Gallium-mediated allyl transfer from bulky homoallyl alcohol to aldehydes or alkynes: Control of dynamic σ-allylgalliums based on retro-allylation reaction

Article abstract of DOI:10.1016/j.jorganchem.2006.08.047

A new method for the preparation and control of dynamic σ-allylgalliums is disclosed. Upon treatment with a Grignard reagent and gallium trichloride, bulky homoallyl alcohols undergo gallium-mediated retro-allylation reaction to provide σ-allylgallium reagents. The σ-allylgallium reagents generated were applied to carbonyl allylation. The retro-allylation reaction generates (Z)- and (E)-σ-crotylgalliums stereospecifically, starting from erythro- and threo-homoallyl alcohols, respectively. The stereochemically defined crotylgallium reagents effected stereoselective allylation of aldehydes. Allylgallation reaction of alkynes with the allylgallium reagents prepared by retro-allylation is also described.

Full text of DOI:10.1016/j.jorganchem.2006.08.047

Journal of Organometallic Chemistry 692 (2007) 505–513
www.elsevier.com/locate/jorganchem
Gallium-mediated allyl transfer from bulky homoallyl alcohol
to aldehydes or alkynes: Control of dynamic r-allylgalliums based
on retro-allylation reaction
*
*
Sayuri Hayashi, Koji Hirano, Hideki Yorimitsu , Koichiro Oshima
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Received 6 February 2006; received in revised form 15 March 2006; accepted 20 March 2006
Available online 30 August 2006
Abstract
A new method for the preparation and control of dynamic r-allylgalliums is disclosed. Upon treatment with a Grignard reagent and
gallium trichloride, bulky homoallyl alcohols undergo gallium-mediated retro-allylation reaction to provide r-allylgallium reagents. The
r-allylgallium reagents generated were applied to carbonyl allylation. The retro-allylation reaction generates (Z)- and (E)-r-crotylgal-
liums stereospecifically, starting from erythro- and threo-homoallyl alcohols, respectively. The stereochemically defined crotylgallium
reagents effected stereoselective allylation of aldehydes. Allylgallation reaction of alkynes with the allylgallium reagents prepared by
retro-allylation is also described.
ꢀ 2006 Elsevier B.V. All rights reserved.
Keywords: Gallium; Retro-allylation; r-Allylgallium; Allylation; Carbon–carbon bond cleavage
1. Introduction [1]
2. Results and discussion
Preparations of allylmetals have been well investigated
because of their importance in organic synthesis [2]. In
addition to conventional preparations such as Barbier–
Grignard-type reductive metalation and transmetalation
of a highly reactive allyl metal to other metals, retro-ally-
lation of metal homoallyloxide also generates allylmetals
[3]. However, its application to organic synthesis is rare
[4]. Here we report a method for the generation of allyl-
gallium reagents by gallium-mediated retro-allylation
reaction of bulky homoallyl alcohols and its application
[5,6].
2.1. Gallium-mediated allyl transfer from bulky homoallyl
alcohol to aldehydes via retro-allylation: Stereoselective
synthesis of both erythro- and threo-homoallyl alcohols
Treatment of homoallyl alcohol 1a (1.2 mmol) with
methylmagnesium iodide (1.2 mmol) in dioxane yielded
the magnesium alkoxide of 1a (Scheme 1). Gallium trichlo-
ride (1.2 mmol) and benzaldehyde (1.0 mmol) were added
to the suspension at 25 ꢁC. Stirring the resulting suspension
for 0.5 h provided homoallyl alcohol 2a in 94% yield. The
reaction showed no erythro/threo selectivity. A substoichio-
metric amount (40 mol%) of gallium trichloride also
effected the crotylation reaction [7], affording 2a in 79%
yield. The use of 20 mol% of gallium trichloride led to a
low yield of 2a and formation of benzyl alcohol as a
byproduct through a Meerwein–Ponndrof–Verley reduc-
tion. A significant drop of the yield was observed when
*
Corresponding authors. Tel.: +81 75 383 2437; fax: +81 75 383 2438.
E-mail addresses: yori@orgrxn.mbox.media.kyoto-u.ac.jp (H. Yori-
mitsu), oshima@orgrxn.mbox.media.kyoto-u.ac.jp (K. Oshima).
0022-328X/$ - see front matter ꢀ 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.08.047

506
S. Hayashi et al. / Journal of Organometallic Chemistry 692 (2007) 505–513
ones underwent the crotylation reaction. Crotylation of
OH
OMgL
n
MeMgI (1.2 mmol)
cyclohexanecarbaldehyde exhibited with high threo selec-
tivity (entry 3). The reaction of pivalaldehyde yielded a
mixture of the desired product and linear homoallyl alco-
hol, 2,2-dimethyl-5-hepten-3-ol, probably due to the steric
hindrance of the t-butyl group (entry 4). Selective 1,2-addi-
tion was observed in the reaction of a,b-unsaturated alde-
hydes (entries 5 and 6). The crotylation of an aldehyde
moiety predominated over that of ester (entry 7). The reac-
tions with ketones furnished the corresponding tertiary
alcohols in good yield (entries 8 and 9).
i
o
i
Pr
i
dioxane, 25 C, 1 h
(1a, 1.2 mmol)
Pr
i
Pr
Pr
GaCl
PhCHO (1.0 mmol)
3
OH
GaL
n
o
25 C, 0.5 h
Ph
2a
GaCl 1.2 mmol 94% (erythro/threo= 48:52)
3
0.4 mmol 79% (erythro/threo= 44:56)
0.2 mmol 60% (erythro/threo= 45:55)
0.1 mmol 16% (erythro/threo=54:46)
The retro-allylation reaction could generate other allyl-
gallium reagents (Table 2). Unsubstituted allyl transfer fur-
nished the desired product 2k in good yield albeit a longer
reaction time was necessary for completion (entry 1).
