Nickel-catalyzed conjugate addition of arylboron reagents to α,β-unsaturated carbonyl compounds with the aid of a catalytic amount of an alkyne

Article abstract of DOI:10.1246/cl.2006.768

Alkynes in combination with a catalytic amount of a nickel complex were found to catalyze the conjugate addition of arylboron reagents to α,β-unsaturated carbonyl compounds, where use of an optically active alkyne induces the asymmetric addition. Copyright

Full text of DOI:10.1246/cl.2006.768

768
Chemistry Letters Vol.35, No.7 (2006)
Nickel-catalyzed Conjugate Addition of Arylboron Reagents to ꢀ,ꢁ-Unsaturated Carbonyl
Compounds with the Aid of a Catalytic Amount of an Alkyne
Eiji Shirakawa,Ã Yuichi Yasuhara, and Tamio HayashiÃ
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
(Received April 25, 2006; CL-060494; E-mail: shirakawa@kuchem.kyoto-u.ac.jp, thayashi@kuchem.kyoto-u.ac.jp)
Table 1. Addition of arylboron reagents to ꢀ,ꢁ-unsaturated
Alkynes in combination with a catalytic amount of a nickel
carbonyl compoundsa
complex were found to catalyze the conjugate addition of aryl-
boron reagents to ꢀ,ꢁ-unsaturated carbonyl compounds, where
use of an optically active alkyne induces the asymmetric addition.
Ni(cod)2 (5 mol %)
PhC≡CPh (1b: 20 mol %)
H2O (1.0 equiv.)
O
O
Ar BR1
+
2
R2
Ar
R2
1,4-dioxane, 24 h
1.2:1
2
3
4
Transition metal-catalyzed addition of organoboron re-
agents to electron-deficient olefins has recently attracted much
attention due mainly to high chemoselectivity and low toxicity
of organoboron reagents. In particular, a vast number of reports
on the rhodium-catalyzed asymmetric reaction have been pub-
lished for a decade.1 Although palladium complexes also are
found to be effective as catalysts,2 there has been no report on
the reaction catalyzed by nickel, a group 10 metal as same as
palladium. On the other hand, we have previously reported a
nickel–alkyne catalyst system for the addition of arylboronates
to aldehydes, where the addition does not take place at all in the
absence of an alkyne.3 Here, we report that the nickel–alkyne
catalyst system is applicable also to the conjugate addition of
arylboronates to ꢀ,ꢁ-unsaturated carbonyl compounds. To the
best of our knowledge, this is the first example of the nickel-
catalyzed conjugate addition of organoboron reagents.
We first examined 4-octyne (1a), the most effective co-cat-
alyst tested for the addition of a p-tolylboronate to benzalde-
hyde,3 as a co-catalyst in the nickel-catalyzed reaction of 2-
phenyl-1,3,2-dioxaborinane (2a) with 3-buten-2-one (3a) (eq
1). Thus, the treatment of 2a (1.2 equiv.) and 3a (1.0 equiv.) with
bis(1,5-cyclooctadiene)nickel (Ni(cod)2: 5 mol %) and H2O (1.0
equiv.) in 1,4-dioxane at 60 ꢀC for 24 h gave 4-phenyl-2-buta-
none (4a) in 22% yield. Use of diphenylacetylene (1b) instead
of 1a as an additive was much more effective to increase the
yield to 65%. Besides alkynes, 1,2- and 1,3-dienes such as 1,3-
diphenyl-1,2-propadiene (1c) and 2,3-dimethyl-1,3-butadiene
(1d) also showed some catalytic activity.4–6 In contrast, the reac-
tion without any additive or with a conventional phosphine
ligand like PPh3 gave 4a only in 1 or 8% yield, respectively.
Use of Ni(acac)2 as a catalyst precursor was totally ineffective.
