Direct addition of Zr-C bonds of alkylzirconocenes to activated alkenes

Article abstract of DOI:10.1021/jo0260701

Direct addition of alkylzirconocenes to activated alkenes was found, for the first time. Octyl- and decylzirconocene chloride reacted with benzylidenemalononitrile to give the corresponding addition products after hydrolysis in 86% and 79% yield, respecti

Full text of DOI:10.1021/jo0260701

Dir ect Ad d ition of Zr -C Bon d s of Alk ylzir con ocen es to Activa ted
Alk en es
Yuanhong Liu, Baojian Shen, Martin Kotora, Kiyohiko Nakajima,† and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University, and
CREST, Science and Technology Corporation (J ST), Sapporo 060-0811, J apan, and Department of
Chemistry, Aichi University of Education, Igaya, Kariya, Aichi 448-8542, J apan
tamotsu@cat.hokudai.ac.jp
Received J une 18, 2002
Direct addition of alkylzirconocenes to activated alkenes was found, for the first time. Octyl- and
decylzirconocene chloride reacted with benzylidenemalononitrile to give the corresponding addition
products after hydrolysis in 86% and 79% yield, respectively. Zirconacyclopentanes showed a similar
reactivity toward activated alkenes with a two-electron-withdrawing group. On the other hand,
treatment of the reaction mixture of zirconacyclopentanes and ylidenemalononitriles with iodine
afforded six-membered cyclic compounds in high yields. The diastereoselectivity of the cyclized
compound was remarkably high and the high selectivity originated from the Zr-promoted cyclization.
The structures of cyclic compounds 10b and the major diastereoisomer of 10d were determined by
X-ray analysis. Zirconacyclopentenes reacted with ylidenemalononitrile with high chemoselectivity
in which the sp3-carbon attached to zirconium reacted with ylidenemalononitrile.
In tr od u ction
Direct addition of organometallic compounds to acti-
vated alkenes is one of the most useful carbon-carbon
bond formation methods.1 Recently, organozirconocene
compounds have become readily and conveniently avail-
able from alkenes and/or alkynes.2,3 Addition of orga-
nozirconocene to activated alkenes has been done only
after transmetalation4 of the organic moiety from zirco-
nium to Cu,5,6 Zn,7 or Ni.8 Herein we would like to report
the first example of the direct addition of the Zr-sp3
carbon bond of organozirconocenes to activated alkene
(eq 1).9,10
of simple alkylzirconocene compounds such as Cp2Zr(Me)-
Cl (1a ) and Cp2ZrMe2 (1b) with activated alkenes. It was
found that the reaction of these compounds with alkenes
bearing one electron-withdrawing group (EWG), namely,
cinnamonitrile or cinnamyl acetate, did not give any
(4) For reviews on conjugate addition of organozirconium after
transmetalation, see: (a) Wipf, P.; J ahn, H. Tetrahedron 1996, 52,
12853-12910. (b) Lipshutz, B. H.; Bhandari, A.; Lindsley, C.; Keil,
R.; Wood, M. R. Pure Appl. Chem. 1994, 66, 1493-1500.
(5) Conjugate addition of alkenylzirconocene compounds after trans-
metalation to Cu, see: (a) Yoshifuji, M.; Loots, M. J .; Schwartz, J .
Tetrahedron Lett. 1977, 1303-1306. (b) Lipshutz, B. M.; Ellsworth,
E. J . Am. Chem. Soc. 1990, 112, 7440-7441. (c) Lipshutz, B. M.; Wood,
M. R. J . Am. Chem. Soc. 1993, 115, 12625-12626. (d) Isobe, M.; Kondo,
S.; Nagasawa, N.; Goto, T. Chem. Lett. 1977, 679. (e) Lipshutz, B. H.;
Wood, M. R. Tetrahedron Lett. 1994, 35, 6433-6436. (f) Lipshutz, B.
H.; Segi, M. Tetrahedron 1995, 51, 4407-4420.
(6) Conjugate addition of alkylzirconocene compounds after trans-
metalation to Cu, see: (a) Wipf, P.; Smitrovich, J . H. J . Org. Chem.
1991, 56, 6494-6496. (b) Wipf, P.; Smitrovich, J . H.; Lehman, R.;
Venanzi, L. M. Tetrahedron 1994, 50, 1935-1954. (c) Wipf, P.;
Smitrovich, J . H.; Moon, X.-W. J . Org. Chem. 1992, 57, 3178-3186.
(d) Lipshutz, B. H.; Wood, M. R.; Tirado, R. J . Am. Chem. Soc. 1995,
117, 6126-6127.
(7) Conjugate addition of organozirconocene compounds after trans-
metalation to Zn, see: Lipshutz, B. H.; Wood, M. R. J . Am. Chem. Soc.
1994, 116, 11689-11702.
Resu lts a n d Discu ssion
R ea ct ion of Alk ylzir con ocen es w it h Act iva t ed
Alk en es. Our initial study was focused on the reaction
* Address correspondence to this author at Hokkaido University.
† Aichi University of Education.
(1) (a) Perlmutter, P. Conjugate Addition Reactions in Organic
Synthesis; Tetrahedron Organic Chemistry Series, No. 9; Pergamon
Press: Oxford, 1992. (b) Lee, V. J . In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, UK, 1991;
Vol. 4, Chapter 1.2. (c) Posner, G. H. Org. React. 1972, 19, 1. (d)
Kozlowski, J . A. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, UK, 1991; Vol. 4, Chapter
1.4. (e) Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J . A. Tetrahedron
1984, 40, 5005.
(2) For
a recent review on zirconacyclopentanes, zirconacyclo-
pentenes, and zirconacyclopentadienes, see: (a) Takahashi, T.; Kotora,
M.; Hara, R.; Xi, Z. Bull. Chem. Soc. J pn. 1999, 72, 2591-2602 and
references therein. For a recent review on zirconium-alkene and
-alkyne complexes, see: (b) Negishi, E.; Takahashi, T. Bull. Chem.
Soc. J pn. 1998, 71, 755-769 and references therein.
(3) For hydrozirconation of alkenes and alkynes, see: (a) Hart, D.
W.; Schwartz, J . J . Am. Chem. Soc. 1974, 96, 8115-8116. (b) Schwartz,
J .; Labinger, J . A. Angew. Chem., Int. Ed. Engl. 1976, 15, 333. (c)
Wailes, P. C.; Weigold, H. J . Organomet. Chem. 1970, 24, 405. (d)
Wailes, P. C.; Weigold, H.; Bell J . Organomet. Chem. 1971, 27, 373.
(e) Hart, D. W.; Blackburn, T. F.; Schwartz, J . J . Am. Chem. Soc. 1975,
97, 679-680.
(8) Ni-catalyzed conjugate addition of organozirconocenes, see: (a)
Loots, M. J .; Schwarz, J . J . Am. Chem. Soc. 1977, 99, 8045-8046. (b)
Loots, M. J .; Schwartz, J . Tetrahedron Lett. 1978, 4381-4382. See
also: (c) Hauske, J . R.; Dorff, P.; J ulin, S.; Martinelli, G.; Bussolari,
J . Tetrahedron Lett. 1992, 33, 3715-3716. (d) Hauske, J . R.; Dorff, P.;
J ulin, S.; DiBrino, J .; Spencer, R.; Williams, R. J . Med. Chem. 1992,
35, 4284-4296. (e) Sun, R. C.; Okabe, M.; Coffen, D. L.; Schwartz, J .
Org. Synth. 1993, 71, 83-88. (f) Schwartz, J .; Loots, M. J .; Kosugi, H.
J . Am. Chem. Soc. 1980, 102, 1333-1340. (g) Dayrit, F. M.; Glad-
kowski, D. E.; Schwartz, J . J . Am. Chem. Soc. 1980, 102, 3976-3978.
(h) Dayrit, F. M.; Schwarz, J . J . Am. Chem. Soc. 1981, 103, 4466-
4473.
10.1021/jo0260701 CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/07/2002
J . Org. Chem. 2002, 67, 7019-7028
7019

Liu et al.
