing the area of the integrated peak of the major isomer
(3) with those of the resulting peaks.
Ack n ow led gm en t. We thank the Swedish Natural
Science Research Council for financial support.
Su p p or tin g In for m a tion Ava ila ble: 1H, 13C NMR spec-
tra and MS data are available for all new compounds (2 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
(22) Acetonitrile from recently opened bottles resulted in better
regioselectivities than acetonitrile from old bottles.
(23) Saa´, J . M.; Dopico, M.; Martorell, G.; Garc´ıa-Raso, A. J . Org.
Chem. 1990, 55, 991. For an excellent review on organic triflates, see:
Ritter, K. Synthesis 1993, 735.
(24) Hsiao, C. N.; Shechter, H. Tetrahedron Lett. 1982, 23, 1963.
(25) (a) Barluenga, J .; Yus, M.; Concellon, J . M.; Bernad, P. J . Org.
Chem. 1983, 48, 3116. The following paper contains more detailed
spectroscopic data of a partly deuterated analogue: (b) Tseng, C. C.;
Paisley, S. D.; Goering, H. L. J . Org. Chem. 1986, 51, 2884.
J O980249N
(26) Augustine, R. L. Catalytic Hydrogenation; Marcel Dekker: New
York 1965; p 57.