Insertion of 1-chloro-1-lithioalkenes into organozirconocenes. A versatile synthesis of stereodefined unsaturated systems

Article abstract of DOI:10.1021/ja9910208

Hydrozirconation of alkenes and alkynes, followed by insertion of 1- halo-1-lithio-1-alkenes, generated in situ by lithium tetramethylpiperidide deprotonation of vinyl halides, affords vinylzirconocene species which may be further elaborated. The method provides easy access to many structures including terminal (3E)- and (3Z)-1,3-dienes and (3E,5E)- and (3Z,5E)-1,3,5- trienes, and internal (E,Z)-dienes,(E,Z,E)-trienes, and (1E, 3Z)1,3-dien-5- ynes. Insertion of 2-monosubstituted 1-halo-1-lithio-1-alkenes occurs with clean inversion of configuration of the sp²-carbenoid carbon. Carbenoids derived by deprotonation of 2,2-disubstituted 1-halo-1-alkenes gave poor stereocontrol probably due to isomerization before insertion into the organozirconium species. Insertion of vinyl carbenoids into alkynylzirconocenes affords terminal (3E)- or (3Z)-1,3-dien-5-ynes, internal (1E,3Z)-1,3-dien-5-ynes, and (Z)-3-en-1,5-diynes.

Full text of DOI:10.1021/ja9910208

J. Am. Chem. Soc. 1999, 121, 7039-7049
7039
Insertion of 1-Chloro-1-lithioalkenes into Organozirconocenes. A
Versatile Synthesis of Stereodefined Unsaturated Systems
Aleksandr Kasatkin and Richard J. Whitby*
Contribution from the Department of Chemistry, Southampton UniVersity,
Southampton, HANTS, SO17 1BJ, U.K.
ReceiVed March 30, 1999
Abstract: Hydrozirconation of alkenes and alkynes, followed by insertion of 1-halo-1-lithio-1-alkenes, generated
in situ by lithium tetramethylpiperidide deprotonation of vinyl halides, affords vinylzirconocene species which
may be further elaborated. The method provides easy access to many structures including terminal (3E)- and
(3Z)-1,3-dienes and (3E,5E)- and (3Z,5E)-1,3,5-trienes, and internal (E,Z)-dienes, (E,Z,E)-trienes, and (1E,3Z)-
1
,3-dien-5-ynes. Insertion of 2-monosubstituted 1-halo-1-lithio-1-alkenes occurs with clean inversion of
2
configuration of the sp -carbenoid carbon. Carbenoids derived by deprotonation of 2,2-disubstituted 1-halo-
-alkenes gave poor stereocontrol probably due to isomerization before insertion into the organozirconium
1
species. Insertion of vinyl carbenoids into alkynylzirconocenes affords terminal (3E)- or (3Z)-1,3-dien-5-ynes,
internal (1E,3Z)-1,3-dien-5-ynes, and (Z)-3-en-1,5-diynes.
Introduction
Hydrozirconation of alkenes and alkynes with the Schwartz
reagent (Cp2Zr(H)Cl, Cp ) C5H5) to give alkyl- and vinyl8-
zirconocene chlorides is a well-established synthetic method.
To be useful in organic synthesis methods for further elaboration
of the organozirconium species are needed. Carbon-carbon
bond-forming reactions include carbonylation, isocyanide inser-
tion, and copper-, nickel-, and palladium-catalyzed reactions.8
A particularly interesting elaboration method is the insertion
of R-haloorganolithium species as described above, reported by
A characteristic of transition metal chemistry is the often
facile insertion of components with carbenoid properties (CO,
RNC) into carbon-metal bonds to generate a new organo-
metallic with the potential for further elaboration. With the
current interest in combinatoric methods, such inherently
iterative reactions are of particular relevance to organic syn-
thesis. A recently developed class of such reactions is the
insertion of metal carbenoids 1 to afford a new organometallic
1
Negishi. Of particular relevance to the work described herein
3
“
, probably occurring via 1,2-rearrangement of an intermediate
is the insertion of (1-lithio-1-bromomethylene)cyclopentane,
generated by Br/Li exchange from the corresponding dibromide,
into n-octylzirconocene chloride to give a good yield of
ate” complex 2 (eq 1).1 Such rearrangements are well-known
-3
1
nonylidenecyclopentane on acid quench (eq 2).
4
in boron chemistry, and have been reported for several other
main group elements.5 We have developed the use of carbenoid
insertions in the elaboration of zirconacycles.7
,6
We recently reported the insertion of 1-lithio-1-halobutadiene
into organozirconocenes providing a stereocontrolled synthesis
of terminal dienes, trienes, and dienynes (e.g., eq 3). We now
(
1) Negishi, E.; Akiyoshi, K.; O’Connor, B.; Takagi, K.; Wu, G. J. Am.
Chem. Soc. 1989, 111, 3089.
(
(
9
2) Kocienski, P.; Barber, C. Pure Appl. Chem. 1990, 62, 1933.
3) Siddure, A.; Rozema, M. J.; Knochel, P. J. Org. Chem. 1993, 58,
report full details of this work, extension to a wide range of
2
694.
(
4) (a) Matteson, D. S. Chem. ReV. 1989, 89, 1535. (b) Negishi, E. In
ComprehensiVe Organometallic Chemistry; Wilkinson, G., Stone, F. G. A.,
Abel, F. W., Eds.; Pergamon Press: Oxford, 1982; Vol. 7, pp 255-363.
(
c) Zweifel, G.; Arzoumanian, H. J. Am. Chem. Soc. 1967, 89, 5086. (d)
Birkinshaw, S.; Kocienski, P. Tetrahedron Lett. 1991, 32, 6961.
5) Al, Mg, Zn, Cd: (a) Negishi, E.; Akiyoshi, K. J. Am. Chem. Soc.
988, 110, 646. Zn: (b) Harada, T.; Katsuhira, T.; Hara, D.; Kotani, Y.;
(
1
Maejima, K.; Kaji, R.; Oku, A. J. Org. Chem. 1993, 58, 4897. (c) Harada,
T.; Katsuhira, T.; Osada, A.; Iwazaki, K.; Maejima, K.; Oku, A. J. Am.
Chem. Soc. 1996, 118, 11377. Al: (d) Miller, J. A. J. Org. Chem. 1989,
other vinylcarbenoids, and functionalization of the carbon-
zirconium bond present in the initial insertion product. Ap-
plication to the synthesis of natural products is also described.
5
4, 998. Si: (e) Achmatowicz, B.; Jankowski, P.; Wicha, J.; Zarecki, A. J.
Organomet. Chem. 1998, 558, 227. (f) Matsumoto, K.; Aoki, Y.; Oshima,
K.; Utimoto, K.; Rahman, N. A. Tetrahedron 1993, 49, 8487. Mg: (g)
Lima, C.; Julia, M.; Verpeaux, J.-N. Synlett 1992, 133
(7) Fillery, S. F.; Gordon, G. J.; Luker, T.; Whitby, R. J. Pure Appl.
Chem. 1997, 69, 633. Gordon, G. J.; Whitby, R. J. Chem. Commun. 1997,
1321. Gordon, G. J.; Whitby, R. J. Chem. Commun. 1997, 1045. Tuckett,
M. W.; Watkins, W. J.; Whitby, R. J. Tetrahedron Lett. 1998, 39, 123.
(8) Wipf, P.; Jahn, H. Tetrahedron 1996, 52, 12853.
(
6) Li: (a) Topolski, M.; Duraisamy, M.; Rachon, J.; Gawronski, J.;
Gawronska, K.; Goedken, V.; Walborsky, H. M. J. Org. Chem. 1993, 58,
46. (b) Nguyen, T.; Negishi, E. Tetrahedron Lett. 1991, 32, 5903. (c)
Nelson, D. J.; Nagarajan, A. J. Organomet. Chem. 1993, 463, 1.
5
(9) Kasatkin, A.; Whitby, R. J. Tetrahedron Lett. 1997, 38, 4857
1
0.1021/ja9910208 CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/16/1999

7040 J. Am. Chem. Soc., Vol. 121, No. 30, 1999
Kasatkin and Whitby
Scheme 1
Table 1. Insertions of â,â-Disubstituted Vinyl Carbenoids
1
2
(
6
Scheme 1, R , R * H; R ) n-C H13.)
Scheme 2
Results and Discussion
Our aim was to extend the insertion of (1-lithio-1-bromo-
a
A: 1.3 equiv of halide, 1.3 equiv of LiTMP, THF, -90 to -80
methylidene)cyclopentane into n-octylzirconocene chloride re-
°
C, 15 min. B: as A but 2 equiv of halide and LiTMP. C: as A, then
1
ported by Negishi (eq 2) to a range of other vinylcarbenoids 5
-60 to -40 °C for 1 h. D: as C but 1.8 equiv of halide and LiTMP.
b
c
After workup with 2 M HCl(aq) except where stated. Stereochemistry
of the trisubstituted alkene, ratio by GC. d Quenched with 3 equiv of
, then 0 °C, 30 min.
and organozirconium species (Scheme 1). In particular we
wished to investigate the stereochemistry of the carbenoid
I
2
insertion. Clean inversion of stereochemistry of the vinyl halide
1
4
is expected from the proposed mechanism via the “ate”
products 13 and 17 in moderate yield, but with poor stereo-
selectivity (Table 1, entries 5, 6, and 12). The (Z) product is
that expected from a 1,2-metalate rearrangement occurring with
inversion of the sp carbon, and was the minor isomer! Insertion
of the carbenoid derived from (Z)-1-chloro-2-methyl-1-octene
15) into n-hexylzirconocene chloride gave 13 with a good 93:7
E:Z ratio in favor of the product derived by inversion of the
reacting sp center (entry 9). The carbenoids derived from (E)-
and (Z)-1-iodo-2-methyl-1-octene (14 and 16) inserted into
n-hexylzirconocene chloride with predominant inversion to give
complex 6, and has been demonstrated with other ele-
2
,4c,d,5b,d,6a,b
ments.
generating stereodefined species, we chose to generate the
-halo-1-lithio-1-alkenyl species 5 by deprotonation of the
For experimental ease, and the possibility of
2
1
10
corresponding vinyl halides 4 in situ. A wide variety of alkyl-
and alkenylzirconocene chlorides 8 and 9 used in this work were
generated by hydrozirconation of the corresponding alkenes
(
8
2
and alkynes (Scheme 2). To our delight, addition of lithium
tetramethylpiperidide (LiTMP) to a mixture of 1-chloro-2-
methyl-1-propene (10) and n-octylzirconocene chloride (8b) at
90 °C followed by protic quench gave an excellent yield of
-methyl-2-undecene (Table 1, entry 1). In a similar way
insertion into (E)-1-octenylzirconocene chloride (9c) gave (E)-
-methyl-2,4-undecadiene, slightly improved yields being ob-
tained by using 2 equiv of the carbenoid (Table 1, entry 3, cf.
). Quenching the reaction with iodine gave the iodide 11 in
good yield, confirming the intermediate formation of a new
vinylzirconocene 7 (Scheme 1), and beginning to demonstrate
the key advantage of carbenoid insertion methods for elaboration
of organometallics: the product retains the organometallic
functionality of the precursor.
2
1
7:73 and 75:25 E:Z ratios respectively of the alkene 13 (Table
, entries 8 and 11). With short reaction times at low temperature
-
2
the vinyl iodide carbenoid precursors gave incomplete reaction.
Interestingly under these conditions the product 13 was obtained
with higher (Z)-selectivity from 14 (Table 1, entry 7, cf. 8) but
lower (E)-selectivity from 16 (Table 1, entry 10, cf. 11). In both
cases iodide was recovered from the protonation and had
partially lost stereochemical integrity (88:12 and 14:84 E:Z,
respectively). Similarly, the reaction of the carbenoid derived
from 14 with (E)-1-hexenylzirconocene chloride led to the diene
2
2
1
7 with partial inversion of configuration (Table 1, entry 13).
