Table 3 Heck arylation of unsaturated alcohols 1c–fa
and as indicated earlier, those that are known are dominated by b
arylation.4a
In summary, we have developed a general and efficient method
for the internal arylation of unsaturated alcohols by using Pd-
DPPP in [bmim][BF4]–DMSO. The method allows for highly
regioselective arylation of these alcohols, including in particular
allyl alcohol, with aryl bromides with no need for halide
scavengers. In contrast to almost all the known arylation reactions
of this class of olefins, the reactions presented here afford
preferentially the branched olefins that are usually difficult to
access.
Yield
a/b (%)
Entry 2
3
1
85/15 79
2
3
88/12 80
88/12 81
Notes and references
1 For examples, see: (a) P. M. O’Neill, M. Pugh, J. Davies, S. A. Ward
and B. K. Park, Tetrahedron Lett., 2001, 42, 4569; (b) X. Han,
B. M. Stoltz and E. J. Corey, J. Am. Chem. Soc., 1999, 121, 7600; (c)
A. M. Evans, J. Clin. Pharmacol., 1996, 36, 7; (d) H. R. Sonawane,
N. S. Bellur, J. R. Ahuja and D. G. Kuikarni, Tetrahedron: Asymmetry,
1992, 3, 163; (e) K. Yamamoto, K. Ikeda and L. K. Yin, J. Organomet.
Chem., 1989, 370, 319; (f) S. M. Ludeman, V. L. Boyd, J. B. Regan,
K. A. Gallo, G. Zon and K. Ishii, J. Med. Chem., 1986, 29, 716.
2 Recent reviews on the Heck reaction: (a) M. Shibasaki, E. M. Vogl and
T. Ohshima, Adv. Synth. Catal., 2004, 346, 1533; (b) V. Farina, Adv.
Synth. Catal., 2004, 346, 1553; (c) A. F. Littke and G. C. Fu, Angew.
Chem., Int. Ed., 2002, 41, 4176; (d) I. P. Beletskaya and A. V. Cheprakov,
Chem. Rev., 2000, 100, 3009; (e) M. Larhed and A. Hallberg, in
Handbook of Organopalladium Chemistry for Organic Synthesis, ed. E.-I.
Negishi, Wiley-Interscience, New York, 2002, vol. 1, p. 1133.
3 (a) J. B. Melpolder and R. F. Heck, J. Org. Chem., 1976, 41, 265; (b)
A. J. Chalk and S. A. Magennis, J. Org. Chem., 1976, 41, 273.
4 For more recent examples: (a) R. C. Larock, W.-Y. Leung and S. Stolz-
Dunn, Tetrahedron Lett., 1989, 30, 6629; (b) T. Jeffery, J. Chem. Soc.,
Chem. Commun., 1991, 324; (c) N. Cheeseman, M. Fox, M. Jackson,
I. C. Lennon and G. Meek, Proc. Natl. Acad. Sci. U. S. A., 2004, 101,
5396; (d) S. A. Forsyth, H. Q. N. Gunaratne, C. Hardacre,
A. McKeown, D. W. Rooney and K. R. Seddon, J. Mol. Catal. A:
Chem., 2005, 231, 61; (e) F. Berthiol, H. Doucet and M. Santelli,
Tetrahedron, 2006, 62, 4372.
4
5
86/14 80
81/19 74
6
7
84/16 75
80/20 72
8
85/15 78
a
The conditions were the same as in Table 2.
5 A recent review on C–C bond formation involving 1: J. Muzart,
Tetrahedron, 2005, 61, 4179.
6 (a) W. Cabri, I. Candiani, A. Bedeschi and R. Santi, J. Org. Chem.,
1992, 57, 3558; (b) W. Cabri, I. Candiani, A. Bedeschi and R. Santi,
J. Org. Chem., 1993, 58, 7421.
of profens via a two-step process involving oxidation and
asymmetric hydrogenation1c,14 and antimalarials via Mukaiyama
hydroperoxysilylation.1a
We next investigated the arylation of the homoallyl alcohol 1b.
Table 2 summarizes the results obtained. As can be seen,
bromobenzenes bearing various substituents at various positions
are all effective substrates, furnishing the a products with good to
excellent regioselectivities. Although the regioselectivities are lower
than those observed with 1a, the reactions proceeded more readily,
requiring a reduced catalyst loading and shorter reaction time.
Unlike the arylation of 1a, 1b could be arylated in [bmim][BF4],
albeit with slightly lower a/b ratios (76/24 in the case of 2c). In
molecular solvents such as DMF and dioxane, the product was
dominated by b-arylated species (60–80%).
7 The arylation of 1a by phenyl triflate was also reported by Hallberg, see:
(a) K. Olofsson, H. Sahlin, M. Larhed and A. Hallberg, J. Org. Chem.,
2001, 66, 544; (b) K. Olofsson, M. Larhed and A. Hallberg, J. Org.
Chem., 2000, 65, 7235.
8 We have recently reported the regioselctive arylation of 1a by heteroaryl
bromides in neat [bmim][BF4]; but the conditions could not be applied
to normal aryl halides: W. Pei, J. Mo and J. Xiao, J. Organomet. Chem.,
2005, 690, 3546. The heteroatom may promote the ionic pathway by
coordination to Pd(II).
9 W. Cabri and I. Candiani, Acc. Chem. Res., 1995, 28, 2.
10 (a) M. M. S. Andappan, P. Nilsson, H. von Schenck and M. Larhed,
J. Org. Chem., 2004, 69, 5212; (b) R. J. Deeth, A. Smith and J. M. Brown,
J. Am. Chem. Soc., 2004, 126, 7144.
11 (a) J. Mo and J. Xiao, Angew. Chem., Int. Ed., 2006, 45, 4152; (b) J. Mo,
L. Xu and J. Xiao, J. Am. Chem. Soc., 2005, 127, 751.
12 Recent reviews on ionic liquids: (a) J. Dupont and J. Spencer, Angew.
Chem., Int. Ed., 2004, 43, 5296; (b) T. Welton, Coord. Chem. Rev., 2004,
248, 2459; (c) R. Sheldon, Chem. Commun., 2001, 2399; (d)
P. Wasserscheid and W. Keim, Angew. Chem., Int. Ed., 2000, 39, 3772.
13 (a) M. A. Klingshirn, G. A. Broker, J. D. Holbrey, K. H. Shanghnessy
and R. D. Rogers, Chem. Commun., 2002, 1394; (b) C. Chiappe and
D. Pieraccini, J. Org. Chem., 2004, 69, 6059.
The Heck arylation of unsaturated alcohols with different chain
lengths has also proved to be viable, as demonstrated by the
examples of 2c and 2o in Table 3. These reactions afforded good a
regioselectivities for the branched alcohols. When n = 3 or 4, the
regioselectivities were slightly higher; but further increase in the
chain length reduced the selectivity. Few literature examples are
known of the arylation of long chain unsaturated alcohols (n ¢ 2)
14 D. K. James, A. P. Komin and J. R. Sieman, US Pat., 5286902, 1994.
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