Diastereoselective coupling of 1,3-diene, ketone, and organometallic reagents by nickel catalyst: stereoselective construction of tetrasubstituted carbon centers

Article abstract of DOI:10.1246/cl.2009.594

A nickel-catalyzed three-component coupling of 1,3-diene, ketone, and organoboron or organosilicon reagents was investigated. While the coupling reaction using PhB(OH)₂ afforded a 1,3-syn-substituted 4-penten-l-ol derivative as a single diaster

Full text of DOI:10.1246/cl.2009.594

594
Chemistry Letters Vol.38, No.6 (2009)
Diastereoselective Coupling of 1,3-Diene, Ketone, and Organometallic Reagents by Nickel
Catalyst: Stereoselective Construction of Tetrasubstituted Carbon Centers
Nozomi Saito, Tetsuro Yamazaki, and Yoshihiro Satoꢀ
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812
(Received March 23, 2009; CL-090295; E-mail: biyo@pharm.hokudai.ac.jp)
Table 1. Coupling reactions of 6, 7a, and 3 using various ligandsa
A nickel-catalyzed three-component coupling of 1,3-diene,
ketone, and organoboron or organosilicon reagents was investi-
gated. While the coupling reaction using PhB(OH)2 afforded a
1,3-syn-substituted 4-penten-1-ol derivative as a single diaster-
eomer, the reaction in the presence of tetraorganosilicon reagent
under similar conditions exclusively produced the corresponding
1,3-anti isomer. In both reactions, a tetrasubstituted carbon cen-
ter was constructed in a highly diastereoselective manner.
MOMO
10 mol% Ni(cod)2
10 mol% ligand
MOMO
3
1
Ph
CH
6
5 equiv PhB(OH)2 (3)
3 equiv Cs2CO3
CPME, 50 °C
syn-8a
1) OsO4
2) NaIO4
3) PDC
HO
Ph
3
O
+
O
Ph
CH3
1
3
O
Ph
7a
H
H
3 steps 72%
H
Ph
CH3
9
NOESY
Run
Ligand
Time/h
Yield of syn-8a/%
1
2
3
4
5
PPh3
PPh2Me
75
17
10
20
9
73
29
40
79
71
Multicomponent coupling reactions have attracted much at-
tention as an efficient methodology in recent organic synthesis.1
We have demonstrated a nickel-catalyzed multicomponent cou-
pling of 1,3-dienes, aldehydes, and silane.2–4 Recently, we also
reported a diastereoselective coupling of 1,3-dienes, aldehydes,
and organoboron or organosilicon reagents (Scheme 1).5,6 That
is, the coupling of 1 and 2 using organoboronic acid 3 gave
syn-4 diastereoselectively. On the other hand, the diastereoselec-
tivity was changed in the reaction using organosilicon reagent 5
under similar conditions, producing the corresponding stereo-
isomer anti-4. In this context, we envisaged that if a ketone
was used instead of aldehyde in this reaction, a coupling product
having a tetrasubstituted carbon should be obtained. Further-
more, the stereochemistry at C1 and C3 positions would be con-
trolled by the class of organometallic reagent.
According to previously optimized conditions,5 diene 6 and
acetophenone (7a) reacted with PhB(OH)2 (3) in the presence of
Ni(cod)2 and PPh3 in CPME (cyclopentyl methyl ether) at 50 ꢁC
for 75 h, giving the coupling product 8a in 73% yield as a single
diastereomer (Table 1, Run 1). As expected, the relative config-
urations of the hydroxy group at the C1 position and the phenyl
group at the C3 position were determined to be 1,3-syn from
a NOESY experiment of 9 derived from 8a.7 After screening
ligands, it was found that P(p-tolyl)3 is suitable in this reaction,
giving syn-8a in good yield (Run 4).
PCy3
P(p-tolyl)3
P(p-MeOC6H4)3
aReaction conditions: 6 (1 equiv), 7a (2 equiv), Ni(cod)2 (10 mol %), ligand
(10 mol %), PhB(OH)2 (5 equiv), Cs2CO3 (3 equiv), CPME, 50 ꢁC. bThe
ratio of syn isomer to anti isomer was >50 to 1.