SCHEME 1
products. On the other hand, the use of alkenes with two
EWG groups, for example, benzylidenemalononitrile 2a ,
resulted in the formation of the desired addition product
2-(1-phenylethyl)propanedinitrile (3a ), although it was
obtained in low yields (20%). However, switching to Cp2-
Zr(n-Oct)Cl (1c) and Cp2Zr(n-Dec)Cl (1d ) which were
prepared in situ by hydrozirconation of 1-octene and
1-decene produced the corresponding 3b and 3c in 86%
and 79% yields, respectively (eq 2).
from alkenes12,13 by Cp2ZrBu2 (Negishi reagent)13a (1
equiv) resulted in an immediate color change from deep-
yellow to light-yellow. After the mixture was stirred for
an appropriate time at 0 or -40 °C, the desired product
9 was formed in up to 96% yield after acidic hydrolysis.
To our surprise, when 2.5 equiv of I2 was added to the
reaction mixture instead of hydrolysis, iodinated products
were not obtained, instead cyclized six-membered car-
bocycles 10 were formed cleanly (Scheme 1). This result
is of potentially synthetic interest because the zircona-
cycles 8 can be converted into highly functionalized
carbocycles in high yields in a one-pot procedure.
Other organozirconocene compounds such as allyl- (4)
and propargylzirconocenes11 (5) reacted with benzyliden-
emalononitrile (2a ) to give conjugate addition products
6 (67%) and 7 (50%).
The results of the reaction with alkylidenepropane-
dinitriles are summarized in Table 1. In all cases,
hydrolysis of the reaction mixture afforded alkylated
propanedinitriles 9 as mixtures of diastereoisomers.
Iodinolysis afforded the corresponding monocyclic or
bicyclic carbocycles 10 as a mixture of diastereoisomers,
which turned out to be easily separated by column
chromatography. However, aliphatic ylidenemalononi-
triles 2d and 2e (entries 8 and 9) did not afford the
desired cyclized products. It is noteworthy that the
reaction of zirconabicyclononane 8b (entry 2) with 2a
afforded 10b as a single isomer after iodinolysis. Also,
in the case of the products 10c, 10d , and 10e (entries 3,
4, and 5) the ratio of the diastereoisomers was unexpect-
edly high (7:1, 10:1, and 8:1). X-ray analysis of 10b and
the major isomer of 10d confirmed their structures as
well as the relative stereochemistry of the substituents
at the bicyclic systems. The influence of a phenyl group
on diastereoselectivity of cyclization is noteworthy. On
The above-mentioned results prompted us to study the
reactions of zirconacycles such as zirconacyclopentanes
and -pentenes as alkylzirconocene derivatives with the
activated alkenes.
Rea ction of Zir con a cyclop en ta n es w ith Activa ted
Alk en es. We chose zirconacyclopentane 8 to investigate
the reactions with activated alkenes. The best results of
the direct addition were obtained with alkenes 2a -k
activated by two electron-withdrawing groups such as
CN, COOR, and SO2Ph. In a typical reaction, addition
(9) For reactions with CO: (a) Negishi, E. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
UK, 1991; Vol. 4, Chapter 1.2. Insertion of aldehydes into the Zr-C
bond: (b) Coperet, C.; Negishi, E.; Xi, Z.; Takahashi, T. Tetrahedron
Lett. 1994, 35, 695-698.
(10) Recently we have reported 1,1-cycloaddition of zirconacyclo-
pentadienes to propynoates without transmetalation: Takahashi, T.;
Sun, W.-H.; Xi, C.; Kotora, M. Chem. Commun. 1997, 2069-2070.
However, substituted propynoates did not react with zirconacyclopen-
tadienes.
(11) Ito, H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y. Tetrahedron
1995, 51, 4507-4518.
(12) (a) Takahashi, T.; Fischer, R.; Xi, Z.; Nakajima, K. Chem. Lett.
1996, 357-358. (b) Xi, Z.; Hara, T.; Takahashi, T. J . Org. Chem. 1995,
60, 4444-4448.
(13) (a) Negishi, E.; Cederbaum, F. E.; Takahashi, T. Tetrahedron
Lett. 1986, 27, 2829. (b) Rousset, C. J .; Swanson, D. R.; Lamaty, F.;
Negishi, E. Tetrahedron Lett. 1989, 30, 5105.
of ylidenemalononitrile (2, 1.2 equiv) to a THF solution
of zirconacyclopentanes (8) at 0 °C or -40 °C prepared
7020 J . Org. Chem., Vol. 67, No. 20, 2002

Direct Addition of Zr-C Bonds to Activated Alkenes
TABLE 1. Rea ction of Zir con zcyclop en ta n es 8 w ith Ylid en em a lon on itr iles 2
a
b
GC or 1H NMR yields. Isolated yields are given in parentheses. Below the yields are given diastereomeric ratios. Unless otherwise
noted, all the reactions were carried out at 0 °C for 1 h for the addition reaction. Cyclization was done by treatment with 2.5 equiv of I2,
d
20 °C, 3 h. c -20 °C, 3 h. -40 °C, 3-9 h. e 0 °C, 9 h. f An inseparable mixture of products was obtained.
the other hand, the use of alkylidenepropanedinitriles 2b
and 2c (entries 6 and 7) bearing thienyl and furyl groups
afforded products in rather low diastereoisomeric ratios
of 2:1 and 2.6:1, respectively. The reaction of zirconabi-
cyclononene 8e with 2a followed by deuteriolysis with
20% DCl in D2O afforded, after workup, dideuterated
compound 9d -D in 92% yield with high deuterium
incorporation (D1 ) 92%, D2 > 98%) (eq 3).
To investigate the scope of the reaction we tested a
number of differently substituted activated alkenes
2f-k . The results are summarized in Table 2. Simple
J . Org. Chem, Vol. 67, No. 20, 2002 7021

Liu et al.
TABLE 2. Rea ction of Zir con a cyclop en ta n es 8 w ith Va r iou s Su btitu ted Alk en es 2
a
GC or 1H NMR yields. Isolated yields are given in parentheses. Below the yields are given diastereomeric ratios.
zirconacyclopentane 8a reacted with both 2f and 2g to
give high yields of products 9i and 9j as a mixture of
diastereoisomers in good yields (72 and 89%). Reaction
of 8d with 2h afforded 9k in almost quantitative yield
(97%) as a mixture of four stereoisomers with a ratio of
3.7:3.7:1.4:1. Reaction proceeded even with tetrasubsti-
tuted 2i to give 9l in a reasonable yield of 51% as a 1.4:1
mixture of diastereoisomers. When tetracyanoethylene
(2j) was used, substitution occurred to afford alkyltri-
cyanoethylene derivative 9m in high yield (87%). Pre-
sumably the addition and elimimation took place. The
reaction with 2k afforded a low yield of 9n (24%).
The reaction of 8a with 2h followed by iodinolysis
afforded substituted cyclohexane 10h as a single isomer
group. It is also reasonable to assume that this config-
uration provides more stable isomer due to steric re-
quirements.
Rea ction of Zir con a cyclop en ten es w ith Activa ted
Alk en es. Zirconacyclopentenes (11),15 which have one
Zr-sp3 C bond, reacted with 2a as well (Scheme 2). The
results are summarized in Table 3. Hydrolysis of the
reaction mixtures afforded substituted 2-(4-pentenyl)-
propanedinitriles (12), and iodinolysis afforded substi-
tuted 2-(5-iodo-4-pentenyl)propanedinitriles (13). The
reaction of 2a proceeded also with zirconaindan 11d
(Table 3, entry 4) to give the products of hydrolysis and
iodinolysis, 12d and 13d , in reasonable yields, respec-
tively. As expected, the formation of cyclic products after
iodinolysis was not detected. It is interesting to note that
the sp3 carbon attached to Zr selectively added to alkenes
(14) (a) Avenoza, A.; Cativiela, C.; Paris, M.; Peregrina, J . M.
Tetrahedron: Asymmetry 1995, 6, 1409-1418. (b) Cativiela, C.;
Avenoza, A.; Paris, M.; Peregrina, J . M. J . Org. Chem. 1994, 59, 7774-
7778.
