Direct Preparation of Allylic Zirconium Reagents from Zirconocene-Olefin Complexes and Alkenes

Article abstract of DOI:10.1021/jo049863r

A novel method for preparation of allylic zirconium reagents directly from 1-alkenes via zirconoceneolefin complex has been developed. Selective transfer of the hydride of zirconocene allyl hydride complex, a tautomer of zirconocene-olefin complex, to diisopropyl ketone generates the corresponding zirconocene alkoxide allyl. The allylic zirconium reagents formed effects stereoselective allylation of aldehyde at 25 °C and -78 °C to provide syn- and anti-homoallyl alcohols, respectively. The anti-isomer is formed via a six-membered chair transition state under kinetic control. The syn-selectivity can be rationalized by considering isomerization of the anti-adduct by a retroallylation process.

Full text of DOI:10.1021/jo049863r

Dir ect P r ep a r a tion of Allylic Zir con iu m Rea gen ts fr om
Zir con ocen e-Olefin Com p lexes a n d Alk en es
Kazuya Fujita, Hideki Yorimitsu, Hiroshi Shinokubo, and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, J apan
oshima@fm1.kuic.kyoto-u.ac.jp
Received J anuary 23, 2004
A novel method for preparation of allylic zirconium reagents directly from 1-alkenes via zirconocene-
olefin complex has been developed. Selective transfer of the hydride of zirconocene allyl hydride
complex, a tautomer of zirconocene-olefin complex, to diisopropyl ketone generates the corre-
sponding zirconocene alkoxide allyl. The allylic zirconium reagents formed effects stereoselective
allylation of aldehyde at 25 °C and -78 °C to provide syn- and anti-homoallyl alcohols, respectively.
The anti-isomer is formed via a six-membered chair transition state under kinetic control. The
syn-selectivity can be rationalized by considering isomerization of the anti-adduct by a retroallylation
process.
SCHEME 1
In tr od u ction
Allylation of carbonyl groups by allylic metals is one
of the most versatile C-C bond formation reactions.1
Although there are a number of precedents for the
synthesis of allylic metals, the preparation usually
requires alkenes that have good leaving groups such as
alkoxide or halide at the allylic position. As far as
zirconium compounds are concerned,2 Taguchi and Han-
zawa reported efficient preparation of allylic zirconium
species through reaction of zirconocene-olefin complex
Cp2Zr(H2CdCHEt) with allylic ether by taking advantage
of the high oxophilicity of zirconium metal (Scheme 1).3
This transformation was achieved through the formation
of zirconacyclopropane 2 (ligand exchange) followed by
elimination of the â-alkoxy group. The allylic zirconium
reagent 4 prepared in a similar way reacted with alde-
hyde in a regio- and diastereoselective manner to afford
the homoallylic alcohol. Suzuki demonstrated that hy-
drozirconation of allenes provided a useful method for
the generation of various allylic zirconocene derivatives,
for example, 8 (Scheme 2).4
SCHEME 2
However, preparation of requisite allyl ethers or al-
lenes is still laborious. A novel method for preparation
of allylic zirconium reagents from readily available
1-alkenes would greatly enhance the synthetic utility of
allylic zirconium reagents. Recently, we have found
zirconocene-olefin complex 1 delivers both hydride and
an allyl group to acid chloride to furnish homoallyl
alcohol 10 (Scheme 3).5 It is assumed that an equilibrium
exists between 1 and 9.6 We then anticipated that
selective capture of hydride in zirconocene allyl hydride
complex 9 with a bulky ketone would provide a new
* To whom correspondence should be addressed. Phone: +81-75-
383-2437. Fax: +81-75-383-2438.
(1) (a) Roush, W. R. Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford 1991; Vol. 2, Chapter 1.1.
(b) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(2) Preparation of allylic zirconium compounds has also been
achieved by transmetalation of allylmetal with Cp2ZrCl2. (a) Yama-
moto, Y.; Maruyama, K. Tetrahedron Lett. 1981, 22, 2895. (b) Yasuda,
H.; Kajihara, Y.; Mashima, K.; Nagasuna, K.; Nakamura, A. Chem.
Lett. 1981, 671. (c) Mashima, K.; Asami, K.; Yasuda, H.; Nakamura,
A. Chem. Lett. 1983, 219.
(3) (a) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33,
1295. (b) Ito, H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y. Tetrahedron
1995, 51, 4507. (c) Hanzawa, Y.; Ito, H.; Taguchi, T. Synlett 1995, 299.
Their allyl zirconium afforded anti-homoallylic alcohols even at ambi-
ent temperature upon treatment with aldehydes. Also see: (d) Rousset,
C. J .; Swanson, D. R.; Lamaty, F.; Negishi, E. Tetrahedron Lett. 1989,
30, 5105.
(5) (a) Fujita, K.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. J . Am.