A discussion of the possible causes of the poor stereocontrol
observed for the insertion of 2,2-disubstituted 1-lithio-1-
haloalkenes follows description of the rest of the preparative
results.
Insertion of the carbenoid derived by deprotonation of (E)-
-chloro-2-methyl-1-octene (12) into either n-hexyl- or (E)-1-
hexenylzirconocene chloride (8a and 9a) gave the expected
1
We next examined insertion of â-monosubstituted 1-lithio-
-halo-1-alkenes. In general such species are very unstable, 1,2-
â-hydride migration with loss of lithium halide to give an
(
10) For reviews on 1-lithio-1-haloalkenes see: Braun, M. In Methoden
1
Org. Chem. (Houbden-Weyl), 4th ed.; Thieme: Stuttgart, 1993; Vol. E 19d,
pp 291-304. Braun, M. Angew. Chem., Int. Ed. Engl. 1998, 37, 430.

Insertion of 1-Chloro-1-lithioalkenes into Organozirconocenes
J. Am. Chem. Soc., Vol. 121, No. 30, 1999 7041
1
2
Table 2. Insertion of â-Monosubstituted Vinyl Carbenoids (Scheme 1, R and/or R ) H)'
a
A: 1.3 equiv of Li-carbenoid, -90 to -80 °C, 15 min, THF. B: as A but 0.83 equiv of Li-carbenoid. C: as B, then -60 to -40 °C, 40 min.
b
c
d
D: as A, then -15 to 20 °C, 2 h. Isomeric purity of products is >95:5 except where stated. 1.5 equiv of NBS, -60 to -40 °C, 1 h. 1.3 equiv
of BuNC, 20 °C, 16 h, then 50% HOAc/H
alkene 86:14 E:Z after purification.
e
f
g
2
O, 20 °C, 1 h. 1.5 equiv of I
2
, -60 to -40 °C, 1 h. 1.5 equiv of NBS, 20 °C, 30 min. Disubstituted
acetylene being facile, and a widely used alkyne synthesis.11
The rearrangement is much faster with a hydrogen trans to the
halide, for example (E)- and (Z)-1-lithio-1-chloro-2-phenyl-
ethene decompose to phenylacetylene at -60 and -110 °C,
respectively.12 The only other reported example of a carbenoid
with a hydrogen trans to the halide being formed and trapped
The base-induced elimination of HX from (E)- or (Z)-1,4-
dihalo-2-butene is known to give predominantly (Z)- or (E)-1-
1
6
halobutadiene, respectively. We found that treatment of (E)-
or (Z)-1,4-dichloro-2-butene with 2 equiv of LiTMP at -90 °C
gave stereoselectively, and in good yield, (Z)- or (E)-1-chloro-
1-lithio-1,3-butadienes (19 and 20) via R-deprotonation of the
in situ formed 1-chlorobutadienes (Scheme 3). Trapping with
benzaldehyde to afford the alcohols 21 and 22 confirmed the
formation and stereochemistry of the novel carbenoids.17 The
formation of 19 is notable as the first efficient deprotonation
of a (Z)-chloroalkene with a proton trans to the chlorine. The
use of lithium diisopropylamide instead of LiTMP as the base
gave similar results. Treatment of (E)- or (Z)-1,4-dibromo-2-
butene with 2 equiv of LiTMP gave the corresponding (Z)- or
(E)-1-bromo-1-lithio-1,3-butadienes, but the stereoselectivity
was lower than for the chloro-substituted case. Reaction of the
in situ generated carbenoids 19 and 20 with n-octyl- and (E)-
13
is the parent 1-lithio-1-chloroethene. â-Monosubstituted 1-lithio-
-chloro-1-alkenes are also difficult to form by deprotonation
1
(
our preferred route to stereospecific species), halogen-lithium
10,14
exchange from 1,1-dihaloalkenes being preferred.
a few examples of deprotonation have been reported.
However,
1
0,12,13,15
Treatment of (E)-â-bromostyrene with LiTMP to generate
E)-1-bromo-1-lithio-2-phenylethene (18) in the presence of
(
n-octylzirconocene chloride followed by hydrolysis gave a 33%
yield of (Z)-1-phenyl-1-decene (Table 2, entry 1) demonstrating
2
clean inversion of the sp center for the first time.
(11) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769. Villieras,
1
-octenylzirconocene chlorides (8b and 9c) followed by acidic
J.; Perriot, P.; Normant, J. F. Synthesis 1975, 458. McIntosh, M. C.; Weinreb,
S. M. J. Org. Chem. 1993, 58, 4823. Tietze, L. F.; Neumann, T.; Kajino,
M.; Pretor, M. Synthesis 1995, 1003. Reetz, M. T.; Strack, T. J.; Kanand,
J.; Goddard, R. J. Chem. Soc., Chem. Commun. 1996, 733.
workup gave (E)- and (Z)-1,3-dodecadiene (27 and 23), and
(3E,5E)- and (3Z,5E)-1,3,5-dodecatriene (28 and 25), as shown
in Table 2 (entries 2, 5, 8, and 9). Workup with DCl/
(
(
12) Schlosser, M.; Ladenberger, V. Chem. Ber. 1967, 100, 3893.
13) (a) Kobrich, G.; Flory, K. Chem. Ber. 1966, 99, 1773. (b) Shimizu,
(16) Heasley, V. L.; Lais, B. R. J. Org. Chem. 1968, 33, 2571. Keegstra,
M. A.; Verkruijsse, H. D.; Andringa, H.; Brandsma, L. Synth. Commun.
1991, 21, 721. Alexakis, A.; Barthel, A.; Normant, J. F.; Fugier, C.; Leroux,
M. Synth. Commun. 1992, 22, 1839.
(17) The stereochemistry of 21 and 22 follows from the γ-gauche effect
in the carbon-13 NMRsthe CH(OH) carbons coming at δC 77.27 and 70.88
ppm, respectively.
N.; Shibata, F.; Tsuno, Y. Bull. Chem. Soc. Jpn. 1987, 60, 777.
14) Grandjean, D.; Pale, P. Tetrahedron Lett. 1993, 34, 1155-1158.
Zweifel, G.; Lewis, W.; On, H. P. J. Am. Chem. Soc. 1979, 101, 5101.
15) (a) Alami, M.; Crousse, B.; Linstrumelle, G. Tetrahedron Lett. 1995,
6, 3687. (b) Richardson, S. K.; Jeganathan, A.; Watt, D. S. Tetrahedron
Lett. 1987, 28, 2335.
(
(
3

7042 J. Am. Chem. Soc., Vol. 121, No. 30, 1999
Kasatkin and Whitby
Scheme 3
Scheme 4
D2O gave >95% deuterium incorporation at the expected site
for a product like 7. Stereoselectivity was consistent with clean
2
inversion of configuration of the carbenoid sp center, allowing
for the isomeric purity of the carbenoids as judged from 21
and 22. Since both isomeric carbenoids were available, the
results prove that the 1,2-metalate rearrangement of vinylzir-
conate species 6 is stereospecific with inversion, not merely
stereoselective. Compounds 25 and 28 are homologues (hexyl
rather than pentyl chain) of the galbanolenessnatural products
and vinylzirconocene chlorides followed by hydrolysis gave the
nonterminal dienes 29a and 30, and trienes 31 and 32 with high
yields and stereoselectivity (Table 2, entries 10 and 14-16).
Diene 30 is the pheromone of Malascoma disstria, the forest
20
tent caterpiller, and triene 31 is the ether component of bretonin
2
1
B. We examined the formation and trapping of the carbenoid
isolated from essential oils of galbanum, and of interest in the
perfumery industry.18 Our synthetic method compares well with
40d in more detail. Butyllithium is the most widely used base
1
0
19
for the deprotonation of vinyl chlorides, and indeed exposure
of (E,E)-1-chloro-1,3-dodecadiene (39d) to 1.05 equiv of
butyllithium at -90 °C, followed by the addition of n-hexyl-
or (E)-1-hexenylzirconocene chloride (8a and 9a) or chloro-
trimethylsilane, gave the expected products (29a, 41, and 42)
in excellent yields (Scheme 4). The relative rates by which the
three species trapped the carbenoid were determined by
competition experiments. Exposing a 1:1 mixture of n-hexyl-
zirconocene chloride and chlorotrimethylsilane to 0.85 equiv
of the carbenoid 40d, generated in situ, gave an 88:12 mixture
of the diene 29a and silylated diene 42. Likewise a 1:1 mixture
of n-hexyl- and (E)-1-hexenylzirconocene chloride gave a
the many published routes to these compounds. The incorpo-
ration of functional groups is important for further applications
of this chemistry so we investigated 3-butyn-1-ol as the
hydrozirconation substrate. Reaction of the alcohol with 2.3
equiv of Cp2Zr(H)Cl followed by 1.3 equiv of the carbenoid
20 and protonolysis gave (3E,5Z)-3,5,7-octatrien-1-ol (26) in
good yield and stereoselectivity (Table 2, entry 6). Careful
control of the quantity of Cp2Zr(H)Cl was required to prevent
overreduction of the alkyne and subsequent formation of 5,7-
octadien-1-ol. Hydrozirconation of 1-tert-butyldimethylsiloxy-
3
-butyne followed by reaction with 20, hydrolysis, and depro-
tection with tetrabutylammonium fluoride (TBAF) also gave
4
1:59 mixture of the diene 29a and triene 41. The relative rates
2
6 (entry 7).
of trapping of the carbenoid 40d by chlorotrimethylsilane, 8a,
and 9a is thus 1:7.3:10.5. Of note is that addition of butyllithium
to a mixture of the chloride 39d and organozirconocene 8a gave
no insertion products, and greater than 90% recovery of the
starting chloride, suggesting fast attack of the butyl anion at
the metal, and confirming the importance of the use of the
nonnucleophilic base LiTMP for in situ deprotonations.
To extend the chemistry to nonterminal dienes and trienes
we examined the deprotonation and trapping of (E,E)-4-alkyl-
-chloro-1,3-butadienes. Treatment of the vinyl halides 39a-d
with LiTMP in the presence of an organozirconium species gave
products consistent with the in situ formation of the novel
carbenoid type illustrated by 40a-d (eq 4). Insertion into alkyl-
1
To allow access to internal (Z,Z)-dienes and (Z,Z,E)-trienes
we examined the insertion of the â-acetylenic carbenoid 40e
eq 4), previously reported by Alami and Linstrumelle,1 into
5a
(
organozirconium species. Reaction of 40e with 8a and 9a
worked well to give the enyne 33a and dienyne 34a in good
yields and excellent stereocontrol (Table 2, entries 17 and 19).
Reduction of the alkyne in systems similar to 33a and 34a to
(
18) Chretien-Bessiere, Y.; Garnero, J.; Benezet, L.; Peyron, L. Bull.
22
afford cis alkenes is well-known. Encouraged by the successful
Soc. Chim. Fr. 1967, 97. Naves, Y. R. Bull. Soc. Chim. Fr. 1967, 3152.
Moore, R. E.; Mistysyn, J.; Pettus, J. A. J. Chem. Soc., Chem. Commun.
1
2
972, 326. Moore, R. E.; Pettus, J.; Mistysyn, J. J. Org. Chem. 1974, 39,
(20) For previous synthesis of pheromone 30 see: Rossi, R.; Carpita,
A. Tetrahedron 1983, 39, 287. Gardette, M.; Jabri, N.; Alexakis, A.;
Normant, J. F. Tetrahedron 1984, 40, 2741. Trost, B. M.; Martin, S. J. J.
Am. Chem. Soc. 1984, 106, 4263. Stille, J. K.; Groh, B. L. J. Am. Chem.
Soc. 1987, 109, 813. Huang, Y.-Z.; Shi, L.; Yang, J. J. Org. Chem. 1987,
52, 3558. Fiandanesse, V.; Marchese, G.; Naso, F.; Ronzini, L.; Rotunno,
D. Tetrahedron Lett. 1989, 30, 243. Tsuboi, S.; Ishii, N.; Sakai, I.; Utaka,
M. Bull. Chem. Soc. Jpn. 1990, 63, 1888.
201.