Methallylation proceeded as smoothly as the crotylation
to provide 2l in excellent yield (entry 2). However, prenyl-
ation was not efficient starting from diisopropyl-substi-
tuted 1d (entry 3). Instead, dimethyl substitution at the
oxygenated carbon strongly enhanced the prenylation
(entry 4). Delicate steric factors around the hydroxy groups
play a crucial role in these allyl transfer reactions.
Paying attention to the delicate steric effect, we further
investigated the crotylation reaction by using other crotyl
sources. We found that homoallyl alcohol 1f, which has
mesityl and methyl groups at its hydroxylated carbon, par-
ticipated in the crotyl transfer reaction in ether even at
ꢀ20 ꢁC. To our delight, the reaction showed stereospecific-
ity when diastereomerically pure 1f was used. Namely, the
reactions of erythro-1f and threo-1f with benzaldehyde pro-
vided erythro- and threo-2a, respectively (Scheme 2). Other
aromatic aldehydes underwent the stereospecific crotyla-
tion reaction (Table 3, entries 1–6). The reactions with
dihydrocinnamaldehyde and cinnamaldehyde resulted in
lower stereoselectivity (entries 7–10).
Scheme 1.
10 mol% of gallium trichloride was employed. Methylmag-
nesium iodide is suitable as a base. Butyllithium instead of
methylmagnesium iodide did not promote the reaction, and
the starting materials were completely recovered. Methyl-
magnesium bromide served as efficiently as methylmagne-
sium iodide (93% yield, erythro/threo = 48:52). Cesium
carbonate in place of methylmagnesium iodide did not
function as a base. Gallium trichloride was much more
effective than indium trichloride. A similar reaction with
indium trichloride provided a 71% yield of 2a (erythro/
threo = 44:56).
The regioselectivity of the reaction suggests that the allyl
transfer reaction proceeds via a mechanism completely dif-
ferent from the Lewis acid-mediated allyl transfer reactions
reported by Nokami and others [8]. Formation of r-crotyl-
gallium species by retro-crotylation is most probable. Ster-
eoselective allyl transfer reaction as well as allylgallation of
alkyne also justifies the retro-allylation mechanism (vide
infra).
A variety of aldehydes were subjected to the crotylation
reaction (Table 1). Aliphatic aldehydes as well as aromatic
Table 1
Crotylation of various carbonyl compounds via retro-crotylationa
OH
OH
MeMgI
GaCl , RCOR'
3
i
Pr
i
o
R
25 C, time
dioxane
25 C, 1 h
Pr
R'
o
1a
2
Entry
RCOR0
Time (h)
2
Yield (%)
erythro/threo
1
2
3
4
5
6
7
8
9
a
p-CH3C6H4CHO
PhCH2CH2CHO
cC6H11CHO
1.5
1
0.5
3
3
3
2.5
0.5
1
2b
2c
2d
2e
2f
88
72
99
45b
70c
71c
85
48:52
55:45
12:88
48:52
54:46
52:48
42:58
–
tC4H9CHO
(E)-PhCH@CHCHO
(E)-nC8H17CH@CHCHO
p-MeOC(@O)C6H4CHO
Cyclohexanone
2g
2h
2i
59
57d
Acetophenone
2j
53:47
Performed as described in Scheme 1 by using 1.2 equiv. of GaCl3.
Linear homoallyl alcohol, 2,2-dimethyl-5-hepten-3-ol, was obtained in 13% yield.
Performed in ether at 0 ꢁC. Conversion of a,b-unsaturated aldehyde under the standard conditions resulted in a lower yield because of the concomitant
b
c
formation of the corresponding triene that followed the crotylation.
d
Linear homoallyl alcohol, 2-phenyl-4-hexen-2-ol, was obtained in 8% yield.

S. Hayashi et al. / Journal of Organometallic Chemistry 692 (2007) 505–513
507
Table 2
Allylation, methallylation, and prenylation of benzaldehyde
GaCl (1.2 mmol)
PhCHO (1.0 mmol)
3
MeMgI
(1.2 mmol)
2
2
OH
R
OH
R
o
Ph
R
dioxane
25 C, 1 h
25 C, time
R
1
1
1
1
o
R
R
2
R
R
(1, 1.2 mmol)
Entry
1
R
R1
R2
Time (h)
2
Yield (%)
1
2
3
4
1b
1c
1d
1e
iPr
iPr
iPr
Me
H
H
Me
Me
H
Me
H
13
0.5
11
1
2k
2l
68
94
32
78
2m
2m
H
3, entries 7–10). The crotylation of benzaldehyde would
proceed via a cyclic transition state, which selectively pro-
vides erythro-2a. Starting from threo-1f, an (E)-r-crotylgal-
lium reagent would be predominantly generated via 4a and
led to threo-2a.
