Alkylation of Allylic Halides with Benzylic Grignard Reagents
J . Org. Chem., Vol. 67, No. 4, 2002 1169
the data for the natural polyprenoid 15,27 hence conclud-
ing that minor substituent changes in the aromatic
portion of the products do not influence the gross chemi-
cal shifts.
tial refractometer and a computer system (column: 7-C-18,
250 × 21 mm, 100% methanol). Elemental analysis was done
in Mu¨lheim an der Ruhr.
Gen er a l P r oced u r e for P a lla d iu m -Ca ta lyzed Alk yla -
tion w ith Gr ign a r d Rea gen ts. Palladium catalyst [(Ph3P)4-
Pd] (0.7 mmol, 5 mol %) was dissolved in THF (10 mL) at room
temperature under an argon atmosphere. The allylic halide
(0.014 mol) was then added via syringe. The initially yellow
mixture gradually became clear within 5 min. The reaction
mixture was cooled to 0 °C, and the Grignard reagent (0.018
mol) was then added via syringe. The reaction was stirred at
room temperature until judged to be complete according to
TLC. The reaction was quenched by addition of water (10 mL).
The organic phase was collected, and the water phase was
extracted with ether (2 × 10 mL). The combined organic layers
were dried (MgSO4) and evaporated in vacuo. The resulting
crude products were purified by column chromatography. In
most cases, a simple filtration through silica gel (washing with
pentane) was enough to obtain the product with >95% purity.
Spectral data for 4-methyl-1-phenyl-3-pentene (2),28 (3E)-
4,8-dimethyl-1-phenyl-3,7-nonadiene (3),29 and (3E)-4,8-di-
methyl-1-(4-methoxyphenyl)-3,7-nonadiene (6)30 were consis-
tent with data reported in the literature.
(3E)-4,8-Dim eth yl-1-(4-m eth ylph en yl)-3,7-n on adien e (4).
Isolated as a colorless oil. IR (KBr): 2966, 1515 cm-1 1H
.
NMR: δ 7.08 (s, 4H), 5.19 (t, J ) 5.9 Hz, 1H), 5.09 (t, J ) 5.3
Hz, 1H), 2.60 (dd, J ) 15.7, 7.5 Hz, 2H), 2.31 (s, 3H), 2.30-
2.26 (m, 2H), 2.07-2.04 (m, 2H), 1.99-1.97 (m, 2H), 1.69 (s,
3H), 1.60 (s, 3H), 1.57 (s, 3H). 13C NMR: δ 139.4, 135.6, 135.0,
131.3, 128.9, 128.3, 124.4, 123.8, 39.7, 35.7, 30.1, 26.7, 25.7,
20.9, 17.7, 15.9. HRMS (EI) m/z: calcd for C18H26, 243.2113;
found, 243.2112. Anal. Calcd for C18H26: C, 89.19; H, 10.81.
Found: C, 89.08; H, 10.90.
Con clu sion s
In this report, we describe a practical, scalable, and
atom economical regioselective allylation of substituted
and unsubstituted benzylic Grignard reagents employing
catalytic amounts of [(Ph3P)4Pd] in THF at room tem-
perature. The reaction can be performed in a multigram
scale (up to 20 g) to obtain the desired R-benzylated
substrates (polyenehomobenzenes) in excellent yields.
The usefulness of this methodology has been illustrated
by preparing podocarpa-type diterpenes as well as tet-
racyclic polyprenoid compounds via cationic cyclization,
allowing ready access to these important products in two
steps only from commercially available starting materi-
als.
(3E)-4,8-Dim et h yl-1-(4-isop r op ylp h en yl)-3,7-n on a d i-
en e (5). Isolated as a colorless oil. IR (KBr): 2925, 1514 cm-1
.
1H NMR: δ 7.19 (d, J ) 1.6 Hz, 4H), 5.27 (dt, J ) 7.1, 1.0 Hz,
1H), 5.17 (tt, J ) 6.7, 1.3 Hz, 1H), 2.94 (sep, J ) 6.9 Hz, 1H),
2.68 (m, 2H), 2.37 (ddd, J ) 7.9, 7.5, 7.3 Hz, 2H), 2.11 (m,
4H), 1.76 (s, 3H), 1.68 (s, 3H), 1.64 (s, 3H), 1.32 (s, 3H), 1.30
(s, 3H). 13C NMR: δ 146.1, 139.7, 135.5, 131.2, 128.3, 126.2,
124.4, 123.8, 39.7, 35.7, 33.7, 29.9, 26.7, 25.7, 24.1, 17.6, 15.9.
HRMS (EI) m/z: calcd for C20H30, 270.2347; found, 270.2346.
Anal. Calcd for C20H30: C, 88.82; H, 11.18. Found: C, 88.73;
H, 10.81.
Exp er im en ta l Section
(3E,7E)-4,8,12-Tr im et h yl-1-p h en yl-3,7,11-t r id eca t r i-
Gen er a l. All manipulations of compounds and solvents
were carried out using standard airless techniques. All glass-
ware was flame-dried and purged with argon prior to use.