(15) (a) Reference 12b. (b) Takahashi, T.; Xi, Z.; Rousset, C. J .;
Suzuki, N. Chem. Lett. 1993, 1001-1004. (c) Takahashi, T.; Kageyama,
M.; Denisov, V.; Hara. R.; Negishi, E. Tetrahedron Lett. 1993, 34, 687-
690. (d) Takahashi, T.; Xi, C.; Xi, Z.; Kageyama, M.; Fischer, R.;
Nakajima, K.; Negishi, E. J . Org. Chem. 1998, 63, 6802-6806.
in high yield (88%).14 Although speculative, it is reason-
able to assume that the initial geometry of the double
bond of 2h was retained during the reaction with the
ethoxycarbonyl group in a trans position to the phenyl
7022 J . Org. Chem., Vol. 67, No. 20, 2002

Direct Addition of Zr-C Bonds to Activated Alkenes
TABLE 3. Dir ect Rea ction of Zir con a cyclop en ten es 11 w ith Ylid en em a lon itr ile 2a
a
b
GC or 1H NMR yields. Isolated yields are given in parentheses. Unless otherwise noted, all the reactions were carried out from 0 to
20 °C, 3 h for the addition reaction. Iodination was done by treatment with 2.5 equiv of I2, 0 °C, 3 h. c -20 °C, 1 h. -78 to 30 °C.
d
SCHEME 2
the direct addition (without transmetalation) to the
activated alkenes occurred on the sp3 carbon selectively.
Rea ction Mech a n ism . Generally, two reaction mech-
anisms for the conjugate addition of organometals can
be considered: (i) single electron transfer (SET) and (ii)
direct nucleophilic addition (Scheme 3). For the case of
conjugate addition of transition metal compounds such
as organocopper and -nickel compounds, evidence sup-
porting both mechanisms has been presented; however,
definitive conclusion remains open.17 On the other hand,
one-electron oxidation of d0 organometallics was docu-
mented by using TTFC, Ag+, TCNQ, or [Cp2Fe]+ as
oxidant.18 For example, J ordan and co-workers have
reported that Cp2ZrR2 (R ) CH3, CH2Ph) reacted with
Ag+ or [Cp2Fe]+ to produce the cationic complexes Cp2-
ZrR(L)+ along with the loss of alkyl radical.18a Thus a
plausible mechanism in a SET pathway might involve
the following: (i) electron transfer between 8 and 2
leading to a transient radical ion pair 14, (ii) homolysis
of the metal-carbon bond to form the radical-cation pair
15, and (iii) addition of the radical to the reduced olefinic
substrate followed by collapse of the pair to give the same
intermediate 16 as in the pathway of nucleophilic addi-
tion. Hydrolysis of 16 afforded linear product 9.
in the case of zirconacyclopentenes. The chemoselectivity
in this case is in sharp contrast to the copper-mediated
Michael addition reactions of zirconacyclopentenes where
the sp2 carbon attached to Zr selectively added to alkenes
as Lipshutz et al reported.5i,16 The sp2 carbon on Zr is
more reactive toward transmetalation to Cu, since the
π-bond can have strong interaction with Cu. On the other
hand, the nucleophilicity of the sp3 carbon is generally
higher than that of the sp2 carbon, and for the radical
path, the sp3 carbon-Zr bond is favorable for the ho-
molytic cleavage over the sp2 carbon-Zr bond. Therefore,
(17) Detailed discussion on the reaction mechanism of conjugate
additions of organometals can be found in the following references:
1a, 8g, and 8h.
(18) (a) J ordan, R. F.; LaPointe, R. E.; Bajgur, C. S.; Echols, B. S.
F.; Willett, R. J . Am. Chem. Soc. 1987, 109, 4111-4113. (b) Burk, M.
J .; Staley, D. L.; Tumas, W. J . Chem. Soc., Chem. Commun. 1990, 809-
810. (c) Burk, M. J .; Tumas, W.; Ward, M. D.; Wheelar, D. R. J . Am.
Chem. Soc. 1990, 112, 6133-6135 and references therein.
(16) Kasai, K.; Kotora, M.; Suzuki, N.; Takahashi, T. J . Chem. Soc.,
Chem. Commun. 1995, 109-110.
J . Org. Chem, Vol. 67, No. 20, 2002 7023

Liu et al.
SCHEME 3
SCHEME 4
SCHEME 5
The other noteworthy observation was high diastereo-
selectivity of the cyclization of the addition products upon
iodinolysis. In many cases, the diastereoselectivity of the
cyclized products was enhanced compared with that of
the corresponding hydrolysis products. To clarify the
origin of this phenomenon it is important to find at which
reaction step the diastereoselection took place. We con-
ducted the reactions shown in Scheme 4 to find this
origin.The reaction of 8d with 2a was carried out at 0
°C and was followed by the addition of iodine (2.5 equiv)
at -20 °C (Scheme 4). Monoiodination product 17 was
obtained as a mixture of two diastereoisomers in 40%
yield along with the formation of 9c in 30% yield. The
formation of 17 at low temperature clearly indicates that
the intermediate for the cyclization after addition of
iodine is 18 (Scheme 5).
The intermediate 18 was in situ prepared by treatment
of 17 with LDA at -60 °C for 1 h and by subsequent
addition of zirconocene dihalides at the same tempera-
ture. When the intermediate 18 in solution was warmed
to room temperature, the expected cyclization proceeded
and the final product 10d was obtained as shown in
Scheme 5. Surprisingly, the diastereoselectivity was
remarkably increased to 5:1 when 18 was prepared in
situ with Cp2ZrI2. Control experiment with NaH afforded
10d without change of the diaseteoselectivity. It is quite
interesting to note that the zirconium-promoted cycliza-
tion controlled the diastereoselectivity of the cyclized
product. This is the origin of the enhancement of the ratio
of diastereoisomers of the cyclized product after addition
of iodine.
The overall reaction mechanism from 8d to 10d is
shown in Scheme 6. It involves the direct addition of the
sp3 carbon attached to zirconium of 8d to 2a and
iodination of the intermediate 16d giving 18. Cyclization
of the major isomer of 18 is much faster than that of the
minor isomer since the minor isomer has a sterical
problem between the Ph group and the I group in its
chair conformation.
Exp er im en ta l Section
All reactions were carried out with the standard Schlenk
technique under nitrogen. THF was distilled over sodium/
benzophenone. All commercial reagents were used without
further purification. Flash chromatography was performed
with Merck silica gel 60 (40-60 µm). n-Butyllithium (1.6 M
solution in hexane) was used as purchased. Zirconacyclopen-
tanes 8a ,12b 8b -c,13b and 8d -f,19 zirconacyclopentenes
11a -c,15c zirconaindan (11d ),20 and allylic and propargylic
zirconocene compounds 4 and 511 were prepared according to
the previously published procedures. Benzylidenemalononitrile
(2a ) and tetracyanoethylene (2j) were used as purchased.
(19) Takahashi, T.; Kotora, M.; Kasai, K. J . Chem. Soc., Chem.
Commun. 1994, 2693-2694. For the preparation of 1,4,7-trienes, see:
Takahashi, T.; Kotora, M.; Kasai, K.; Suzuki, N. Tetrahedron Lett.
1994, 35, 5685-5688.
7024 J . Org. Chem., Vol. 67, No. 20, 2002

Direct Addition of Zr-C Bonds to Activated Alkenes
SCHEME 6
Other ylidenemalononitriles 2b-i were prepared by the
condensation reaction of malononitrile with aldehydes or
ketones.21
127.72, 128.64, 129.07, 136.78. HRMS calcd for C18H24N2
268.1938, found 268.1939.
Rea ction of Allylzir con iu m (4) w ith Ben zylid en em a -
lon on itr ile. 2-(1-P h en yl-3-bu ten yl)p r op a n ed in itr ile (6).23
To a solution of allylzirconium compound 4 (prepared from 1.1
mmol of Cp2ZrCl2)11 was added benzylidenemalononitrile (0.17
g, 1.1 mmol) at 0 °C with stirring for 3 h. The reaction mixture
was qeunched with 3 N HCl and extracted with Et2O. Column
chromatography on silica gel (hexane/EtOAc) afforded the
product. GC yield 67%. Isolated yield 60%. A colorless liquid:
1H NMR (CDCl3, Me4Si) δ 2.69-2.80 (m, 2H), 3.25-3.31 (m,
1H), 4.00 (d, J ) 5.7 Hz, 1H), 5.15-5.26 (m, 2H), 5.60-5.71
(m, 1H), 7.24-7.43 (m, 5H); 13C NMR (CDCl3, Me4Si) δ 28.88,
36.36, 45.80, 111.49, 111.91, 119.76, 127.86, 128.90, 129.14,
132.95, 136.3. HRMS calcd for C13H12N2 196.1000, found
196.1002.