OH
OH
MeMgI
ether,
GaCl , PhCHO
3
o
Mes
Ph
–20 C, 17 h
o
–20 C, 1 h
erythro-1f (>99:1)
erythro-2a 94% (96:4)
Mes = 2,4,6-Me C H
6 2
3
OH
OH
GaCl , PhCHO
3
MeMgI
ether,
Attempted NMR analysis of the retro-allylation process
1
failed. For instance, H and 13C NMR analysis of a mix-
o
Mes
Ph
–20 C, 17 h
o
–20 C, 1 h
ture of methylmagnesium iodide, 1a, and gallium trichlo-
ride showed no detectable crotylgallium reagents. The
overall allyl transfer process is likely to be in equilibrium.
Once the crotylgallium is formed, it would immediately
react with carbonyl compounds of less steric hindrance.
Homopropargyl alcohol 1g transferred the propargyl
moiety to aldehydes (Scheme 4). In contrast, allenylation
of benzaldehyde with 1h resulted in the formation of a
complex mixture including 2r and 2p. Transfer from homo-
allyl alcohol 1i to benzaldehyde suffered from very low con-
version, albeit the regioselectivity was good.
Stereoselective preparations of r-crotylmetals represent
an important challenge. Stereochemically defined r-cro-
tylmetals should always be prepared in advance of the
crotylation reaction. Our new method utilizes stable and
easy-to-handle homoallyl alcohols as the precursors of a
r-crotylmetal. The first selective generations of (E)- and
threo-1f (<1:99)
threo-2a 89% (2:98)
Scheme 2.
We rationalize the stereospecific allyl transfer as out-
lined in Scheme 3. Upon the retro-crotylation reaction of
erythro-1f, a chair transition state 3a would be most stable,
because of the least steric demand, in comparison to other
possible transition states such as another chair transition
state 3b. Formation of the (Z)-r-crotylgallium reagent is
thus favored. The (Z)-r-crotylgallium reagent probably
reacts so rapidly with benzaldehyde in the same pot that
its isomerization into the (E)-form is limited. Aliphatic
aldehyde 2c and a,b-unsaturated aldehyde 2f are less reac-
tive. The lower reactivity allowed the (Z)-r-crotylgallium
reagent to isomerize into the (E)-r-crotylgallium (Table
Table 3
Selective synthesis of erythro- and threo-homoallyl alcohols
OH
OH
MeMgI
GaCl , RCHO
3
o
Mes
R
ether,
–20 C, 1 h
–20 C, 17 h
o
1f
2
Mes = 2,4,6-Me C H
3
6 2
Entry
1f
R
2
Yield (%)
erythro/threo of 2
1
2
3
4
5
6
7
8
9
erythro
threo
p-CF3C6H4
p-CF3C6H4
o-ClC6H4
2n
2n
2o
2o
2b
2b
2c
2c
2f
84
92
87
83
95a
64a
87
62
86
66
96:4
2:98
99:1
3:97
98:2
2:98
69:31
42:58
91:9
21:79
erythro
threo
o-ClC6H4
erythro
threo
p-CH3C6H4
p-CH3C6H4
PhCH2CH2
PhCH2CH2
PhCH@CH
PhCH@CH
erythro
threo
erythro
threo
10
a
2f
Reaction time was 30 h.

508
S. Hayashi et al. / Journal of Organometallic Chemistry 692 (2007) 505–513
Mes
GaL
n
GaL
n
O
(E)-σ-crotylgallium
3b disfavored
slow
OH
H
GaL
fast
fast
GaL
O
n
n
Mes
O
GaL
erythro-1f
threo-1f
Ph
n
Ph
(Z)-σ-crotylgallium
3a favored
erythro-2a
OH
H
GaL
GaL
n
O
n
GaL
n
Ph
threo-2a
O
Mes
Ph
(E)-σ
-crotylgallium
slow
4a favored
GaL
n
O
GaL
n
Mes
(Z)-
σ
-crotylgallium
4b disfavored
Scheme 3.
(Z)-r-crotylgallium were established in situ via the gal-
lium-mediated retro-allylation.
of the reaction is the same as previously reported [9]. It is
worth noting that the highly coordinating amino moiety
of 5d did not retard the allylgallation. Not only crotylation
but also allylation (entries 6 and 7) and methallylation
(entries 8–12) were successful. Methallylation of alkynes
generally led to high yields. Unfortunately, attempted pre-
nylation encountered very low conversion (entries 13 and
14). Aliphatic acetylene 5e as well as arylacetylenes
undergo the allylation reaction (entries 5 and 12). The reac-
tions of 5a with 1a in the presence of 40 mol% and 20 mol%
of gallium trichloride provided 6a in 23% and 7% yields,
respectively.
