Studies on the zirconium-mediated alkyne-aldehyde coupling reactions: a facile synthesis of stereodefined allylic alcohols and (Z)-2-en-4-yn-1-ols

Article abstract of DOI:10.1016/j.tet.2006.12.051

An improved zirconium-mediated alkyne-aldehyde cross-coupling reaction has been achieved to afford the stereodefined (Z)-allylic alcohols or 3-iodinated allylic alcohols selectively via protonolysis or iodinolysis of the corresponding five-membered oxazirconacycles. This method has also been successfully applied to the synthesis of (Z)-enynols through cross-coupling reactions of three different components involving alkyne, aldehyde, and alkynyl bromide in a one-pot procedure.

Full text of DOI:10.1016/j.tet.2006.12.051

Tetrahedron 63 (2007) 2009–2018
Studies on the zirconium-mediated alkyne–aldehyde coupling
reactions: a facile synthesis of stereodefined allylic alcohols and
(Z)-2-en-4-yn-1-ols
*
Shenghai Guo, Hao Zhang, Feijie Song and Yuanhong Liu
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Received 24 October 2006; revised 15 December 2006; accepted 18 December 2006
Available online 20 December 2006
Abstract—An improved zirconium-mediated alkyne–aldehyde cross-coupling reaction has been achieved to afford the stereodefined (Z)-al-
lylic alcohols or 3-iodinated allylic alcohols selectively via protonolysis or iodinolysis of the corresponding five-membered oxazirconacycles.
This method has also been successfully applied to the synthesis of (Z)-enynols through cross-coupling reactions of three different components
involving alkyne, aldehyde, and alkynyl bromide in a one-pot procedure.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
found that when the reaction was run at low temperature
(ꢀ25 ꢁC), the insertion product 3 became the major product,
while the formation of 5 was less than 2%. Recently, we have
developed an efficient synthetic approach to stereodefined
dihydrofurans or furans via gold-catalyzed cyclization of
(Z)-2-en-4-yn-1-ols.3 Within this program, (Z)-enynols
derived from zirconium-mediated alkyne–aldehyde coupling
reactions were substrates.
The selective coupling of alkynes with unsaturated mole-
cules such as alkynes, alkenes, ketones, aldehydes, nitriles,
etc. by use of a low-valent zirconocene equivalent has
been shown to lead to a variety of carbo- and heterometalla-
cycles.1 The in situ generated zirconacycles are important
intermediates in a wide range of selective (including
chemo-, regio-, and stereoselective) reactions.1 Although
much progress has been achieved in this area, there are
only a limited number of reports on the alkyne coupling re-
actions with aldehydes to give five-membered oxazircona-
cycles.2 The known procedures involve: (i) addition of
aldehyde to zirconocene–alkyne complexes.2e–g The alkyne
complexes used for this type of reaction are usually prepared
by hydrozirconation of an alkyne followed by methylation
with MeLi and elimination of methane from the alkenyl-
(methyl)zirconocene. The resulting alkyne complexes are
trapped with trimethylphosphine.2e,f This method requires
costly phosphine ligands and Cp2Zr(H)Cl. (ii) Reaction
of zirconacyclopentenes with aldehydes as reported by
Takahashi et al. (only one alkyne was tested to afford mod-
erate NMR yields of oxazirconacycles).2a,b However, there is
no systematic studies on this chemistry. In principle, two
types of reactions of zirconacyclopentenes with aldehydes
have been reported, one involves insertion of aldehydes at
alkyl–zirconium bond (Scheme 1, path a)2b and the other
involves the coupling of alkynes with aldehydes with con-
comitant extrusion of ethylene (path b).2a Negishi et al.
R
R
R
R
insertion
path a
H+
OH
R'
R
Zr
R
O
Zr
2
R'
3
R
1
R
R
R
+
H+
coupling
path b
Zr
R'CHO
O
4
R'
OH
R'
5
R= alkyl or aryl
Scheme 1. Reaction patterns of aldehyde addition with metallacyclopen-
tenes.
Initially, we applied the literature reaction conditions2a (ad-
dition of aldehyde to zirconacycle at 0 ꢁC, then warmed up
to 50 ꢁC) for the alkyne–aldehyde coupling via zirconacy-
clopentenes. However, it was found that the byproducts of
direct insertion reactions were always formed in comparable
yields along with desired allylic alcohols. For example, the
reaction between 1,2-dipropylzirconacyclopentene 1a and
benzaldehyde (1.5 equiv) afforded insertion product 1-phen-
yl-4-propyloct-4-en-1-ol 3a and coupling product 1-phenyl-
2-propylhex-2-en-1-ol 5a in 98% combined NMR yield with
* Corresponding author. E-mail: yhliu@mail.sioc.ac.cn
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.12.051

2010
S. Guo et al. / Tetrahedron 63 (2007) 2009–2018
a ratio of 1:1 (determined by NMR). These unsatisfactory re-
sults prompted us to optimize the reaction conditions to en-
hance the selectivity of the desired cross-coupling reactions.
In this paper, we describe the detailed studies on Zr-medi-
ated alkyne–aldehyde coupling reactions under improved
conditions, in which the above-mentioned insertion reac-
tions are mostly suppressed. This reaction has also been
applied to an efficient and one-pot synthesis of highly
substituted, stereodefined allylic alcohols and (Z)-2-en-
4-yn-1-ols.
(Table 1, entry 1–4). We checked two cases of the reaction
with aryl-substituted alkyne, the results indicated that there
was no significant difference in product yields and selectiv-
ity under the above two reaction conditions.6,7 The coupling
product 5 was formed predominantly with >98% selectivity
(entry 5–10). When bis(thienyl)alkyne was employed, the
corresponding alcohol 5h was formed in a good yield of
72% (entry 8). Substitution at C-1 with a thienyl group re-
sulted in a quick allylic isomerization during the acidic
quenching, and the two products of 5i were obtained in a ratio
of 3:1 with a combined yield of 88% (entry 9). When the al-
dehyde tethered with an alkyne moiety such as 4-(phenyl-
ethynyl)benzaldehyde was used, the coupling reaction
selectively occurred at the carbonyl moiety, furnishing the
product 5j in 90% yield, while the triple bond in the substrate
remained intact (entry 10). Interestingly, with 1-trimethyl-
silyl-1-hexyne, two regioisomers of 5k and 5l were formed
in 22% and 33% yields, respectively (entry 11). The regiose-
lectivity is lower than that observed in the coupling reaction
of silylated alkynes with nitriles,4a in which only one
regioisomer (silyl group substituted at the a-position in aza-
zirconacycles) was observed.
2. Results and discussion
2.1. Zirconium-mediated alkyne–aldehyde coupling
reactions
Zirconacyclopentenes are known to undergo cross-coupling
reaction with unsaturated compounds through facile b,b0-
carbon–carbon bond cleavage reaction along with elimina-
tion of one ethylene molecule.4 It seems that once the system
is ‘preactivated’, the behavior of ethylene ligand should be
more labile and easy to be eliminated from the metal center.