Chem. Soc. 2001, 123, 12115. (b) Fujita, K.; Shinokubo, H.; Oshima,
K. Angew. Chem., Int. Ed. 2003, 42, 2550. (c) Fujita, K.; Yorimitsu,
H.; Oshima, K. Chem. Rec. 2004, 4, 110.
(6) Harrod has also proved that 1 and 9 are in an equilibrium that
is significantly shifted toward 1: Dioumaev, V. K.; Harrod, J . F.
Organometallics 1997, 16, 1452. Also see: Negishi, E.; Maya, J . P.;
Choueiry, D. Tetrahedron 1995, 51, 4447.
(4) Chino, M.; Matsumoto, T.; Suzuki, K. Synlett 1994, 359.
10.1021/jo049863r CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/14/2004
3302
J . Org. Chem. 2004, 69, 3302-3307

Preparation of Allylic Zirconium Reagent from Alkene
SCHEME 3
TABLE 1. Rea ction of Allylic Zir con iu m Rea gen ts w ith
Ald eh yd es
SCHEME 4
yield
entry methoda
R
R′
product (%) anti/syn
1
2
3
4
5
6
7
8
A
A
A
A
A
A
A
A
n-C3H7 Ph
15a
15b
15c
15d
15e
15f
15g
15h
98
94
99
97
98
85
80
95
91/9
>99/1
94/6
n-C3H7 n-C9H19
n-C3H7 c-C6H11
n-C3H7 Ph(CH2)3
93/7
CH3
CH3
CH3
Ph
Ph
68/32
86/14
77/23
95/5
n-C9H19
PhCHdCH
Ph
9
10
11
12
13
14
15
16
B
B
B
B
B
B
B
B
n-C3H7 Ph
15a
15b
15c
15d
15e
15f
15g
15h
98
91
95
94
99
99
95
99
23/77
43/57
17/83
15/85
35/65
26/74
14/86
25/75
n-C3H7 n-C9H19
n-C3H7 c-C6H11
n-C3H7 Ph(CH2)3
CH3
CH3
CH3
Ph
Ph
n-C9H19
PhCHdCH
Ph
allylzirconium reagent 11. When 9 reacted with aldehyde,
attacks of the hydride and allyl group competed to afford
a mixture of the parent primary alcohol and the corre-
sponding homoallylic alcohol. In contrast, the reaction
of 11 with aldehyde never suffers from the competitive
nucleophilic attack. Here, we describe a novel method to
prepare versatile allylic zirconium reagents directly from
1-alkenes.
a
Reaction conditions. Method A: Cp2ZrCl2 (3.0 mmol), Grignard
reagent (1.0 M in THF, 6.0 mL, 6.0 mmol), diisopropyl ketone (4.5
mmol), aldehyde (1.0 mmol), and toluene (30 mL) were employed
at -78 °C. Method B: Cp2ZrCl2 (2.0 mmol), Grignard reagent (1.0
M in THF, 4.0 mL, 4.0 mmol), diisopropyl ketone (3.0 mmol),
aldehyde (1.0 mmol), and toluene (20 mL) were employed at
25 °C.
Resu lts a n d Discu ssion
SCHEME 5
Treatment of Cp2ZrCl2 (3.0 mmol) with n-C6H13MgBr
(1.0 M THF solution, 6.0 mL, 6.0 mmol) in toluene (30
mL) at 0 °C provided zirconocene complex 12a (R )
n-C3H7).7,8 After 30 min of stirring at 0 °C, an addition
of diisopropyl ketone (4.5 mmol) to the solution at the
same temperature resulted in reduction of the ketone and
afforded allylzirconium 14a (R ) n-C3H7) in situ. Reaction
with benzaldehyde (1.0 mmol) at -78 °C for 5 h yielded
homoallyl alcohol 15a in 98% yield with a high level of
anti stereoselectivity (Scheme 4). Use of 2.0 equiv of
allylzirconium provided 15a in only 60% yield along with
the recovered benzaldehyde. In this method, the employ-
ment of diisopropyl ketone as a hydrogen scavenger is
crucial for the successful formation of allylzirconium
reagent. For instance, the use of a ketone without steric
hindrance, such as acetone or 2-pentanone, instead of
diisopropyl ketone decreased the yield of 15a , and a
significant amount of benzyl alcohol was obtained. Other
results are shown in Table 1 (Method A). The use of
butylmagnesium bromide and 3-phenylpropylmagnesium
bromide in place of n-C6H13MgBr also provided the
corresponding homoallylic alcohols (Table 1, entries 5-8).