Reaction of P r opar gylic Zir con iu m 5 with Ben zyliden e-
m a lon on itr ile. 2-(4-ter t-Bu tyld im eth ylsilyl-1-p h en yl-3-
bu tyn yl)p r op a n ed in itr ile (7). To a solution of propargylzir-
conium compound 5 (prepared from 1.1 mmol of Cp2ZrCl2)11
was added benzylidenemalononitrile (0.17 g, 1.1 mmol) at 0
°C. After being stirred at room temperature for 3 h, the
reaction mixture was qeunched with 3 N HCl and extracted
with Et2O. Column chromatography on silica gel (hexane/
EtOAc) afforded the product. Isolated yield 58%. A colorless
liquid: 1H NMR (CDCl3, Me4Si) δ 0.09 (s, 6H), 0.89 (s, 9H),
2.89 (t, J ) 6.6 Hz, 2H), 3.40-3.45 (m, 1H), 4.36 (d, J ) 6.2
Hz, 1H), 7.37-7.45 (m, 5H); 13C NMR (CDCl3, Me4Si) δ -4.75,
16.36, 23.93, 25.93, 28.10, 45.23, 88.40, 101.27, 111.18, 111.77,
127.65, 129.14, 129.20, 135.58. HRMS calcd for C19H24N2Si
308.1707, found (M + 1) 309.1788.
1H and 13C NMR spectra were recorded in CDCl3 (containing
1% TMS) solutions at 400 and 100 MHz, respectively. All
melting points were determined by a micro melting point
apparatus and are uncorrected. GC analysis was performed
on a SHIMADZU GC-14A equipped with a fused silica capil-
lary column SHIMADZU CBP1-M25-O25 and a SHIMADZU
C-R6A-Chromatopac integrator. Single-crystal X-ray diffrac-
tion data were collected in Enraf-Nonius CAD4 diffractometers
with molybdenum or copper cathodes. The characterization
data of compounds 3c, 9(d -D), 9f, 9l, 10a , 10c, 10g, and 13b,
and structures of 10b and 10d are given in the Supporting
Information.
Gen er a l P r oced u r e for t h e R ea ct ion of Alk ylzir -
con ocen e Com p ou n d s w ith Ben zylid en em a lon on itr ile
(2a ). To a suspension of Cp2ZrHCl (0.26 g, 1 mmol) in THF (5
mL) was added 1-alkene (1 mmol) with stirring at room
temperature for 1 h. Then benzylidenemalononitrile (0.23 g,
1.5 mmol) was added and the mixture stirred at room tem-
perature for 12 h. The reaction mixture was extracted with
Et2O (3 × 10 mL) and the combined organic extracts were
washed with water, aq NaHCO3, and brine and dried (MgSO4).
Filtration and evaporation followed by column chromatography
on silica gel (hexane/EtOAc) afforded the products.
2-(1-P h en yleth yl)p r op a n ed in itr ile (3a ). This compound
was formed by the reaction of 1a or 1b with 2a . Its spectra
were consistent with the published data.22 GC yield 20%.
2-(1-P h en yln on yl)p r op a n ed in itr ile (3b). GC yield 86%.
Isolated yield 75%. A colorless liquid: 1H NMR (CDCl3, Me4-
Si) δ 0.86 (t, J ) 7.0 Hz, 3H), 1.22-1.29 (m, 12H), 1.94-2.00
(m, 2H), 3.17 (td, J ) 7.0, 6.2 Hz, 1H), 3.88 (d, J ) 6.2 Hz,
1H), 7.29-7.41 (m, 5H); 13C NMR (CDCl3, Me4Si) δ 13.92,
22.46, 26.77, 28.96, 29.05, 30.07, 31.59, 31.94, 46.33, 111.97,
Gen er a l P r oced u r e for th e P r ep a r a tion of 9. To a
solution of zirconacyclopentane 8 (prepared from 1.1 mmol of
Cp
2ZrCl2)12b,13b,19 was added ylidenemalononitrile 2 (1.2-2
mmol) at -40 °C or 0 °C with stirring for the appropriate time
(see Table 1). The reaction mixture was quenched with 3 N
HCl and extracted with ether. Combined organic extracts were
washed with aqueous NaHCO3 and water, dried (MgSO4), and
concetrated in vacuo. Column chromatography on silica gel
(hexane/EtOAc) afforded the products.
(20) (a) Erker, G. J . Organomet. Chem. 1977, 134, 189. (b) Erker,
G.; Kropp, K. J . Am. Chem. Soc. 1979, 101, 3659. (c) Kropp, K.; Erker,
G. Organometallics 1982, 1, 1246. See also: (d) Buchwald, S. L.;
Watson, B. T.; Huffman, J . C. J . Am. Chem. Soc. 1986, 108, 7411-
7413.
(21) Allen, C. F. H.; Spangler, F. W. Organic Syntheses; Wiley: New
York, 1955; Collect. Vol. 3, pp 377-379.
(22) Chikashita, H.; Nishida, S.; Miyazaki, M.; Morita, Y.; Itoh, K.
Bull. Chem. Soc. J pn. 1987, 60, 737.
(23) This compound was reported, but the NMR data were not
available. Kazuhiko, M.; Munehiro, I.; Yoshio, O. Chem. Lett. 1988, 9,
1507.
J . Org. Chem, Vol. 67, No. 20, 2002 7025

Liu et al.
2-(1-P h en ylpen tyl)pr opan edin itr ile (9a).24 GC yield 90%.
Isolated yield 73%. A colorless liquid: 1H NMR (CDCl3, Me4-
Si) δ 0.85 (t, J ) 7.2 Hz, 3H), 1.10-1.41 (m, 4H), 1.94-2.00
(m, 2H), 3.17-3.20 (m, 1H), 3.88 (d, J ) 6.3 Hz, 1H), 7.29-
7.41 (m, 5H); 13C NMR (CDCl3, Me4Si) δ 13.56, 22.04, 28.85,
30.03, 31.63, 46.26, 111.98, 127.70, 128.61, 129.05, 136.78.
HRMS calcd for C14H16N2 212.1313, found 212.1306.
2-[2-(cis-2-Meth ylcycloh exyl)-1-p h en yleth yl]p r op a n e-
d in itr ile (9b). GC yield 84%. Isolated yield 70% (3.4:1 mixture
of diastereoisomers). A colorless liquid. The major isomer: 1H
NMR (CDCl3, Me4Si) δ 0.83 (d, J ) 7.1 Hz, 3H), 1.09-1.64
(m, 9H), 1.76-1.93 (m, 3H), 3.22-3.28 (m, 1H), 3.85 (d, J )
6.1 Hz, 1H), 7.29-7.40 (m, 5H); 13C NMR (CDCl3, Me4Si) δ
12.98, 21.21, 25.39, 28.19, 30.24, 30.39, 32.50, 35.06, 36.85,
43.88, 112.21, 127.91, 128.75, 129.19, 137.13. The minor
isomer: 1H NMR (CDCl3, Me4Si) δ 0.91 (d, J ) 7.0 Hz, 3H),
other peaks were overlapped by the signals of the major
diastereoisomer; 13C NMR (CDCl3, Me4Si) δ 15.14, 22.66, 23.73,
26.82, 30.64, 31.72, 32.88, 33.46, 36.38, 44.12, 112.18, 127.97,
136.89, other peaks were overlapped by the signals of the
major diastereoisomer. HRMS calcd for C18H22N2 266.1783,
found 266.1778.
NMR (CDCl3, Me4Si) δ 13.12, 28.43, 31.85, 33.08, 34.80, 34.84,
38.40, 38.59, 109.21, 111.58, 125.78, 125.80, 127.65, 132.26,
133.05, 142.71, 143.10, other peaks were overlapped by the
signals of the major diastereoisomer. HRMS calcd for C28H26N2O
406.2044, found 406.2032.
2-[2-(cis-3,4-Dieth yl-6-m eth ylcycloh ex-3-en yl)-1-(1-m e-
th yleth yl)eth yl]p r op a n ed in itr ile (9g). GC yield 70%. Iso-
lated yield 58% (2.8:1 mixture of diastereoisomers). A colorless
liquid. The major isomer: 1H NMR (CDCl3, Me4Si) δ 0.79 (d,
J ) 6.9 Hz, 3H), 0.90-1.11 (m, 13H), 1.39-1.44 (m, 1H), 1.52-
1.64 (m, 1H), 1.68-1.80 (m, 2H), 1.80-2.21 (m, 9H), 3.79 (d,
J ) 4.0 Hz, 1H); 13C NMR (CDCl3, Me4Si) δ 12.96, 13.11, 13.24,
18.94, 19.37, 25.09, 25.46, 29.37, 30.06, 30.68, 32.05, 34.39,
36.16, 42.94, 112.55, 112.89, 128.80, 129.31. The minor
isomer: 1H NMR (CDCl3, Me4Si) δ 0.87 (d, J ) 6.8 Hz, 3H),
3.82 (d, J ) 4.3 Hz, 1H), other peaks were overlapped with
the signals of the major isomer; 13C NMR (CDCl3, Me4Si) δ
13.01, 13.17, 14.65, 18.54, 19.82, 25.09, 25.43, 29.17, 30.24,
30.68, 31.96, 34.60, 35.61, 43.15, 112.65, 112.80, 128.40,
129.88, other peaks were overlapped with the signals of the
major isomer. HRMS calcd for C19H30N2 286.2407, found
286.2418.