Thus this system is expected to be feasible to perform the
desired alkyne–aldehyde cross-coupling reactions, and min-
imize the possibility of direct insertion reactions. Conse-
quently, we found that simply heating the reaction mixture
of zirconacycle 1a up to 50 ꢁC for a few minutes followed
by slow addition of benzaldehyde, the desired coupling
product 5a was formed in 82% NMR yield with high isomer-
ical purity (>99%) as shown in Scheme 2. The amount of 3a,
which is the major product at 0 ꢁC, was <1%. Interestingly,
when the reaction mixture of 4a was quenched with 3 N HCl
for overnight, the stereodefined product 6 could be generated
in 38% isolated yield through acid-induced allylic isomeri-
zation.5 The (E)-configuration of C]C bond in 6 was deter-
mined by the 1H–1H NOESY spectrum.
2.2. Iodination of oxazirconacycles 4
The oxazirconacycles 4 produced by this method are ver-
satile synthetic intermediates, which can be trapped with
electrophiles to afford tetrasubstituted olefins with high
stereoselectivity. We found that iodination of zirconacycle
4a with 3 equiv of iodine at room temperature proceeded
at the alkenyl-zirconium moiety to afford stereodefined
(Z)-3-iodo-1-phenyl-2-propylhex-2-en-1-ol 7a8 in 59%
yield (Scheme 3). The use of 1.5 equiv of I2 resulted in a
prolonged reaction time (55% for 5 h).
Takahashi et al. had reported that addition of copper salt is
effective for the iodination of C(sp2)–Zr bond in zircona-
cyclopentadienes and zirconacyclopentenes.9 With the use
of 20% CuI, the amount of iodination reagent (I2) could
be reduced to 1.2 equiv, and the product 7a was formed
in 56% yield but prolonged reaction time (8 h) was required.
The results of iodination are summarized in Table 2.
ICl could also be used as an effective iodination reagent
(Table 2, entries 2, 4–7). It should be noted that in most
cases, ICl was more effective than I2. Interestingly, when
diphenyl-substituted zirconacycle 4b was subjected to
CuI-mediated iodination condition, the product was formed
as a mixture of Z and E isomers in 76% yield with the ratio
The results of the preparation of allylic alcohols from al-
kynes and aldehydes are summarized in Table 1. As shown
in Table 1, alkyl, aryl, and heteroaryl aldehydes are all
compatible with coupling conditions. The corresponding
allylic alcohols were formed in good to high yields. For
alkyl-substituted alkyne, addition of aldehyde at 0 ꢁC (then
warmed up to 50 ꢁC) always resulted in the formation of
byproducts of type 3. The ratio of 3/5 is varied from 0.6:1
to 2.5:1.6 However, under the ‘preactivated’ conditions, the
selectivity was significantly improved to more than 89%, im-
plying the undesired formation of 3 was mostly suppressed
Pr
Pr
Pr
Pr
Pr
Pr
3N HCl
1.5 eq PhCHO
Pr
Ph
Ph
OH
Pr
+
Cp2Zr
Cp2Zr
50 °C 2 h
O
OH
5a, 82%
Ph
3a, < 1%
1a
4a
preactivated at 50 C
Pr
3N HCl
4a
Pr
HO
overnight
H
H
NOE
6, 38%
Scheme 2. Alkyne–aldehyde coupling reaction through a preactivated zirconacyclopentene.

S. Guo et al. / Tetrahedron 63 (2007) 2009–2018
2011
Table 1. Formation of stereodefined allylic alcohols via alkyne–aldehyde coupling reactions
Entry
Alkyne
Aldehyde
Product
Yielda %
Selectivity %
5
3
C3H7
C3H7
C3H7
5a
5b
C3H7
C3H7
C3H7
C3H7
Ph
C3H7
C3H7
C3H7
C3H7
Ph
1
2
3
4
5
6
7
8
PhCHO
82 (63)
61 (56)
69 (59)
80 (63)b
86 (66)
98 (60)
93 (69)
72 (57)
>99
90
<1
10
Ph
HO
C3H7
iPrCHO
HO
C3H7
C3H7
5c
5d
p-MeC6H4CHO
p-ClC6H4CHO
nPrCHO
97
3
p-MeC6H4
C3H7
p-ClC6H4
HO
C3H7
89
11
HO
Ph
Ph
nPr
5e
99
<1
<2
<1
<1
HO
Ph
Ph
Ph
Ph
5f
p-MeOC6H4CHO
p-ClC6H4CHO
p-MeC6H4CHO
98
p-MeOC6H4
Ph
HO
Ph
5g
Ph
Ph
>99
>99
p-ClC6H4
Thic
HO
Thi
5h
p-MeC6H4
S
S
HO
Ph
Ph
Ph
Ph
+
9
Ph
Ph
CHO
S
88 (70)
90 (64)
>99
>99
<1
<1
HO
S
S
HO
Ph
a
b
5id
Ph
10
Ph
Ph
CHO
HO
Bu
Ph
5j
TMS
Bu
TMS
Ph
HO
5l
+
11
TMS
Bu
PhCHO
77 (55)e
—
—
HO
5k
a
NMR yields and isolated yields are given in parentheses. All the reactions were carried out at 50 ꢁC for 1–3 h by the addition of 1.5 equiv of aldehyde to
a reaction mixture of zirconacyclopentenes preactivated at 50 ꢁC.
The product was concomitant with small amount of byproduct.
b
c
d
e
Thi is 2-thienyl group.
The ratio of a/b (or b/a)¼3:1. Only one alkene isomer of b was obtained, the geometry of C]C bond in isomer b was not defined.
Combined yield. Compounds 5k and 5l were isolated in 22% and 33% yields, respectively.
Pr
copper salt, no isomerization occurred as shown in Table 2,
entry 5.
Pr
Pr
3 eq I2
rt, 1 h
Pr
Ph
OH
7a, 59%
Cp2Zr
O
I
Ph
2.3. One-pot procedure for the formation of (Z)-enynols
4a
(Z)-2-En-4-yn-1-ols have been utilized in recent years as
highly versatile precursors for diversity-oriented organic
synthesis. They undergo a variety of transformations to gen-
erate heterocycles such as furans or dihydrofurans, which are
useful intermediates in the synthesis of natural products and
pharmaceuticals.11 Therefore, a stereoselective and efficient
synthesis of these intermediates is of great interest. The
Scheme 3. Iodination of oxazirconacycles 4.
of 4:1 (Scheme 4). This result indicated that stereoisomeri-
zation occurred during the reaction. A similar isomerization
was observed in the iodination of phenyl-substituted vinyl
zirconocene complexes.10 However, without the use of

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S. Guo et al. / Tetrahedron 63 (2007) 2009–2018
Table 2. Synthesis of iodinated allylic alcohols via iodinolysis of oxazirconacyclopentenes
Entry
1
Alkyne
Aldehyde
PhCHO
Product
Yielda (%)
59b
C3H7
I
C3H7
7a
C3H7
C3H7
C3H7
C3H7
Ph
C3H7
C3H7
C3H7
C3H7
Ph
Ph
HO
C3H7
I
C3H7
iPr
iPrCHO
42
58b
53
55
50
7b
2
3
4
5
6
HO
C3H7
C3H7
p-MeC6H4
HO
C3H7
7c
7d
p-MeC6H4CHO
p-MeOC6H4CHO
nPrCHO
I
C3H7
I
p-MeOC6H4
HO
Ph
Ph
7e
I
nPr
HO
Ph
Ph
I
7f
Ph
Ph
p-ClC6H4CHO
p-ClC6H4
HO
Ph
Ph
7g
S
7
Ph
Ph
CHO
S
40
I
HO
a
Isolated yields. Unless noted, all the reactions were carried out at 0 ꢁC for 1 h using 3 equiv of ICl.