Decanal or cyclohexanecarbaldehyde also yielded the
desired homoallylic alcohols.9,10 Most of the reactions
accomplished satisfactory yields with good to excellent
anti stereoselectivity. In all cases, none of the regio-
isomer, linear R-adduct, was detected. A six-membered
chairlike transition state 16 can explain the regio- and
diastereoselectivity.2,5a
To our surprise, warming up the reaction mixture
before aqueous workup reversed the sense of the di-
astereoselectivity (Scheme 5). Thus, the reaction of
allylzirconium reagent 14a (R ) n-C3H7) with decanal
at ambient temperature furnished homoallyl alcohol in
(7) (a) Negishi, E.; Cederbaum, F. E.; Takahashi, T. Tetrahedron
Lett. 1986, 27, 2829. (b) Negishi, E.; Holms, S. J .; Tour, J . M.; Miller,
J . A.; Cederbaum, F. E.; Swanson, D. R.; Takahashi, T. J . Am. Chem.
Soc. 1989, 111, 3336.
(8) For leading reviews, see: (a) Negishi, E.; Takahashi, T. Acc.
Chem. Res. 1994, 27, 124. (b) Negishi, E.; Kondakov, D. Y. Chem. Soc.
Rev. 1996, 26, 417. (c) Negishi, E.; Takahashi, T. Bull. Chem. Soc. J pn.
1998, 71, 755. (d) Takahashi, T.; Kotora, M.; Hara, R.; Xi, Z. Bull.
Chem. Soc. J pn. 1999, 72, 2591.
(9) The reaction with acetophenone yielded the allylation product
in only 19% yield.
(10) The reaction with pivalaldehyde led to the sole production of
the syn isomer regardless of the reaction temperatures.
J . Org. Chem, Vol. 69, No. 10, 2004 3303

Fujita et al.
TABLE 2. Rea ction of Cr otylzir con iu m Rea gen t,
Der ived fr om Cp 2Zr Cl2 a n d n -C4H9Li, w ith Ald eh yd es
SCHEME 6
quantitative yield with syn selectivity (anti/syn ) 23/77).
A range of aldehydes and Grignard reagents were
screened (Table 1, Method B). In all cases, the reaction
exhibited high syn selectivity with excellent yields of the
desired products.
entry methoda
R′
product yield (%) anti/syn
1
2
3
A
A
A
Ph
15e
15f
15g
66
72
69
84/16
91/9
88/12
n-C9H19
PhCHdCH
To elucidate the reaction pathway, we carried out the
following experiment (Scheme 6). Crotylzirconium 14b
(R ) CH3) was treated with benzaldehyde at -78 °C for
5 h. A small portion of the reaction mixture was taken
out by a syringe and hydrolyzed. The stereochemistry of
the major product was anti (anti/syn ) 72/28), and
benzaldehyde was not detected in the reaction mixture.
The remaining mixture was then warmed to room tem-
perature. Protonolysis afforded the syn isomer as a main
product (anti/syn ) 26/74).
On the basis of these facts, we are tempted to propose
that the fact that the stereoselectivity depended on the
reaction temperature is attributed to isomerization of the
product via a retroallylation reaction. The anti-zirconium
alkoxide 17 is formed predominantly under kinetic
control at -78 °C. At ambient temperature, however, 17
undergoes the retroallylation reaction affording crotyl
zirconium reagent and benzaldehyde. Finally, the reac-
tion provides syn-alkoxide 18 as a major product. The
result indicates that syn-alkoxide 18 would be thermo-
dynamically more stable than anti-adduct 17. Knochel
et al. reported that generation of a zinc alkoxide of a
sterically hindered tertiary homoallyl alcohol would
result in decomposition to the parent ketone and an
allylic zinc reagent.11 On the other hand, we have
demonstrated the first example of a reversible addition
process of allylic metals to aldehyde.
4
5
6
B
B
B
Ph
15e
15f
15g
81
84
82
41/59
47/53
49/51
n-C9H19
PhCHdCH
a
Reaction conditions. Method A: Cp2ZrCl2 (3.0 mmol), n-C4H9Li
(1.6 M in hexane, 3.75 mL, 6.0 mmol), diisopropyl ketone (4.5
mmol), aldehyde (1.0 mmol), and toluene (30 mL) were employed
at -78 °C. Method B: Cp2ZrCl2 (2.0 mmol), n-C4H9Li (1.6 M in
hexane, 2.5 mL, 4.0 mmol), diisopropyl ketone (3.0 mmol), alde-
hyde (1.0 mmol), and toluene (20 mL) were employed at 25 °C.
The reaction also worked well with n-C4H9Li instead
of n-C4H9MgBr. Additionally, it was found that the use
of n-C4H9Li influences the stereochemical outcome of the
reaction. The results are summarized in Table 2. When
the reaction was conducted with n-C4H9Li at -78 °C, the
stereoselectivity was improved compared to the case of
n-C4H9MgBr (entries 1-3). On the other hand, the
reaction at 25 °C lacked the stereoselectivity (entries
4-6). We assume that the metal halide, which was
formed by transmetalation, plays an important role.