2-[1,1-Dieth yl-2-(cis-6-m eth yl-3,4-d ip h en ylcycloh ex-3-
en yl)eth yl]p r op a n ed in itr ile (9h ). Isolated yield 45%. A
colorless liquid: 1H NMR (CDCl3, Me4Si) δ 0.98 (t, J ) 7.4
Hz, 6H), 1.07 (d, J ) 6.7 Hz, 3H), 1.51-1.73 (m, 6H), 2.07-
2.36 (m, 4H), 2.50-2.55 (m, 1H), 2.69-2.75 (m, 1H), 3.67 (s,
1H), 6.95-7.11 (m, 10H); 13C NMR (CDCl3, Me4Si) δ 8.05, 8.09,
13.80, 27.95, 28.39, 31.07, 32.22, 32.39, 36.99, 37.66, 39.36,
43.90, 112.24, 125.78, 125.85, 127.55, 127.64, 128.83, 133.12,
133.27, 142.90, 143.12. HRMS calcd for C28H32N2 396.2564,
found 396.2580.
2-Cya n o-3-isop r op ylh ep ta n oic Acid Eth yl Ester (9i).
GC yield 72%. Isolated yield 61% (1.2:1 mixture of diastere-
oisomers). A colorless liquid. Major isomer: 1H NMR (CDCl3,
Me4Si) δ 0.88-1.02 (m, 8H), 1.26-1.40 (m, 8H), 1.52-1.57 (m,
2H), 1.83-2.01 (m, 2H), 3.61 (d, J ) 3.5 Hz, 1H), 4.24-4.30
(m, 2H); 13C NMR (CDCl3, Me4Si) δ 13.77, 13.87, 19.05, 20.13,
22.74, 27.97, 29.57, 30.30, 39.62, 44.97, 62.58, 116.11, 166.93.
Minor isomer: 1H NMR (CDCl3, Me4Si) δ 3.62 (d, J ) 5.57,
1H), other peaks were overlapped by the signals of the major
isomer; 13C NMR (CDCl3, Me4Si) δ 13.81, 13.86, 18.31, 21.55,
22.56, 29.35, 29.71, 29.97, 40.62, 44.87, 62.48, 115.95, 166.72.
HRMS calcd for C13H23NO2 225.1729, found (M + 1) 226.1807.
3-P h en yl-2-p h en ylsu lfon ylh ep ta n en itr ile (9j). Isolated
yield 89% (1.8:1 mixture of diastereoisomers). A colorless
liquid. Major isomer: 1H NMR (CDCl3, Me4Si) δ 0.83 (t, J )
7.6 Hz, 3H), 1.10-1.31 (m, 4H), 1.89-2.19 (m, 2H), 3.64 (ddd,
J ) 11.95, 11.91, 3.2 Hz, 1H), 4.04 (d, J ) 2.9 Hz, 1H), 7.23-
7.98 (m, 10H); 13C NMR (CDCl3, Me4Si) δ 13.65, 22.07, 28.91,
30.94, 42.09, 63.45, 113.02, 127.43 (2C), 127.93, 129.01, 129.03,
129.47, 134.97, 136.69, 139.32. Minor isomer: 1H NMR (CDCl3,
Me4Si) δ 0.80 (t, J ) 7.6 Hz, 3H), 1.10-1.31 (m, 4H), 1.89-
2.19 (m, 2H), 3.56 (ddd, J ) 9.69, 9.60, 5.6 Hz, 1H), 4.30 (d, J
) 5.4 Hz, 1H), 7.23-7.98 (m, 10H); 13C NMR (CDCl3, Me4Si)
δ 13.63, 22.02, 28.85, 34.28, 43.25, 62.60, 113.43, 127.89,
128.44, 128.48, 129.15, 134.50, 136.45, 137.20, one peak was
overlapped by the signals of the major isomer. HRMS calcd
for C19H21NO2S 327.1293, found 327.1293.
2-Cya n o-4-(cis-3,4-d ieth yl-6-m eth ylcycloh ex-3-en yl)-3-
p h en ylbu tyr ic Acid Eth yl Ester (9k ). GC yield 97%.
Isolated yield 90% (3.7:3.7:1.4:1 mixture of diastereoisomers).
A colorless liquid. One of the major diastereoisomers: 1H NMR
(CDCl3, Me4Si) δ 0.76-0.97 (m, 9H), 1.09 (t, J ) 7.2 Hz, 3H),
1.42-1.99 (m, 12H), 3.41-3.45 (m, 1H), 3.62 (d, J ) 6.4 Hz,
1H), 4.04-4.16 (m, 2H), 7.29-7.32 (m, 5H); 13C NMR (CDCl3,
Me4Si) δ 12.71, 13.49, 13.81, 13.85, 25.47, 25.58, 28.14, 32.50,
34.14, 34.71, 36.40, 43.52, 45.53, 62.70, 115.89, 128.22, 128.69,
128.85, 138.83, 139.33, 165.47. HRMS calcd for C24H33NO2
367.2511, found 367.2511.
2-[2-(cis-3,4-Dieth yl-6-m eth ylcycloh ex-3-en yl)-1-p h en -
yleth yl]p r op a n ed in itr ile (9c). GC yield 95%. Isolated yield
92% (3.7:1 mixture of diastereoisomers). A colorless liquid. The
major isomer: 1H NMR (CDCl3, Me4Si) δ 0.79-0.97 (m, 9H),
1.68-1.99 (m, 12H), 3.28-3.31 (m, 1H), 3.88 (d, J ) 6.2 Hz,
1H), 7.30-7.40 (m, 5H); 13C NMR (CDCl3, Me4Si) δ 12.91,
12.98, 13.03, 25.31, 25.41, 28.50, 30.20, 32.14, 34.25, 34.44,
36.23, 44.08, 111.97, 112.01, 121.71, 127.83, 128.62, 128.79,
129.07, 136.97. The monor isomer: 1H NMR (CDCl3, Me4Si) δ
3.85 (d, J ) 6.1 Hz, 1H), other peaks were overlapped by the
signals of the major diastereoisomer; 13C NMR (CDCl3, Me4-
Si) δ 13.20, 14.93, 25.45, 25.50, 30.61, 31.20, 31.40, 32.83,
34.00, 35.51, 44.29, 128.31, 128.65, 129.12, 136.61, other peaks
were overlapped by the signals of the major diastereoisomer.
Anal. Calcd for C22H28N2: C, 82.45; H, 8.81; N, 8.74. Found:
C, 82.40; H, 8.91; N, 8.67.
2-[2-(cis-6-Meth yl-3,4-diph en ylcycloh ex-3-en yl)-1-ph en -
yleth yl]p r op a n ed in itr ile (9d ). GC yield 96%. Isolated yield
88% (2.8:1 mixture of diastereoisomers). A colorless liquid. The
major isomer: 1H NMR (CDCl3, Me4Si) δ 1.00 (d, J ) 6.9 Hz,
3H), 1.66-1.72 (m, 1H), 1.96-2.34 (m, 5H), 2.45-2.56 (m, 2H),
3.30-3.38 (m, 1H), 3.80 (d, J ) 6.2 Hz, 1H), 6.84-7.41 (m,
15H); 13C NMR (CDCl3, Me4Si) δ 15.00, 30.86, 31.38, 33.03,
34.10, 34.67, 38.72, 44.45, 111.82, 111.93, 125.85, 125.95,
127.61, 127.73, 127.91, 128.82, 128.86, 128.98, 129.37, 132.33,
133.74, 136.44, 143.08, 143.11. The minor isomer: 1H NMR
(CDCl3, Me4Si) δ 1.06 (d, J ) 6.9 Hz, 3H), 1.77-1.81 (m, 1H),
3.83 (d, J ) 6.3 Hz, 1H), other peaks were overlapped with
the signals of the major isomer; 13C NMR (CDCl3, Me4Si) δ
13.30, 28.70, 30.52, 34.27, 34.57, 35.29, 38.90, 44.37, 112.16,
112.23, 126.01, 127.78, 127.80, 127.93, 127.99, 129.08, 129.70,
132.71, 133.03, 136.79, 142.74, 143.12, other peaks were
overlapped with the signals of the major isomer. HRMS calcd
for C30H28N2 416.2251, found 416.2252.