(
19) (a) Solladie, G.; Urbano, A.; Stone, G. B. Synlett 1993, 548 and
references therein. (b) Alami, M.; Gueugnot, S.; Domingues, E.; Lin-
strumelle, G. Tetrahedron 1995, 51, 1209. (c) Furber, M.; Herbert, J. M.;
Taylor, R. J. K. J. Chem. Soc., Perkin Trans. 1 1989, 683. (d) Tellier, F.;
Descoins, C.; Sauvetre, R. Tetrahedron 1991, 47, 7767. (e) Hodgetts, K.
J.; Saengchantara, S. T.; Wallis, C. J.; Wallace, T. W. Tetrahedron Lett.
1
993, 34, 6321.
(21) Mancini, I.; Guella, G.; Pietra, F. HelV. Chim. Acta 1991, 74, 941.

Insertion of 1-Chloro-1-lithioalkenes into Organozirconocenes
J. Am. Chem. Soc., Vol. 121, No. 30, 1999 7043
formation of carbenoid 19 we also tried to generate and trap
the carbenoid 43 from (Z)-1-chlorodec-1-en-3-yne (eq 5).
Scheme 5a
Although Alami and Linstrumelle report failure to trap species
such as 43,1 we obtained a low yield of the expected adduct
5a
3
5 from insertion into n-hexylzirconocene chloride (8a) (Table
a
2
Reaction conditions: 0.8 equiv of halide, 1.0 equiv of ZnCl , 5
2, entry 21), indicating the great speed with which the zirconium
mol % [Pd(PPh
3
)
2
Cl
2
+ 2PPh + 2EtMgBr], THF, 20 °C, 16 h.
3
species traps the anion, and the advantages of in situ generation
using an amide base.
Scheme 6
We next examined the insertion of the parent vinyl carbenoid,
1
-chloro-1-lithioethene (44). Kobrich found that metalation of
13a
vinyl chloride with butyllithium at -110 °C was quantitative,
and 44 has been generated and trapped in situ using LDA/
chlorotrimethylsilane at -78 °C.1 For convenience we treated
a mixture of the organozirconium species 8c or 9d and 1,
3b
2
-dichloroethane with 2 equiv of LiTMP, vinyl chloride being
generated, and metalated in situ (eq 6). Moderate yields of the
expected terminal alkene 36 and (E)-1,3-diene 27 were obtained
(Table 2, entries 22 and 23). The later was formed with complete
stereocontrol, cf. the alternative route to terminal (E)-dienes
using carbenoid 19 (Table 2, entry 8).
Finally we examined insertion of (E)-1,2-dichloro-1-lithio-
coupling with vinyl or allyl halides24 to give the products 46-
ethene (45).13a Treatment of a mixture of (E)-1,2-dichloroethene
and organozirconium species 8c and 9d with LiTMP at -90
4
8 with >95:5 stereopurity (Scheme 5).
Prompted by our successful in situ formation of 19 and 20,
we examined the generation of unusual 1-lithio-1-chloro-1,2,3-
°
C gave rise to the terminal acetylene 37 and enyne 38 in
excellent yield (Table 2, entries 24 and 25), presumably via
anti-elimination of zirconocene dichloride from the intermediate
E)-2-chloroalkenylzirconocene chloride (eq 7).
triene carbenoids 51 from 1,4-dichloro-2-alkynes 49 on treat-
2
5
ment with 2 equiv of LiTMP (Scheme 6). Trapping with
n-octylzirconocene chloride (8b) presumably gave the interme-
diate 52, which underwent regioselective protonation to afford
enynes 53a-c. It is interesting that the 1,2,3-triene product 54
which could also be formed was not observed. In the nonter-
minally substituted cases (53b and 53c) a mixture of double
bond stereoisomers was formed, favoring the trans isomer. We
believe that the regio- and stereochemistry of the protonated
products 53a-c is best explained by the intermediate zirconium
species existing in the enyne form 52b, this protonating on the
carbon carrying the zirconium with retention of configuration.
It is known that hydrolysis of 2-metallo-1,3-dienes gives 1,3-
dienes, rather than the 1,2-dienes which would result from
(
An important feature of the carbenoid insertion route to
unsaturated systems described above is the presence of a
carbon-zirconium bond in the primary products. Workup with
iodine or NBS gave the corresponding vinyl halide in good yield
and excellent stereocontrol (Table 2, entries 3, 11, 12, 18, and
2
6
reaction with allylic rearrangement. The stereochemistry of
the alkene component of 53b,c thus derives from the initial
elimination of hydrogen chloride to afford 50, predominantly
as the cis isomer.
2
0). Formation of bromides was preferred since we found it
difficult to avoid some isomerization of the dienyliodide 29b
during workup (>98% E,E in the crude product by GC, only
(
24) Negishi, E.; Okukado, N.; King, A. O.; Van Horn, D. E.; Spiegel,
B. I. J. Am. Chem. Soc. 1978, 100, 2254. Matsushita, H.; Negishi, E. J.
Am. Chem. Soc. 1981, 103, 2882. Negishi, E.; Takahashi, T.; Baba, S.;
Van Horn, D. E.; Okukado, N. J. Am. Chem. Soc. 1987, 109, 2393.
8
6% E,E after purification). Formation of a new carbon-carbon
2
3
bond was illustrated by the insertion of n-butyl isocyanide,
(
25) We can find no previous reports on elimination of 1,4-dihalo-2-
mild acidic workup giving the aldehydes 24b and 29d as single
geometric isomers (Table 2, entries 4 and 13). Carbon-carbon
bond formation was also achieved by palladium-catalyzed
1
2
1 2
alkynes. For elimination/metalation of R R CXCtCCH2X to afford R R -
CdCdCdCMX (M ) Li, Na; X ) OR, SR) see: Montijn, P. P.; Van
Boom, J. H.; Brandsma, L.; Arens, J. F. Recl. TraV. Chim. 1967, 86, 115.
Mantione, R.; Alves, A.; Montijn, P. P.; Wildschut, G. A.; Bos, H. J. T.;
Brandsma, L. Recl. TraV. Chim. 1970, 89, 97. Visser, R. G.; Bos. H. J. T.;
Brandsma, L. Recl. TraV. Chim. 1981, 100, 34.
(
22) Boland, W.; Schroer, N.; Sieler, C.; Feigel, M. HelV. Chim. Acta
987, 70, 1025. Also refs 19b,d.
23) Negishi, E.; Swanson, D. R.; Miller, S. R. Tetrahedron Lett. 1988,
9, 1631. Buchwald, S. L.; LaMaire, S. J. Tetrahedron Lett. 1987, 28, 295.
1
(
(26) Okamoto, S.; Sato, H.; Sato, F. Tetrahedron Lett. 1996, 37, 8865
and references therein.
2

7044 J. Am. Chem. Soc., Vol. 121, No. 30, 1999
Kasatkin and Whitby
Scheme 7
7). The reaction of 55b with the carbenoid 20 followed by
protonolysis gave 57 in an improved yield of 55% based on
the alkyne (Table 3, entry 3). In similar fashion reaction of 19
with 56b gave (E)-1,3-dodecadien-5-yne (58) in reasonable
yield, and good stereoselectivity. Use of 1-tert-butyldimethyl-
siloxy-3-butyne as the acetylenic component and 20 as the
carbenoid gave (Z)-5,7-octadien-3-yn-1-ol (59) after deprotec-
tion. Reduction of 1,3-dien-5-ynes to (5Z)-1,3,5-trienes with
activated zinc is well-known. In the case of 58 this leads to a
homologue (n-hexyl- rather that n-pentyl-saturated chain) of the
major galbanolene used in the perfumery industry.18 Coupling
of 1-hexynylzirconocene chloride (55a) with the dienyl car-
benoid 40d gave a good yield of the internal (E,Z)-dienyne 60,
and provides potential access to (E,Z,Z) conjugated trienes.
Coupling of the dialkynylzirconocene 56b with the carbenoid
2
2
Table 3. Insertions into Alkynyl Zirconocenes (Scheme 1, R )
CtCR)
4
0e gave the (Z)-3-en-1,5-diyne 61, a motif characteristic of
2
9
the enediyne antitumor compounds. Finally, reaction of the
dialkynylzirconocene 56c with lithiated (E)-1,2-dichloroethene
(45) gave rise to the terminal diyne 62.
Mechanism of the Insertion Reaction and Reasons for
Loss of Stereochemistry of â,â-Disubstituted Vinyl Car-
benoids. For the insertion of â-monosubstituted 1-halo-1-
lithioalkenes the clean inversion of configuration of the sp2
center strongly supports a concerted 1,2-migration mechanism
as shown in Scheme 1. The speed of the insertion and the fact
7
,30
that zirconacycles work wel,
suggest that rearrangement is
of an “ate” complex as shown in eq 1 and Scheme 1; however,
we cannot disprove initial loss of halide to afford a neutral
zirconocene species which undergoes a diotropic rearrangement
3
1
(eq 8).
a
A: 1.3 equiv of Li-carbenoid, THF, -90 to -80 °C, 15 min. B:
as A, then 1 h at -30 °C. C: as A, then 1 h at -50 °C. D: as A, then
For the insertion of â,â-disubstituted vinyl carbenoids the
b
2
h at -15 to 20 °C. After workup with 2 M HCl(aq). c Based on
results given in Table 1 indicate either that the insertion does
not occur by the concerted stereospecific mechanism suggested
in Scheme 1 or that isomerization is occurring before rear-
rangement. In the later case it may be the lithium carbenoid, or
an organozirconium intermediate, that isomerizes. Kobrich
observed rapid isomerization below -85 °C of (Z)- to (E)-1-
d
Cp
2
ZrCl
2
.
After desilylation with TBAF.
With the above methods we can synthesize most geometric
isomers of terminal and nonterminal dienes and trienes. To
complete the scope we needed access to systems which might
be considered derived from a (Z)-alkenylzirconocene. Unfor-
tunately these are only accessible in a few special cases (from
32
chloro-1-lithio-2-phenylpropene. Similar loss of stereochemical
integrity of 2,2-disubstituted 1-lithio-1-haloalkenes generated
by deprotonation has been described by Walborsky and at-
2
7
zirconacycles), so we examined insertions into alkynyl zir-
conocenes. Di(1-octynyl)zirconocene (56b) was readily prepared
in situ from the lithiated alkyne and zirconocene dichloride
6a,33
tributed to “metal assisted ionization” (eq 9).
Harada reported
28
(
Scheme 7). Treatment with 1.3 equiv of the lithium carbenoid
2
0 followed by aqueous workup gave (Z)-1,3-dodecadien-5-
yne (57) in good yield (72%) based on Cp2ZrCl2 but only 36%
yield based on the alkyne (Table 3, entry 1). To obtain the high
yield it was found necessary to warm the reaction mixture to
the rapid isomerization of 1-lithio-1-bromoalkenes derived by
Br/Li exchange, and proved the mechanism to be via rapid
reversible halogen/lithium exchange with unreacted dibromide.34
-20 °C before quenching (Table 3, entry 1, cf. 2). Use of 2
equiv of the carbenoid did not increase the yield of 57 implying
that only one of the two alkyne moieties in 56b reacts. Addition
of 1 equiv of lithiated 1-octyne to zirconocene dichloride gave
predominantly (1-octynyl)zirconocene chloride (55b, Scheme
(29) Nicolaou, K. C.; Smith, A. L. Acc. Chem. Res. 1992, 25, 497.
(30) Fillery, S. M.; Kasatkin, A.; Whitby, R. J. Unpublished results.
(31) Erker, G.; Petrenz, R.; Kruger, C.; Lutz, F.; Weiss, A.; Werner, S.
(
27) Aoyagi, K.; Kasai, K.; Kondakov, D. Y.; Hara, R.; Suzuki, N.;
Organometallics 1992, 11, 1646. Kasai, K.; Liu, Y. H.; Hara, R.; Takahashi,
T. Chem. Commun. 1998, 1989.
(32) Kobrich, G.; Ansari, F. Chem. Ber. 1967, 100, 2011.