The reaction could employ imines as an electrophile
and afforded homoallylamines. The addition to aldimines
21 provided the corresponding secondary amines 22 in
good to excellent yields. Interestingly, in the reaction with
imines, syn-homoallylic amines were obtained predomi-
nantly regardless of the reaction temperatures (Table
3).12
We also conducted the following experiment to estab-
lish the mechanism involving the retroallylation reaction
(Scheme 7). Crotylzirconium 14b (2.0 mmol) was treated
with cyclohexanecarbaldehyde (2.4 mmol) at -78 °C for
5 h. Quenching of the reaction mixture with aqueous
hydrochloric acid yielded 1.4 mmol of 1-cyclohexyl-2-
methyl-3-buten-1-ol (20). Thus, zirconium alkoxide 19
was formed in situ at this point. Before quenching,
addition of benzaldehyde (2.4 mmol) to 19 at -78 °C
followed by warming up the reaction temperature af-
forded syn-adduct 15e exclusively (1.4 mmol) with con-
tamination by syn-20. The result proves that zirconium
alkoxide 19 fragmented to furnish crotylzirconium re-
agent 14b and that allylation of aldehyde with 14b is
thus reversible.
Zirconocene-olefin complexes can also be prepared
from 1-alkenes directly upon treatment with zirconocene-
cyclopentene complex 23 derived from Cp2ZrCl2 and
cyclopentylmagnesium bromide (Scheme 8).13 The zirco-
nium reagent prepared in this manner could effect
allylation of carbonyl compounds. Thus, an addition of
diisopropyl ketone followed by various aldehydes yielded
the corresponding homoallyl alcohols (Table 4).14
(12) The syn selectivity can be explained by six-membered chairlike
transition state 24. See: (a) Yamamoto, Y.; Nishi, S.; Maruyama, K.;
Komatsu, T.; Ito, W. J . Am. Chem. Soc. 1986, 108, 7778. (b) Gao, Y.;
Sato, F. J . Org. Chem. 1995, 60, 8136.
(11) (a) J ones, P.; Millot, N.; Knochel, P. Chem. Commun. 1998,
2405. (b) J ones, P.; Knochel, P. Chem. Commun. 1998, 2407. (c) Millot,
N.; Knochel, P. Tetrahedron Lett. 1999, 40, 7779. (d) J ones, P.; Knochel,
P. J . Org. Chem. 1999, 64, 186. In their reaction system, the
employment of a sterically hindered tertiary allylic alcohol is crucial
for the successful formation of allylzinc species.
(13) A similar ligand exchange utilizing a titanium reagent was
reported: (a) Lee, J .; Kim, H.; Cha, J . K. J . Am. Chem. Soc. 1995,
117, 9919. (b) Lee, J .; Kim, H.; Cha, J . K. J . Am. Chem. Soc. 1996,
118, 4198. (c) Kulinkovich, O. G.; de Meijere, A. Chem. Rev. 2000, 100,
2789. (d) Sato, F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000, 100, 2835.
Also see ref 5a.
3304 J . Org. Chem., Vol. 69, No. 10, 2004

Preparation of Allylic Zirconium Reagent from Alkene
SCHEME 7
TABLE 3. Rea ction of Cr otylzir con iu m Rea gen t w ith
Im in es
SCHEME 8
entry
methoda
R
product
yield (%)
anti/syn
1
2
3
A
A
A
Ph
i-C3H7
c-C6H11
22a
22b
22c
67
73
69
11/89
17/83
18/82
4
5
6
B
B
B
Ph
i-C3H7
c-C6H11
22a
22b
22c
87
87
74
25/75
22/78
22/78
a
Reaction conditions. Method A: Cp2ZrCl2 (3.0 mmol), butyl-
magnesium bromide (1.0 M in THF, 6.0 mL, 6.0 mmol), diisopropyl
ketone (4.5 mmol), aldimine (1.0 mmol), and toluene (30 mL) were
employed at -78 °C. Method B: Cp2ZrCl2 (2.0 mmol), butylmag-
nesium bromide (1.0 M in THF, 4.0 mL, 4.0 mmol), diisopropyl
ketone (3.0 mmol), aldimine (1.0 mmol), and toluene (20 mL) were
employed at 25 °C.
hydride to diisopropyl ketone. In general, direct formation
of allylic metals from alkenes employs highly basic and
nucleophilic organolithium reagent.15 Thus, the easy
accessiblility to allylic zirconocene and its moderate
reactivity is beneficial in organic synthesis. In addition,
we have revealed that changing the reaction temperature
from -78 to 25 °C can switch the sense of stereoselec-
tivity of the products. Our study of this thermodynamic
conversion proposes a retroallylation reaction to generate
the parent aldehyde and allylic zirconocene.