The reaction was carried out at room temperature using 3 equiv of I2.
b
Ph
stirring the mixture for 12 h afforded (Z)-enynol 9e in 56%
yield after hydrolysis. However, further optimization of the
reaction condition revealed that the reaction proceeded
with 20% of CuCl and 1.2 equiv of alkynyl bromide in the ab-
sence of LiCl to afford the higher yield of 79% (Scheme 5).
The reaction mechanism for this alkynylation was assumed
through transmetalation of Zr–C(sp2) bond to a Cu–C
bond,13 which would be more reactive toward electrophiles,
followed by subsequent sp–sp2 coupling reaction along with
the elimination of CuBr. CuBr can also effect the transmeta-
lation reactions. Therefore, the alkynylation can be carried
out with a catalytic amount of CuCl. This reaction also indi-
cated that aldehyde-derived zirconacycles 4 are very reactive
toward electrophiles and may have valuable synthetic poten-
tial for other transformations. The representative reactions of
various alkynyl bromides with zirconacycles 4 are listed in
Table 3. Alkynyl bromide bearing alkyl or aryl substituent
reacted very well with oxazirconacycles to afford enynols 9
in 46–83% yields. The cyclohexenyl substituted alkynyl
bromide has also been examined, and the corresponding
product 9h was formed smoothly in 80% yield (Table 3, entry
8). A wide range of aromatic aldehydes could be used, fur-
nishing the corresponding enynols in good to high yields.
When an aliphatic aldehyde such as butyraldehyde was sub-
jected to the reaction, the product 9i was formed in a satisfied
yield of 59% (Table 3, entry 9). On the other hand, this alky-
nylation could be efficiently applied to the seven-membered
oxazirconacycles 2 that was formed in high yield through
direct insertion reactions.2a As shown in Scheme 6, the reac-
tion of 2a with a variety of alkynyl bromide in the presence of
a stoichiometric amount of CuCl afforded 10a–d in good
yields.
Ph
Ph
Ph
20% CuI
1.2 eq I2,
rt, overnight
Ph
C3H7
I
C3H7
Cp2Zr
+
O
I
OH
Ph OH
C3H7
4b
7e
8e
76%, 7e/8e=4:1
Scheme 4. Stereoisomerization during the iodination process.
preparation of (Z)-enynols is usually achieved through
multi-step transformations involving Pd/Cu-catalyzed cou-
pling of the terminal alkynes with vinylic halides, addition
of alk-1-ynes to vinyl ketones followed by acid-catalyzed
allylic isomerization, reduction of methyl (Z)-2-en-4-ynoates,
KOtBu-promoted coupling reactions of aldehydes and
alkynes, etc.11a,c,i Nevertheless, enhancing the efficiency of
the synthesis of these compounds is still highly demanded.
We recently reported an efficient synthetic approach to
stereodefined (Z)-enynols 1 via zirconium-mediated cross-
coupling reactions of three different components involving
alkyne, ketone, and alkynyl bromide in a one-pot proce-
dure.12 This method is useful for the construction of (Z)-
enynols with a tertiary alcoholic group at C-1. We envisioned
that the same methodology could be used here to provide
(Z)-enynols with a secondary alcoholic group at C-1. Our first
target was to find suitable reaction conditions under which
alkynylation of oxazirconacycles 4 would efficiently pro-
ceed. Thus the coupling reaction of zirconacycle 4a with
alkynyl bromide was chosen to be tested under our standard
reactionconditionsusedinalkyne–ketonecouplingsystem.12
Treatment of 4a with 2 equiv of CuCl, 2 equiv of LiCl, and
p-chlorophenyl ethynyl bromide at room temperature and

S. Guo et al. / Tetrahedron 63 (2007) 2009–2018
2013
C3H7
Pr
C3H7
C3H7
Ph
p-ClC H
20% CuCl, rt, 12 h
Br
1.2
Pr
i)
6
4
Pr
C3H7
Ph
Pr
i)
1.0
1.0 CuCl, rt, 1 h
ii) H+
R
Br
Cp2Zr
ii) H+
Cp2Zr
R
O
HO
O
p-ClC6H4
Ph
9e, 79%
4a
HO
Ph
2a
10
Scheme 5. Alkynylation of oxazirconacycle 4.
R= p-CH3C6H4, 65%, (10c)
R= C6H5, 56%, (10b) R= p-ClC6H4, 63%, (10d)
R= Bu, 53%, (10a)
In summary, we have developed an improved procedure for
zirconium-mediated alkyne–aldehyde coupling reactions.
The stereodefined allylic alcohols or 3-iodinated allylic
alcohols were selectively formed via protonolysis or iodino-
lysis of the corresponding five-membered oxazirconacycles.
The method has also been successfully applied to the syn-
thesis of (Z)-enynols through three-component coupling
reactions of alkyne, aldehyde, and alkynyl bromide in a
one-pot procedure. We are currently exploring the new syn-
thetic potential of oxazirconacycles.
Scheme 6. Alkynylation of seven-membered oxazirconacycles.
3. Experimental section
3.1. General methods
All reactions were carried out using standard Schlenk tech-
niques under nitrogen. THF was distilled from sodium/
Table 3. Formation of (Z)-2-en-4-yn-1-ol through three-component coupling reactions
Entry
Alkyne
Aldehyde
Alkynyl bromide
Product
Pr
Yielda (%)
Pr
9a
1
Pr
Pr
p-MeOC6H4CHO
Bu
Br
p-MeOC6H4
46
HO
Bu
Ph
Pr
Pr
9b
2
3
4
Pr
Pr
p-MeC6H4CHO
PhCHO
Ph
Ph
Br
Br
p-MeC6H4
83
77
68
HO
Bu
Bu
9c
Bu
Bu
Ph
HO
Ph
Bu
Bu
9d
p-ClC6H4
Br
Br
p-MeC6H4
Bu
Pr
Bu
Et
Bu
Pr
Bu
Et
p-MeC6H4CHO
HO
Pr
p-ClC6H4
Pr
9e
p-ClC6H4
p-MeOC6H4
p-MeOC6H4
Ph
5
6
7
8
PhCHO
PhCHO
PhCHO
79
73
78
HO
p-ClC6H4
Bu
Bu
9f
Br
Ph
Ph
HO
Et
p-MeOC6H4
Et
9g
Br
HO
p-MeOC6H4
Et
Et
9h
Et
Et
p-ClC6H4CHO
p-ClC6H4
80
59
Br
HO
Cyb
Ph
Ph
9i
p-MeOC6H4
Br
Pr
Ph
Ph
9
PrCHO
HO
p-MeOC6H4
a
Isolated yields. All the reactions were carried out at room temperature for overnight using 20% CuCl and 1.2 equiv of alkynyl bromide.