Tetrahydrofuran was distilled under sodium/benzophenone
prior to use as a solvent. Melting points are uncorrected.
Infrared Spectra (IR) were measured as KBr pellets. Spectro-
scopic measurements were recorded for CDCl3 solutions with
en e (7). Isolated as a colorless oil. IR (KBr): 2966, 1496 cm-1
.
1H NMR: δ 7.28-7.24 (m, 2H), 7.18-7.16 (m, 3H), 5.17 (dt,
J ) 0.9, 7.0 Hz, 1H), 5.11-5.08 (m, 2H), 2.63 (dd, J ) 15.7,
7.4 Hz, 2H), 2.32-2.26 (m, 2H), 2.07-2.03 (m, 4H), 1.99-1.96
(m, 4H), 1.67 (s, 3H), 1.59 (s, 6H), 1.55 (s, 3H). 13C NMR: δ
142.4, 135.8, 134.9, 131.2, 128.4, 128.2, 125.6, 124.4, 124.2,
123.6, 39.7, 39.7, 36.1, 29.9, 26.8, 26.6, 25.7, 17.7, 15.9, 15.9.
HRMS (EI) m/z: calcd for C22H32, 297.2582; found, 297.2583.
Anal. Calcd for C22H32: C, 89.12; H, 10.88. Found: C, 88.84;
H, 10.79.
1
the following instruments: a DRX-500 (500 MHz for H, 125.8
1
MHz for 13C), an AM-400 (400 MHz for H, 100.6 MHz for 13C),
or an ARX-250 (250 MHz for 1H, 62.9 MHz for 13C). Chemical
shifts are reported in δ units (parts per million) assigning the
1
residual CHCl3 resonance in H spectra at 7.24 ppm and CDCl3
(3E,7E)-4,8,12-Tr im eth yl-1-(4-m eth ylp h en yl)-3,7,11-tr i-
d eca tr ien e (8). Isolated as a colorless oil. IR (KBr): 2966,
resonance in 13C spectra at 77.0 ppm. All coupling constants,
J , are reported in Hertz. High-resolution mass spectrometry
(HRMS) was recorded at 70 eV ionization energy. Column
chromatography was performed on a silica gel 60 (0.063-0.20
or 0.04-0.063 mm). All reactions were monitored by TLC on
silica gel 60 F254 precoated aluminum plates and were devel-
oped with UV light followed by spraying with acidic vanillin
solution. High-performance liquid chromatography (HPLC)
was performed on a gradient system coupled with a differen-
1
1515 cm-1. H NMR: δ 7.07 (s, 4H), 5.17 (t, J ) 7.0 Hz, 1H),
5.11-5.07 (m, 2H), 2.58 (dd, J ) 15.8, 7.5 Hz, 2H), 2.31 (s,
3H), 2.30-2.28 (m, 2H), 2.06-1.96 (m, 8H), 1.67 (s, 3H), 1.59
(s, 6H), 1.55 (s, 3H). 13C NMR: δ 139.3, 135.6, 135.0, 134.9,
131.2, 128.9, 128.9, 128.3, 124.4, 124.2, 123.7, 39.7, 39.7, 35.7,
30.1, 26.8, 26.6, 25.7, 20.9, 17.7, 16.0. HRMS (EI) m/z: calcd
for C23H34 310.2661, found 310.2660. Anal. Calcd for C23H34
C, 88.96; H, 11.04. Found: C, 89.10; H, 10.95.
:
(3E,7E,11E)-4,8,12,16-Tet r a m et h yl-1-p h en yl-3,7,11,15-
h ep t a d eca t et r a en e (9). Isolated as a colorless oil after
(26) The experimental protocol using SnCl4 (4 equiv)/CH2Cl2 (-78
°C) was reported by: Godefroi, E. F.; J anssen, C. G. M. J . Org. Chem.
1984, 49, 3600-3603. For comments on the mechanism of this
“adventitious H+-initiated” cascade cyclization, see: (a) Bartlett, P. A.
In Asymmetric Synthesis; Morrison, J . D., Ed.; Academic Press: New
York, 1984; Vol. 3, pp 341-40. (b) ref 21.
(27) Schaeffer, P.; Poinsot, J .; Hauke, V.; Adam, P.; Wehrung, P.;
Trendel, J .-M.; Albrecht, P.; Dessort, D.; Connan, J . Angew. Chem.,
Int. Ed. Engl. 1994, 33, 1166-1169.
(28) (a) Elings, J . A.; Downing, R. S.; Sheldon, R. A. Eur. J . Org.
Chem. 1999, 4, 837-846. (b) Orita, A.; Watanaba, A.; Tsuchiya, H.;
Otera, J . Tetrahedron 1999, 55, 2889-2898.
(29) J ulia, M.; Mansuy, D. Bull. Soc. Chim. Fr. 1972, 2689-2695.
(30) Nasipuri, D.; Chaudhury, S. R.; Mitra, A.; Ghosh, C. K. Ind. J .
Chem. 1972, 136-139.