TABLE 4. P r ep a r a tion of Allylic Zir con iu m Rea gen t
fr om Alk en es
entry
methoda
R
product
yield (%)
anti/syn
1
2
3
4
A
A
A
A
C2H5
15i
15a
15j
15h
83
82
64
76
81/19
89/11
89/11
96/4
n-C3H7
n-C5H11
Ph
5
6
7
8
B
B
B
B
C2H5
15i
15a
15j
15h
93
85
72
60
26/74
23/77
28/72
13/87
Exp er im en ta l Section
n-C3H7
n-C5H11
Ph
Unless otherwise noted, materials obtained from commercial
suppliers were used without further purification. Tetrahydro-
furan (THF) was freshly distilled from sodium benzophenone
ketyl before use. Toluene was dried over slices of sodium.
Gen er a l P r oced u r e for Rea ction of Allylic Zir con iu m
Rea gen ts w ith Ald eh yd es a t -78 °C (Meth od A). Toluene
(30 mL) and Cp2ZrCl2 (878 mg, 3.0 mmol) were placed in a
reaction flask under argon. After the mixture was cooled to 0
a
Reaction conditions. Method A: Cp2ZrCl2 (3.0 mmol), cyclo-
pentylmagnesium bromide (1.0 M in THF, 6.0 mL, 6.0 mmol),
diisopropyl ketone (4.5 mmol), aldehyde (1.0 mmol), and toluene
(30 mL) were employed at -78 °C. Method B: Cp2ZrCl2 (2.0 mmol),
cyclopentylmagnesium bromide (1.0 M in THF, 4.0 mL, 4.0 mmol),
diisopropyl ketone (3.0 mmol), aldehyde (1.0 mmol), and toluene
(20 mL) were employed at 25 °C.
(14) Reduction of Cp2ZrCl2 with Mg metal in the presence of an
alkene also furnishes zirconium-olefin complex. However, in this
procedure, pinacol coupling of an aldehyde predominates to yield
hydrobenzoin without formation of the desired homoallyl alcohol. See
ref 5a.
(15) From a simple alkene: (a) Heus-Kloos, Y. A.; de J ong, R. L. P.;
Verkruijsse, H. D.; Brandsma, L.; J ulia, S. Synthesis 1985, 958. (b)
Akiyama, S.; Hooz, J . Tetrahedron Lett. 1973, 14, 4115. From an alkene
having a metal directing group: (c) Hoppe, D.; Hense, T. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2282. (d) Prasad, K. R. K.; Hoppe, D. Synlett
2000, 1067. (e) Pippel, D. J .; Weisenberger, G. A.; Faibish, N. C.; Beak,
P. J . Am. Chem. Soc. 2001, 123, 4919.
Con clu sion
In summary, we have developed a novel protocol to
prepare an allylzirconium reagent from alkene. The
present method involves formation of a zirconocene-
olefin complex, allylic C-H bond activation of the alkene
on zirconium to form zirconocene allyl hydride complex,
and selective removal of the hydride by transferring the
J . Org. Chem, Vol. 69, No. 10, 2004 3305

Fujita et al.
°C in an ice-water bath, hexylmagnesium bromide (6.0 mL,
1.0 M THF solution, 6.0 mmol) was added dropwise. The
solution immediately became a viscous black suspension, and
the resulting mixture was stirred for 30 min at 0 °C. A solution
of diisopropyl ketone (515 mg, 4.5 mmol) in toluene (2 mL)
was added at 0 °C, and the mixture was stirred for 3 h at 0
°C. A solution of benzaldehyde (106 mg, 1.0 mmol) in toluene
was added dropwise to the reaction mixture at -78 °C. After
stirring for another 5 h at the same temperature, the mixture
was poured into aqueous HCl (50 mL, 3 M) and extracted with
hexane/ethyl acetate. The combined organic layer was dried
over Na2SO4 and concentrated in vacuo. The crude oil was
purified on silica gel to yield 2-ethenyl-1-phenyl-1-pentanol
(15a , 186 mg, 0.98 mmol) in 98% yield.
Typ ica l P r oced u r e Usin g Allylic Zir con iu m Rea gen ts
w ith Ald eh yd es a t 25 °C (Meth od B). Hexylmagnesium
bromide (4.0 mL, 1.0 M THF solution, 4.0 mmol) was added
dropwise to a solution of Cp2ZrCl2 (585 mg, 2.0 mmol) in
toluene (20 mL) at 0 °C, and the mixture was stirred at the
same temperature for 30 min. To the reaction mixture was
added a solution of diisopropyl ketone (343 mg, 3.0 mmol) in
toluene (2 mL) at 0 °C. After 3 h of stirring at 0 °C,
benzaldehyde (106 mg, 1.0 mmol) was added at 0 °C, and the
mixture was stirred at 25 °C for 5 h. The mixture was poured
into aqueous hydrochloric acid (50 mL, 3 M). Extraction with
hexane/ethyl acetate followed by silica gel column purification
afforded 2-ethenyl-1-phenyl-1-pentanol (15a , 186 mg, 0.98
mmol) in 98% yield.