When the reaction was quenched with DCl, a mixture of
6g, monodeuterated (E)-6g-d1, and dideuterated 6g-d2 was
obtained (Scheme 5). Furthermore, allylgallation of 1-phe-
nyl-2-deuterioacetylene followed by quench with HCl affor-
ded 6g and (Z)-6g-d1. The results of these two experiments
can be explained by the reaction mechanism as depicted in
Scheme 6. Allylgallation of phenylacetylene proceeds via a
six-membered transition state 7a to produce vinylgallium
8a. The vinylgallium 8a is partially quenched with alkyne
in situ to afford 6g with no deuterium incorporation. The
remaining 8a reacted with DCl upon workup to give (E)-
6g-d1. Meanwhile, deprotonation of the acetylenic proton
of phenylacetylene takes place by the action of basic gal-
lium species. The gallium acetylide 5b-Ga undergoes allyl-
gallation to provide 1,1-dimetalated alkene 8b.
Deuteriolysis of 8b provided 6g-d2.
2.2. Allylgallation of alkynes with allylgallium reagents
generated by retro-allylation
Allylgallation of alkynes is among the most interesting
reactions in organogallium chemistry [9]. As described
above, we proposed the generation of crotylgallium
reagents by retro-allylation. To confirm the generation of
the crotylgallium reagents, allylgallation reaction of alkynes
with homoallyl alcohol via retro-allylation was examined.
As anticipated, the allylgallation with homoallyl alcohol
proceeded smoothly (Table 4). Homoallyl alcohol 1a was
treated with methylmagnesium iodide and gallium trichlo-
ride in dioxane. Alkyne 5a was added to the suspension,
and the whole mixture was heated at reflux for 2 h. The
reaction was terminated with aqueous hydrochloric acid
to give 6a in excellent yield (entry 1). The regioselectivity
1) MeMgI
2) GaCl , ArCHO
OH
OH
3
i
Ar
Pr
i
i
Pr
Ar = Ph
2p 62%, 1.5 h
Ar = p-CF C H
2q 74%, 1 h
6 4
1g
•
GaL
n
3
1) MeMgI
2) GaCl , PhCHO
OH
OH
3
•
+
2p
•
i
Ph
Pr
Pr
2r trace, 3 h
16%
GaL
n
1h
3. Summary
1) MeMgBr
2) GaCl , PhCHO
OH
OH
3
i
Ph
Stereoselective preparations and uses of r-allylmetals
represent an interesting challenge since r-allylmetals are
generally dynamic complexes that are difficult to control,
except for allylmetals of group 14 and allylboranes. As
Pr
i
GaL
n
Pr
2s 8%, E/Z = 45:55
60 C, 2.5 h
1i
o
Scheme 4. The conditions were the same as those in Table 1.

S. Hayashi et al. / Journal of Organometallic Chemistry 692 (2007) 505–513
509
Table 4
Allylgallation of terminal alkynes with homoallyl alcohol via retro-allylation
GaCl (2.0 mmol)
4
3
H
H
R
R
MeMgI
(2.0 mmol) H C C R
OH
R
4
(5, 1.0 mmol)
R
1
R
1
2
dioxane
reflux, 2 h
dioxane
R
R
2
3
3
R
R
o
25 C, 1 h
6
1 (2.0 mmol)
Entry
1
R1
R2
R3
R4
5
R
6
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a
1a
1a
1a
1a
1b
1b
1c
1c
1c
1c
1c
1e
1e
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
Me
Me
Me
Me
Me
Me
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
H
5a
5b
5c
5d
5e
5a
5b
5a
5b
5c
5d
5e
5a
5b
p-MeOC6H4
C6H5
p-FC6H4
p-Me2NC6H4
nC10H21
p-MeOC6H4
C6H5
p-MeOC6H4
C6H5
p-FC6H4
p-Me2NC6H4
nC10H21
p-MeOC6H4
C6H5
6a
6b
6c
6d
6e
6f
96
43a
35a
57
49a
52
81
99
94
71
66
85
6g
6h
6i
6j
H
H
Me
Me
6k
6l
6m
6n
41
13a
H
GaCl
3
OH
Pr
H
H
Ph
Ph
H
Ph
D
D
Ph
MeMgI
DCl
H
C
C
Ph
+
+
+
i
Pr
i
D
(
E
dioxane
reflux, 2 h
dioxane
1b
o
6g
6g
)-6g-d1
6g-d2
25 C, 1 h
7 : 40 : 53
GaCl
3
OH
H
H
D
Ph
MeMgI
D
C
C
Ph
HCl
i
Pr
i
H
dioxane
reflux, 2 h
dioxane
Pr
1b
o
25 C, 1 h
( )-6g-d1
Z
56 : 44
Scheme 5.
illustrated in the Section 2.1, our retro-allylation strategy
offers control of r-allylmetals and will be applicable to syn-
thesis of other r-allylmetals [10].
and were recorded in CDCl3. Chemical shifts (d) are in
parts per million relative to tetramethylsilane at 0.00 ppm
1
for H and relative to CDCl3 at 77.23 ppm for 13C unless
otherwise noted. IR spectra were determined on a SHIMA-
DZU FTIR-8200PC spectrometer. TLC analyses were per-
formed on commercial glass plates bearing 0.25-mm layer
of Merck Silica gel 60F254. Silica gel (Wakogel 200 mesh)
was used for column chromatography. Elemental analyses
were carried out at the Elemental Analysis Center of Kyoto
University.
