Angewandte
Chemie
workup, the residue was purified by flash chromatography to afford
Negishi, A. de Meijere), Wiley-Interscience, New York, 2002,
2
3
1
1
0A (231 mg, 71%). [a] = + 358 (c = 2.8, CH Cl ); H NMR
chap. III.2.6, pp. 335 – 408; b) B. H. Lipshutz in Handbook of
Organopalladium Chemistry for Organic Synthesis (Eds.: E.
Negishi, A. de Meijere), Wiley-Interscience, New York, 2002,
chap.III.2.17.1, pp. 807 – 823; c) E. Negishi, Q. Hu, Z. Huang, M.
Qian, G. Wang, Aldrichimica Acta 2005, 38, 71 – 88; for our
recent paper on oligoene synthesis, see: d) F. Zeng, E. Negishi,
Org. Lett. 2002, 4, 703 – 706.
D
2
2
(
300 MHz, [D ]benzene): d = 0.07 (s, 6H), 0.14 (s, 3H), 0.16 (s, 3H),
6
0
.19 (s, 3H), 0.23 (s, 3H), 1.00 (s, 9H), 1.01 (s, 9H), 1.04 (s, 9H), 1.23
(
d, J = 5.9 Hz, 3H), 1.87 (s, 6H, 4-CH and 6-CH ), 1.82 (s, 3H, 10-
3
3
CH ), 1.95–2.05 (m, 2H), 3.21 (s, 3H), 3.95–4.0 (m, 1H), 4.2–4.25 (m,
3
3
H), 4.45 (d, J = 6.4 Hz, 1H), 4.61 (dd, J = 5.3, 9.4 Hz, 1H), 4.71 (d,
J = 6.4 Hz, 1H), 5.55 (d, J = 10.0 Hz, 1H, 11-H), 5.80 (dt, J = 4.7,
1
6
5.8 Hz, 1H, 2-H), 5.88 (s, 1H, 5-H), 6.3–6.4 (m, 2H, 7-H and 9-H),
[7] F. Zeng, E. Negishi, Org. Lett. 2001, 3, 719 – 722.
.61 (dd, J = 11.1, 14.6 Hz, 1H, 8-H), 7.17 ppm (d, J = 15.8 Hz, 1H, 3-
[8] a) J.-C. Shi, X. Zeng, E. Negishi, Org. Lett. 2003, 5, 1825 – 1828;
b) X. Zeng, Q. Hu, M. Qian, E. Negishi, J. Am. Chem. Soc. 2003,
125, 13636 – 13637; c) J.-C. Shi, E. Negishi, J. Organomet. Chem.
2003, 687, 518 – 524; d) X. Zeng, M. Qian, Q. Hu, E. Negishi,
Angew. Chem. 2004, 116, 2309 – 2313; Angew. Chem. Int. Ed.
1
3
H); C NMR (75 MHz, [D ]benzene): d = À4.7, À4.0, À3.7, À3.4,
6
1
7
1
7
3.8, 18.2, 18.7, 18.8, 22.2, 24.6, 26.5, 26.7, 44.9, 55.7, 64.3, 66.5, 73.3,
5.1, 94.2, 125.9, 128.6, 129.7, 130.8, 132.0, 133.5, 134.2, 135.6, 137.5,
+
39.7 ppm; HRMS (ESI): calcd. for C H O Si Na: [M+Na]
3
9
76
5
3
31.4898; found: 731.4884.
2004, 43, 2259 – 2263; e) Z. Tan, E. Negishi, Angew. Chem. 2006,
2
D
3
1
2
A: [a] = + 268 (c = 3.5, CH Cl ); H NMR (300 MHz,
2 2
118, 776 – 779; Angew. Chem. Int. Ed. 2006, 45, 762 – 765.