(m, 20H), 1.53 (bs, 1H), 1.96-2.08 (m, 1H), 3.45 (ddd, J ) 3.6,
5.4, 9.0 Hz, 1H), 5.08 (dd, J ) 2.1, 17.1 Hz, 1H), 5.17 (dd, J )
2.1, 10.2 Hz, 1H) 5.64 (ddd, J ) 9.3, 10.2, 17.1 Hz, 1H); 13C
NMR (CDCl3) δ 14.2, 14.2, 20.6, 22.8, 25.8, 29.4, 29.7, 29.7,
29.8, 32.0, 33.1, 34.8, 50.1, 73.6, 117.6, 138.9. Anal. Calcd for
C
16H32O: C, 79.93; H, 13.41. Found: C, 79.65; H, 13.15.
1-P h en yl-2-p r op yl-3-bu ten -1-ol (a n ti-15d , m ixtu r e of
isom er s, a n ti/syn ) 96/4; syn -15d , m ixtu r e of isom er s,
a n ti/syn ) 15/85): IR (neat) 3412, 3065, 3026, 2930, 2872,
1724, 1638, 1603, 1497, 1454, 1032, 1001, 914, 748, 700 cm-1
;
1H NMR (CDCl3) for anti adduct δ 0.80 (t, J ) 6.9 Hz, 3H),
1.06-1.44 (m, 4H), 1.57 (bs, 1H), 1.58-1.82 (m, 2H), 1.90-
2.02 (m, 1H), 2.52-2.91 (m, 2H), 3.39 (ddd, J ) 3.6, 3.6, 7.2
Hz, 1H), 5.02 (dd, J ) 2.1, 17.4 Hz, 1H), 5.10 (dd, J ) 2.1,
10.2 Hz, 1H), 5.55 (ddd, J ) 9.3, 10.2, 17.4 Hz, 1H), 7.06-
7.24 (m, 5H); for syn adduct δ 0.78 (t, J ) 7.2 Hz, 3H), 1.03-
1.43 (m, 4H), 1.49 (bs, 1H), 1.52-1.74 (m, 2H), 1.87-2.00 (m,
1H), 2.45-2.84 (m, 2H), 3.30 (ddd, J ) 3.3, 3.6, 6.9 Hz, 1H),
4.94 (dd, J ) 1.8, 16.8 Hz, 1H), 5.02 (dd, J ) 1.8, 10.2 Hz,
1H), 5.45 (ddd, J ) 9.0, 10.2, 16.8 Hz, 1H), 7.04-7.22 (m, 5H);
13C NMR (CDCl3) for anti adduct δ 14.1, 20.5, 32.2, 32.9, 36.6,
50.3, 73.0, 117.9, 125.6, 128.2, 128.3, 138.6, 142.2; for syn
adduct δ 14.2, 20.5, 32.1, 32.8, 36.6, 47.3, 73.0, 117.9, 125.9,
128.2, 128.5, 138.6, 142.2. Anal. Calcd for C15H22O: C, 82.66;
H, 10.35. Found: C, 82.52; H, 10.16.
4-Meth yl-1-p h en yl-1,5-h exa d ien -3-ol (15g, m ixtu r e of
ster eoisom er s, a n ti/syn ) 77/23): IR (neat) 3400, 3061,
3026, 2974, 2872, 1639, 1495, 1450, 966, 916, 750, 692 cm-1
;
Gen er a l P r oced u r e for Syn t h esis of H om oa llylic
Am in es w ith Allylic Zir con iu m Rea gen ts. Toluene (30 mL)
was added to Cp2ZrCl2 (878 mg, 3.0 mmol) in a flask under
argon. After the mixture was cooled to 0 °C in an ice-water
bath, butylmagnesium bromide (6.0 mL, 1.0 M THF solution,
6.0 mmol) was added, and the resulting mixture was stirred
for 30 min 0 °C. A solution of diisopropyl ketone (515 mg, 4.5
mmol) in toluene (2 mL) was added at 0 °C, and the mixture
was stirred at the same temperature for 3 h. N-Benzylideneben-
zylamine (195 mg, 1.0 mmol) was added at 0 °C, and the
mixture was stirred for another 5 h at -78 °C. Quenching the
reaction with aqueous hydrochloric acid followed by extraction,
concentration, and silica gel column purification provided
N-phenylmethyl-2-methyl-1-phenyl-3-buten-1-amine (22a , 168
mg, 0.67 mmol) in 67% yield as a colorless oil.
Typ ica l P r oced u r e via Olefin Exch a n ge. Cyclopentyl-
magnesium bromide (6.0 mL, 1.0 M THF solution, 6.0 mmol)
was added to a solution of Cp2ZrCl2 (878 mg, 3.0 mmol) and
1-pentene (631 mg, 9.0 mmol) in toluene (30 mL) at 0 °C. The
reaction mixture was stirred for 30 min at 0 °C and then for
an additional 1 h at 25 °C. Next, the resulting mixture was
cooled to 0 °C again, diisopropyl ketone (515 mg, 4.5 mmol)
was added, and the resulting mixture was stirred for 3 h at
25 °C. After the solution was cooled to -78 °C, a solution of
benzaldehyde (106 mg, 1.0 mmol) was added. The mixture was
stirred for another 5 h at -78 °C and poured into aqueous
hydrochloric acid (50 mL, 3 M). Extraction with hexane/ethyl
acetate followed by silica gel column purification afforded
2-ethenyl-1-phenyl-1-butanol (15i, 158 mg, 0.83 mmol) in 83%
yield.