(33) Nelson, D. J.; Matthews, M. K. G. J. Organomet. Chem. 1994, 469,
1.
(34) Harada, T.; Katsuhira, T.; Hattori, K.; Oku, A. Tetrahedron 1994,
50, 7987.
Takahashi, T. Inorg. Chim. Acta 1994, 220, 319. Suzuki, N.; Kondakov,
D. Y.; Kageyama, M.; Kotora, M.; Hara, R.; Takahashi, T. Tetrahedron
1
995, 51, 4519. Hara, R.; Liu, Y. H.; Sun, W. H.; Takahashi, T. Tetrahedron
Lett. 1997, 38, 4103.
28) Erker, G.; Froemberg, W.; Benn, R.; Mynott, R.; Angermund, K.;
Krueger, C. Organometallics 1989, 8, 911.
(

Insertion of 1-Chloro-1-lithioalkenes into Organozirconocenes
J. Am. Chem. Soc., Vol. 121, No. 30, 1999 7045
Scheme 8
Scheme 9
6
1
7 (Scheme 9). The slight increase in stereochemical purity of
3 formed from 15 in the presence (Table 4, entry 4) rather
Table 4. Competition and Isomerization Results for
â,â-Disubstituted Carbenoids (Scheme 8)a
than absence (Table 1, entry 9) of chlorotrimethylsilane is
consistent with the model. The chlorotrimethylsilane removes
around a third of the 66 formed by isomerization of 67, without
competing significantly with 8a for 67. The increase in
stereochemical purity of the silane product 63 derived from 12
in the presence rather than absence of 8a (Table 4, entry 3, cf.
%
composition of productsb
8
a, ClSiMe
3
,
entry halide equiv equiv
13 (E:Z)c 63/64 (E:Z)c 65 halide
1
2
3
4
5
6
12
15
12
15
14
14
1.1
1.1
1.2
1.2
1.1
1.2
44 (75:25) 41 15
40 (25:75) 38 22
31 (47:53) 14 (92:8)
1.2
1.2
19 36
10 15
1
) is also consistent with the model. The zirconium species 8a
72 (96:4)
3 (-)
traps most of the organolithium 67 formed by isomerization of
100 (>95:5)
0
0
0
0
6
6 reducing the formation of (Z)-63.
1.2
10 (34:66) 90 (85:15)
In preparative experiments the vinyl iodides 14 and 16 both
a
Conditions: 1 equiv of halide, 1.1 equiv of LiTMP, THF, -90 to
gave around 50% loss of stereochemical integrity in the
formation of 13 (Table 1, entries 8 and 11). Deprotonation/
chlorotrimethylsilane trap of 14 gave (E)-64 with no isomer-
ization or rearrangement to 65 (Scheme 8, Table 4, entry 5).
Competitive trapping of lithiated 14 with 8a and chlorotri-
methylsilane showed the later to be around 9 times faster than
the former. The result is in marked contrast to the analogous
vinyl chloride 12, and consistent with the much larger size of
the halogen and bulky zirconium electrophile. Under the
conditions used in the preparative experiments we believe that
isomerization of the lithiated vinyliodide via “metal assisted
ionization” (eq 9) is the most likely explanation for the loss of
stereochemical integrity. The recovery of partially isomerized
iodide from reactions stopped early (Table 1, entries 7 and 10)
provides evidence that the isomerization occurs prior to 1,2-
metalate rearrangement on the zirconium. No vinyl chloride 12
or 15 was detected in the products providing strong evidence
against a diotropic rearrangement (as eq 10) of a zirconate
intermediate as the mechanism of isomerization. Our failure to
observe either the 1,1-bis-iodide or 2-methyl-1-octene by GC
in reactions of 14 or 16 argues against fast I/Li exchange.
Addition of the vinyl halide 14 slowly to premixed 8a and
LiTMP gave the same results as the usual addition order, again
suggesting that I/Li exchange is not the mechanism of isomer-
ization.
b
c
-
60 °C, 1 h. Combined yield (GC) was >95% in all cases. E:Z
ratios by GC for 13 and 64, by NMR of the crude product for 63.
For isomerization on the zirconium, a diotropic rearrangement
of an intermediate zirconate species is possible (eq 10).
3
1
To probe the mechanisms of loss of stereochemical integrity
we examined the formation/trapping of the carbenoids derived
from (E)- and (Z)-1-chloro-2-methyloctenes 12 and 15 (Scheme
8
). Lithiation of 12 and 15 with an in situ trap of chlorotri-
methylsilane gave the vinyl silanes 63 in around 40% yield,
and with around 50% loss of stereochemical integrity (Table 4,
entries 1 and 2). In each case around 40% of 2-nonyne (65)
derived by Fritsch-Buttenberg-Wiechell rearrangement was
also formed. The results show that the rate of isomerization of
the lithiated vinyl chlorides in the absence of a zirconium species
is around half both their rate of trapping by ClSiMe3 and
decomposition to 65. For the two stereoisomers 12 and 15 the
ratio of isomerization to rearrangement rates is similar. In further
experiments LiTMP was added to a mixture of the vinyl chloride
11
The clean inversion of configuration of lithiated â-monosub-
stituted vinyl halides observed on reaction with organozir-
conocenes is best explained by much slower rates of isomer-
ization of the carbenoid compared with â,â-disubstituted
examples. In the “metal assisted ionization” mechanism for
carbenoid isomerization (eq 9) it is reasonable that â-alkyl
substituents will stabilize the cationic component of the dipolar
intermediate more than â-hydrogens. Furthermore, there should
be greater relief of steric strain accompanying the ionization of
the â,â-disubstituted lithiated vinyl halides compared with the
monosubstituted analogues.
1
2 or 15, chlorotrimethylsilane, and n-hexylzirconocene chloride
(8a) to give the products shown in Table 4 (entries 3 and 4)
after protic workup. At first sight the much greater loss of
stereochemical integrity of the zirconium trapped product 13
compared to the silylated product 63 obtained from lithiated
1
2 (Table 4, entry 3) indicates isomerization on the metal.
However, the relative amounts of zirconium and trimethylsilyl
trapped products in entries 3 and 4, and the reduced amount of
rearrangement product 65 in the second case, are consistent with
8
1
a trapping lithiated 15 (67) around 10 times faster than lithiated
2 (66) (Scheme 9). The greater steric hindrance of the n-hexyl
chain compared with a methyl group to approach of the very
bulky zirconium electrophile provides a reasonable explanation.
Given the much faster trapping of 67 compared with 66 by 8a
the experimental results are consistent with the loss of stereo-
chemical integrity arising from rapid interconversion of 66 and
Conclusion
2-Alkenyl- or 2-alkynyl-1-lithio-1-haloalkenes insert ste-
reospecifically into alkyl-, terminal alkenyl-, and alkynylzir-
conocene chlorides to give new organozirconium species which

7046 J. Am. Chem. Soc., Vol. 121, No. 30, 1999
Kasatkin and Whitby
may be further elaborated. 2,2-Dialkylsubstitued 1-lithio-1-
haloalkenes also insert, but stereochemistry of the vinyl halide
precursor is partially lost, probably via “metal assisted ioniza-
tion”. 1-Lithio-1-chloroethene inserts, but in moderate yield. The
insertion of (E)-1,2-dichloro-1-lithioethylene is followed by 1,2-
elimination of zirconocene chloride to give a terminal alkyne.
0.80 (m, 3H), 1.15-1.45 (m, 6H), 1.78 (m, 2H), 4.02 (d, J ) 1.7 Hz,
2
6
H), 4.41 (m, 1H). IR 2956, 2860, 2220, 1466, 1430, 1263, 1164, 704,
-
1
9 2
49 cm . Anal. Calcd for C H14Cl : C, 55.97; H, 7.31; Cl, 36.72.
Found: C, 55.94; H, 7.16; Cl, 36.69.
General Procedure for the Reaction of Lithium Carbenoids with
Organozirconium Compounds. (A) Preparation of Alkenylzirco-
nium Reagents. To a stirred suspension of Cp Zr(H)Cl (0.402 g, 1.56
2
mmol) in THF (12.0 mL) was added 1-alkene or 1-alkyne (1.30 mmol).
The mixture was stirred at 20 °C for 1 h to give a clear yellow solution
of 8 or 9, respectively. After the mixture was cooled to -90 °C
1-chloro- or 1-iodo-1-alkene (1.69 mmol), 1-chloro-1,3-diene (1.08
mmol), or 1-chloro-1-en-3-yne (1.08 mmol) was added followed by a
solution of LiTMP (1.69 or 1.08 mmol, 0.7 M in THF, freshly formed
from TMP and 1 equiv of BuLi at 0 °C). The reaction mixture was
stirred at -90 to -80 °C for 15 min (for other conditions see Tables
1-3) to give a solution of the alkenylzirconium reagent ready for the
next reaction.
Experimental Section
Materials. Cp
2
Zr(H)Cl (Schwartz reagent) was purchased from
Aldrich. 1-Chloro-2-methyl-1-propene (10), (E)- and (Z)-1,4-dichloro-
2
-butene, â-bromostyrene (E:Z ) 91:9), (E)-1,2-dichloroethylene, 1,2-
dichloroethane, and 1,4-dichloro-2-butyne purchased from a commercial
source were distilled and stored under argon. (E)-1-Iodo-2-methyl-1-
3
5
19b
octene (14), (E,E)-1-chloro-1,3-nonadiene (39c), (E)-1-chloro-1-
3
6
37
decene-3-yne (39e), 1,4-dichloro-2-pentyne, and (E)-1-iodo-1-
3
8
decene were prepared according to procedures described in the
literature.
The lithium carbenoids 19, 20, 44, and 51 were generated from (E)-
and (Z)-1,4-dichloro-2-butene (0.211 g, 1.69 mmol), 1,2-dichloroethane
(
E)-1-Chloro-2-methyl-1-octene (12) was prepared by the reaction
35
of 1-octyne with Me
mixture with N-chlorosuccinimide (0 to 20 °C, 3 h). H NMR δ 0.89
t, J ) 7.2 Hz, 3H), 1.20-1.45 (m, 8H), 1.77 (s, 3H), 2.08 (t, J ) 7.3
3
Al followed by the treatment of the crude reaction
(0.167 g, 1.69 mmol), and substituted 1,4-dichloro-2-butynes (1.69
1
mmol), respectively, by using 2.0 equiv of LiTMP (4.83 mL, 0.7 M in
THF, 3.38 mmol). The alkynylzirconium compounds 55 and 56 were
prepared in solution by treatment of 1-alkyne (1.3 mmol) with BuLi
(
1
3
Hz, 2H), 5.80 (s, 1H). C NMR δ 14.07, 16.34, 22.58, 27.46, 28.76,
3
1.63, 37.09, 111.60, 138.97. IR 3071, 2928, 2857, 1639, 1466, 1378,
(
0.52 mL, 2.5 M in hexane, 1.30 mmol) in THF (12.0 mL) at -20 °C
followed by addition of Cp ZrCl (0.380 g, 1.30 mmol or 0.190 g, 0.65
mmol) and stirring at 0 °C for 2 h.
B) Hydrolysis. To the solution of the alkenylzirconium reagent
-
1
1
9
309, 1180, 1111, 856, 788, 771, 724 cm . Anal. Calcd for C H17Cl:
2
2
C, 67.28; H, 10.66; Cl, 22.06. Found: C, 67.33; H, 10.70; Cl, 22.46.
(Z)-1-Iodo-2-methyl-1-octene (16) was prepared by the reaction of
(
3
9 1
6
propyne with C H13MgBr‚CuBr followed by iodinolysis. H NMR δ
prepared above was added 2 M HCl (aq) (8.0 mL) at -80 °C. The
mixture was warmed to room temperature and stirred for 30 min. After
extraction with ether (12 mL) the organic layer was washed with 2 M
HCl (aq) (10 mL), saturated NaHCO (aq) (10 mL), dried over MgSO ,
3 4
and concentrated under reduced pressure. The residue was purified by
0
1
1
6
.85 (m, 3H), 1.20-1.45 (m, 8H), 1.82 (s, 3H), 2.15 (m, 2H), 5.75 (s,
13
H). C NMR δ 14.26, 22.77, 23.44, 27.09, 29.14, 31.87, 38.83, 73.94,
48.01. IR 3052, 2923, 2855, 1616, 1464, 1377, 1270, 1146, 762, 723,
-
1
76 cm . HRMS calcd for C
9
H17I 252.0375, found 252.0371.