Entry
2
R2 in 3
Yield/%b
1
2
3
4
PhB[O(CH2)3O] (2a)
4-CF3C6H4B[O(CH2)3O] (2b)
4-MeOC6H4B[O(CH2)3O] (2c) Me (3a)
Me (3a)
Me (3a)
65
51
41
65
41
67
Ph3B (2d)
B-Ph-9BBN (2e)
PhB[O(CH2)3O] (2a)
Me (3a)
Me (3a)
OEt (3b)
5
6c
aThe reaction was carried out in 1,4-dioxane (0.45 mL) at 60 ꢀC
for 24 h under a nitrogen atmosphere using an arylboron reagent
(0.36 mmol) and an ꢀ,ꢁ-unsaturated carbonyl compound (0.30
mmol) in the presence of Ni(cod)2 (15 mmol), diphenylacetylene
(60 mmol), and H2O (0.30 mmol). bIsolated yield based on the
ꢀ,ꢁ-unsaturated carbonyl compound. Temperature = 80 ꢀC.
c
group underwent the reaction with 3a (Entries 2 and 3). Other
arylboron reagents such as triphenylborane (2d) and 9-phenyl-
9-borabicyclo[3.3.1]nonane (2e) also added to 3a (Entries 4
and 5), whereas the reaction did not take place at all with phenyl-
boronic acid. Ethyl acrylate (3b) also accepted the addition of 2a
(Entry 6).
ꢁ-Substituted enones including a cyclic one also reacted with
phenylboronate 2a in the presence of the Ni–1b catalyst (eq 2).8
Here again, the reaction of 3-nonen-2-one (3c) in the absence of
an alkyne resulted in a poor yield (<1%). Necessity of an alkyne
functionality was confirmed also by the result that enone 3f hav-
ing an alkyne moiety at an appropriate position underwent the
conjugate addition with 2a in the absence of an extra alkyne such
as 1b to give ꢁ-phenylated ketone 4f (eq 3).9,10 If alkynes play a
critical role in the carbon–carbon bond-forming step, namely the
enantioface-differentiating step, use of an optically active alkyne
should induce the asymmetric addition. Actually, the reaction of
2a with 2-cyclopentenone (3e) in the presence of (S)-4-methoxy-
1,4-diphenyl-1-butyne (1e)11 gave (R)-3-phenylcyclopentanone
(4e) albeit in a low enantioselectivity (eq 4).
Ni(cod)2 (5 mol %)
co-catalyst (20 mol %)
O
H2O (1.0 equiv.)
O
O
+
(1)
Ph
B
1,4-dioxane, 60 °C, 24 h
O
Ph
1.2:1
O
Ph
O
Ni(cod)2 (5 mol %)
PhC≡CPh
(1b: 20 mol %)
H2O (1.0 equiv.)
2a
3a
4a
R3
R4
R3
R4
O
co-catalyst
Pr
O
O
3c, 3d
4c, 4d
Ph
+
or
or
(2)
•
Ph
B
none
PPh3
Pr Ph
Ph
1,4-dioxane
60 °C, 24 h
Ph
1a
1b
65%
1c
1d
14%
O
1.2:1
yield
2a
Ph
22%
32%
1%
8%
3e
4e
The Ni–PhCꢁCPh catalyst was applied to other combina-
tions of substrates (Table 1).7 In addition to phenylboronate 2a
(Entry 1), those having an electron-withdrawing or -donating
3c, 4c: R3 = Pent, R4 = Me
3d, 4d: R3 = Me, R4 = t-Bu
4c: 53% (without 1b: <1%)
4d: 34%
4e: 23%
Copyright ꢀ 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.7 (2006)
769
For alkynes: E. Shirakawa, G. Takahashi, T. Tsuchimoto,
Y. Kawakami, Chem. Commun. 2001, 2688; For 1,3-dienes:
E. Shirakawa, G. Takahashi, T. Tsuchimoto, Y. Kawakami,
Chem. Commun. 2002, 2210; For 1,2-dienes: G. Takahashi,
E. Shirakawa, T. Tsuchimoto, Y. Kawakami, Adv. Synth.
Catal. 2006, 348, 837.
Ph
O
Ni(cod)2 (5 mol %) Ph
H2O (1.0 equiv.)