4. Experimental
4.1. Instrumentation and chemicals
1H NMR (500 MHz) and 13C NMR (126 MHz) spectra
were taken on Varian UNITY INOVA 500 spectrometers
protonation
with alkyne
H
Ph
Ph
H C C Ph
H C C Ph
6g
L Ga
n
L Ga
n
deuteriolysis
deuteriolysis
deprotonation
7a
8a
8b
( )-6g-d1
E
L Ga
n
L Ga C C Ph
n
L Ga C C Ph
n
6g-d2
L Ga
n
L Ga
n
5b-Ga
7b
Scheme 6.

510
S. Hayashi et al. / Journal of Organometallic Chemistry 692 (2007) 505–513
Unless otherwise noted, materials obtained from com-
Diethyl ether (40 mL) and crotylmagnesium chloride
(0.95 M THF solution, 17.4 mL, 16.5 mmol) were added
to a 100-mL reaction flask under argon. At 0 ꢁC, the
ketone (2.43 g, 15.3 mmol) was added dropwise to the
solution. After being stirred for 2 h at room temperature,
the mixture was poured into 30 mL of 1 M HCl. The
products were extracted with ether three times (30 mL
each). Concentration left a colorless oil. Silica gel column
purification with toluene as an eluent twice allowed com-
plete separation of erythro-1f (1.80 g, 8.26 mmol, 54%,
faster moving band, Rf = 0.31, toluene) and threo-1f
(0.77 g, 3.52 g, 23%, slower moving band, Rf = 0.24,
toluene).
mercial suppliers were used without further purification.
Aldehydes were purified by distillation prior to use. Meth-
ylmagnesium iodide was prepared from magnesium metal
and iodomethane in ether. Dioxane was purchased from
Wako Pure Chemical Co. and stored over slices of sodium.
Gallium trichloride was purchased from Aldrich and was
diluted in a grove box under argon to prepare 1.0 M hex-
ane solution. All reactions were carried out under argon
atmosphere.
4.2. Typical procedure for allyl transfer reaction via
allylgallium reagent (Scheme 1)
A solution of 1a (0.204 g, 1.20 mmol) in 1,4-dioxane
(10 mL) was placed in a 30-mL reaction flask. Methyl-
magnesium iodide (1.0 M ether solution, 1.20 mL,
1.2 mmol) was added dropwise to the solution at ambient
temperature. After the mixture was stirred for 1 h, gallium
trichloride (1.0 M hexane solution, 1.20 mL, 1.2 mmol)
and benzaldehyde (0.106 g, 1.00 mmol) were sequentially
added to the resulting suspension. The mixture was stirred
for an additional 30 min at ambient temperature, 1 M
hydrochloric acid (10 mL) was added. The products were
extracted with hexane/ethyl acetate (5:1, 10 mL · 3). The
combined organic layer was dried over anhydrous
MgSO4, and concentrated in vacuo. Silica gel column
purification (hexane/ethyl acetate = 10:1) gave homoallyl
alcohol 2a (0.152 g, 0.94 mmol, erythro/threo = 48:52) in
94% yield.
4.4. Stereoselective crotylation from diastereomerically pure
1f (Scheme 2)
Carbinol erythro-1f (0.262 g, 1.20 mmol) was dissolved
in ether (10 mL) under argon. Methylmagnesium iodide
(1.0 M, 1.20 mL. 1.2 mmol) in ether was added to the solu-
tion at ꢀ20 ꢁC, and the resulting mixture was stirred for
1 h. At the same temperature, gallium trichloride (1.0 M
hexane solution, 1.20 mL, 1.2 mmol) and benzaldehyde
(0.11 g, 1.0 mmol) were added. After the mixture was stir-
red at ꢀ20 ꢁC for 17 h, the reaction was quenched with
1 M hydrochloric acid at ꢀ20 ꢁC. The mixture was allowed
to warm to ambient temperature and was stirred for
10 min. Extraction, evaporation, and purification on silica
gel (hexane/ethyl acetate = 10:1) furnished 2a (0.152 g,
0.94 mmol, 94% yield) as a 96:4 mixture of erythro and
threo isomers.
4.3. Preparation of erythro- and threo-1f
Under an atmosphere of argon, 2,4,6-trimethylbenzal-
dehyde (2.96 g, 20.0 mmol) was added dropwise to meth-
ylmagnesium bromide (1.17 M THF solution, 20.5 mL,
24.0 mmol) in 30 mL of ether at 0 ꢁC in a 100-mL reac-
tion flask. After being stirred for 2 h at 25 ꢁC, the mixture
was poured into 1 M hydrochloric acid (30 mL). The
products were extracted with ether (30 mL · 3). The
organic layer was dried over MgSO4, and solvent was
removed under reduced pressure. Chromatographic purifi-
cation on silica gel (hexane/ethyl acetate = 5:1) afforded
2.96 g of 1-mesitylethanol (18.3 mmol) in 91% yield as a
white solid.