Table 2. Coupling reactions of 1,3-diene 6 and various ketones 7a
MOMO
Ni(cod)2, P(p-tolyl)3
O
R1
HO R2
+
6
CsCO3, PhB(OH)2 (3)
CPME, 50 °C
R1
R2
Ph
7
syn-8
Yield of
syn-8/%
Ketone 7
Run
Time/h
R1 =
R2 =
4-MeOC6H4
4-MeO2CC6H4
F
CF3
CF3
i-Pr
t-Bu
Me
Me
Me
Me
Et
1
2
3
4
5
6
7
8
9
7b
7c
7d
7e
7f
7g
7h
7i
15
13
14
13
11
13
15
12
13
12
8b: 25
8c: 92
8d: 85
8e: 89
8f: 77
8g: 29
8h: 24
8i: 32
8j: 66
8k: 29
Me
Me
O
n = 1
7j
7k
n = 2
n = 3
10
n
aReaction conditions: diene 6 (1 equiv), ketone 7 (2 equiv), Ni(cod)2 (10 mol %),
P(p-tolyl)3 (10 mol %), PhB(OH)2 (5 equiv), Cs2CO3 (3 equiv), CPME, 50 ꢁC.
bThe ratio of syn isomer to anti isomer was >50 to 1.
Coupling reactions of 6 and various ketones 7 under optimal
conditions were investigated (Table 2). While the reaction of 6
and 7b with a methoxy group on the aromatic ring gave syn-
8b in low yield, the reaction of 7c–7e bearing an electron-with-
drawing group on the aromatic ring afforded the corresponding
syn-8c–8e in high yields (Runs 2–4).8 Coupling with propiophe-
none derivative 7f also proceeded diaseteoselectively to give the
product 8f in 77% yield (Run 5). Although aliphatic ketones 7g–
7h and cycloalkanones 7i–7k were also applicable to this reac-
tion, the yields of products 8g–8k were moderate to low (Runs
6–10). On the other hand, the reaction of an internal diene
(e.g. 1,4-diphenylbuta-1,3-diene) and acetophenone (7a) gave
no coupling product and only starting diene was recovered, prob-
ably due to the steric repulsion.
Ar B(OH)2
3
R1
R1
R2
3
1
Ln = PPh3
1
Ar
syn-4
OH
cat. Ni(cod)2-Ln
Next, we turned our attention to multicomponent coupling
of 1,3-diene, ketone, and organosilicon reagent 59 (Table 3). Ac-
cording to our previous protocol,5 the reaction of 6, 7, and 5 was
+
R1
HO
PhMe2Si
R1
R2
R2
3
1
5
O
H
Ni
Ln
O
Ph OH
anti-4
.
R2
H
I
carried out in the presence of Ni(cod)2, IMes HCl, and Cs2CO3
N
N
Mes
Ln =
Mes
2
in CPME at 50 ꢁC. As a result, the coupling product anti-8a was
obtained in 32% yield as a single diastereomer (Run 1), whose
stereochemistry was determined from a NOESY experiment of
IMes
Scheme 1.
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.6 (2009)
595
Table 3. Coupling reactions of 1,3-diene, ketone, and silicon reagent 5a
1,3-syn products exclusively. On the other hand, the use of a
tetraorganosilicon reagent as a coupling partner provided the
corresponding 1,3-anti isomers under similar conditions. In both
reactions, a tetrasubstituted carbon center was constructed in a
highly diastereoselective manner.
20 mol% Ni(cod)2
20 mol% IMes·HCl
2.6 equiv Cs2CO3
6
+
7
+
MOMO
R1
HO R2
CPME, 50 °C
Ph
anti-8
O
1) OsO4
2) NaIO4
3) PDC
O
1
Ph
CH3
HO
PhMe2Si
3
This work was supported by a Grant-in-Aid for Science Re-
search on Priority Areas (Nos. 19027005 and 20036005, Syner-
gy of Elements) from MEXT, Japan and a Grant-in-Aid for Sci-
entific Research (B) (No. 19390001) from JSPS. The authors are
also grateful to ZEON Corporation, Japan for kindly providing
CPME.