Cy is cyclohexenyl group.
b

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S. Guo et al. / Tetrahedron 63 (2007) 2009–2018
benzophenone. All commercial reagents were used without
further purification. Zirconocene dichloride, aldehydes,
and alkynes were used as purchased. Ethylmagnesium bro-
mide (1.0 M solution in THF) was used as purchased and/
or prepared in this lab (titrated14 as 0.94–1.07 M THF solu-
tion). Zirconacyclopentenes 12a were prepared according to
the previously published procedures. 1H and 13C NMR spec-
tra were recorded at 300 and 75.4 MHz, respectively, in
1.92–2.13 (m, 4H), 2.32 (s, 3H), 5.07 (s, 1H), 5.60 (t,
J¼7.2 Hz, 1H), 7.11 (d, J¼8.1 Hz, 2H), 7.21 (d, J¼8.1 Hz,
2H); 13C NMR (CDCl3, Me4Si) d 13.9, 14.4, 21.0, 22.6, 22.9,
29.6, 29.9, 77.7, 126.5, 126.6, 128.8, 136.8, 139.9, 141.2; IR
(neat) 3380, 2958, 2930, 2870, 1512, 1464, 1036 cmꢂ1
;
HRMS (EI) calcd for C16H24O 232.1827, found 232.1837.
3.2.4. (2E)-1-(4-Chlorophenyl)-2-propylhex-2-en-1-ol
(5d). Purification of the crude product by column chro-
matography on neutral Al2O3 (petroleum ether/ethyl
acetate¼8:1) afforded the title product in 63% isolated yield.
1H NMR (CDCl3, Me4Si) d 0.81 (t, J¼7.2 Hz, 3H), 0.92 (t,
J¼7.2 Hz, 3H), 1.16–1.45 (m, 4H), 1.76–2.08 (m, 5H), 5.10
(s, 1H), 5.58 (t, J¼7.2 Hz, 1H), 7.26–7.28 (m, 4H);
13C NMR (CDCl3, Me4Si) d 13.90, 14.40, 22.75, 22.86,
29.65, 29.74, 77.58, 127.85, 127.93, 128.23, 132.86,
141.02, 141.22; IR (neat) 3382, 2958, 2871, 1596, 1489,
1464, 1091, 828 cmꢂ1; HRMS (EI) calcd for C15H21OCl
252.1281, found 252.1281.
1
CDCl3 (containing 1% TMS) solutions. H NMR spectra
were recorded with tetramethylsilane (0.00 ppm) as an inter-
nal standard; 13C NMR spectra were recorded with CDCl3
(77.00 ppm) as an internal standard. NMR yields were deter-
mined using dibromomethane as an internal standard.
3.2. A typical procedure for zirconium-mediated al-
kyne–aldehyde coupling reactions under ‘preactivated’
conditions
To a solution of Cp2ZrCl2 (0.365 g, 1.25 mmol) in THF
(5 mL) was added EtMgBr (1.0 M THF solution,
2.5 mmol) at ꢂ50 ꢁC. After stirring for 1 h at the same tem-
perature, 4-octyne (0.11 g, 1 mmol) was added and the reac-
tion mixture was warmed up to 0 ꢁC and stirred for 3 h. The
thus formed zirconacyclopentene was heated up to 50 ꢁC for
a few minutes (ca. 5 min), followed by slow addition of
benzaldehyde (0.15 mL, 1.5 mmol) at the same temperature.
After stirring for 2 h, the mixture was quenched with 3 N
HCl solution (usually, within 2 min) and extracted with
ether. The extract was washed with NaHCO3, brine, and
dried over Na2SO4. The solvent was evaporated in vacuo
and the residue was purified by chromatography on neutral
Al2O3 (petroleum ether/ethyl acetate¼15:1). An orange-yel-
low liquid of allylic alcohol 5a (137 mg, 63%) was obtained.
NMR yield: 82%.
3.2.5. (E)-1,2-Diphenylhex-1-en-3-ol (5e). Purification of
the crude product by column chromatography on neutral
Al2O3 (petroleum ether/ethyl acetate¼5:1) afforded the title
1
product in 66% isolated yield. H NMR (CDCl3, Me4Si)
d 0.89 (t, J¼6.6 Hz, 3H), 1.37–1.56 (m, 4H), 1.87 (br s,
1H), 4.45 (t, J¼6.0 Hz, 1H), 6.65 (s, 1H), 6.90–6.93 (m,
2H), 7.05–7.10 (m, 3H), 7.16–7.20 (m, 2H), 7.29–7.36 (m,
3H); 13C NMR (CDCl3, Me4Si) d 13.9, 18.9, 37.54, 77.1,
126.6, 126.7, 127.3, 127.8, 128.6, 129.2, 129.2, 136.5,
138.4, 144.9; IR (neat) 3488, 2870, 1598, 1494 cmꢂ1
HRMS (EI) calcd for C18H20O 252.1514, found 252.1510.
;
3.2.6. (E)-1-(4-Methoxyphenyl)-2,3-diphenylprop-2-en-
1-ol (5f). The mixture was quenched with 1 N HCl. Purifica-
tion of the crude product by column chromatography on
neutral Al2O3 (petroleum ether/ethyl acetate¼5:1 to 2:1)
1
3.2.1. (E)-1-Phenyl-2-propylhex-2-en-1-ol (5a). H NMR
1
(CDCl3, Me4Si) d 0.80 (t, J¼7.2 Hz, 3H), 0.92 (t,
J¼7.2 Hz, 3H), 1.14–1.47 (m, 4H), 1.75–1.99 (m, 2H),
2.04 (q, J¼7.2 Hz, 2H), 2.32 (br s, 1H), 5.08 (s, 1H), 5.58
(t, J¼7.8 Hz, 1H), 7.19–7.33 (m, 5H); 13C NMR (CDCl3,
Me4Si) d 13.8, 14.3, 22.6, 22.9, 29.6, 29.8, 77.9, 126.5,
127.0, 127.1, 128.0, 141.2, 142.8; IR (neat) 3421, 2958,
2930, 2871, 1491, 1454, 1034 cmꢂ1; HRMS (EI) calcd for
C15H22O 218.1671, found 218.1679.
afforded the title product in 60% isolated yield. H NMR
(CDCl3, Me4Si) d 2.41 (br s, 1H), 3.74 (s, 3H), 5.45 (s,
1H), 6.77–7.24 (m, 15H); 13C NMR (CDCl3, Me4Si)
d 55.1, 78.5, 113.6, 126.5, 126.7, 127.2, 127.8, 128.1,
128.4, 129.2, 129.3, 133.7, 136.4, 138.2, 144.1, 158.9; IR
(neat) 3419, 2930, 1609, 1510, 1249, 1173, 1033 cmꢂ1
;
HRMS (EI) calcd for C22H20O2 316.1463, found 316.1466.