[
D ]benzene): d = 0.14 (s, 3H), 0.17 (s, 3H), 0.20 (s, 3H), 0.24 (s,
6
[9] a) A. Minato, K. Suzuki, K. Tamao, J. Am. Chem. Soc. 1987, 109,
3
1
5
4
1
1
H), 1.01 (s, 9H), 1.05 (s, 9H), 1.23 (d, J = 6.4 Hz, 3H), 1.63 (s, 3H),
.78 (s, 3H), 1.87 (s, 3H), 1.9–2.0 (m, 2H), 3.32 (s, 3H), 3.97 (sext., J =
.9 Hz, 1H), 4.00 (q, J = 6.5 Hz, 1H), 4.39 (dd, J = 4.6, 10.0 Hz, 1H),
.49 (d, J = 6.5 Hz, 1H), 4.60 (d, J = 7.0 Hz, 1H), 5.58 (d, J = 9.4 Hz,
H), 5.95–6.0 (m, 2H), 6.13 (d, J = 10.6 Hz, 1H), 6.35 (d, J = 15.2 Hz,
H), 6.47 (dd, J = 10.5, 15.2 Hz, 1H), 8.29 ppm (d, J = 15.8 Hz, 1H);
1
257 – 1258; b) A. Minato, J. Org. Chem. 1991, 56, 4052 – 4056;
c) W. Shen, L. Wang, J. Org. Chem. 1999, 64, 8873 – 8879; d) J.
Uenishi, K. Matsui, Tetrahedron Lett. 2001, 42, 4353 – 4355; e) J.
Uenishi, K. Matsui, H. Ohmiya, J. Organomet. Chem. 2002, 653,
1
41 – 149; f) J. Uenishi, M. Ohmi, K. Matsui, M. Iwano,
Tetrahedron 2005, 61, 1971 – 1979; g) J. Uenishi, K. Matsui, M.
Ohmi, Tetrahedron Lett. 2005, 46, 225 – 228; h) J. Uenishi, K.
Matsui, Tetrahedron Lett. 2005, 46, 359.
1
3
C NMR (75 MHz, [D ]benzene): d = À4.0, À3.7, À3.5, 13.7, 17.7,
6
1
1
8.7, 18.8, 21.3, 24.6, 26.5, 26.6, 45.0, 55.7, 66.5, 73.2, 75.2, 94.5, 118.7,
25.4, 131.4, 131.7, 135.0, 135.5, 139.3, 139.5, 142.8, 145.3, 173.5 ppm;
[8]
[
10] Before we conducted a series of recent investigations, the two-
+
HRMS (ESI): calcd. for C H O Si Na: [M+Na] 631.3826; found:
6
3
3
60
6
2
stage double substitution of 1,1-dihalo-1-alkenes with two
different organometals had been reported only in a few
papers.
the first-stage trans-selective monoalkylation of b, b-dichloros-
tyrene with n-butylzinc chloride in the presence of [Cl Pd-
31.3848.
B: [a] = + 338 (c = 6.6, CH Cl ); H NMR (300 MHz,
2
D
3
1
2
[9a–d]
2
2
Moreover, there was just one successful example of
[
D ]benzene): d = 0.17 (s, 3H), 0.19 (s, 3H), 0.22 (s, 3H), 0.26 (s,
6
3H), 1.04 (s, 9H), 1.08 (s, 9H), 1.26 (d, J = 6.0 Hz, 3H), 1.67 (s, 3H),
1.73 (s, 3H), 1.92 (s, 3H), 1.9–2.1 (m, 2H), 3.24 (s, 3H), 4.05 (q, J =
6.1 Hz, 1H), 4.22 (sext., J = 6.0 Hz, 1H), 4.49 (d, J = 6.6 Hz, 1H), 4.64
2
(dppb)] (1 mol%; dppb = 1,4-bis(diphenylphosphino)butane) in
[9a]
81% yield.
This reaction was followed by second-stage
(dd, J = 5.3, 9.8 Hz, 1H), 4.72 (d, J = 6.6 Hz, 1H), 5.68 (d, J = 9.8 Hz,
alkylation with n-hexylmagnesium bromide in the presence of
1
1
H), 6.48 (d, J = 15.4 Hz, 1H), 6.10–6.15 (m, 2H), 6.40 (d, J = 15.2 Hz,
H), 6.52 (dd, J = 10.9, 15.1 Hz, 1H), 7.68 ppm (d, J = 15.4 Hz, 1H);
[
Cl Ni(dppp)] (dppp = 1,3-bis(diphenylphosphino)propane) in
2
[9a]
77% yield.