Pyridinium chlorochromate (5.82 g, 27 mmol) and silica
gel (Wako Pure Chemical C-200, 5.82 g) were ground in a
mortar. The resulting orange powder was transferred to a
100-mL reaction flask. Dichloromethane (50 mL) and 1-
mesitylethanol (2.96 g, 18.3 mmol) were added with swirl-
ing under argon at 0 ꢁC. The mixture turned black and
was stirred for 12 h at room temperature. The mixture
was diluted with ether (30 mL) and filtered through a pad
of Celite. The filtrate was evaporated in vacuo. Silica gel
column purification (hexane/ethyl acetate = 5:1) provided
mesityl methyl ketone (2.43 g, 15.3 mmol, 85% yield) as a
colorless oil.
4.5. Stereochemical assignment of erythro-1f
THF (5.0 mL) was placed in a 30-mL reaction flask
under argon. The oil of 1f (109 mg, 0.50 mmol), which
was the faster moving band of Rf = 0.31 (toluene), was dis-
solved in THF (1.5 mL), and the solution was added to the
reaction flask. 9-Borabicyclo[3.3.1]nonane (9-BBN,
0.183 g, 1.5 mmol) in THF (1.5 mL) was added at ambient
temperature. After the mixture was stirred for 3 h, water
(0.30 mL), 6 M NaOH (0.25 mL, 1.5 mmol), and 30%
hydrogen peroxide (0.50 mL, 4.5 mmol) were sequentially
added. A slightly exothermic reaction took place. The reac-
tion was quenched with aqueous sodium thiosulfate, and
the products were extracted with ethyl acetate. After
removal of solvent, silica gel column purification yielded
0.043 g of 3-methyl-4-(2,4,6-trimethylphenyl)-1,4-pentane-
diol (0.18 mmol, 36% yield, unoptimized). X-ray quality
crystals were grown from pentane/dichloromethane
(Fig. 1). Crystallographic data for the structure has been
deposited with the Cambridge Crystallographic Data Cen-
tre (CCDC 265711). Copies of the data can be obtained,
free of charge, on application to the Director, CCDC, 12
Union Road, Cambridge CB2 1EZ, UK. Fax: 44-1223-
3360033 or e-mail: deposit@ccdc.cam.ac.uk.

S. Hayashi et al. / Journal of Organometallic Chemistry 692 (2007) 505–513
511
4.6. Allylgallation of alkynes (Table 4)
NMR (CDCl3, some signals overlap) d 14.34, 15.09,
16.39, 22.89, 29.35, 29.38, 29.40, 29.50, 29.65, 32.10,
32.51, 43.88, 44.83, 76.21, 76.54, 115.86, 116.59, 130.21,
130.63, 133.57. 134.24, 140.36, 140.87; Anal. Calc. for
C15H28O: C, 80.29; H, 12.58. Found: C, 80.54; H, 12.75%.
Homoallyl alcohol 1a (0.170 g, 1.00 mmol) and dioxane
(5 mL) were placed in a 20-mL two-necked reaction flask
equipped with a Dimroth condenser. Methylmagnesium
iodide (1.0 M ethereal solution, 1.0 mL, 1.0 mmol) was
then added to the reaction flask at ambient temperature.
After the reaction mixture was stirred for 1 h, a hexane
solution of gallium trichloride (1.0 M, 1.0 mL. 1.0 mmol)
was added to the resulting suspension. Alkyne 5a (66 mg,
0.50 mmol) in dioxane (1.0 mL) was added. The mixture
was heated at reflux for 2 h. After cooling, the reaction
was quenched with 10 mL of 1 M hydrochloric acid. The
product was extracted with hexane/ethyl acetate (10:1,
10 mL each, three times). The combined organic layer
was dried over sodium sulfate. Evaporation under a
reduced pressure yielded an oil. Silica gel column chroma-
tography of the oil (hexane/ethyl acetate = 40:1) provided
90.3 mg of 6a (0.48 mmol, 96% yield) as a colorless oil.
4.7.2. 2-(4-Methoxyphenyl)-3-methyl-1,4-pentadiene (6a)
IR (neat) 2835, 1609, 1512, 1246, 1180, 1036, 999, 897,
1
835 cmꢀ1; H NMR (CDCl3) d 1.21 (d, J = 6.5 Hz, 3H),
3.35–3.41 (m, 1H), 3.81 (s, 3H), 5.00–5.08 (m, 3H), 5.21
(d, J = 1.5 Hz, 1H), 5.91 (ddd, J = 17.0, 10.5, 7.0 Hz,
1H), 6.85 (d, J = 9.0 Hz, 2H), 7.33 (d, J = 9.0 Hz, 2H);
13C NMR (CDCl3) d 19.47, 41.97, 55.46, 111.03, 113.69,
113.80, 127.89, 134.75, 142.75, 152.08, 159.09; Anal. Calc.
for C13H16O: C, 82.94; H, 8.57. Found: C, 82.70; H,
8.60%.