3.2.7. (E)-1-(4-Chlorophenyl)-2,3-diphenylprop-2-en-1-
ol (5g). Purification of the crude product by column chro-
matography on neutral Al2O3 (petroleum ether/ethyl
acetate¼10:1 to 5:1) afforded the title product in 69% iso-
3.2.2. (E)-2-Methyl-4-propyloct-4-en-3-ol (5b). Purifica-
tion of the crude product by column chromatography on
silica gel (petroleum ether/ethyl acetate¼30:1) afforded
1
1
the title product in 56% isolated yield. H NMR (CDCl3,
lated yield. H NMR (CDCl3, Me4Si) d 2.49 (br s, 1H),
Me4Si) d 0.83 (d, J¼6.6 Hz, 3H), 0.86–0.93 (m, 9H),
1.29–1.48 (m, 5H), 1.69–1.80 (m, 1H), 1.86–2.03 (m, 4H),
3.61 (d, J¼7.2 Hz, 1H), 5.32 (t, J¼7.2 Hz, 1H); 13C NMR
(CDCl3, Me4Si) d 13.9, 14.6, 18.1, 19.8, 22.9, 23.2, 29.6,
30.0, 31.6, 82.7, 127.7, 141.1; IR (neat) 3442, 2958, 2871,
1466, 1379, 1006 cmꢂ1; HRMS (EI) calcd for C9H17O
[MꢂC3H7]+ 141.1279, found 141.1282.
5.48 (s, 1H), 6.82 (s, 1H), 6.88–6.94 (m, 4H), 7.05–7.09
(m, 3H), 7.18–7.28 (m, 7H); 13C NMR (CDCl3, Me4Si)
d 78.5, 127.0, 127.4, 127.4, 127.9, 128.1, 128.3, 128.5,
129.2, 129.3, 133.2, 136.0, 137.6, 140.1, 143.5; IR (neat)
3385, 3055, 1598, 1491, 1446, 1090 cmꢂ1; HRMS (EI)
calcd for C21H17ClO 320.0968, found 320.0952.
3.2.8. (Z)-2,3-Di(2-thienyl)-1-p-tolylprop-2-en-1-ol (5h).
Purification of the crude product by column chromatography
on silica gel (300–400 mesh) (petroleum ether/ethyl
acetate¼25:1 to 20:1) afforded the title product in 57% iso-
lated yield. 1H NMR (CDCl3, Me4Si) d 2.24 (br s, 1H), 2.33
(s, 3H), 5.43 (s, 1H), 6.70 (dd, J¼3.3, 1.2 Hz, 1H), 6.87–7.24
(m, 9H), 7.36 (dd, J¼5.1, 1.2 Hz, 1H); 13C NMR (CDCl3,
3.2.3. (E)-2-Propyl-1-p-tolylhex-2-en-1-ol (5c). Purifica-
tion of the crude product by column chromatography on silica
gel (petroleum ether/ethyl acetate¼15:1) afforded the title
1
product in 59% isolated yield. H NMR (CDCl3, Me4Si)
d 0.82 (t, J¼6.9 Hz, 3H), 0.92 (t, J¼7.5 Hz, 3H), 1.20–
1.30 (m, 2H), 1.42 (q, J¼7.3 Hz, 2H), 1.74–1.84 (m, 1H),

S. Guo et al. / Tetrahedron 63 (2007) 2009–2018
2015
Me4Si) d 21.2, 78.5, 104.8, 124.1, 126.1, 126.7, 126.9,
127.3, 128.6, 129.0, 129.4, 134.3, 136.8, 137.6, 138.3,
139.5; IR (neat) 3415, 2920, 2859, 1511, 1439, 1423,
1376, 1035, 700 cmꢂ1; HRMS (EI) calcd for C18H16OS2
312.0643, found 312.0641.
1.75 (br s, 1H), 2.10–2.20 (m, 1H), 2.26–2.36 (m, 1H),
4.21 (t, J¼6.6 Hz, 1H), 6.51 (s, 1H), 7.18–7.35 (m, 5H);
13C NMR (CDCl3, Me4Si) d 14.0, 14.5, 19.1, 22.5, 30.5,
38.1, 76.2, 125.3, 126.3, 128.1, 128.6, 137.7, 145.5; IR
(neat) 3374, 2958, 2931, 2871, 1493, 1455, 1022, 748,
698 cmꢂ1; HRMS (EI) calcd for C15H20 [MꢂH2O]+
200.1565, found 200.1567.
3.2.9. (E)-2,3-Diphenyl-1-(2-thienyl)prop-2-en-1-ol and
1,2-diphenyl-3-(2-thienyl)prop-2-en-1-ol (5i). Purification
of the crude product by column chromatography on silica gel
(petroleum ether/ethyl acetate¼20:1) afforded the title prod-
ucts as a mixture of two isomers in the ratio of 3:1 with
a combined yield of 70%. 1H NMR (CDCl3, Me4Si) two iso-
mers d 2.79 (br s, 1H), 2.95 (br s, 1H), 5.36 (s, 1H), 5.66 (s,
1H), 6.75–7.23 (m); 13C NMR (CDCl3, Me4Si) two isomers
d 74.7, 78.7, 120.2, 125.0, 125.1, 125.9, 125.9, 126.6, 126.7,
126.8, 126.9, 127.3, 127.5, 127.8, 127.8, 128.0, 128.4, 128.4,
128.6, 129.2, 129.3, 129.7, 136.1, 137.1, 137.6, 139.9, 141.2,
141.9, 143.2, 146.2; HRMS (EI) calcd for C19H16OS
292.0922, found 292.0930.
3.3. A typical procedure for iodination reactions
To a mixture of oxazirconacycle 4a prepared as above was
added iodine (0.76 g, 3 mmol) at room temperature. After
stirring for 1 h, the mixture was quenched with 3 N HCl
solution and extracted with ether. The extract was washed
with NaHCO3, Na2S2O3, brine, and dried over Na2SO4. The
solvent was evaporated in vacuo and the residue was purified
by chromatography on silica gel (petroleum ether/ethyl
acetate¼30:1 to 20:1). A light-yellow liquid of allylic
alcohol 7a (204 mg, 59%) was obtained. The spectral data
are the same as previous published one.8
3.2.10. (E)-2,3-Diphenyl-1-(4-phenylethynyl-phenyl)-
prop-2-en-1-ol (5j). Purification of the crude product by col-
umn chromatography on silica gel (petroleum ether/ethyl
acetate¼20:1) afforded the title product in 64% isolated
3.3.1. (Z)-5-Iodo-2-methyl-4-propyloct-4-en-3-ol (7b).
Purification of the crude product by column chromatography
on neutral Al2O3 (petroleum ether/ethyl acetate¼30:1 to
20:1) afforded the title product in 42% isolated yield.
1H NMR (CDCl3, Me4Si) d 0.86 (d, J¼6.9 Hz, 3H), 0.91–
0.96 (m, 6H), 1.06 (d, J¼6.6 Hz, 3H), 1.25–1.63 (m, 4H),
1.67 (s, 1H), 1.77–1.88 (m, 1H), 2.00–2.10 (m, 1H),
2.19–2.29 (m, 1H), 2.41–2.64 (m, 2H), 4.29 (d, J¼8.7 Hz,
1H); 13C NMR (CDCl3, Me4Si) d 13.0, 14.6, 18.9,
19.2, 23.1, 24.3, 31.1, 32.5, 43.1, 87.1, 108.5, 144.3; IR
(neat) 3417, 2960, 2871, 1615, 1464, 1379, 1095,
1022 cmꢂ1; HRMS (EI) calcd for C12H23IO 310.0794,
found 310.0800.
