Nickel-catalyzed carbometalation reactions of [2-(1-propynyl)phenyl] methanol with 1-alkenylmagnesium reagents

Article abstract of DOI:10.1246/cl.2007.1066

Treatment of [2-(1-propynyl)phenyl]methanol with 1-alkenyl Grignard reagents under nickel catalysis results in carbomagnesiation across the alkynyl part. The 1-alkenylation reaction proceeds in a syn fashion to yield the corresponding 1,3-butadienyl-subst

Full text of DOI:10.1246/cl.2007.1066

1066
Chemistry Letters Vol.36, No.8 (2007)
Nickel-catalyzed Carbometalation Reactions of [2-(1-Propynyl)phenyl]methanol
with 1-Alkenylmagnesium Reagents
Kei Murakami, Hirohisa Ohmiya, Hideki Yorimitsu,ꢀ and Koichiro Oshimaꢀ
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510
(Received May 24, 2007; CL-070558; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp, oshima@orgrxn.mbox.media.kyoto-u.ac.jp)
Treatment of [2-(1-propynyl)phenyl]methanol with 1-alken-
yl Grignard reagents under nickel catalysis results in carbomag-
nesiation across the alkynyl part. The 1-alkenylation reaction
proceeds in a syn fashion to yield the corresponding 1,3-buta-
dienyl-substituted benzyl alcohol.
Table 1. 1-Alkenylation of [2-(1-propynyl)phenyl]methanol
(1) with 1-alkenyl Grignard reagents under nickel catalysis
OH
10 mol %
BrMg
R3
R1
R2
OH
C
NiBr2(PPh3)2
+
R1
R2
C
THF, 50 °C, 2 h
Me
Then H3O+
Me
1
(6 equiv.)
R3
2
Transition-metal-catalyzed carbometalation of alkynes is a
powerful tool for the synthesis of multisubstituted alkenes.1
However, 1-alkenylation reaction of alkyne with 1-alkenylmetal
reagents is difficult to achieve, while there are many examples
of addition reactions of aryl-,2 allyl-,3 alkynyl-,4 and alkylmetal5
reagents to alkynes. Here, we report an example of 1-alkenyla-
tion reaction of an alkyne, [2-(1-propynyl)phenyl]methanol
(1), with 1-alkenylmagnesium bromide.
Entry
R1
R2
R3
2
Yield
1a
2b
3
H
H
H
2a
2a
2b
2c
2d
2e
72%
70%
H
Me
H
H
H
H
63%
4
Me3Si
Ph
H
H
<20%
<5%
75%
5
H
Me (H)
H
H (Me)
(2:8)c
6
H
Treatment of 1 with an excess of vinylmagnesium bromide
in the presence of NiBr2(PPh3)2 in THF at 20 ꢁC for 5 h provided
the vinylated product 2a in good yield (Table 1, Entry 1).6
The vinylation reaction proceeded to completion within 1 h at
50 ꢁC (Entry 2). The alkenylation reactions with Grignard re-
agents bearing a substituent R1, R2, or R3 did not proceed at
20 ꢁC. The reaction of 1 with isopropenylmagnesium bromide
provided the adduct 2b in good yield (Entry 3). However, a
trimethylsilyl or a phenyl group as R1 considerably retarded
the reaction (Entries 4 and 5). The reaction is sensitive to the
steric factor at the 1 positions of the 1-alkenyl Grignard reagents.
The reaction with 1-propenylmagnesium bromide (E/Z = 2:8)7
afforded the product 2e in good yield in a 1E, 3E/1E, 3Z ratio
of 25:75 (Entry 6). The stereochemistry of the product reflects
that of the Grignard reagent. Interestingly, the reaction with
2-trimethylsilylethenylmagnesium bromide yielded the 1E, 3E
isomer exclusively (Entry 7). The exclusive formation indicates
that (E)-2-trimethylsilylethenylmagnesium bromide would
be more reactive than its Z form because of the steric hindrance.
The use of a 1:1 mixture of (E)- and (Z)-styrylmagnesium
reagent provided the E adduct predominantly (Entry 8). A
1-alkenyl Grignard reagent, 2-methyl-1-propenylmagnesium
bromide, reacted smoothly with 1 under the nickel catalysis
(Entry 9).