1H NMR (CDCl3) δ 1.04 (d, J ) 6.9 Hz, 2.31H), 1.07 (d, J )
7.5 Hz, 0.69H), 2.01 (bs, 0.23H), 2.09 (bs, 0.77H), 2.28-2.40
(m, 0.77H), 2.38-2.51 (m, 0.23H), 4.03 (dd, J ) 6.9, 6.9 Hz,
0.77H), 4.17 (dd, J ) 6.6, 6.6 Hz, 0.23H), 5.14 (dd, J ) 1.8, 9.3
Hz, 1H), 5.16 (dd, J ) 1.8, 18.3 Hz, 1H), 5.80 (ddd, J ) 7.8,
9.3, 18.3 Hz, 0.77H), 5.82 (ddd, J ) 7.8, 9.3, 18.3 Hz, 0.23H),
6.19 (dd, J ) 6.9, 15.6 Hz, 0.77H), 6.20 (dd, J ) 6.6, 15.6 Hz,
0.23H), 6.56 (d, J ) 15.6 Hz, 0.23H), 6.58 (d, J ) 15.6 Hz,
0.77H), 7.18-7.41 (m, 5H); 13C NMR (CDCl3) for major isomer
δ 16.0, 44.6, 76.1, 116.4, 126.3, 127.5, 128.4, 130.1, 131.5, 136.6,
140.0; for minor isomer δ 14.9, 43.9, 75.7, 115.8, 126.3, 127.4,
128.4, 129.8, 131.0, 136.5, 139.8. Anal. Calcd for C13H16O: C,
82.94; H, 8.57. Found: C, 82.64; H, 8.60.
N-P h en ylm et h yl-2-m et h yl-1-p h en yl-3-b u t en -1-a m in e
(22a , m ixtu r e of ster eoisom er s, a n ti/syn ) 11/89): IR
(neat) 3333, 3063, 3026, 2970, 2799, 1638, 1603, 1495, 1454,
1362, 1198, 1115, 1072, 1028, 1001, 916, 845, 700 cm-1 1H
;
NMR (CDCl3) δ 0.66 (d, J ) 6.6 Hz, 0.33H), 0.89 (d, J ) 6.6
Hz, 2.67H), 1.63 (bs, 1H), 2.23-2.35 (m, 0.11H), 2.36-2.49 (m,
0.89H), 3.11 (d, J ) 8.7 Hz, 0.11H), 3.32 (d, J ) 13.5 Hz,
0.11H), 3.40 (d, J ) 13.5 Hz, 0.89H), 3.53 (d, J ) 5.7 Hz,
0.89H), 3.53 (d, J ) 13.5 Hz, 0.11H), 3.60 (d, J ) 13.5 Hz,
0.89H), 4.89 (dd, J ) 2.1, 10.2 Hz, 0.89H), 4.90 (dd, J ) 2.1,
17.4 Hz, 0.89H), 5.00 (dd, J ) 2.1, 10.2 Hz, 0.11H), 5.06 (dd,
J ) 2.1, 17.4 Hz, 0.11H), 5.61 (ddd, J ) 7.2, 10.2, 17.4 Hz,
0.11H), 5.63 (ddd, J ) 7.2, 10.2, 17.4 Hz, 0.89H), 7.10-7.27
(m, 10H); 13C NMR (CDCl3) for major isomer δ 15.41, 43.78,
51.46, 66.14, 114.72, 126.63, 126.71, 127.83, 127.98, 128.06,
128.14, 140.59, 140.93, 141.69; for minor isomer δ 17.9, 45.7,
51.3, 66.7, 115.9, 126.8, 127.0, 128.0, 128.0, 128.1, 128.3, 140.9,
142.1, 142.3. Anal. Calcd for C18H21N: C, 86.01; H, 8.42.
Found: C, 85.97; H, 8.39.