1
yield. H NMR (CDCl3, Me4Si) d 2.35 (br s, 1H), 5.53 (s,
1H), 6.85 (s, 1H), 6.90–6.96 (m, 3H), 7.06–7.09 (m, 3H),
7.19–7.23 (m, 3H), 7.28–7.34 (m, 6H), 7.45–7.53 (m, 4H);
13C NMR (CDCl3, Me4Si) d 78.9, 89.3, 89.5, 122.4, 123.1,
126.7, 126.9, 127.4, 127.5, 127.9, 128.2, 128.3, 128.5,
129.3, 129.4, 131.5, 131.5, 136.1, 137.6, 141.8, 143.5; IR
(neat) 3564, 3401, 2974, 2855, 1598, 1508, 1494, 1443,
1069 cmꢂ1; HRMS (EI) calcd for C29H22O 386.1671, found
386.1672.
3.2.11. (E)-1-Phenyl-2-((trimethylsilyl)methylene)hexan-
1-ol (5k). Purification of the crude product by column
chromatography on silica gel (petroleum ether/ethyl
acetate¼30:1) afforded the title product in 22% isolated
3.3.2. (Z)-3-Iodo-2-propyl-1-p-tolylhex-2-en-1-ol (7c). Pu-
rification of the crude product by column chromatography
on silica gel (petroleum ether/ethyl acetate¼30:1) afforded
1
1
yield. H NMR (CDCl3, Me4Si) d 0.03 (s, 9H), 0.73 (t,
the title product in 58% isolated yield. H NMR (CDCl3,
J¼6.9 Hz, 3H), 1.10–1.28 (m, 4H), 1.68–1.77 (m, 1H),
1.90 (br s, 1H), 1.98–2.08 (m, 1H), 5.01 (s, 1H), 5.68 (d,
J¼1.2 Hz, 1H), 7.13–7.27 (m, 5H); 13C NMR (CDCl3,
Me4Si) d 0.3, 13.9, 23.1, 32.3, 33.1, 77.6, 122.2, 127.0,
127.7, 128.4, 142.4, 159.5; IR (neat) 3416, 2957, 2872,
1614, 1494, 1454, 1248, 836, 699 cmꢂ1; HRMS (EI) calcd
for C16H26OSi 262.1753, found 262.1757.
Me4Si) d 0.77 (t, J¼7.2 Hz, 3H), 0.94 (t, J¼7.5 Hz, 3H),
0.99–1.06 (m, 1H), 1.29–1.39 (m, 1H), 1.57–1.69 (m, 2H),
1.92–2.02 (m, 1H), 2.09–2.19 (m, 2H), 2.30 (s, 3H), 2.48–
2.59 (m, 2H), 5.89 (s, 1H), 7.13 (d, J¼8.1 Hz, 2H), 7.33
(d, J¼8.4 Hz, 2H); 13C NMR (CDCl3, Me4Si) d 13.0, 14.5,
21.1, 23.1, 23.9, 30.8, 43.1, 82.4, 108.3, 125.2, 128.8,
136.7, 138.6, 145.1; IR (neat) 3423, 2959, 2929, 2870,
1511, 1459, 1171, 1098, 1034 cmꢂ1; HRMS (EI) calcd for
C16H23IO 358.0794, found 358.0804.
3.2.12. (Z)-1-Phenyl-2-(trimethylsilyl)hept-2-en-1-ol (5l).
Purification of the crude product by column chromatography
on silica gel (petroleum ether/ethyl acetate¼30:1) afforded
the title product in 33% isolated yield. The structure was
3.3.3. (Z)-3-Iodo-1-(4-methoxyphenyl)-2-propylhex-2-
en-1-ol (7d). The solvent was evaporated in vacuo (a small
amount of Et3N was added in order to avoid the decomposi-
tion of the product during the evaporation) and the residue
was purified by chromatography on silica gel (petroleum
ether/ethyl acetate¼15:1). The title compound was formed
1
also confirmed by 2D NMR experiments of H–1H COSY,
1
HMQC, and HMBC. H NMR (CDCl3, Me4Si) d 0.20 (s,
9H), 1.12 (t, J¼6.6 Hz, 3H), 1.52–1.64 (m, 4H), 2.08 (br s,
1H), 2.44 (q, J¼7.2 Hz, 2H), 5.46 (s, 1H), 6.50 (dt, J¼7.8,
0.9 Hz, 1H), 7.41–7.54 (m, 5H); 13C NMR (CDCl3,
Me4Si) d 0.5, 14.1, 22.6, 31.5, 32.1, 78.8, 126.9, 127.1,
128.1, 140.9, 143.2, 144.2; IR (neat) 3403, 2957, 2927,
2873, 1609, 1493, 1453, 1248, 840, 700 cmꢂ1; HRMS (EI)
calcd for C16H26OSi 262.1753, found 262.1758.
1
in 53% isolated yield. H NMR (CDCl3, Me4Si) d 0.78 (t,
J¼7.5 Hz, 3H), 0.94 (t, J¼7.2 Hz, 3H), 0.99–1.07 (m, 1H),
1.25–1.41 (m, 1H), 1.57–1.69 (m, 2H), 1.93–2.19 (m, 3H),
2.51–2.57 (m, 2H), 3.79 (s, 3H), 5.87 (d, J¼3.6 Hz, 1H),
6.86 (d, J¼6.6 Hz, 2H), 7.36 (d, J¼6.9 Hz, 2H); 13C NMR
(CDCl3, Me4Si) d 13.0, 14.5, 23.1, 23.9, 30.8, 43.1, 55.2,
82.2, 108.2, 113.5, 126.5, 133.7, 145.2, 158.7; IR (neat)
3471, 2931, 2870, 1611, 1510, 1463, 1248, 1170,
1
3.2.13. (E)-1-Phenyl-2-propylhex-1-en-3-ol (6). H NMR
(CDCl3, Me4Si) d 0.89–0.98 (m, 6H), 1.36–1.67 (m, 6H),

2016
S. Guo et al. / Tetrahedron 63 (2007) 2009–2018
1036 cmꢂ1; HRMS (EI) calcd for C16H23IO2 374.0743,
found 374.0728.