2-[2-(cis-6-Met h yl-3,4-d ip h en ylcycloh ex-3-en yl)-1-(2-
fu r yl)eth yl]p r op a n ed in itr ile (9e). Isolated yield 79% (1.4:1
mixture of diastereoisomers). A colorless liquid. The major
isomer: 1H NMR (CDCl3, Me4Si) δ 1.0 (d, J ) 6.9 Hz, 3H),
1.78-2.41 (m, 6H), 2.41-2.62 (m, 2H), 3.46-3.54 (m, 1H), 3.91
(d, J ) 5.9 Hz, 1H), 6.35-6.40 (m, 2H), 6.89-7.09 (m, 10H),
7.41 (dd, J ) 8.4, 1.5 Hz, 1H); 13C NMR (CDCl3, Me4Si) δ 14.93,
28.75, 28.80, 31.16, 34. 43, 34.67, 38.54, 39.38, 109.38, 110.63,
111.45, 111.51, 125.81, 125.87, 127.55, 128.77, 128.82, 132.70,
133.70, 142.99, 143.12, 143.17. The minor isomer: 1H NMR
(CDCl3, Me4Si) δ 3.94 (d, J ) 6.0 Hz, 1H), other peaks were
overlapped by the signals of the major diastereoisomer; 13C
(24) This compound was reported, but the NMR data were not
available. Kazuhiko, M.; Kazuhisa, N.; Atsushi, T.; Yoshio, O. J . Chem.
Soc., Chem. Commun. 1991, 5, 344-345.
2-[1-Cya n o-2-(cis-3,4-d ieth yl-6-m eth ylcycloh ex-3-en yl)-
eth ylid en e]p r op a n ed in itr ile (9m ). GC yield 87%. Isolated
7026 J . Org. Chem., Vol. 67, No. 20, 2002

Direct Addition of Zr-C Bonds to Activated Alkenes
yield 65%. A colorless liquid: 1H NMR (CDCl3, Me4Si) δ 0.92-
0.99 (m, 9H), 1.69-2.21 (m, 10H), 2.66-2.68 (m, 2H); 13C NMR
(CDCl3, Me4Si) δ 13.00, 13.17, 15.46, 25.53, 30.91, 32.11, 35.17,
36.30, 38.09, 99.47, 109.68, 109.70, 113.52, 127.79, 130.44,
148.78. HRMS calcd for C17H21N3 267.1734, found 267.1852.
13C NMR (CDCl3, Me4Si) δ 29.45, 31.16, 31.23, 34.77, 37.39,
37.93, 39.86, 50.91, 116.00, 116.30, 126.10, 126.16, 127.75,
127.77, 128.60, 128.78, 128.84, 128.89, 131.76, 132.22, 137.38,
142.30, 142.73. HRMS calcd for C30H26N2 414.2095, found
414.2099. The minor isomer, mp 228-230 °C: 1H NMR
(CDCl3, Me4Si) δ 1.95 (dd, J ) 14.2, 3.2 Hz, 1H), 2.34-2.59
(m, 8H), 2.94-2.99 (m, 1H), 3.33 (dd, J ) 13.2, 3.5 Hz, 1H),
6.96-7.48 (m, 15H); 13C NMR (CDCl3, Me4Si) δ 30.08, 30.77,
31.38, 32.44, 36.80, 37.05, 41.07, 43.85, 114.23, 115.68, 126.31,
126.35, 127.87, 127.88, 128.57, 128.90, 128.98, 132.09, 132.33,
137.01, 142.34, 142.37. HRMS calcd for C30H26N2 414.2095,
found 414.2080.
(3S*,4a S*,8a S*)-3-(2-F u r yl)-6,7-d ip h en yl-3,4,4a ,5,8,8a -
h exa h yd r o-1H-n a p h th a len e-2,2-d ica r bon itr ile (10f). Iso-
lated yield 82% (2:1 mixture of diastereoisomers). A white
solid. The major isomer, mp 135-138 °C: 1H NMR (CDCl3,
Me4Si) δ 1.92 (dt, J ) 13.9, 2.9 Hz, 1H), 2.13-2.52 (m, 6H),
2.67 (dd, J ) 14.3, 1.5 Hz, 1H), 2.90-3.02 (m, 1H), 3.22-3.34
(m, 1H), 3.36 (dd, J ) 12.4, 3.0 Hz, 1H), 6.39-6.40 (m, 1H),
6.49 (d, J ) 3.2 Hz, 1H), 6.95-7.12 (m, 10H), 7.45 (d, J ) 1.4
Hz, 1H); 13C NMR (CDCl3, Me4Si) δ 28.16, 30.99 (2C), 33.95,
35.33, 37.67, 39.05, 44.62, 108.42, 110.54, 115.72, 116.35,
126.05, 126.10, 127.70, 128.71, 128.76, 131.60, 132.12, 142.20,
142.64, 142.88, 151.14. HRMS C28H24N2O 404.1887, found
404.1890. The minor isomer, mp 208-209 °C: 1H NMR
(CDCl3, Me4Si) δ 2.03 (dd, J ) 14.5, 3.2 Hz, 1H), 2.29-2.49
(m, 8H), 2.92-2.96 (m, 1H), 3.53 (dd, J ) 13.1, 3.5 Hz, 1H),
6.37-6.38 (m, 1H), 6.43 (d, J ) 3.3 Hz, 1H), 6.95-7.21 (m,
10H), 7.41-7.43 (m, 1H); 13C NMR (CDCl3, Me4Si) δ 29.85,
30.16, 31.20, 31.34, 35.91, 36.89, 37.99, 39.28, 108.40, 110.52,
113.83, 115.66, 126.24, 126.27, 127.80, 128.79, 128.87, 131.94,
132.11, 142.19, 142.27, 142.94, 151.13. HRMS C28H24N2O
404.1887, found 404.1877.
E t h yl (1R*,2S*)-1-cya n o-2-p h en yl-1-cycloh exa n eca r -
boxyla te (10h ). Isolated yield 88%. A colorless liquid: 1H
NMR (CDCl3, Me4Si) δ 0.96 (t, J ) 7.2 Hz, 3H), 1.30-1.51 (m,
1H), 1.85-2.17 (m, 7H), 3.05 (dd, J ) 12.9, 3.1 Hz, 1H), 3.98
(q, J ) 7.1 Hz, 2H), 7.24-7.34 (m, 5H); 13C NMR (CDCl3, Me4-
Si) δ 13.81, 21.63, 25.23, 28.65, 34.51, 48.74, 52.93, 62.00,
117.91, 127.56, 127.85, 128.20, 139.64, 168.54. HRMS calcd
for C16H19NO2 257.1416, found 257.1416. Methyl (1R*,2S*)-
1-cyano-2-phenyl-1-cyclohexanecarboxylate was also prepared
in 70% isolated yield to compare the NMR data of the known
compound. The spectral data were consistent with published
values.25
A Rep r esen ta tive P r oced u r e for th e Rea ction of Ben z-
ylid en em a lon on itr ile (2a ) w ith Zir con a cyclop en ten es.
Syn th esis of 12a a n d 13a . To a solution of diethylzircona-
cyclopentene 11 (prepared from 3.6 mmol of Cp2ZrCl2 and 7.2
mmol of EtMgBr) in THF (20 mL) was added benzylidenepro-
panedinitrile (6.6 mmol, 1.02 g) at 0 °C and the mixture was
stirred for 3 h at room temperature. The reaction mixture was
then quenched with 3 N HCl at room temperature or with
iodine (6.6 mmol, 1.67 g) at 0 °C. The reaction mixture was
extracted with Et2O (3 × 30 mL), and combined organic
extracts were washed with water, aq NaHCO3, and brine and
dried (MgSO4). Filtration and evaporation followed by column
chromatography on silica gel (hexane/EtOAc) afforded the
products.