4.7.3. 2-(4-Fluorophenyl)-3-methyl-1,4-pentadiene (6c)
IR (neat) 3085, 2972, 2934, 2876, 1627, 1604, 1509,
1456, 1232, 1160, 1015, 913, 840, 812 cmꢀ1 1H NMR
;
4.7. Characterization data
(CDCl3) d 1.21 (d, J = 7.0 Hz, 3H), 3.33–3.39 (m, 1H),
5.03 (dm, J = 10.5 Hz, 1H), 5.06 (dm, J = 17.0 Hz, 1H),
5.08 (d, J = 1.0 Hz, 1H), 5.22 (d, J = 1.0 Hz, 1H), 5.89
(ddd, J = 17.0, 10.5, 7.0 Hz, 1H), 6.98–7.03 (m, 2H),
7.32–7.36 (m, 2H); 13C NMR (CDCl3) d 19.37, 42.22,
112.43, 114.11, 115.13 (d, J = 21.1 Hz), 128.43 (d,
J = 7.7 Hz), 138.35 (d, J = 2.9 Hz), 142.37, 151.76,
162.35 (d, J = 245.8 Hz); 19F NMR (CDCl3) d ꢀ115.90;
Anal. Calc. for C12H13F: C, 81.78; H, 7.44. Found: C,
81.51; H, 7.46%.
The following compounds were characterized according
to the literature: 2a [11], 2b [12], 2c [11], 2d [11], 2e [13], 2f
[11], 2h [14], 2i [15], 2j [15], 2k–m [11], 2n [16], 2o [14], 2p
[17], 2q [17], 6b [18], 6f [18], 6g [18], 6g-d2 [19], 6g-d1 [20],
6i [18], and 6n [21].
4.7.1. (E)-3-Methyl-1,5-tetradecadien-4-ol (2 g, mixture of
diastereomers)
IR (neat) 3355, 2925, 2855, 1640, 1456, 1372, 1250, 969,
1
911 cmꢀ1; H NMR (CDCl3) d 0.88 (t, J = 7.0 Hz, 3H),
4.7.4. 2-[4-(N,N-Dimethylamino)phenyl]-3-methyl-1,4-
pentadiene (6d)
0.98 (d, J = 7.0 Hz, 0.48 · 3H), 1.01 (d, J = 7.0 Hz,
0.52 · 3H), 1.26 (m, 10H), 1.36 (m, 2H), 1.60 (br s, 1H),
2.09 (m, 2H), 2.22 (m, J = 7.0 Hz, 0.48 · 1H), 2.36 (m,
J = 7.0 Hz, 0.52 · 1H), 3.79 (t, J = 7.0 Hz, 0.48 · 1H),
3.96 (t, J = 7.0 Hz, 0.52 · 1H), 5.07–5.16 (m, 2H), 5.39–
5.46 (m, 1H), 5.61–5.69 (m, 1H), 5.82–5.70 (m, 1H); 13C
IR (neat) 3082, 2968, 2930, 2880, 2800, 1611, 1522,
1445, 1354, 1227, 1202, 1169, 910, 820 cmꢀ1 1H NMR
;
(CDCl3) d 1.23 (d, J = 6.5 Hz, 3H), 2.96 (s, 6H), 3.41
(quintet of doublet, J = 6.5, 1.5 Hz, 1H), 4.94 (s, 1H),
5.01 (dt, J = 10.5, 1.5 Hz, 1H), 5.07 (dt, J = 17.0, 1.5 Hz,
1H), 5.21 (d, J = 1.5 Hz, 1H), 5.95 (ddd, J = 16.5, 10.0,
6.5 Hz, 1H), 6.70 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 9.0 Hz,
2H); 13C NMR (CDCl3) d 19.57, 40.77, 41.59, 109.33,
112.33, 113.50, 127.43, 130.17, 143.12, 150.07, 152.16;
Anal. Calc. for C14H19N: C, 83.53; H, 9.51. Found: C,
83.78; H, 9.58%.
4.7.5. 2-Decyl-3-methyl-1,4-pentadiene (6e)
IR (neat) 3404, 3082, 2961, 2926, 2855, 1636, 1466, 910,
1
893 cmꢀ1; H NMR (CDCl3) d 0.88 (t, J = 7.0 Hz, 3H),
1.13 (d, J = 6.5 Hz, 3H), 1.20 (br s, 14H), 1.42 (m, 2H),
2.00 (t, J = 7.5 Hz, 2H), 2.79 (quintet of doublet 7.0,
1.0 Hz, 1H), 4.75 (q, J = 1.5 Hz, 1H), 4.77 (br s, 1H),
4.97 (ddd, J = 10.5, 1.5, 1.0 Hz, 1H), 5.01 (dt, J = 17.5,
1.5 Hz, 1H), 5.76 (ddd, J = 17.5, 10.0, 7.5 Hz, 1H); 13C
NMR (CDCl3) d 14.35, 18.98, 22.92, 28.20, 29.57, 29.73,
29.81, 29.86 (·2), 32.14, 34.74, 43.79, 108.16, 113.32,
143.18, 153.50; Anal. Calc. for C16H30: C, 86.40; H,
13.60. Found: C, 86.19; H, 13.31%.
Fig. 1. ORTEP diagram of erythro-3-methyl-4-(2,4,6-trimethylphenyl)-
1,4-pentanediol. Some hydrogen atoms are omitted for clarity.