Ph
9'
NOESY
H
5
H
3 steps 70%
Yield of anti-8/%b
8a (R1 = C6H5, R2 = Me): 32
Run
Ketone 7
Time/h
1
2
3
4
7a
7c
7d
7j
13
24
48
48
8c (R1 = 4-MeO2CC6H4, R2 = Me): 52
8d (R1 = 4-FC6H4, R2 = Me): 26
8j (R1, R2 = –(CH2)5–): 46
References and Notes
´
a) Multicomponent Reactions, ed. by J. Zhu, H. Bienayme, Wiley-VCH
aReaction conditions: diene 6 (1 equiv), ketone 7 (2 equiv), Ni(cod)2
1
´
Verlag Gmbh and Co. KGaA, Weinheim, Germany, 2005. b) D. J. Ramon,
.
(20 mol %), IMes HCl (10 mol %), 5 (1.1 equiv), Cs2CO3 (2.6 equiv), CPME,
M. Yus, Angew. Chem., Int. Ed. 2005, 44, 1602.
50 ꢁC. bThe ratio of anti isomer to syn isomer was >50 to 1.
2
a) M. Takimoto, Y. Hiraga, Y. Sato, M. Mori, Tetrahedron Lett. 1998, 39,
4543. b) Y. Sato, R. Sawaki, M. Mori, Organometallics 2001, 20, 5510.
c) R. Sawaki, Y. Sato, M. Mori, Org. Lett. 2004, 6, 1131. d) Y. Sato, Y.
Hinata, R. Seki, Y. Oonishi, N. Saito, Org. Lett. 2007, 9, 5597. For multi-
component coupling using Me3SiSnBu3 instead of silane, see: e) Y. Sato,
N. Saito, M. Mori, Chem. Lett. 2002, 18. f) N. Saito, M. Mori, Y. Sato,
J. Organomet. Chem. 2007, 692, 460.
RL
O
Ar
RL
Rs
3
Ar
Ar
Ar
1
Ni
Ni
Ln
Rs
O
6
+
H
Ln
Ln
Ni(cod)2-Ligand
10
11: favored
(1)
RL = Larger group
RS = Smaller group
Rs
O
O
Ar
3
4
For reviews of Ni-catalyzed multicomponent coupling, see: a) S. Ikeda,
Acc. Chem. Res. 2000, 33, 511. b) J. Montgomery, Acc. Chem. Res.
2000, 33, 467. c) J. Montgomery, Angew. Chem., Int. Ed. 2004, 43, 3890.
For recent examples of Ni-catalyzed multicomponent coupling, see:
a) G. M. Mahandru, G. Liu, J. Montgomery, J. Am. Chem. Soc. 2004,
126, 3698. b) J. Terao, S. Nii, F. A. Chowdhury, A. Nakamura, N. Kambe,
Adv. Synth. Catal. 2004, 346, 905. c) M. Kimura, A. Miyachi, K. Kojima, S.
Tanaka, Y. Tamaru, J. Am. Chem. Soc. 2004, 126, 14360. d) E. Shirakawa,
Y. Yamamoto, Y. Nakao, S. Oda, T. Tsuchimoto, T. Hiyama, Angew.
Chem., Int. Ed. 2004, 43, 3448. e) M. Kimura, A. Ezoe, M. Mori, Y.
Tamaru, J. Am. Chem. Soc. 2005, 127, 201. f) M. Kimura, K. Kojima, Y.
Tatsuyama, Y. Tamaru, J. Am. Chem. Soc. 2006, 128, 6332. g) P. G. Cozzi,
E. Rivalta, Angew. Chem., Int. Ed. 2005, 44, 3600. h) S.-S. Ng, C.-Y. Ho,
T. F. Jamison, J. Am. Chem. Soc. 2006, 128, 11513. i) C. C. Chrovian, J.
Montgomery, Org. Lett. 2007, 9, 537. j) T. T. Jayanth, C.-H. Cheng, Angew.
Chem., Int. Ed. 2007, 46, 5921. k) M. Kimura, Y. Tatsuyama, K. Kojima, Y.
Tamaru, Org. Lett. 2007, 9, 1871. l) A. Herath, W. Li, J. Montgomery, J.
Am. Chem. Soc. 2008, 130, 469.