3.4.1. (Z)-5-(4-Chlorophenyl)-1-phenyl-2,3-dipropyl-
pent-2-en-4-yn-1-ol (9e). H NMR (CDCl3, Me4Si) d 0.80
1
(t, J¼7.2 Hz, 3H), 0.97 (t, J¼7.5 Hz, 3H), 1.26–1.36 (m,
2H), 1.61–1.71 (m, 2H), 1.94–2.09 (m, 2H), 2.23 (t,
J¼7.2 Hz, 2H), 2.44 (s, 1H), 6.27 (s, 1H), 7.19–7.32 (m,
7H), 7.47–7.49 (m, 2H); 13C NMR (CDCl3, Me4Si) d 13.8,
14.7, 21.8, 23.7, 29.7, 33.8, 75.1, 90.2, 92.2, 120.7, 121.9,
125.3, 126.9, 128.0, 128.5, 132.4, 133.8, 142.4, 149.8; IR
(neat) 3446, 3061, 2960, 2930, 2871, 1489, 1465, 1091,
3.3.4. (Z)-1-Iodo-1,2-diphenylhex-1-en-3-ol (7e). Purifica-
tion of the crude product by column chromatography on
silica gel (300–400 mesh) (petroleum ether/ethyl
acetate¼25:1) afforded the title product in 55% isolated
1
yield. H NMR (CDCl3, Me4Si) d 0.98 (t, J¼5.7 Hz, 3H),
1.43–1.67 (m, 5H), 4.92–4.97 (m, 1H), 6.95–7.16 (m,
10H); 13C NMR (CDCl3, Me4Si) d 14.0, 19.0, 37.7, 80.3,
101.5, 127.0, 127.2, 127.5, 127.7, 129.2, 130.0, 136.1,
143.9, 149.6; IR (neat) 3406, 2957, 2931, 2871, 1488,
1441, 1117, 1072, 697 cmꢂ1; HRMS (EI) calcd for
C18H19IO 378.0481, found 378.0491.
827, 701 cmꢂ1
; HRMS (EI) calcd for C23H25ClO
352.1594, found 352.1581.
The spectral data of 9a,b,f,h,i have been reported.3
3.4.2. (Z)-2,3-Dibutyl-1,5-diphenylpent-2-en-4-yn-1-ol
(9c). Purification of the crude product by column chro-
matography on neutral Al2O3 (petroleum ether/ethyl
acetate¼15:1) afforded the title product in 77% isolated
3.3.5. (Z)-1-(4-Chlorophenyl)-3-iodo-2,3-diphenylprop-
2-en-1-ol (7f). Purification of the crude product by column
chromatography on silica gel (300–400 mesh) (petroleum
ether/ethyl acetate¼25:1) afforded the title product in 50%
1
yield. H NMR (CDCl3, Me4Si) d 0.80 (t, J¼7.2 Hz, 3H),
1
isolated yield. H NMR (CDCl3, Me4Si) d 2.29 (s, 1H),
0.95 (t, J¼6.9 Hz, 3H), 1.21–1.43 (m, 6H), 1.59–1.69 (m,
2H), 1.99–2.12 (m, 2H), 2.19 (s, 1H), 2.27 (t, J¼8.1 Hz,
2H), 6.30 (s, 1H), 7.22–7.51 (m, 10H); 13C NMR (CDCl3,
Me4Si) d 13.7, 14.1, 22.5, 23.3, 27.2, 30.8, 31.7, 32.5,
75.2, 89.3, 93.4, 121.1, 123.6, 125.4, 126.9, 127.9, 128.1,
128.3, 131.3, 142.5, 149.1; IR (neat) 3443, 2956, 2870,
1596, 1490, 1450, 1023, 754, 690 cmꢂ1; HRMS (EI) calcd
for C25H30O 346.2297, found 346.2310.
6.26 (s, 1H), 6.66–6.69 (m, 2H), 6.94–7.09 (m, 8H), 7.28–
7.41 (m, 4H); 13C NMR (CDCl3, Me4Si) d 81.1, 103.1,
127.1, 127.3, 127.4, 127.6, 127.6, 128.4, 129.2, 130.2,
133.2, 135.0, 139.6, 143.6, 148.8; IR (neat) 3416, 1705,
1597, 1488, 1441, 1090, 1013 cmꢂ1; HRMS (EI) calcd for
C21H16ClO [MꢂI]+ 319.0890, found 319.0881.
3.3.6. (Z)-3-Iodo-2,3-diphenyl-1-thiophen-2-ylprop-2-en-
1-ol (7g). The solvent was evaporated in vacuo (a small
amount of Et3N was added in order to avoid the decomposi-
tion of the product during the evaporation) and the residue
was purified by chromatography on silica gel (petroleum
ether/ethyl acetate¼20:1). The title compound was formed
3.4.3. (Z)-2,3-Dibutyl-5-(4-chlorophenyl)-1-p-tolylpent-
2-en-4-yn-1-ol (9d). Purification of the crude product by
column chromatography on neutral Al2O3 (petroleum
ether/ethyl acetate¼10:1) afforded the title product in 68%
isolated yield. 1H NMR (CDCl3, Me4Si) d 0.81 (t,
J¼6.9 Hz, 3H), 0.94 (t, J¼7.5 Hz, 3H), 1.19–1.26 (m, 3H),
1.3–1.42 (m, 3H), 1.57–1.67 (m, 2H), 1.94–2.14 (m, 2H),
2.25 (t, J¼8.1 Hz, 2H), 2.30 (s, 3H), 2.47 (s, 1H), 6.23 (s,
1H), 7.10 (d, J¼7.5 Hz, 2H), 7.22 (d, J¼8.7 Hz, 2H), 7.30
(d, J¼8.7 Hz, 2H), 7.36 (d, J¼7.5 Hz, 2H); 13C NMR
(CDCl3, Me4Si) d 13.6, 14.0, 20.9, 22.4, 23.2, 27.2, 30.8,
31.6, 32.5, 75.1, 90.4, 92.1, 120.4, 122.1, 125.2, 128.5,
128.7, 132.4, 133.7, 136.3, 139.4, 149.9; IR (neat) 3442,
2957, 2928, 2871, 1512, 1489, 1465, 1091, 1033, 1014,
827 cmꢂ1; HRMS (EI) calcd for C26H31ClO 394.2063,
found 394.2071.
1
in 40% isolated yield. H NMR (CDCl3, Me4Si) d 2.34
(s, 1H), 6.39 (s, 1H), 6.85–6.88 (m, 2H), 6.99–7.16 (m,
10H), 7.27–7.29 (d, J¼5.1 Hz, 1H); 13C NMR (CDCl3,
Me4Si)
d 79.5, 102.0, 124.2, 125.1, 126.9, 127.5,
127.5, 127.7, 127.8, 129.2, 130.2, 135.0, 143.7, 145.4,
148.7; IR (neat) 3409, 3054, 1488, 1441, 1068, 1030,
697 cmꢂ1; HRMS (EI) calcd for C19H15IOS 417.9888,
found 417.9900.
3.3.7. (E)-1-Iodo-1,2-diphenylpent-1-en-3-ol (8e). 1H
NMR (CDCl3, Me4Si) d 0.76 (t, J¼6.9 Hz, 3H), 1.23–1.47
(m, 5H), 4.43 (t, J¼6.6 Hz, 1H), 7.24–7.47 (m, 10H); 13C
NMR (CDCl3, Me4Si) d 13.73, 18.79, 38.31, 70.05,
103.17, 127.77, 128.09, 128.25, 128.31, 128.34, 129.25,
141.97, 142.95, 151.17; IR (neat) 3431, 3055, 2930, 2871,
1598, 1492, 1443, 1012, 700 cmꢂ1; HRMS (EI) calcd for
C18H19IO 378.0481, found 378.0497.