[2-(cis-3,4-Dieth yl-6-m eth ylcycloh ex-3-en yl)-1-p h en yl-
eth yl]bis(p h en ylsu lfon yl)m eth a n e (9n ). Isolated yield 24%
(2.0:1 mixture of diastereoisomers). A colorless liquid. Major
isomer: 1H NMR (CDCl3, Me4Si) δ 0.70 (d, J ) 6.6 Hz, 3H),
0.87 (t, J ) 7.5 Hz, 3H), 0.95 (t, J ) 7.5 Hz, 3H), 1.23-1.37
(m, 4H), 1.58-2.04 (m, 7H), 2.60 (td, J ) 10.8, 3.1 Hz, 1H),
3.82-3.87 (m, 1H), 4.75 (d, J ) 1.3 Hz, 1H), 7.21-7.99 9m,
15H); 13C NMR (CDCl3, Me4Si) δ 13.08, 13.35, 13.85, 25.67,
25.83, 30.57, 30.82, 31.66, 34.98, 36.67, 42.80, 89.31, 127.33,
127.67, 128.60, 128.62, 128.83, 128.88, 129.25, 129.44, 129.92,
133.87, 134.59, 138.11, 140.17, 141.30. Minor isomer: 1H NMR
(CDCl3, Me4Si) δ 3.84-3.90 (m, 1H), 4.71 (d, J ) 1.2 Hz, 1H),
other peaks were overlapped by the signals of the major
isomer; 13C NMR (CDCl3, Me4Si) δ 12.71, 13.08, 13.15, 25.50,
25.62, 28.29, 30.62, 32.44, 37.00, 37.78, 42.77, 88.66, 127.28,
128.45, 128.60, 128.73, 128.83, 129.33, 129.48, 133.82, 133.88,
134.52, 134.62, 138.34, 140.39, 141.33. HRMS calcd for
C
32H38O4S2 550.2211, found 520.2211.
Gen er a l p r oCed u r e for th e P r ep a r a tion of 10. To a
solution of zirconacyclopentane 8 (prepared from 1.1 mmol of
Cp2ZrCl2)12b,13b,19 was added ylidenemalononitrile (1.2-2 mmol)
at -40 or 0 °C (Table 1) with stirring for the appropriate time
(see Table 1). Then iodine (0.64 g, 2.5 mmol) was added and
the reaction mixture was warmed to room temperature and
stirred for an additional 1-3 h. The reaction mixture was
quenched with 3 N HCl and extracted with Et2O. Combined
organic extracts were washed with aqueous NaHCO3 and
water, dried (MgSO4), and concentrated in vacuo. Column
chromatography on silica gel (hexane/EtOAc) afforded the
products.
(3R*,4a R*,8a S*)-3-P h en ylocta h yd r o-1H-n a p h th a len e-
2,2-d ica r bon itr ile (10b). GC yield 86%. Isolated yield 73%.
A colorless solid, mp 111-112 °C: 1H NMR (CDCl3, Me4Si) δ
1.21 (ddddd, J ) 12.8, 12.8, 12.8, 3.5, 3.5 Hz, 1H), 1.33-1.45
(m, 1H), 1.50-1.70 (m, 5H), 1.80-1.88 (m, 1H), 1.95-2.05 (m,
2H), 2.15 (dddd, J ) 13.0, 13.0, 13.0, 3.5 Hz, 1H), 2.32 (dd, J
) 14.2, 2.5 Hz, 1H), 2.45 (ddd, J ) 13.3, 13.3, 12.9 Hz, 1H),
2.52 (dd, J ) 14.2, 1.4 Hz, 1H), 3.00 (dd, J ) 12.8, 2.9 Hz,
1H), 7.34-7.47 (m, 5H); 13C NMR (CDCl3, Me4Si) δ 20.90,
26.47, 26.88, 28.13, 31.70, 35.09, 36.26, 37.52, 41.76, 51.03,
116.00, 116.45, 128.53, 128.77, 128.80, 137.83. HRMS calcd
for
18H20N2: C, 81.78; H, 7.63; N, 10.60. Found: C, 82.0; H, 7.81;
N, 10.74.
(3R *,4a S *,8a S *)-6,7-Die t h yl-3-p h e n yl-3,4,4a ,5,8,8a -
C18H20N2 264.1626, found 264.1617. Anal. Calcd for
C
h exa h yd r o-1H-n a p h th a len e-2,2-d ica r bon itr ile (10d ). GC
yield 84%. Isolated yield 62% (10:1 mixture of diastereoiso-
mers). A white solid. The major isomer, mp 139-140 °C: 1H
NMR (CDCl3, Me4Si) δ 0.93-1.02 (m, 6H), 1.55-2.50 (m, 12H),
2.63 (dd, J ) 14.2, 1.5 Hz, 1H), 2.73-2.85 (m, 1H), 3.08 (dd, J
) 12.8, 2.8 Hz, 1H), 7.25-7.45 (m, 5H); 13C NMR (CDCl3, Me4-
Si) δ 13.19, 25.44, 25.54, 28.18, 29.15, 31.25, 34.80, 34.93,
37.31, 40.13, 50.91, 116.05, 116.52, 128.17, 128.55, 128.59,
128.66, 128.73, 137.62. HRMS C22H26N2 318.2095, found
318.2100. The minor isomer, mp 141-143 °C: 1H NMR
(CDCl3, Me4Si) δ 0.94-1.01 (m, 6H), 1.76-2.40 (m, 14H), 3.26
(dd, J ) 13.3, 3.4 Hz, 1H), 7.38-7.47 (m, 5H); 13C NMR (CDCl3,
Me4Si) δ 13.17, 13.31, 25.45, 25.62, 28.24, 30.03, 30.66, 32.65,
33.96, 36.64, 41.03, 43.83, 114.35, 115.87, 128.34, 128.45,
128.59, 128.83, 128.85, 137.27. HRMS calcd for C22H26N2
318.2095, found 318.2097.
2-(4-Eth yl-1-ph en yl-4E-h epten yl)pr opan edin itr ile (12a).
GC yield 81%. Isolated yield 67%. A colorless liquid: 1H NMR
(CDCl3, Me4Si) δ 0.88-0.96 (m, 6H), 1.81-2.14 (m, 8H), 3.16-
3.22 (m, 1H), 3.89 (d, J ) 6.2 Hz, 1H), 5.01 (t, J ) 7.2 Hz,
1H), 7.29-7.42 (m, 5H); 13C NMR (CDCl3, Me4Si) δ 13.20,
14.63, 20.84, 22.64, 30.20, 30.24, 33.33, 45.82, 112.05, 127.95,
128.02, 128.85, 129.24, 136.69, 138.02. HRMS calcd for C18H22N2
266.1783, found 266.1788.
(3R*,4aS*,8aS*)-3,6,7-Tr iph en yl-3,4,4a,5,8,8a-h exah ydr o-
1H-n a p h th a len e-2,2-d ica r bon itr ile (10e). Isolated yield
69%. A white solid. The major isomer: 1H NMR (CDCl3, Me4-
Si) δ 1.78-1.82 (m, 1H), 2.22-2.57 (m, 6H), 2.70 (d, J ) 14.1
Hz, 1H), 2.96-3.02 (m, 1H), 3.15 (dd, J ) 12.7, 2.8 Hz, 1H),
3.34-3.41 (m, 1H), 6.97-7.13 (m, 10H), 7.38-7.51 (m, 5H);
(25) (a) Avenoza, A.; Cativiela, C.; Paris, M.; Peregrina, J . M.
Tetrahedron: Asymmetry 1995, 6, 1409-1418. (b) Cativiela, C.;
Avenoza, A.; Paris, M.; Peregrina, J . M. J . Org. Chem. 1994, 59, 7774-
7778.
J . Org. Chem, Vol. 67, No. 20, 2002 7027

Liu et al.
2-(4-E t h yl-5-d eu t er io-1-p h en yl-4E-h ep t en yl)-2-d eu t e-
r iop r op a n ed in itr ile (12a -D). GC yield 81%. Isolated yield
68%. A colorless liquid: 1H NMR (CDCl3, Me4Si) δ 0.90 (t, J
) 7.6 Hz, 3H), 0.94 (t, J ) 7.5 Hz, 3H), 1.80-2.11 (m, 8H),
3.15-3.21 (m, 1H), 3.89 (d, J ) 6.3 Hz, 1H), 7.29-7.41 (m,
5H); 13C NMR (CDCl3, Me4Si) δ 13.21, 14.62, 20.74, 22.62,
30.18, 30.23, 33.26, 45.75, 112.17, 127.54, 128.05, 128.82,
129.21, 136.76, 137.95. HRMS calcd for C18H20D2N2 267.1845,
found 267.1843.