Rs
RL
3
1
Ni
RL
RS
Ni
Ln
RL
O
H
7
12
13: disfavored
Cs
5'
O
Si
Ph
Ar
RL
Rs
RL
Rs
3
1
3
1
Ar
14
Ar
path A
path B
15
RL
Rs
Ni
O
Ni
Ph
O
(2)
Ph
B(OR)2
Ph
Cs
O
Ni(0)
11
Ni(0)
B(OH)2
syn-8
anti-8
Scheme 2.
90 in the same way as that of syn-8a. Reactions of 6 with ketones
bearing an ester group (8c) or a fluoro group (8d) on the aromatic
ring gave the corresponding products anti-8c and anti-8d, re-
spectively (Runs 2 and 3). Cyclohexanone (7j) was applicable
to coupling reaction using 5, giving 8j in 46% yield (Run 4).
A possible reaction mechanism is shown in Scheme 2. First,
oxidative cycloaddition of diene 6 and ketone 7 to a Ni0 complex
occurs to give a nickelacycle 10 or 12, and two diastereomers of
ꢀ-allylnickel intermediate 11 and 13 would be formed through
10 and 12, respectively.10 It was thought that the complex 11
might be more stable than 13 because 1,3-diaxial interaction be-
tween a pseudo-axially oriented larger substituent (RL) at C1 and
a hydrogen atom at C3 in 13 is greater than that between a small-
er substituent (Rs) and hydrogen atom in 11. Therefore, the equi-
librium between 11 and 13 would lie toward the intermediate 11.
In the reaction using PhB(OH)2 (3), transmetallation between 3
and 11 proceeded to give intermediate 14, and finally syn-8 was
obtained as a single diastereomer (eq 2, path A). On the other
hand, when organosilicon reagent 5 was used, nucleophilic back-
side attack of the phenyl group of silicate 50 generated from 5
and Cs2CO39 to 11 would occur, producing anti-8 in a diastereo-
selective manner (path B).
5
6
N. Saito, T. Yamazaki, Y. Sato, Tetrahedron Lett. 2008, 49, 5073.
For reductive or alkylative coupling of 1,3-diene and aldehyde via trans-
metallation of nickelacycle with organometallic reagent, see: a) M. Kimura,
A. Ezoe, K. Shibata, Y. Tamaru, J. Am. Chem. Soc. 1998, 120, 4033. b) M.
Kimura, H. Fujimatsu, A. Ezoe, K. Shibata, M. Shimizu, S. Matsumoto, Y.
Tamaru, Angew. Chem., Int. Ed. 1999, 38, 397. c) M. Kimura, S. Matsuo, K.
Shibata, Y. Tamaru, Angew. Chem., Int. Ed. 1999, 38, 3386. d) Y. Sato, R.
Sawaki, N. Saito, M. Mori, J. Org. Chem. 2002, 67, 656. For an alkylative
cyclization of 1,3-diene and aldehyde via nickelacycle see: e) Y. Sato,
T. Takanashi, M. Mori, Organometallics 1999, 18, 4891. f) Y. Sato, T.
Takanashi, M. Hoshiba, M. Mori, J. Organomet. Chem. 2003, 688, 36.
Supporting Information is available electronically on the CSJ-Journal Web
site, http://www.csj.jp/journals/chem-lett/index.html.
7
8
In the case of coupling with aldehyde, the use of that bearing an electron-
donating group on the aromatic ring gave good results (see, ref 5). Although
the reason is unclear yet, it is interesting that the contrary results with
respect to the effect of substituents on the aromatic ring were obtained in
the reaction using ketones.
9
Y. Nakao, H. Imanaka, A. K. Sahoo, A. Yada, T. Hiyama, J. Am. Chem.
Soc. 2005, 127, 6952.
10 Recently the ꢁ3-allylalkoxynickel complex from 1,3-diene and aldehyde
was isolated: S. Ogoshi, K. Tonomori, M. Oka, H. Kurosawa, J. Am. Chem.
Soc. 2006, 128, 7077.
In summary, we have demonstrated a diastereoselective
three-component coupling of 1,3-diene, ketone, and organome-
tallic reagent. The reaction using organoboronic acid provided
Published on the web (Advance View) May 23, 2009; doi:10.1246/cl.2009.594