(25:75)d
7
H
H
H
Me3Si (H)
H (Me3Si)
2f
2g
2h
74%
(>99:1)d
74%
(83:17)d
74%
(8:2)c
8e
9
Ph (H)
H (Ph)
Me
(5:5)c
Me
aPerformed at 20 ꢁC for 5 h. bPerformed for 1 h. cE/Z ratio of the
Grignard reagent. d1E, 3E/1E, 3Z ratio of 2.
OH
NH2
little conversion
C
C
C
O
C
C
Me
Me
OH
C
OH
C
complex mixture
C
Me
Me
Figure 1.
position enhanced the signal of the proton at the 1 position,
geminal to the aromatic ring. We also performed spectroscopic
comparison of 8 with an authentic sample prepared by the Wittig
methylenation reaction of (E)-ꢀ-methylcinnamaldehyde.
The reactions of other alkynes were unsatisfactory. The
methyl ether 3 was much less reactive (eq 1). Replacement of
the methyl group of 1 with a butyl group resulted in significant
decrease in reaction efficiency (eq 2). The reaction of 1-phenyl-
propyne (7) having no heteroatom for 12 h provided 1,3-diene 8
in a similar yield (eq 3). A diphenylacetylene derivative 9 under-
went the vinylation slowly, providing a mixture of regioisomers
10 and 11 (eq 4). The reactions of other alkynes shown in
Figure 1 resulted in failure.
OMe
OMe
C
BrMg
cat. NiBr2(PPh3)2
(1)
+
C
THF, 20 °C, 10 h
Me
Then H3O+
Me
3
4 44%
The syn mode of the carbometalation was confirmed by
NOE analysis of 2b. Irradiation of the methyl group at the 3
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.8 (2007)
1067
Lipshutz, S. Sengupta, Org. React. 1992, 41, 135; E.
Negishi, Dalton Trans. 2005, 827; I. Marek, J. Chem. Soc.,
Perkin Trans. 1 1999, 535; N. Asao, Y. Yamamoto, Bull.
Chem. Soc. Jpn. 2000, 73, 1071; H. Shinokubo, K. Oshima,
Eur. J. Org. Chem. 2004, 2081; A. G. Fallis, P. Forgione,
Tetrahedron 2001, 57, 5899.
T. Yamagami, R. Shintani, E. Shirakawa, T. Hayashi, Org.
Lett. 2007, 9, 1045; E. Shirakawa, T. Yamagami, T. Kimura,
S. Yamaguchi, T. Hayashi, J. Am. Chem. Soc. 2005, 127,
17164; H. Yorimitsu, J. Tang, K. Okada, H. Shinokubo,
K. Oshima, Chem. Lett. 1998, 11; K. Murakami, H. Ohmiya,
H. Yorimitsu, K. Oshima, Org. Lett. 2007, 9, 1569; K. Itami,
T. Kamei, J. Yoshida, J. Am. Chem. Soc. 2003, 125, 14670;
H. Oda, M. Morishita, K. Fugami, H. Sano, M. Kosugi,
Chem. Lett. 1996, 811.
K. Okada, K. Oshima, K. Utimoto, J. Am. Chem. Soc. 1996,
118, 6076; T. Nishikawa, H. Shinokubo, K. Oshima, Org.
Lett. 2002, 4, 2795; H. Yasui, T. Nishikawa, H. Yorimitsu,
K. Oshima, Bull. Chem. Soc. Jpn. 2006, 79, 1271.
E. Shirakawa, H. Yoshida, T. Kurahashi, Y. Nakao, T.
Hiyama, J. Am. Chem. Soc. 1998, 120, 2975; M. Suginome,
M. Shirakura, A. Yamamoto, J. Am. Chem. Soc. 2006, 128,
14438.
S. Nishimae, R. Inoue, H. Shinokubo, K. Oshima, Chem.
Lett. 1998, 785; M. Hojo, Y. Murakami, H. Aihara, R.
Sakuragi, Y. Baba, A. Hosomi, Angew. Chem., Int. Ed.
2001, 40, 621; D. Zhang, J. M. Ready, J. Am. Chem. Soc.