(Z)-1-Chloro-2-methyl-1-octene (15) was prepared by treatment of
column chromatography on silica gel (40-60 petroleum ether).
4
0 1
the iodide 16 with CuCl in N-methylpyrrolidinone (130 °C, 2 h).
NMR δ 0.85 (m, 3H), 1.20-1.45 (m, 8H), 1.65 (s, 3H), 2.12 (t, J )
H
1
(
E)-2-Methyl-2,4-undecadiene (entries 2 and 3 in Table 1). H NMR
1
3
δ 0.90 (t, J ) 6.9 Hz, 3H), 1.25-1.45 (m, 8H), 1.76 (s, 3H), 1.79 (s,
H), 2.09 (m, 2H), 5.58 (dt, J ) 15.4, 7.7 Hz, 1H), 5.82 (d, J ) 9.9
Hz, 1H), 6.26 (dd, J ) 15.4, 9.9 Hz, 1H). IR 3020, 2950, 2825, 2650,
7
3
1
.3 Hz, 2H), 5.68 (s, 1H). C NMR δ 14.24, 20.95, 22.76, 26.89, 29.16,
1.86, 31.96, 111.39, 139.10. Anal. Calcd for C 17Cl: C, 67.28; H,
0.66; Cl, 22.06. Found: C, 67.41; H, 10.72; Cl, 22.24.
E,E)-1-Chloro-1,3-dodecadiene (39d) was prepared by Ni(PPh
catalyzed cross-coupling reaction of (E)-1,2-dichloroethylene with (E)-
3
9
H
-
1
1
615, 1464, 1375, 960, 878 cm . HRMS calcd for C22
H22 166.1722,
(
3 4
)
found 166.1721.
1
9b 1
7-Methyl-7-tetradecene (13, entries 8 and 9 in Table 1). 13C NMR
δ 14.27, 22.84, 23.44, 27.81, 28.05, 28.96, 29.31, 30.12, 31.75, 31.86,
125.43, 135.55 (Z-isomer); 14.27, 16.00, 22.84, 27.91, 27.96, 28.96,
C
8
H
17CHdCHAl(i-Bu)
2
.
H NMR δ 0.85 (t, J ) 7.2 Hz, 3H), 1.15-
1
.40 (m, 12H), 2.00 (m, 2H), 5.63 (dt, J ) 15.8, 7.3 Hz, 1H), 5.89 (dd,
J ) 15.8, 10.3 Hz, 1H), 6.00 (d, J ) 14.2 Hz, 1H), 6.33 (dd, J ) 14.2,
1
3
1
1
3
2
0.3 Hz, 1H). C NMR δ 14.09, 22.67, 29.05, 29.19, 29.28, 29.44,
29.02, 29.89, 31.81, 31.84, 39.74, 124.71, 135.27 (E-isomer). H NMR
1.88, 32.65, 118.18, 126.01, 133.86, 136.30. IR 3063, 3014, 2923,
and IR spectral data were in good agreement with those described in
853, 1643, 1583, 1466, 975, 822, 722 cm- . Anal. Calcd for C12
1
H
-
the literature for both (Z)-13 and (E)-13. An authentic sample of (E)-
43
21
Cl: C, 71.80; H, 10.54; Cl, 17.66. Found: C, 72.43; H, 10.73; Cl,
13 was prepared by the reaction of (E)-C
13ZnCl (THF, 20 °C, 5 mol % Pd(PPh
-Methyl-5,7-tetradecadiene (17, entry 13 in Table 1). H NMR δ
6
H13C(Me)dCHI (14) with
4
1
44
1
7.83. (E,E)-1-Chloro-1,3-heptadiene (39a) and (E,E)-1-chloro-1,3-
C
6
H
3 4
) ).
4
2
octadiene (39b) were prepared similarly.
Z)-1-Chloro-1-decen-3-yne was prepared by the treatment of (Z)-
,2-dichloroethylene with 1-octyne in the presence of BuNH and Pd-
H NMR δ 0.92 (t, J ) 7.3 Hz, 3H), 1.25-1.60 (m,
1
8
(
0
.82 (m, 6H), 1.15-1.40 (m, 12H), 1.67 (s, 3H), 1.90-2.10 (m, 4H),
1
2
5
.56 (dt, J ) 14.7, 7.0 Hz, 1H), 5.80 (d, J ) 11.0 Hz, 1H), 6.24 (dd,
1
9b 1
Cu catalyst.
J ) 14.7, 11.0 Hz, 1H) (5E,7Z-isomer); 1.65 (s, 3H), 5.58 (dt, J )
4.7, 7.0 Hz, 1H), 6.26 (dd, J ) 14.7, 11.0 Hz, 1H) (5E,7E-isomer).
13
8
H), 2.41 (m, 2H), 5.85 (d, J ) 7.4 Hz, 1H), 6.30 (d, J ) 7.4 Hz, 1H).
1
1
3
C NMR δ 14.03, 19.65, 22.54, 28.47, 28.48, 31.31, 74.61, 99.43,
C NMR δ 14.12, 14.27, 22.41, 23.82, 28.31, 29.40, 31.95, 32.38,
2.73, 125.43, 126.56, 132.30, 137.23 (5E,7Z-isomer); 14.12, 14.27,
6.62, 22.45, 22.80, 28.03, 29.22, 31.95, 32.78, 40.02, 124.62, 126.79,
1
1
12.51, 126.68. IR 3085, 2931, 2858, 2215, 1624, 1591, 1466, 1429,
3
1
1
1
2
334, 1133, 850, 818, 721 cm-1. Anal. Calcd for C10
H15Cl: C, 70.37;
H, 8.86; Cl, 20.77. Found: C, 70.51; H, 8.75; Cl, 21.03.
32.45, 136.93 (5E,7E-isomer). IR 3016, 2955, 2821, 2653, 1619, 1464,
1
,4-Dichloro-2-nonyne was prepared from 2-nonyn-1,4-diol by
-1
376, 960, 874 cm . HRMS calcd for C15H28 208.2191, found
3
7 1
treatment with SOCl in the presence of 2,4,6-collidine. H NMR δ
2
08.2195. An authentic sample of the (5E,7E)-17 was prepared by the
13C(Me)dCHI (14) with (E)-BuCHdCHZr(Cl)Cp
2
reaction of (E)-C
THF, 20 °C, 5 mol % Pd(PPh
(Z)-1-Phenyl-1-decene (entry 1 in Table 2). An authentic sample
6
H
(
35) Negishi, E.; Van Horn, D. E.; Yoshida, T. J. Am. Chem. Soc. 1985,
07, 6639.
36) Negishi, E.; Okukado, N.; Lovich, S. F.; Luo, F.-T. J. Org. Chem.
984, 49, 2629.
37) Montijn, P. P.; Brandsma, L.; Arens, J. F. Recl TraV. Chim. 1967,
6, 129.
24
(
3 4
) ).
1
1
8
(
45
of the title compound was prepared by reduction of 1-phenyl-1-decyne.
Its NMR spectral data were in good agreement with those described in
the literature.46
(
(
(
(
38) Suseela, Y.; Periasamy, M. J. Organomet. Chem. 1993, 450, 47.
39) Hoffmann, R. W.; Schlapbach, A. Lieb. Ann. Chem. 1990, 1243.
40) Commercon, A.; Normant, J.; Villieras, J. J. Organomet. Chem.
(43) Obayashi, M.; Utimoto, K.; Nozaki, H. Bull. Chem. Soc. Jpn. 1979,
52, 1760.
1
975, 93, 415.
(
(
41) Zhang, X.; Schlosser, M. Tetrahedron Lett. 1993, 34, 1925.
42) Ratovelomanana, V.; Linstrumelle, G. Tetrahedron Lett. 1984, 25,
(44) Negishi, E.; Valente, L. F.; Kobayashi, M. J. Am. Chem. Soc. 1980,
102, 3298.
6
001.
(45) Kauffmann, T.; Rauch, E.; Schulz, J. Chem. Ber. 1973, 106, 1612.

Insertion of 1-Chloro-1-lithioalkenes into Organozirconocenes
J. Am. Chem. Soc., Vol. 121, No. 30, 1999 7047
1
(
3Z,5E)-1,3,5-Dodecatriene (25, entry 5 in Table 2). H NMR δ
(E)-7-Hexadecen-9-yne (35, entry 21 in Table 2). An authentic
sample of the title compound was prepared by the reaction of (E)-1-
iodo-1-octene with 1-octyne in the presence of CuI.51 Its NMR spectral
0
)
1
1
1
1
1
.88 (t, J ) 6.8 Hz, 3H), 1.25-1.45 (m, 8H), 2.17 (m, 2H), 5.12 (d, J
10.3 Hz, 1H), 5.21 (d, J ) 16.9 Hz, 1H), 5.77 (dt, J ) 15.1, 7.0 Hz,
H), 5.90 (dd, J ) 10.7, 10.3 Hz, 1H), 5.99 (dd, J ) 10.7, 10.3 Hz,
H), 6.52 (dd, J ) 15.1, 10.3 Hz, 1H), 6.82 (ddd, J ) 16.9, J , J )
0.3 Hz, 1H). C NMR δ 14.26, 22.78, 29.09, 29.40, 31.90, 33.14,
5
1
data were in good agreement with those described in the literature.
1
2
3
1
(E)-3-Dodecen-1-yne (38, entry 25 in Table 2). H NMR δ 0.89 (t,
J ) 6.8 Hz, 3H), 1.25-1.45 (m, 12H), 2.13 (m, 2H), 2.78 (d, J ) 1.7
Hz, 1H), 5.47 (d, J ) 15.8 Hz, 1H), 6.25 (dt, J ) 15.8, 6.9 Hz, 1H).
IR spectral data were in good agreement with those described in the
literature.52
1
3
17.27, 125.66, 127.89, 130.45, 132.43, 137.04. IR 3027, 2956, 2855,
-
1
688, 1640, 1618, 1466, 1439, 1378, 973, 941, 900, 724, 645 cm
20 164.1565, found 164.1567.
3E,5Z)-3,5,7-Octatrien-1-ol (26, entries 6 and 7 in Table 2). The
crude tert-butyldimethylsilyl-protected alcohol prepared by the reaction
of 9f with 20 followed by hydrolysis with saturated aqueous NH Cl
was dissolved in THF (5.0 mL). To the solution was added Bu NF
1.30 mL, 1.0 M in THF, 1.30 mmol) and the reaction mixture was
stirred for 2 h at room temperature. After concentration under reduced
pressure the residue was dissolved in ether (10.0 mL), the solution was
4
washed with 2 M HCl (aq) (2.0 mL), dried over MgSO , and
.
HRMS calcd for C12
(
H
1
1-Dodecen-3-yne (53a, Scheme 6). H NMR δ 0.90 (t, J ) 6.8 Hz,
3H), 1.25-1.60 (m, 12H), 2.30 (td, J ) 7.5, 1.7 Hz, 2H), 5.38 (d, J )
10.2 Hz, 1H), 5.57 (d, J ) 17.1 Hz, 1H), 5.80 (dd, J ) 17.1, 10.2 Hz,
1H). IR spectral data were in good agreement with those described in
4
4
53
(
the literature.