3.4.4. (Z)-2,3-Diethyl-5-(4-methoxyphenyl)-1-phenyl-
pent-2-en-4-yn-1-ol (9g). Purification of the crude product
by column chromatography on neutral Al2O3 (petroleum
ether/ethyl acetate¼10:1) afforded the title product in 78%
isolated yield. 1H NMR (CDCl3, Me4Si) d 0.80 (t,
J¼7.5 Hz, 3H), 1.20 (t, J¼7.5 Hz, 3H), 2.00–2.18 (m, 2H),
2.28 (q, J¼7.5 Hz, 2H), 2.52 (s, 1H), 3.74 (s, 3H), 6.30 (s,
1H), 6.80 (d, J¼8.1 Hz, 2H), 7.18–7.35 (m, 5H), 7.50 (d,
J¼7.8 Hz, 2H); 13C NMR (CDCl3, Me4Si) d 13.3, 14.9,
20.0, 25.1, 55.1, 75.1, 87.7, 93.3, 113.8, 115.7, 122.3,
125.3, 126.7, 127.9, 132.7, 142.6, 148.9, 159.2; IR (neat)
3460, 2965, 2932, 2873, 1603, 1463, 1450, 1248,
831 cmꢂ1; HRMS (EI) calcd for C22H24O2 320.1776, found
320.1780.
3.4. A typical procedure for alkynylation reactions
To a mixture of oxazirconacycle 4a prepared as above were
added CuCl (0.02 g, 0.2 mmol) and 1-bromoethynyl-4-chlo-
ro-benzene (0.26 g, 1.2 mmol). After stirring at room tem-
perature for overnight, the mixture was quenched with 3 N
HCl solution and extracted with ether. The extract was
washed with NaHCO3, brine, and dried over Na2SO4. The
solvent was evaporated in vacuo and the residue was purified
by chromatography on neutral Al2O3 (petroleum ether/ethyl
acetate¼15:1). A yellow liquid of (Z)-enynol 9e (0.28 g,
79%) was obtained.
3.4.5. (Z)-1-Phenyl-4,5-dipropylundec-4-en-6-yn-1-ol
(10a). Purification of the crude product by column chroma-
tography on silica gel (petroleum ether/ethyl acetate¼20:1)

S. Guo et al. / Tetrahedron 63 (2007) 2009–2018
2017
1
afforded the title product in 53% isolated yield. H NMR
Supplementary data
(CDCl3, Me4Si) d 0.82–0.94 (m, 9H), 1.26–1.68 (m, 9H),
1.78–1.91 (m, 2H), 1.95–2.18 (m, 4H), 2.28–2.37 (m, 2H),
2.48–2.58 (m, 1H), 2.65–2.72 (m, 1H), 4.62 (t, J¼6.9 Hz,
1H), 7.23–7.35 (m, 5H); 13C NMR (CDCl3, Me4Si)
d 13.55, 13.69, 14.21, 19.05, 21.74, 21.96, 31.08, 33.01,
33.94, 37.47, 73.60, 81.05, 92.59, 119.11, 125.74, 127.13,
128.18, 144.49, 145.14; HRMS (EI) calcd for C23H34O
326.2610, found 326.2618.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.12.051.
References and notes
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3.4.6. (Z)-1,7-Diphenyl-4,5-dipropylhept-4-en-6-yn-1-ol
(10b). Purification of the crude product by column chroma-
tography on silica gel (petroleum ether/ethyl acetate¼20:1)
1
afforded the title product in 56% isolated yield. H NMR
(CDCl3, Me4Si) d 0.89–0.97 (m, 6H), 1.34–1.48 (m, 2H),
1.54–1.67 (m, 2H), 1.86–1.98 (m, 2H), 2.03–2.23 (m, 4H),
2.39–2.61 (m, 3H), 4.63–4.67 (m, 1H), 7.2–7.4 (m, 10H);
13C NMR (CDCl3, Me4Si) d 13.74, 14.23, 21.75, 22.08,
31.44, 33.41, 33.63, 37.60, 73.96, 90.26, 92.00, 118.68,
123.85, 125.78, 127.22, 127.50, 128.12, 128.26, 131.19,
144.44, 147.83; HRMS (EI) calcd for C25H30O 346.2297,
found 346.2293.
3.4.7. (Z)-1-Phenyl-4,5-dipropyl-7-(p-tolyl)hept-4-en-6-
yn-1-ol (10c). Purification of the crude product by column
chromatography on silica gel (petroleum ether/ethyl
acetate¼20:1) afforded the title product in 65% isolated
yield. 1H NMR (CDCl3, Me4Si) d 0.91 (t, J¼7.2 Hz,
3H), 0.94 (t, J¼7.2 Hz, 3H), 1.32–1.45 (m, 2H), 1.60
(sex, J¼7.5 Hz, 2H), 1.85–1.97 (m, 2H), 2.03–2.20 (m,
4H), 2.31 (s, 3H), 2.38–2.61 (m, 3H), 4.62–4.67 (m, 1H),
7.05–7.33 (m, 9H); 13C NMR (CDCl3, Me4Si) d 13.72,
14.20, 21.32, 21.74, 22.05, 31.40, 33.37, 33.64, 37.58,
73.92, 89.54, 92.11, 118.77, 120.76, 125.77, 127.16,
128.22, 128.87, 131.06, 137.47, 144.43, 147.30; IR (neat)
3408, 3027, 2958, 2929, 2870, 1509, 1453, 816,
700 cmꢂ1; HRMS (EI) calcd for C26H32O 360.2453, found
360.2463.
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3.4.8. (Z)-7-(4-Chlorophenyl)-1-phenyl-4,5-dipropyl-
hept-4-en-6-yn-1-ol (10d). Purification of the crude prod-
uct by column chromatography on silica gel (petroleum
ether/ethyl acetate¼20:1) afforded the title product in
1
63% isolated yield. H NMR (CDCl3, Me4Si) d 0.95 (t,
J¼7.2 Hz, 3H), 0.97 (t, J¼7.2 Hz, 3H), 1.41–1.48 (m,
2H), 1.57–1.65 (m, 2H), 1.92–1.99 (m, 2H), 2.12–2.25
(m, 4H), 2.30 (br s, 1H), 2.46–2.57 (m, 2H), 4.67–4.71
(m, 1H), 7.27–7.37 (m, 9H); 13C NMR (CDCl3, Me4Si)
d 13.75, 14.25, 21.77, 22.11, 31.45, 33.46, 33.57, 37.56,
74.08, 90.87, 91.28, 118.51, 122.40, 125.83, 127.36,
128.36, 128.45, 132.42, 133.41, 144.42, 148.49; IR (neat)
3394, 2958, 2930, 2870, 1489, 1454, 1089, 827,
700 cmꢂ1; HRMS (EI) calcd for C25H27Cl [MꢂH2O]+
362.1801, found 362.1809.
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the coupling product of 5e was formed as a major product in
52% isolated yield after 6 h at 0 ꢁC, along with the formation
of 3e in 12% isolated yield.
Acknowledgements
We thank the National Natural Science Foundation of China
(Grant No. 20402019, 20121202, 20423001), Chinese Acad-
emy of Science, and the Science and Technology Commis-
sion of Shanghai Municipality (04QMX1446) for financial
support.
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