2-(4-Bu tyl-1-ph en yl-4E-n on en yl)pr opan edin itr ile (12b).
GC yield 79%. Isolated yield 60%. A pale yellow liquid: 1H
NMR (CDCl3, Me4Si) δ 0.83-0.97 (m, 6H), 1.20-1.35 (m, 8H),
1.81-2.20 (m, 8H), 3.16-3.22 (m, 1H), 3.89 (d, J ) 6.2 Hz,
1H), 5.03 (t, J ) 7.1 Hz, 1H), 7.29-7.43 (m, 5H); 13C NMR
(CDCl3, Me4Si) δ 13.99, 14.01, 22.46, 22.72, 27.41, 29.34, 30.20,
30.27, 30.60, 32.21, 33.71, 45.82, 111.96, 126.98, 128.01,
128.88, 129.26, 136.67, 136.94. HRMS calcd for C22H30N2
322.2409, found 322.2397.
2-(1,4,5-Tr ip h en yl-4E-p en ten yl)p r op a n ed in itr ile (12c).
GC yield 77%. Isolated yield 51%. A pale yellow liquid: 1H
NMR (CDCl3, Me4Si) δ 2.01-2.13 (m, 2H), 2.31-2.38 (m, 1H),
2.47-2.54 (m, 1H), 3.22-3.07 (m, 1H), 3.76 (d, J ) 6.2 Hz,
1H), 6.28 (s, 1H), 6.88-6.91 (m, 2H), 7.04-7.11 (m, 5H), 7.24-
7.32 (m, 5H), 7.37-7.45 (m, 3H); 13C NMR (CDCl3, Me4Si) δ
29.93, 30.25, 37.34, 45.62, 111.73, 126.57, 127.43, 127.82,
127.92, 128.06, 128.47, 128.83, 128.99, 129.04, 129.35, 136.15,
136.70, 139.83, 140.15. Anal. Calcd for C26H22N2: C, 86.15; H,
6.12; N, 7.73. Found: C, 86.25; H, 6.34; N, 7.70.
2-(1,3-Dip h en yln on yl)p r op a n ed in itr ile (12d ). GC yield
55%. Isolated yield 43%. A colorless liquid: 1H NMR (CDCl3,
Me4Si) δ 0.81 (t, J ) 7.1 Hz, 3H), 0.92-1.32 (m, 8H), 1.52-
1.62 (m, 2H), 2.17 (ddd, J ) 12.1, 12.1, 3.2 Hz, 1H), 2.20-3.30
(m, 1H), 2.37 (ddd, J ) 12.2, 12.2, 2.4 Hz, 1H), 2.83 (ddd, J )
11.8, 6.3, 3.5 Hz, 1H), 3. 66 (d, J ) 6.2 Hz, 1H), 6.96-7.46 (m,
10H); 13C NMR (CDCl3, Me4Si) δ 14.01, 22.54, 27.28, 29.12,
30.51, 31.60, 37.60, 38.52, 53.05, 44.26, 111.84, 111.87, 126.81,
127.59, 128.12, 128.78, 128.92, 129.27, 136.28, 143.2. HRMS
calcd for C24H28N2 344.2252, found 344.2265.
2.67-2.78 (m, 2H), 3.18-3.23 (m, 1H), 3.85 (d, J ) 6.1 Hz,
1H), 6.87-7.10 (m, 10H), 7.24-7.41 (m, 5H); 13C NMR (CDCl3,
Me4Si) δ 29.54, 30.21, 42.44, 45.95, 101.43, 111.63, 111.68,
127.13, 127.28, 127.65, 128.07, 128.17, 128.91, 129.03, 129.25,
129.74, 135.86, 138.83, 144.04, 146.81. HRMS calcd for C26H21
IN2 488.0749, found 488.0732.
-
2-[3-(2-Iod op h en yl)-1-p h en yln on yl]p r op a n ed in it r ile
(13d ). Isolated yield 41%. A pale brown liquid: 1H NMR
(CDCl3, Me4Si) δ 0.83 (t, J ) 6.6 Hz, 3H), 1.01-1.59 (m, 10H),
2.26-2.45 (m, 2H), 2.86-2.91 (m, 2H), 3.71 (d, J ) 6.2 Hz,
1H), 6.91 (ddd, J ) 7.7, 7.5,1.4 Hz, 1H), 7.11-7.47 (m, 7H),
7.78 (d, J ) 7.7 Hz, 1H); 13C NMR (CDCl3, Me4Si) δ 14.02,
22.54, 26.66, 29.24, 30.58, 31.56, 37.51, 38.10, 44.25, 45.70,
103.01, 111.82, 111.86, 126.61, 128.25, 128.38, 128.96, 129.01,
129.41, 136.02, 139.91, 145.78. HRMS calcd for C24H27IN2
470.1219, found 470.1225.
2-[2-(cis-3,4-Diet h yl-6-iod om et h ylcycloh ex-3-en yl)-1-
p h en yleth yl]p r op a n ed in itr ile (17). The title compound was
obtained by iodinolysis of the reaction mixture at -40 °C.
Isolated yield 38% (1.5:1 mixture of diastereoisomers). A
colorless liquid. Major isomer: 1H NMR (CDCl3, Me4Si) δ 0.83-
0.98 (m, 6H), 1.85-2.01 (m, 12H), 3.06-3.40 (m, 3H), 3.84 (d,
J ) 6.4 Hz, 1H), 7.33-7.45 (m, 5H); 13C NMR (CDCl3, Me4Si)
δ 9.57, 13.75, 13.85, 25.89, 25.94, 31.01, 31.28, 32.48, 33.59,
34.07, 41.22, 44.97, 111.71, 111.82, 128.29, 128.41, 128.54,
129.56, 129.71, 135.96. Minor isomer: 13C NMR (CDCl3, Me4-
Si) δ 8.64, 13.56, 13.70, 25.74, 25.86, 30.75, 33.05, 33.50, 34.07,
35.22, 39.59, 45.20, 111.74, 111.84, 129.04, 129.18, 129.47,
129.79, 129.94, 136.71. HRMS calcd for C22H27IN2 446.1219,
found 446.1219.
Cycliza tion of 17 to 10d u n d er Con tr olled Rea ction
Con d ition s. To a THF solution of 17 (diastereomeric ratio is
1:1) was added 1 equiv of NaH at room temperature with
stirring for 3 h; 10d was formed in 90% GC yield with the
same diastereomeric ratio. Addition of LDA (1 equiv) to the
THF solution of 17 (diastereomeric ratio is 1:1) at -60 °C for
1 h was followed by the addition of Cp2ZrX2 (X) Cl or I, 1
equiv) at the same temperature with stirring for 1 h. The
mixture was warmed to room temperature and stirred for 12
h. 10d was formed with increased diastereomeric ratio (for X
) Cl, the diastereomeric ratio is 1.8:1, 90% GC yield; for X )
I, the diastereomeric ratio is 5:1, 52% GC yield).
2-(4-E t h yl-5-iod o-1-p h en yl-4Z-h ep t en yl)p r op a n ed in i-
tr ile (13a ). GC yield 76%. Isolated yield 65%. A pale brown
liquid: 1H NMR (CDCl3, Me4Si) δ 0.92 (t, J ) 7.5 Hz, 3H),
1.03 (t, J ) 7.3 Hz, 3H), 2.06-2.18 (m, 6H), 2.51 (q, J ) 7.4
Hz, 2H), 3.20-3.22 (m, 1H), 3.98 (d, J ) 6.1 Hz, 1H), 7.36-
7.42 (m, 5H); 13C NMR (CDCl3, Me4Si) δ 13.47, 14.68, 24.58,
29.87, 30.11, 34.94, 39.62, 46.25, 107.93, 111.90, 111.96,
Su p p or tin g In for m a tion Ava ila ble: Tables of crystal-
lographic data, atomic coordinates, thermal parameters, and
bond lengths and angles for 10b and 10d and NMR spectra of
all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
128.00, 128.92, 129.17, 136.28, 142.89. HRMS calcd for C18H21
IN2 392.0749, found 392.0734.
-
2-(5-Iod o-1,4,5-t r ip h e n yl-4E -p e n t e n yl)p r op a n e d in i-
tr ile (13c). GC yield 69%. Isolated yield 65%. A colorless
liquid: 1H NMR (CDCl3, Me4Si) δ 2.12 (q, J ) 8.0 Hz, 2H),
J O0260701
7028 J . Org. Chem., Vol. 67, No. 20, 2002