2-Tridecen-4-yne54 (53b, Scheme 6). H NMR δ 0.89 (t, J ) 6.9
Hz, 3H), 1.25-1.60 (m, 12H), 1.76 (d, J ) 7.0 Hz, 3H), 2.28 (td, J )
7.3, 1.7 Hz, 2H), 5.47 (d, J ) 15.8 Hz, 1H), 6.06 (dq, J ) 15.8, 7.0
Hz, 1H) (E-isomer); 1.86 (d, J ) 6.6 Hz, 3H), 2.36 (td, J ) 7.3, 1.7
Hz, 2H), 5.89 (dq, J ) 10.7, 6.6 Hz, 1H) (Z-isomer). 13C NMR δ 14.26,
18.59, 19.47, 22.82, 29.01, 29.07, 29.28, 29.36, 32.00, 79.23, 88.71,
111.23, 138.06 (E-isomer); 15.84, 19.68, 110.54, 136.98 (Z-isomer).
1
concentrated again. Purification of the residue by column chromatog-
raphy (silica gel, 40-60 petroleum ether-EtOAc, 2:1) gave the title
alcohol (0.100 g, 62% yield). H NMR δ 1.61 (br s, 1H), 2.35 (dt, J ,
1
1
2
J ) 6.3 Hz, 2H), 3.62 (m, 2H), 5.15 (d, J ) 10.3 Hz, 1H), 5.23 (d, J
1
)
1
1
16.9 Hz, 1H), 5.73 (dt, J ) 15.1, 7.3 Hz, 1H), 5.93 (dd, J ) 10.7,
6-Heptadecen-8-yne (53c, Scheme 6). H NMR δ 0.92 (m, 6H),
0.3 Hz, 1H), 6.00 (dd, J ) 10.7, 10.3 Hz, 1H), 6.62 (dd, J ) 15.1,
1.25-1.60 (m, 18H), 2.08 (m, 2H), 2.36 (td, J ) 7.3, 1.7 Hz, 2H),
5.45 (d, J ) 15.8 Hz, 1H), 6.08 (dt, J ) 15.8, 6.9 Hz, 1H) (E-isomer);
2.32 (m, 4H), 5.55 (d, J ) 10.7 Hz, 1H), 5.80 (dt, J ) 10.7, 6.9 Hz,
1
2
3
13
0.3 Hz, 1H), 6.81 (ddd, J ) 16.9 Hz, J , J ) 10.3 Hz, 1H).
C
NMR δ 36.44, 62.05, 117.94, 128.36, 128.88, 129.60, 131.72, 132.02.
-
1
13
IR 3416, 2930, 1640, 1440, 1109, 1046, 976 cm . HRMS calcd for
1H) (Z-isomer). C NMR δ 14.04, 14.10, 14.13, 19.36, 19.53, 22.51,
C
8
H
(
12O 124.0888, found 124.0887.
22.67, 22.70, 28.52, 28.59, 28.86, 28.89, 28.94, 29.13, 29.15, 29.20,
29.25, 30.00, 31.29, 31.43, 31.85, 32.93, 79.16, 88.71, 94.45, 109.28,
109.76, 142.65, 143.38 (E- and Z-isomers). IR 2950, 2200, 1450, 1000
4
7
1
3E,5E)-1,3,5-Dodecatriene (28, entry 9 in Table 2). H NMR δ
.82 (t, J ) 6.8 Hz, 3H), 1.15-1.40 (m, 8H), 2.02 (m, 2H), 5.05 (d, J
9.9 Hz, 1H), 5.19 (d, J ) 16.9 Hz, 1H), 5.75 (dt, J ) 15.1, 7.0 Hz,
0
-
1
)
cm . HRMS calcd for C17H30 234.2348, found 234.2345.
1
1
1
1
1
H), 6.08 (dd, J ) 15.1, 10.3 Hz, 1H), 6.14 (dd, J ) 14.7, 10.3 Hz,
(Z)-1,3-Dodecadien-5-yne (57, entry 1 in Table 3). H NMR δ 0.88
(t, J ) 6.8 Hz, 3H), 1.25-1.60 (m, 8H), 2.38 (m, 2H), 5.24 (d, J ) 9.6
Hz, 1H), 5.35 (d, J ) 16.9 Hz, 1H), 5.47 (d, J ) 10.8 Hz, 1H), 6.33
H), 6.23 (dd, J ) 14.7, 9.6 Hz, 1H), 6.38 (ddd, J ) 16.9, 9.9, 9.6 Hz,
1
3
H). C NMR δ 14.26, 22.79, 29.05, 29.40, 31.90, 33.01, 116.32,
1
2
13
30.24, 131.11, 133.80, 136.35, 137.35.
(dd, J , J ) 10.8 Hz, 1H), 6.88 (ddd, J ) 16.9, 10.8, 9.6 Hz, 1H).
C
4
8
1
(7Z,9E)-7,9-Octadecadiene (29a, entry 10 in Table 2). H NMR
NMR δ 14.20, 19.82, 22.71, 28.75, 28.91, 31.50, 77.59, 97.32, 110.77,
δ 0.88 (t, J ) 6.8 Hz, 6H), 1.30 (m, 20H), 2.15 (m, 4H), 5.32 (dt, J )
119.48, 134.28, 139.26. HRMS calcd for C12
162.1407.
H18 162.1409, found
1
1
2
3
0.7, 7.7 Hz, 1H), 5.67 (dt, J ) 15.1, 7.0 Hz, 1H), 5.96 (dd, J ) 11.0,
13
0.7 Hz, 1H), 6.32 (dd, J ) 15.1, 11.0 Hz, 1H). C NMR δ 14.25,
2.81, 22.84, 27.86, 29.12, 29.42, 29.45, 29.58, 29.65, 29.88, 31.92,
2.06, 33.05, 125.76, 128.75, 130.23, 134.82.
(Z)-5,7-Octadien-3-yn-1-ol (59, entry 5 in Table 3). The crude tert-
butyldimethylsilyl-protected alcohol from the reaction of 56d with 20
4
followed by hydrolysis with saturated aqueous NH Cl was treated with
1
2
1
Bu NF as described above for 26 to afford the title compound. H NMR
(4E,6Z,8E)-4,6,8-Dodecatrien-1-ol (31, entry 15 in Table 1). For
4
δ 1.96 (br s, 1H), 2.60 (m, 2H), 3.69 (t, J ) 6.4 Hz, 2H), 5.27 (d, J )
deprotection the reaction mixture after addition of 2 M HCl (aq) was
stirred overnight at room temperature and then treated as described
above. H NMR δ 0.80 (t, J ) 7.7 Hz, 3H), 1.32 (m, 2H), 1.50 (br s,
1
0.3 Hz, 1H), 5.37 (d, J ) 17.3 Hz, 1H), 5.47 (d, J ) 10.7 Hz, 1H),
1 2
1
6.36 (dd, J , J ) 10.7 Hz, 1H), 6.85 (ddd, J ) 17.3, 10.7, 10.3 Hz,
1
1
H). 13C NMR δ 24.19, 61.30, 79.38, 93.07, 110.05, 120.26, 134.05,
40.17. IR 3420, 2930, 2215, 1640, 1440, 1109, 1046, 990, 910 cm
1
2
5
3
H), 1.62 (m, 2H), 2.00 (m, 2H), 2.13 (m, 2H), 3.56 (t, J ) 6.8 Hz,
-
1
.
H), 5.70 (dt, J ) 14.7, 7.4 Hz, 1H), 5.72 (dt, J ) 15.1, 7.0 Hz, 1H),
1
3
8 10
HRMS calcd for C H O 122.0732, found 122.0723.
.87 (m, 2H), 6.52 (m, 2H). C NMR δ 13.89, 22.65, 29.37, 32.38,
5.18, 62.58, 125.96, 126.56, 127.40, 128.26, 134.30, 135.79.
1
(7Z,9E)-7,9-Octadecadien-5-yne (60, entry 6 in Table 3). H NMR
4
9
1
δ 0.90 (m, 6H), 1.25-1.60 (m, 16H), 2.15 (m, 2H), 2.41 (m, 2H),
(
6E,8Z,10E)-6,8,10-Hexadecatriene (32, entry 16 in Table 2). H
NMR δ 0.89 (t, J ) 7.3 Hz, 3H), 1.25-1.45 (m, 12H), 2.13 (m, 4H),
.72 (dt, J ) 15.1, 7.7 Hz, 2H), 5.86 (m, 2H), 6.47 (dd, J ) 15.1, 8.6
5
.32 (d, J ) 10.3 Hz, 1H), 5.83 (dt, J ) 15.4, 7.7 Hz, 1H), 6.30 (dd,
2 13
1
J , J ) 10.3 Hz, 1H), 6.58 (dd, J ) 15.4, 10.3 Hz, 1H). C NMR
13.78, 14.26, 19.55, 22.15, 22.83, 29.28, 29.42, 29.63, 31.09, 32.04,
5
13
Hz, 2H). C NMR δ 14.20, 22.70, 29.22, 31.61, 33.10, 125.90, 127.77,
3
3.07, 77.95, 96.30, 107.53, 127.84, 138.24, 139.32. IR 3021, 2925,
1
35.69.
-
1
Z)-7-Hexadecen-9-yne (33a, entry 17 in Table 2). 13C NMR δ
2852, 2211, 1686, 1638, 1464, 1430, 1377, 1326, 980, 957, 743 cm .
(
HRMS calcd for C18H30 246.2348, found 246.2350.
1
4.21, 14.25, 19.68, 22.74, 28.71, 29.02, 30.18, 31.53, 31.84, 94.59,
1
1
(Z)-9-Octadecen-7,11-diyne (61, entry 7 in Table 3). H NMR δ
0.80 (t, J ) 6.8 Hz, 6H), 1.20-1.55 (m, 16H), 2.32 (t, J ) 7.5 Hz,
4H), 5.66 (s, 2H). 13C NMR δ 14.23, 19.95, 22.72, 28.71, 28.83, 31.56,
1
09.42, 142.82. H NMR and IR spectral data were in good agreement
5
0
with those described in the literature.
1
(
5E,7Z)-5,7-Hexadecadien-9-yne (34a, entry 19 in Table 2). H
NMR δ 0.90 (t, J ) 6.8 Hz, 6H), 1.30-1.60 (m, 12H), 2.16 (m, 2H),
.40 (td, J ) 7.5, 1.7 Hz, 2H), 5.32 (d, J ) 10.3 Hz, 1H), 5.86 (dt, J
7
1
8.40, 98.11, 119.07. IR 3027, 3043, 2956, 2917, 2851, 2216, 1685,
-
1
581, 1438, 1400, 1376, 749 cm . HRMS calcd for C18
H
28 244.2191,
Spectral data for 2-methyl-2-undecene55 (entry 1 in Table 1), (Z)-
50) Carlton, L.; Read, G. J. Chem. Soc., Perkin Trans. 1 1978, 1631.
2
found 244.2195.
)
15.4, 7.0 Hz, 1H), 6.28 (dd, J ) 11.0, 10.3 Hz, 1H), 6.57 (dd, J )
5.4, 11.0 Hz, 1H). 13C NMR δ 14.07, 14.21, 19.86, 22.45, 22.75, 28.76,
1
2
8.97, 31.44, 31.53, 32.74, 77.97, 96.37, 107.55, 127.89, 138.17, 139.30.
(
IR 3022, 2928, 2856, 2212, 1686, 1638, 1465, 1377, 1327, 1119, 980,
(51) Ogawa, T.; Kusume, K.; Tanaka, M.; Hayami, K.; Suzuki, H. Synth.
Commun. 1989, 19, 2199.
-
1
9
56 cm . HRMS calcd for C16
H26 218.2035, found 218.2036.
(
52) Rodin, J. O.; Leaffer, M. A.; Silverstein, R. M. J. Org. Chem. 1970,
35, 3152.
(53) Petrov, A. A.; Kupin, B. S.; Yakovleva, T. V.; Mingaleva, K. S.
(46) Periasamy, M.; Prasad, A. S. B.; Suseela, Y. Tetrahedron 1995,
5
1, 2743.
(
47) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918.
Zh. Obshch. Khim. 1959, 29, 3732.
(54) Hamada, T.; Daikai, K.; Irie, R.; Katsuki, T. Tetrahedron: Asym-
metry 1995, 6, 2441.