N-P h en ylm eth yl-2,4-d im eth yl-5-h exen -3-a m in e (22b,
m ixtu r e of ster eoisom er s, a n ti/syn ) 17/83): IR (neat)
3352, 3065, 3028, 2961, 2872, 1639, 1605, 1495, 1454, 1369,
1292, 1101, 1028, 999, 910, 741, 698 cm-1; 1H NMR (CDCl3) δ
0.94 (d, J ) 10.8 Hz, 2.49H), 0.96 (d, J ) 10.8 Hz, 2.49H),
0.96 (d, J ) 8.4 Hz, 0.51H), 0.98 (d, J ) 8.4 Hz, 0.51H), 1.07
(d, J ) 6.9 Hz, 0.51H), 1.07 (d, J ) 6.9 Hz, 2.49H), 1.38 (bs,
1H), 1.75-1.89 (m, 1H), 2.16 (dd, J ) 5.7, 5.7 Hz, 0.17H), 2.22
(dd, J ) 5.7, 5.7 Hz, 0.83H), 2.31-2.48 (m, 1H), 3.82 (d, J )
6.3 Hz, 2H), 4.99 (dd, J ) 1.8, 10.2 Hz, 1H), 5.03 (dd, J ) 1.8,
17.7 Hz, 1H), 5.86 (ddd, J ) 7.8, 10.2, 17.7 Hz, 0.83H), 5.87
(ddd, J ) 7.8, 10.2, 17.7 Hz, 0.17H), 7.20-7.39 (m, 5H); 13C
Ch a r a cter iza tion Da ta . Spectral data for several com-
pounds (15a , 15c, 15e, 15f, 15h , 15i, 15j, and 20) were found
in the literatures.5a,16,17 Identification of syn and anti isomers
1
of new compounds was carried out by comparing their H NMR
spectra with known compounds such as 15e. The syn/anti
1
ratios were determined by H NMR.
3-P r op yl-1-tr id ecen -4-ol (15b, m ixtu r e of ster eoiso-
m er s, a n ti/syn ) 94/6): IR (neat) 3379, 3074, 2926, 2855,
1638, 1466, 1421, 1379, 1001, 912, 721 cm-1; 1H NMR (CDCl3)
δ 0.88 (t, J ) 6.6 Hz, 3H), 0.90 (t, J ) 6.9 Hz, 3H), 1.20-1.53
(16) Matsumoto, K.; Oshima, K.; Utimoto, K. J . Org. Chem. 1994,
59, 7152.
(17) Tan, K. T.; Chng, S. S.; Cheng, H. S.; Loh, T. P. J . Am. Chem.
Soc. 2003, 125, 2958.
3306 J . Org. Chem., Vol. 69, No. 10, 2004

Preparation of Allylic Zirconium Reagent from Alkene
NMR (CDCl3) for major isomer δ 15.7, 18.0, 21.5, 30.8, 41.1,
55.4, 67.3, 113.2, 126.7, 128.1, 128.1, 141.2, 143.4; for minor
isomer δ 15.7, 18.2, 20.8, 30.9, 41.2, 55.4, 67.4, 114.3, 126.,7,
128.1, 128.1, 141.2, 142.1. Anal. Calcd for C15H23N: C, 82.89;
H, 10.67. Found: C, 82.78; H, 10.38.
(ddd, J ) 7.2, 10.2, 17.4 Hz, 0.18H), 7.13-7.30 (m, 5H); 13C
NMR (CDCl3) for major isomer δ 15.2, 26.6, 26.7, 26.8, 28.8,
31.4, 40.2, 41.3, 55.5, 66.8, 113.2, 126.7, 128.1, 128.1, 141.2,
143.4; for minor isomer δ 18.2, 26.7, 26.8, 26.9, 28.8, 31.1, 40.4,
41.7, 55.5, 66.9, 114.3, 126.7, 128.1, 128.1, 141.2, 142.0. Anal.
Calcd for C18H27N: C, 83.99; H, 10.57. Found: C, 84.08; H,
10.72.
N -P h e n ylm e t h yl-1-cycloh e xyl-2-m e t h yl-3-b u t e n -1-
a m in e (22c: m ixtu r e of ster eoisom er s, a n ti/syn ) 18/
82): IR (neat) 3350, 3065, 3028, 2924, 2853, 1638, 1602, 1495,
1450, 1418, 1072, 1028, 999, 968, 908, 698 cm-1 1H NMR
;
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research and COE Research
from the Ministry of Education, Culture, Sports, Sci-
ence, and Technology, J apan. K.F. acknowledges J SPS
for financial support.
(CDCl3) δ 0.96 (d, J ) 6.9 Hz, 2.46H), 0.97 (d, J ) 6.9 Hz,
0.54H), 1.08-1.25 (m, 5H), 1.31-1.44 (m, 1H), 1.52 (bs, 1H),
1.53-1.79 (m, 5H), 2.07 (dd, J ) 5.4, 5.4 Hz, 0.18H), 2.14 (dd,
J ) 5.4, 5.4 Hz, 0.82H), 2.27-2.43 (m, 1H), 3.70 (d, J ) 2.7
Hz, 2H), 4.91 (dd, J ) 1.8, 10.2 Hz, 1H), 4.94 (dd, J ) 1.8,
17.4 Hz, 1H), 5.78 (ddd, J ) 7.2, 10.2, 17.4 Hz, 0.82H), 5.79
J O049863R
J . Org. Chem, Vol. 69, No. 10, 2004 3307