C O M M U N I C A T I O N S
Although electronic effects of R5 were insignificant (entries 6-8),
those of R1 were of crucial importance. Thus, alkenyl and alkynyl12
groups as R1 can totally inhibit stereoisomerization (entries 19 and
20), while Ph as R1 led to partial stereoinversion (entry 18). These
results may tentatively be attributed to chelation shown in 9.
Table 1. Reaction of (Z)-2-Bromo-1,3-dienes with Organozinc
Derivatives in the Presence of 5 mol % of Cl2Pd(DPEphos)
5
b
c
entry
2a
R ZnX
3
yield, %
Z,E, %
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
2a
2a
2b
2a
2a
2a
2a
2a
2c
2d
2d
2e
2f
2g
2h
2i
2j
2k
2l
Me2Zn
Me2Zn
MeZnBr
EtZnBr
3a
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
90
93
95
93
91
92
96
96
85
70
95
84
88
87
72
92
90
92
61
95
g97d
g99
g98
g98
g98
g98(E,E)
g98
g98(E,E)
g98
g98
g98
g98
g97
g98
n-BuZnBr
PhZnBr
H2CdCHZnBr
HCtCZnBr
MeZnBr
MeZnBr
EtZnBr
MeZnBr
Me2Zn
Me2Zn
Me2Zn
Me2Zn
Me2Zn
MeZnBr
Me2Zn
In summary, the Pd-catalyzed cross-coupling reaction of 2-bromo-
1,3-dienes derived from alkyl aldehydes, especially with Cl2Pd-
(DPEphos) as a catalyst, proceeds with clean stereoinversion of
the Br-bearing CdC bond to produce in high yields and in high
stereoselectivity (g97-98%) conjugated Z,E dienes of potentially
high utility in the synthesis of complex natural products. The
observed stereoinversion cannot be readily accommodated by the
widely accepted π-σ-π rearrangement mechanism for isomer-
ization of ordinary allylpalladium derivatives.
g97(Z)
g98(Z,Z)
g98
50e
e3f
2m
Me2Zn
e1g
Acknowledgment. We thank NSF (CHE-0309613), NIH (GM
36792), and Purdue University for support of this research. Stimuli
provided by related investigations with Drs. Z. Tan and J. Shi are
acknowledged.
Supporting Information Available: Experimental procedures,
spectroscopic data, and spectra. This material is available free of charge
References
(1) (a) For a recent extensive survey, see: Negishi, E., Ed. Handbook of
Organopalladium Chemistry for Organic Synthesis; Wiley-Interscience:
New York, 2002; Part III. (b) For recent examples of undesirable partial
E-Z isomerization, see Shi, J.; Zeng, X.; Negishi, E. Org. Lett. 2003, 5,
1825.
(2) (a) Kobayashi, M.; Higuchi, K.; Murakami, N.; Tajima, H.; Aoki, S.
Tetrahedron Lett. 1997, 38, 2859. (b) Enders, D.; Vicario, J. L.; Job, A.;
Wolberg, M.; Mu¨ller, M. Chem. Eur. J. 2002, 8, 4272.
a Fully identified as g98% Z,E isomer. b Isolated yield. c Percentage of
the Z,E isomer unless otherwise indicated in parentheses. d Pd(PPh3)4 was
used as a catalyst. e Z,E/E,E ) 50/50. f E,Z,E/E,E,E e 3/97. g Z,E/E,E e
1/99.
(3) (a) Hamamoto, T.; Gunji, S.; Tsuji, H.; Beppu, T. J. Antibiot. 1983, 36,
639. (b) Kobayashi, M.; Wang, W.; Tsutsui, Y.; Sugimoto, M.; Murakami,
N. Tetrahedron Lett. 1998, 39, 8291.
Scheme 2
(4) (a) Schummer, D.; Gerth, K.; Reichenbach, H.; Ho¨fle, G. Liebigs Ann.
1995, 685. (b) Williams, D. R.; Ihle, D. C.; Plummer, S. V. Org. Lett.
2001, 3, 1383.
(5) (a) Negishi, E.; Qian, M.; Zeng, F.; Anastasia, L.; Babinski, D. Org. Lett.
2003, 5, 1597. (b) Zeng, F.; Negishi, E. Org. Lett. 2001, 3, 3039. (c)
Zeng, F.; Negishi, E. Org. Lett. 2002, 4, 703.
(6) Comparable results were obtained with Me2Zn or MeZnBr derived from
either MeLi or MeMgBr.
(7) All ligands used in this study are commercially available. DPEphos )
bis(2-diphenylphosphinophenyl) ether. TFP ) tris(2-furyl)phosphine.
(8) (a) Minato, A.; Suzuki, K.; Tamao, K. J. Am. Chem. Soc. 1987, 109, 1257.
(b) Xu, C.; Negishi, E. Tetrahedron Lett. 1999, 40, 431. (c) Ogasawara,
M.; Ikeda, H.; Hayashi, T. Angew. Chem., Int. Ed. 2000, 39, 1042. (d)
Roush, W. R.; Moriarty, K. J.; Brown, B. B. Tetrahedron Lett. 1990, 31,
6509. (e) Roush, W. R.; Koyama, K.; Curtin, M. L.; Moriarty, K. J. J.
Am. Chem. Soc. 1996, 118, 7502. (f) Shen, W.; Wang, L. J. Org. Chem.
1999, 64, 8873.
(9) For related Pd-catalyzed reaction of 2,3-butadienyl electrophiles, see:
Djahanbini, D.; Cazes, B.; Gore, J. Tetrahedron Lett. 1984, 25, 203;
Tetrahedron 1984, 40, 3645; Tetrahedron 1987, 43, 3441. Possible
intermediacy of 4 has been suggested in a different context for the Pd-
catalyzed allylation producing allenes.8c
(10) See, for example, Acemoglu, L.; Williams, J. M. J. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
Wiley-Interscience: New York, 2002; Chapter V.2.1.2, p 1689. With
ordinary allyl derivatives, one each of E-Z and R-S inversions have
been observed.
(11) Shi, J.; Negishi, E. J. Organomet. Chem. 2003, in press.
(12) Retention of configuration was reported for the Pd-catalyzed reaction of
(Z)-1-iodo-1-en-3-ynes with alkynylzinc chlorides: Stracker, E. C.;
Zweifel, G. Tetrahedron Lett. 1991, 32, 3329.
tively (entries 1, 2, 9, 10, 15-17). All alkenyl groups were
introduced in good yields in g98% trans-selectivity to produce the
corresponding 2. Their subsequent reaction with Me2Zn or MeZnBr
in the presence of 5 mol % of Cl2Pd(DPEphos) proceeded with
clean stereoinversion (g97-98%) in high yields. Particularly
noteworthy and puzzling is the fact that stereoisomerization was
confined to the Br-bearing CdC bond even in the case in which
(Z)-1-hexenylzinc bromide was used, and yet, it is definitely not a
phenomenon observable with any types of bromoalkenes. Thus,
the corresponding reaction of 6 showed no sign of stereoinversion.
Furthermore, our recent studies have shown that the corresponding
reactions of R-bromostyrenes 7 underwent stereoisomerization only
to the extent of <5%,11 while those of 2-bromo-1-en-3-ynes 8 were
accompanied by significant but partial stereoisomerization.1b It is
therefore clear that the observed clean and essentially full stereo-
inversion is induced by the presence of the CdC bond that is in
conjugation with the Br-bearing CdC bond and allylic to Br.
JA0304392
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J. AM. CHEM. SOC. VOL. 125, NO. 45, 2003 13637