(48) Bestmann, H. J.; Vostrowsky, O.; Paulus, H.; Billmann, W.;
Stransky, W. Tetrahedron Lett. 1977, 121.
49) Stewart, S. K.; Whiting, A. Tetrahedron Lett. 1995, 36, 3925.
(
(55) Hernandez, D.; Larson, G. L. J. Org. Chem. 1984, 49, 4285.

7048 J. Am. Chem. Soc., Vol. 121, No. 30, 1999
Kasatkin and Whitby
and (E)-1,3-dodecadiene56 (23 and 27, entries 2 and 8 in Table 2),
1323, 1084, 956, 821, 733 cm-1. HRMS calcd for C16
found 296.1135.
H25Br 296.1140,
2
0
(
5Z,7E)-5,7-dodecadien-1-ol (30, entry 14 in Table 2), (E)-1,3-
dodecadien-5-yne (58, entry 4 in Table 3), and 1,3-dodecadiyne58 (62,
entry 8 in Table 3) were in good agreement with those described in
the literature.
57
(E) Reaction with Butyl Isocyanide. To the solution of the
alkenylzirconium reagent prepared above (see A) was added butyl
isocyanide (1.3 equiv). The reaction mixture was warmed to 20 °C
and stirred at room temperature for 16 h. The resulting solution was
cooled to -78 °C, and 50% HOAc (aq) (5.0 mL) was added. After
being warmed to room temperature and stirred for 1 h, water (6.0 mL)
was added and the mixture was extracted with ether (2 × 10 mL). The
(C) Iodinolysis. To the solution of the alkenylzirconium reagent
prepared above (see A) was added a solution of iodine (1.5 or 3.0 equiv)
in THF (2.5 mL) at -80 °C. The mixture was stirred at -60 to -40
°
C over 1.5 h or stirred at 0 °C for 30 min and quenched by addition
of saturated aqueous Na
2
S O
2 3
(8.0 mL). After being stirred at room
organic layer was washed with saturated aqueous NaHCO (3 × 10
3
temperature for 30 min and extracted with ether (12 mL) the organic
layer was washed with brine (10 mL), 2 M HCl (aq) (10 mL), dried
over MgSO , and concentrated under reduced pressure. The crude
4
mL) and brine (10 mL), dried over MgSO , and concentrated under
4
reduced pressure. The residue was purified by column chromatography
(silica gel, 40-60 petroleum ether-EtOAc, 10:1) to afford an aldehyde.
1
product was purified by column chromatography on silica gel (40-60
(E)-2-Hexyl-2,4-pentadienal (24b, entry 4 in Table 2). H NMR δ
petroleum ether) to afford an alkenyl iodide.
0
.78 (m, 3H), 1.20 (m, 8H), 2.27 (t, J ) 7.7 Hz, 2H), 5.50-5.75 (m,
1
13
(E)-2-Methyl-3-iodo-2,4-undecadiene (11, entry 4 in Table 1). H
2H), 6.65-6.85 (m, 2H), 9.44 (s, 1H). C NMR δ 14.19, 22.71, 24.34,
29.28, 29.40, 31.74, 126.44, 132.04, 143.28, 148.86, 195.19. IR 2927,
2857, 2712, 1681, 1630, 1461, 1428, 1366, 1230, 1087, 1004, 930,
NMR δ 0.89 (m, 3H), 1.25-1.50 (m, 8H), 2.02 (s, 3H), 2.10 (s, 3H),
1
3
2
2
.21 (m, 2H), 5.93 (m, 2H). C NMR δ 14.26, 21.15, 22.76, 29.07,
-
1
9.61, 31.86, 32.45, 32.67, 100.51, 128.39, 138.65, 139.36. HRMS calcd
11 18
870, 726 cm . HRMS calcd for C H O 166.1358, found 166.1357.
for C12
H
21I 292.0688, found 292.0710.
1
(
2E,4E)-2-Hexyl-2,4-tridecadienal (29d, entry 13 in Table 2). H
NMR δ 0.80 (m, 6H), 1.15-1.45 (m, 20H), 2.10-2.30 (m, 4H), 6.23
dt, J ) 15.1, 7.0 Hz, 1H), 6.50 (dd, J ) 15.1, 11.0 Hz, 1H), 6.78 (d,
1
7
-Iodo-7,9-octadecadiene (29b, entry 11 in Table 2). H NMR δ
0
2
6
1
.90 (m, 6H), 1.20-1.55 (m, 20H), 2.08 (m, 2H), 2.50 (t, J ) 7.7 Hz,
H), 5.67 (dt, J ) 15.1, 7.0 Hz, 1H), 6.15 (dd, J ) 15.1, 11.0 Hz, 1H),
.74 (d, J ) 11.0 Hz, 1H) (7E,9E-isomer); 5.41 (dt, J ) 10.6, 7.0 Hz,
H), 6.10 (m, 1H), 7.03 (d, J ) 11.0 Hz, 1H) (7E,9Z-isomer). 13C NMR
(
13
J ) 11.0 Hz, 1H), 9.38 (s, 1H). C NMR δ 14.23, 22.75, 22.81, 24.26,
2
1
1
2
8.90, 29.23, 29.36, 29.38, 29.55, 31.79, 32.00, 33.60, 125.91, 140.86,
46.20, 149.77. IR 2930, 2880, 1680, 1631, 1458, 1371, 1209, 1180,
087, 1005, 973, 729 cm . HRMS calcd for C19H34O 278.2610, found
δ 14.25, 22.75, 22.83, 28.13, 29.25, 29.33, 29.43, 29.59, 31.79, 32.03,
-1
3
2.84, 39.16, 104.74, 125.71, 136.57, 140.83 (7E,9E-isomer); 27.83,
78.2613.
2
9.82, 107.50, 123.63, 133.50, 136.28 (7E,9Z-isomer). HRMS calcd
(F) Cross-Coupling with Alkenyl and Allyl Halides. To the
for C18
D) Brominolysis. To the solution of the alkenylzirconium reagent
prepared above (see A) was added N-bromosuccinimide (1.5 equiv) at
80 °C. The mixture was stirred at -60 to -40 °C over 1 h or stirred
H33I 376.1627, found 376.1618.
solution of the alkenylzirconium reagent prepared according to the
general procedure (see A) by the reaction of 8a with 20 and warmed
to room temperature was added anhydrous zinc chloride (0.57 mL, 2.3
M in THF, 1.30 mmol). After the mixture was stirred for 15 min at 20
(
-
at 20 °C for 30 min and hydrolyzed by addition of 2 M HCl (aq) (8.0
mL). After being stirred at room temperature for 30 min and extractive
workup as described above the crude product was purified by column
chromatography on silica gel (40-60 petroleum ether) to afford an
°
1
C, allyl bromide (0.126 g, 1.04 mmol), (E)-â-bromostyrene (0.190 g,
.04 mmol), or (E)-1-iodo-1-decene (0.277 g, 1.04 mmol) was added
followed by a solution of Pd catalyst [preformed by the treatment of
PdCl (PPh (0.037 g, 0.052 mmol) and PPh (0.027 g, 0.104 mmol)
2
3
)
2
3
alkenyl bromide.
with EtMgBr (0.052 mL, 2.0 M in ether, 0.104 mmol) in THF (2.0
mL) at 20 °C]. The reaction mixture was stirred overnight at room
temperature and hydrolyzed by the addition of 2 M HCl (aq) (8.0 mL).
After extraction with ether (12 mL) the organic layer was washed with
2 M HCl (aq) (10 mL) and saturated aqueous NaHCO (10 mL), dried
over MgSO , and concentrated under reduced pressure. The crude
1
(
E)-4-Bromo-1,3-decadiene (24a, entry 3 in Table 2). H NMR δ
0
5
1
2
2
.88 (m, 3H), 1.30 (m, 6H), 1.59 (m, 2H), 2.58 (t, J ) 7.7 Hz, 2H),
.11 (d, J ) 8.8 Hz, 1H), 5.23 (d, J ) 16.2 Hz, 1H), 6.42 (ddd, J )
6.2, 11.0, 8.8 Hz, 1H), 6.52 (d, J ) 11.0 Hz, 1H). 1 C NMR δ 14.20,
2.70, 28.32, 31.72, 36.24, 118.06, 130.66, 131.52, 132.91. IR 2926,
3
3
4
-
1
836, 1719, 1631, 1466, 1377, 1174, 1127, 1068, 982, 908, 725 cm
17Br 216.0514, found 216.0519.
.
product was purified by column chromatography on silica gel (40-60
petroleum ether).
HRMS calcd for C10
H
1
1
(7E,9E)-7-Bromo-7,9-octadecadiene (29c, entry 12 in Table 2). H
(E)-4-Hexyl-1,3,6-heptatriene (46, Scheme 5). H NMR δ 0.91 (m,
NMR δ 0.82 (m, 6H), 1.22 (m, 18H), 1.50 (m, 2H), 1.98 (m, 2H),
.45 (t, J ) 7.7 Hz, 2H), 5.68 (dt, J ) 15.1, 7.0 Hz, 1H), 6.08 (dd, J
3H), 1.25-1.50 (m, 8H), 2.18 (t, J ) 7.7 Hz, 2H), 2.83 (d, J ) 6.9
Hz, 2H), 5.00-5.18 (m, 4H), 5.75-5.85 (m, 1H), 5.88 (d, J ) 10.5
Hz, 1H), 6.61 (ddd, J ) 17.3 Hz, J , J ) 10.5 Hz, 1H). C NMR δ
14.25, 22.78, 28.67, 29.46, 30.92, 31.89, 41.81, 115.39, 116.37, 126.45,
133.25, 136.57, 142.46. IR 3079, 3002, 2953, 2924, 2855, 1634, 1596,
2
)
15.1, 11.0 Hz, 1H), 6.44 (d, J ) 11.0 Hz, 1H). 13C NMR δ 14.24,
1
2
3
13
2
3
1
2.73, 22.82, 28.29, 28.33, 29.28, 29.31, 29.42, 29.59, 31.76, 32.02,
2.99, 36.09, 124.95, 127.27, 132.46, 136.29. IR 2930, 2860, 1680,
633, 1459, 1377, 1075, 970, 888, 725 cm- . HRMS calcd for C18
1
H
33
-
-1
1466, 1429, 1377, 986, 912, 897 cm . HRMS calcd for C H
22
1
3
Br 328.1766, found 328.1764.
E)-7-Bromo-7-hexadecen-9-yne (33b, entry 18 in Table 2). H
NMR δ 0.83 (t, J ) 6.9 Hz, 6H), 1.15-1.50 (m, 16H), 2.21 (td, J )
178.1722, found 178.1727.
1
(
1
(3E,5E)-4-Hexyl-1,3,5-tetradecatriene (47, Scheme 5). H NMR
δ 0.82 (m, 6H), 1.15-1.40 (m, 20H), 2.07 (m, 2H), 2.26 (t, J ) 7.7
Hz, 2H), 5.09 (d, J ) 9.9 Hz, 1H), 5.21 (d, J ) 16.6 Hz, 1H), 5.75 (dt,
J ) 15.4, 7.0 Hz, 1H), 5.96 (d, J ) 11.0 Hz, 1H), 5.99 (d, J ) 15.4
7
.5, 1.7 Hz, 2H), 2.60 (t, J ) 7.9 Hz, 2H), 5.80 (t, J ) 1.7 Hz, 1H).
C NMR δ 14.23, 19.70, 22.72, 27.91, 28.20, 28.70, 31.48, 31.69,
7.74, 76.94, 95.51, 113.10, 139.95. IR 2930, 2860, 2220, 1680, 1633,
1
3
3
1
13
Hz, 1H), 6.67 (ddd, J ) 16.6, 11.0, 9.9 Hz, 1H). C NMR δ 14.26,
-1
459, 1375, 1070, 870, 725 cm . HRMS calcd for C16H27Br 298.1296,
2
1
2.81, 22.84, 27.32, 29.37, 29.45, 29.67, 29.70, 31.90, 32.05, 33.26,
16.60, 129.21, 130.56, 133.36, 133.42, 141.06. IR 3081, 3014, 2923,
found 298.1281.