However, it was recently shown that the high
1
3
C NMR (75 MHz, [D ]benzene): d = À4.0, À3.7, À3.5, 13.7, 14.3,
6
stereoselectivity observed in the second-stage alkylation is due
to the presence of the Ph group in the b position, as the use of an
alkyl group such as n-octyl in place of Ph under comparable
conditions leads to a mixture of the E and Z isomers.
Fortunately, the use of [Pd(tBu P) ] in place of [Cl Ni(dppp)]
1
1
7.2, 18.7, 18.8, 24.5, 26.5, 26.6, 44.9, 55.7, 66.5, 73.2, 75.2, 94.4, 116.6,
25.3, 131.5, 133.1, 135.2, 136.1, 139.4, 139.7, 145.1, 153.5, 173.6 ppm;
+
HRMS (ESI): calcd. for C H O Si Na: [M+Na] 631.3826; found:
6
[8e]
3
3
60
6
2
31.3828.
3
2
2
[
8e]
suppressed the extent of isomerization to ꢁ 3–4%. A second-
Received: January 3, 2006
Published online: March 24, 2006
stage alkylation that represents the only prior example of
[9c]
methylation was performed with a bromostilbene derivative.
A few additional examples of the second-stage alkylation of (Z)-
[
9d]
Keywords: asymmetric synthesis · cross-coupling · haloalkenes ·
natural products · palladium
2-bromo-1-en-3-ynes were also reported. However, the details
of the stereochemical results obtained in their case were
.
[
8a–d]
questionable in view of recent related results reported by us.
[
9f–h]
Despite subsequent publications
from that same group,
[
9h]
including one corrigendum that came to our attention after
the submission of this paper, the stereochemical details remain to
be fully clarified. No other Pd-or N ic- atalyzed seconds -t age
alkylation with alkyl metals that produces trisubstituted alkenes
appears to have been reported prior to our development of the
Pd-catalyzed stereoselective method with essentially full reten-
[
1] a) K. M. George, D. Chatterjee, G. Gunawardana, D. Welty, J.
Hayman, R. Lee, P. L. C. Small, Science 1999, 283, 854 – 857;
b) G. Gunawardana, D. Chatterjee, K. M. George, P. Brennan,
D. Whittern, P. L. C. Small, J. Am. Chem. Soc. 1999, 121, 6092 –
6093.
[
[
[
2] A. B. Benowitz, S. Fidanze, P. L. C. Small, Y. Kishi, J. Am. Chem.
Soc. 2001, 123, 5128 – 5129.
3] F. Song, S. Fidanze, A. B. Benowitz, Y. Kishi, Org. Lett. 2002, 4,
[
8a,c,d]
[8b]
tion
or inversion of configuration.
11] Z. Huang, E. Negishi, unpublished results.
[
647 – 650.
[12] a) A. O. King, N. Okukado, E. Negishi, J. Chem. Soc. Chem.
Commun. 1977, 683; b) E. Negishi, M. Kotora, C. Xu, J. Org.
Chem. 1997, 62, 8957 – 8960.
[13] For a recent review of Pd-catalyzed alkynylation, see: E.
Negishi, L. Anastasia, Chem. Rev. 2003, 103, 1979 – 2017.
[14] For a recent review of the Sonogashira alkynylation, see: K.
Sonogashira in Handbook of Organopalladium Chemistry for
Organic Synthesis (Eds.: E. Negishi, A. de Meijere), Wiley-
Interscience, New York, 2002, chap. III.2.8.1, pp. 494 – 529.
[15] I. Paterson, P. A. Craw, Tetrahedron Lett. 1989, 30, 5799 – 5802.
4] For a nonstereoselective synthesis of tribenzyl-protected ethyl
esters of the C15 epimers of the mycolactone A and B side
chains, see: M. K. Gurjar, J. Cherian, Heterocycles 2001, 55,
1095 – 1103.
[
5] For a recent report on attempts to synthesize the side chains of
mycolactones A and B, see: R. P. van Summeren, B. L. Feringa,
A. J. Minnaard, Org. Biomol. Chem. 2005, 3, 2524 – 2533.
[
6] For recent reviews, see: a) S. Huo, E. Negishi in Handbook of
Organopalladium Chemistry for Organic Synthesis, (Eds.: E.
Angew. Chem. Int. Ed. 2006, 45, 2916 –2920
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2919