512
S. Hayashi et al. / Journal of Organometallic Chemistry 692 (2007) 505–513
4.7.6. 2-(4-Methylphenyl)-4-methyl-1,4-pentadiene (6h)
IR (neat) 2968, 2936, 2910, 2835, 1609, 1512, 1440,
Acknowledgements
1
1288, 1248, 1180, 1036, 891, 835 cmꢀ1; H NMR (CDCl3)
This work is supported by Grant-in-Aid for Scientific
Research on Priority Areas, Reaction Control of Dynamic
Complexes, from the Ministry of Education, Culture,
Sports, Science, and Technology, Japan. K.H. thanks JSPS
for financial support. We thank Professor Masaki Shimizu
(Kyoto University) for helping with the X-ray crystallo-
graphic analysis.
d 1.72 (s, 3H), 3.19 (s, 2H), 3.81 (s, 3H), 4.76 (m, 1H), 4.81
(m, 1H), 5.03 (dd, J = 2.5, 1.5 Hz, 1H), 5.36 (d,
J = 1.5 Hz, 1H), 6.85 (d, J = 9.0 Hz, 2H), 7.38 (d,
J = 9.0 Hz, 2H); 13C NMR (CDCl3) d 22.51, 44.32,
55.45, 112.62, 112.93, 113.72, 127.40, 133.59, 143.87,
145.07, 159.20; Anal. Calc. for C13H16O: C, 82.94; H,
8.57. Found: C, 82.67; H, 8.48%.
References
4.7.7. 2-(4-Fluorophenyl)-4-methyl-1,4-pentadiene (6j)
IR (neat) 3080, 2972, 2914, 1651, 1626, 1602, 1510,
[1] Throughout this manuscript, we use the unambiguous erythro/threo
nomenclature of Noyori: R. Noyori, I. Nishida, J. Sakata, J. Am.
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1443, 1375, 1234, 1161, 895, 841 cmꢀ1
;
1H NMR
(CDCl3) d 1.72 (s, 3H), 3.20 (s, 2H), 4.76 (br s, 1H),
4.82 (br s, 1H), 5.11 (d, J = 1.5 Hz, 1H), 5.39 (d,
J = 1.5 Hz, 1H), 7.00 (dd, J = 9.0, 9.0 Hz, 2H), 7.40
(dd, J = 9.0, 5.0 Hz, 2H); 13C NMR (CDCl3) d 22.45,
44.41, 112.87, 114.48, 115.18 (d, J = 21.5 Hz), 127.91
(d, J = 8.2 Hz), 137.18, 143.48, 144.82, 162.44 (d,
J = 246.4 Hz); Anal. Calc. for C12H13F: C, 81.78; H,
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IR (neat) 3078, 3042, 2968, 2912, 2853, 2800, 1611,
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1524, 1445, 1354, 818 cmꢀ1 1H NMR (CDCl3) d 1.73
;
(s, 3H), 2.95 (s, 6H), 3.19 (s, 2H), 4.78 (m, 1H), 4.81
(m, 1H), 4.95 (d, J = 1.5 Hz, 1H), 5.34 (d, J = 1.5 Hz,
1H), 6.68 (d, J = 9.0 Hz, 2H), 7.36 (d, J = 9.0 Hz, 2H);
13C NMR (CDCl3) d 22.56, 40.73, 44.18, 111.08, 112.26,
112.38, 127.00, 129.04, 144.23, 145.11, 150.12; Anal. Calc.
for C14H19N: C, 83.53; H, 9.51. Found: C, 83.74; H,
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IR (neat) 3406, 3387, 3074, 2957, 2926, 2855, 1639, 1466,
[7] For convenience, throughout the manuscript, crotylation, methally-
lation, and prenylation are defined as introductions of 1-methyl-2-
propenyl, 2-methyl-2-propenyl, and 1,1-dimethyl-2-propenyl groups,
respectively. On the other hand, crotyl, methallyl, and prenyl groups
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1
1439, 891 cmꢀ1; H NMR (CDCl3) d 0.88 (t, J = 7.0 Hz,
3H), 1.26 (br s, 14H), 1.41 (m, 2H), 1.67 (m, 3H), 1.96 (t,
J = 7.5 Hz, 2H), 2.72 (s, 2H), 4.73 (m, 1H), 4.76 (m, 1H),
4.79 (br s, 2H); 13C NMR (CDCl3) d 14.35, 22.04, 22.92,
27.87, 29.58, 29.63, 29.78, 29.86 (·2), 32.14, 35.42, 45.70,
110.93, 112.25, 144.03, 147.82; Anal. Calcd for C16H30:
C, 86.40; H, 13.60. Found: C, 86.13; H, 13.38%.
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(6m)
IR (neat) 3085, 2930, 2835, 1609, 1511, 1464, 1442, 1413,
1375, 1287, 1245, 1175, 1038, 910, 834 cmꢀ1 1H NMR
;
(CDCl3) d 1.17 (s, 6H), 3.80 (s, 3H), 4.91 (d, J = 1.5 Hz,
1H), 5.01 (dd, J = 17.0, 1.0 Hz, 1H), 5.02 (dd, J = 11.0,
1.0 Hz, 1H), 5.18 (d, J = 1.5 Hz, 1H), 5.97 (dd, J = 17.0,
11.0 Hz, 1H), 6.80 (d, J = 9.0 Hz, 2H), 7.14 (d,
J = 9.0 Hz, 2H); 13C NMR (CDCl3) d 27.19, 42.65,
55.38, 111.51, 112.86, 113.33, 130.05, 135.60, 147.62,
156.83, 158.46; Anal. Calc. for C14H18O: C, 83.12; H,
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