-
1
(
5E,7E)-7-Bromo-5,7-hexadecadien-9-yne (34b, entry 20 in Table
2854, 1614, 1465, 1377, 1146, 984, 962, 897 cm . HRMS calcd for
C H 276.2817, found 276.2829.
1
2
(
1
2
1
). H NMR δ 0.91 (m, 6H), 1.30-1.65 (m, 12H), 2.25 (m, 2H), 2.38
td, J ) 7.5, 1.7 Hz, 2H), 5.90 (br s, 1H), 6.24 (dt, J ) 14.7, 7.0 Hz,
H), 6.63 (d, J ) 14.7 Hz, 1H). C NMR δ 14.06, 14.21, 19.92, 22.48,
2.74, 28.69, 28.74, 31.33, 31.50, 32.34, 77.45, 98.23, 112.17, 125.66,
33.66, 140.72. IR 2952, 2854, 2207, 1702, 1632, 1464, 1431, 1377,
20
36
3E,5E)-4-Hexyl-6-phenyl-1,3,5-hexatriene (48, Scheme 5). 1
(
H
13
NMR δ 0.88 (t, J ) 6.8 Hz, 3H), 1.25-1.60 (m, 8H), 2.50 (t, J ) 7.8
Hz, 2H), 5.23 (d, J ) 9.9 Hz, 1H), 5.35 (d, J ) 16.9 Hz, 1H), 6.25 (d,
J ) 11.0 Hz, 1H), 6.66 (d, J ) 16.2 Hz, 1H), 6.76 (ddd, J ) 16.9,
1
3
1
1.0, 9.9 Hz, 1H), 6.80 (d, J ) 16.2 Hz, 1H), 7.25-7.50 (m, 5H).
NMR δ 14.32, 22.85, 27.21, 29.70, 29.76, 31.93, 118.09, 126.52,
27.43, 127.80, 132.43, 132.50, 133.35, 137.87, 140.96. IR 3078, 3021,
2925, 2854, 1620, 1493, 1465, 1446, 1416, 1072, 984, 957, 899, 829
C
(
56) Baudin, J. B.; Hareau, G.; Julia, S. A.; Lorne, R.; Ruel, O. Bull.
Soc. Chim. Fr. 1993, 130, 856.
57) Mitsudo, T.; Nakagawa, Y.; Watanabe, K.; Hori, Y.; Misawa, H.;
Watanabe, H.; Watanabe, Y. J. Org. Chem. 1985, 50, 565.
58) Miller, J. A.; Zweifel, G. Synthesis 1983, 128.
1
(
-
1
(
cm . HRMS calcd for C18H24 240.1878, found 240.1879.

Insertion of 1-Chloro-1-lithioalkenes into Organozirconocenes
J. Am. Chem. Soc., Vol. 121, No. 30, 1999 7049
Reaction of the Lithium Carbenoids 19 and 20 with Benzalde-
hyde (Scheme 3). To a solution of (Z)-1,4-dichloro-2-butene (0.150 g,
5,7,9-octadecatriene (41) in 80 and 74% yield, respectively. 41: 1H
NMR δ 0.91 (m, 6H), 1.25-1.50 (m, 16H), 2.17 (m, 4H), 5.71 (dt, J
) 15.1, 7.0 Hz, 2H), 5.86 (m, 2H), 6.50 (dd, J ) 15.1, 8.8 Hz, 2H).
1
(
.20 mmol) in THF (12 mL) was added dropwise a solution of LiTMP
3.43 mL, 0.7 M in THF, 2.40 mmol, freshly formed from TMP and 1
equiv of BuLi at 0 °C) at -90 °C. The reaction mixture was stirred for
13
C NMR δ 14.10, 14.26, 22.45, 22.84, 29.44, 29.56, 29.65, 31.69,
32.06, 32.81, 33.15, 125.92, 127.76, 135.58, 135.66. IR 3025, 2922,
-
1
1
5 min at -90 °C to afford 1, then benzaldehyde (0.165 g, 1.56 mmol)
1688, 1639, 1463, 1378, 1341, 1132, 986, 963, 886, 841, 739 cm
HRMS calcd for C18 32 248.2504, found 248.2505.
Trapping the Lithium Carbenoids Generated from 12 and 14
with Me SiCl (Table 4, entries 1, 5). To a solution of (E)-1-chloro-
2-methyl-1-octene (12, 0.12 g, 0.75 mmol) and Me SiCl (0.090 g, 0.825
.
was added and the mixture was allowed to warm to -40 °C over 1 h.
H
After hydrolysis with 2 M HCl (aq) (8.0 mL) and extraction with ether
(
3 × 5 mL), the organic layer was washed with 2 M HCl (aq) (10 mL)
3
and saturated aqueous NaHCO (10 mL), dried over MgSO , and
3
4
3
concentrated under reduced pressure. The residue was purified by
column chromatography (silica gel, 40-60 petroleum ether-EtOAc,
mmol) in THF (10.0 mL) was added LiTMP (1.18 mL, 0.7 M in THF,
0.825 mmol, freshly prepared from TMP and BuLi) at -90 °C. The
mixture was slowly warmed to -60 °C over 1 h and hydrolyzed by
addition of 2 M HCl (aq) (6.0 mL). After the usual extractive workup
the residue was dried under vacuum (0.5 mmHg, 20 °C, 3 h) to remove
2-nonyne and the unreacted 12. 1-Chloro-1-trimethylsilyl-2-methyl-1-
octene (63, 0.066 g, 38% yield) was isolated as the mixture (75:25) of
3
7
:1) to give (E)-2-chloro-1-phenyl-2,4-pentadien-1-ol (22) (0.180 g,
7% yield). H NMR δ 2.40 (br s, 1H), 5.30 (d, J ) 9.4 Hz, 1H), 5.39
1
(
d, J ) 16.3 Hz, 1H), 5.97 (s, 1H), 6.48 (d, J ) 9.4 Hz, 1H), 6.72
1 2 3 13
(ddd, J ) 16.3 Hz, J , J ) 9.4 Hz, 1H), 7.39 (m, 5H). C NMR δ
0.88, 121.10, 125.88, 128.14, 128.62, 130.02, 130.95, 137.23, 140.07.
7
-1
1
IR 3377, 1493, 1448, 1050, 1011, 984, 917, 696, 657 cm . Anal. Calcd
for C11 11ClO: C, 67.87; H, 5.70; Cl, 18.21. Found: C, 67.73; H,
.66; Cl, 18.60.
(E)- and (Z)-isomers. H NMR δ 0.28 (s, 9H), 0.91 (m, 3H), 1.25-
H
1.45 (m, 8H), 1.92 (s, 3H), 2.15 (m, 2H) (E-isomer); 1.83 (s, 3H),
2.30 (m, 2H) (Z-isomer). 13C NMR δ 0.61, 14.20, 20.68, 22.75, 29.08,
29.44, 31.91, 36.95, 130.22, 149.05 (E-isomer); 0.45, 21.04, 27.15,
36.50, 148.45 (Z-isomer). IR 2927, 2857, 1601, 1466, 1408, 1371, 1250,
5
2
In a similar way the reaction of 19 generated from (E)-1,4-dichloro-
-butene and LiTMP with benzaldehyde gave the mixture (87:13) of
-
1
(
Z)-2-chloro-1-phenyl-2,4-pentadien-1-ol (21) and 22 in 68% yield.
901, 841, 758, 693, 632 cm . HRMS calcd for C12H25ClSi 232.1414,
1
2
5
1
1
1: H NMR δ 2.70 (br s, 1H), 5.32 (s, 1H), 5.35 (d, J ) 9.4 Hz, 1H),
found 232.1416. For confirmation of the stereochemistry (E)-63 was
prepared independently by the reaction of the corresponding (E)-iodide
64 (see below) with CuCl (N-methylpyrrolidinone, 130 °C, 1.5 h) with
complete retention of the configuration.40
1
.41 (d, J ) 16.3 Hz, 1H), 6.58 (d, J ) 9.4 Hz, 1H), 6.72 (ddd, J )
2
3
13
6.3 Hz, J , J ) 9.4 Hz, 1H), 7.39 (m, 5H). C NMR δ 77.27, 121.47,
26.42, 126.87, 128.50, 128.70, 131.59, 136.30, 140.14.
Generation of the Lithium Carbenoid 40d by the Reaction of
In a similar way treatment of (E)-1-iodo-2-methyl-1-octene (14) and
(
E,E)-1-Chloro-1,3-dodecadiene (39d) with BuLi (Scheme 4). To a
3
Me SiCl with LiTMP afforded (E)-1-iodo-1-trimethylsilyl-2-methyl-
1
solution of 39d (0.15 g, 0.75 mmol) in THF (10.0 mL) was added
BuLi (0.30 mL, 2.5 M in hexane, 0.75 mmol) at -90 °C. The mixture
was stirred at -90 °C for 15 min to give a clear yellow solution of
1-octene (64) in 95% yield as only one stereoisomer. H NMR δ 0.29
(s, 9H), 0.92 (m, 3H), 1.25-1.50 (m, 8H), 2.08 (s, 3H), 2.32 (m, 2H).
1
3
C NMR δ 2.16, 14.05, 22.58, 29.08, 29.22, 31.71, 32.50, 38.01,
107.57, 156.49. IR 2957, 2926, 2856, 1641, 1588, 1466, 1407, 1369,
4
3
0d. Me SiCl (0.098 g, 0.90 mmol) was added, and the mixture was
-
1
warmed to -60 °C over 1 h and hydrolyzed with 2 M HCl (aq) (6.0
mL). After extraction with petroleum ether (10 mL) the organic layer
1260, 1097, 1019, 877, 839, 805, 758, 626 cm . HRMS calcd for
25ISi 324.0770, found 324.0768. For confirmation of the stereo-
12
C H
was washed with brine (10 mL), dried over MgSO
under reduced pressure. The residue was purified by column chroma-
4
, and concentrated
chemistry the product was treated with BuLi (ether, -60 °C, 10 min)
followed by hydrolysis to give (Z)-1-trimethylsilyl-2-methyl-1-octene
whose spectral data were in good agreement with those described in
the literature.59
tography on silica gel (40-60 petroleum ether) to give 1-chloro-1-
trimethylsilyl-1,3-dodecadiene (42, 0.161 g, 79% yield) as only one
1
(
presumably 1E,3E) stereoisomer. H NMR δ 0.29 (s, 9H), 0.91 (m,
3
1
H), 1.25-1.45 (m, 12H), 2.10 (m, 2H), 5.74 (dt, J ) 15.1, 7.0 Hz,
Acknowledgment. We thank the EPSRC (grant GR/K19907)
for a postdoctoral award to A.K. R.J.W. thanks Pfizer central
research, Glaxo-Wellcome, and Zeneca for generous uncom-
mitted support.
H), 6.20 (dd, J ) 15.1, 11.4 Hz, 1H), 6.93 (d, J ) 11.4 Hz, 1H). 13
C
NMR δ -0.21, 14.25, 22.81, 29.08, 29.29, 29.42, 29.56, 32.02, 32.94,
126.15, 136.82, 138.57, 143.55. IR 2925, 2854, 1638, 1561, 1466, 1250,
-
1
9
65, 868, 842, 757, 644 cm . Anal. Calcd for C15H29ClSi: C, 66.01;
JA9910208
H, 10.71; Cl, 12.99; Si, 10.29. Found: C, 66.21; H, 10.69; Cl, 12.78;
Si, 10.21.
(
59) Snider, B. B.; Karras, M.; Conn, R. S. E. J. Am. Chem. Soc. 1978,
00, 4624. For the (E)-isomer, see: Chatani, N.; Amishiro, N.; Morii, T.;
Yamashita, T.; Murai, S. J. Org. Chem. 1995, 60, 1834.
In a similar way the reaction of 40d with the zirconium reagents
a, and 9a afforded (7Z,9E)-7,9-octadecadiene (29a) and (5E,7Z,9E)-
1
8