2006, 128, 15050.
Typical experimental procedure: NiBr2(PPh3)2 (19 mg,
0.025 mmol) was placed in a 20-mL reaction flask under ar-
gon. [2-(1-Propynyl)phenyl]methanol (1, 47 mg, 0.25 mmol)
in THF (1.0 mL) was added to the flask. A solution of
vinylmagnesium bromide (1.5 mL, 1.0 M THF solution,
1.5 mmol) was then added at 20 ꢁC. The mixture was stirred
at 20 ꢁC for 5 h. A saturated solution of NH4Cl (2 mL) was
added. The organic compounds were extracted with ethyl
acetate three times. The combined organic part was dried
over Na2SO4 and concentrated in vacuo. Chromatographic
purification on silica gel by using hexane/ethyl acetate =
5:1 as an eluent afforded 2a (31 mg, 0.18 mmol) in 72%
OH
OH
C
BrMg
cat. NiBr2(PPh3)2
(2)
(3)
+
C
THF, 50 °C, 2 h
C4H9
Then H3O+
C4H9
5
6 34%
2
BrMg
cat. NiBr2(PPh3)2
+
C
THF, 50 °C, 12 h
Me
C
Then H3O+
Me
7
8 47%
OH
OH
3
4
5
Ph
OH
C
BrMg
cat. NiBr2(PPh3)2
10
+
+
(4)
C
THF, 50 °C, 2 h
Then H3O+
Ph
9
Ph
11
ca. 20% combined yield
OMgX
MgX
BrMg
cat. NiBr2(PPh3)2
1 +
THF, 50 °C, 1 h
6
Me
12
•
10 mol% CuCN 2LiCl
10 equiv. MeI
15 equiv.
CD3COOD
OH
Me
OH
D
Me
14, 58%
Me
13
62%, 91%D
Scheme 1.
yield.
(E)-[2-(2-Methyl-1,3-butadienyl)phenyl]methanol
(2a): IR(neat): 752, 1015, 1448, 1604, 2918, 3319 cmꢂ1
.
The vinylmagnesiated adduct 12 was trapped with
CD3COOD or iodomethane in the presence of CuCN 2LiCl
1H NMR (300 MHz, CDCl3): ꢁ 1.61 (t, J ¼ 6:0 Hz, 1H),
1.85 (d, J ¼ 1:2 Hz, 3H), 4.66 (d, J ¼ 6:0 Hz, 2H), 5.16 (d,
J ¼ 10:8 Hz, 1H), 5.31 (d, J ¼ 17:4 Hz, 1H), 6.59 (dd,
J ¼ 10:8, 17.4 Hz, 1H), 6.63 (s, 1H), 7.19–7.30 (m, 3H),
7.42–7.45 (m, 1H). 13C NMR (75 MHz, CDCl3): ꢁ 13.45,
63.66, 113.67, 127.47, 127.51, 127.76, 129.06, 129.98,
136.24, 137.61, 139.09, 141.35. Anal. Calcd for C12H14O:
C, 82.72: H, 8.10%. Found: C, 82.59: H, 8.12%.
The E/Z ratios of the Grignard reagents were determined
as follows: The reaction of benzaldehyde with an equimolar
amount of alkenylmagnesium bromide afforded the corre-
sponding allyl alcohol in excellent yield. The E/Z ratio of
the allyl alcohol would be roughly equal to the E/Z ratio
of the Grignard reagent used.
.
(Scheme 1). Unfortunately, many attempts to trap the intermedi-
ate 12 with I2, allyl bromide, benzoyl chloride, benzaldehyde,
and iodobenzene resulted in failure. The intermediate is not
reactive probably because of the proximal alkoxide moiety and
steric hindrance.
In summary, we have found examples of carbometalation
with 1-alkenylmetal reagents. The reaction proceeds in a syn
fashion, yielding 1,3-butadiene skeleton.
7
Dedicated to the memory of the late Prof. Yoshihiko Ito.
References and Notes
1
J. F. Normant, A. Alexakis, Synthesis 1981, 841; L. H.
Published on the web (Advance View) July 21, 2007; doi:10.1246/cl.2007.1066