O
O
O
+
(3)
Ph
B
Ph
1,4-dioxane
12 °C, 24 h
1.2:1
27%
(75% conversion)
2a
3f
4f
7
General procedure: A solution (0.45 mL) of diphenylacety-
lene (10.7 mg, 60.0 mmol) in 1,4-dioxane was degassed by
three freeze–thaw cycles. After Ni(cod)2 (4.1 mg, 15 mmol)
was dissolved in the solution, an enone (0.30 mmol), water
(5.4 mg, 0.30 mmol), and an arylboronate (0.36 mmol) were
added successively to the resulting solution. After the mix-
ture was stirred at 60 ꢀC for 24 h, the resulting mixture was
treated with a saturated NH4Cl aqueous solution (10 mL)
and extracted with diethyl ether (15 mL Â 3). The combined
organic layer was washed with a saturated NaHCO3 aqueous
solution (10 mL) and brine (10 mL), and then dried over
anhydrous sodium sulfate. Filtration and evaporation of the
solvent followed by PTLC on silica gel (hexane–ethyl ace-
tate) gave the corresponding ketone. The results are summa-
rized in Table 1.
Unfortunately, the addition to enals does not proceed regio-
selectively. The reaction of 2-hexenal with 2a under the
same conditions as Table 1 and eq 2 gave a 59:13:28 mixture
of the 1,2-adduct (1-phenyl-2-hexen-1-ol), the 1,4-adduct
(3-phenylhexanal), and diarylation products (diastereomers
of 1,3-diphenyl-1-hexanol) in 71% yield (determined by
1H NMR using nitromethane as an internal standard).
GC and 1H NMR analyses show that the yields of other prod-
ucts derived from enone 3f should be less than 3% and most
of 3f seems to undergo oligomerization and/or polymeriza-
tion. The reaction at a higher temperature resulted in a com-
plex mixture.
Ni(cod)2 (5 mol %)
Ph
OMe
(20 mol %)
1e
O
O
Ph
O
H2O (1.0 equiv.)
+
Ph
B
(4)
1,4-dioxane, 60 °C, 24 h
O
1.2:1
Ph
2a
3e
25%, 7% ee (R)
4e
In conclusion, the nickel-catalyzed conjugate addition of
arylboron reagents to ꢀ,ꢁ-unsaturated carbonyl compounds
was accomplished for the first time by use of alkynes as co-
catalysts. The catalyst system features the first asymmetric
synthesis induced by a catalytic amount of an optically active
alkyne, showing the promising possibility of optically active
alkynes as chiral sources.
8
9
References and Notes
1
For the first non-asymmetric reaction, see: M. Sakai, H.
Hayashi, N. Miyaura, Organometallics 1997, 16, 4229; For
the asymmetric version, see: Y. Takaya, M. Ogasawara,
T. Hayashi, M. Sakai, N. Miyaura, J. Am. Chem. Soc.
1998, 120, 5579; T. Hayashi, M. Takahashi, Y. Takaya, M.
Ogasawara, J. Am. Chem. Soc. 2002, 124, 5052; For a
review, see: T. Hayashi, K. Yamasaki, Chem. Rev. 2003,
103, 2829.
C.-S. Cho, S. Motofusa, K. Ohe, S. Uemura, J. Org. Chem.
1995, 60, 883; T. Nishikata, Y. Yamamoto, N. Miyaura,
Angew. Chem., Int. Ed. 2003, 42, 2768; T. Nishikata, Y.
Yamamoto, N. Miyaura, Organometallics 2004, 23, 4317;
X. Lu, S. Lin, J. Org. Chem. 2005, 70, 9651; F. Gini, B.
Hessen, A. J. Minnaard, Org. Lett. 2005, 7, 5309; T.
Yamamoto, M. Iizuka, T. Ohta, Y. Ito, Chem. Lett. 2006,
35, 198.
2
10 Although we do not have any evidence to clarify the reaction
mechanism, the results that alkynes in addition to 1,3- and
1,2-dienes were much more effective than triphenylphos-
phine may imply that these hydrocarbons do not behave
merely as conventional ligands. As these hydrocarbons in
combination with aldehydes or conjugated enones are con-
sidered to readily undergo oxidative cyclization to nickel(0)
complexes, there may be some possibility that the present re-
action involves thus formed nickelacycles, which react with
arylboronates with cleavage of the proximately-formed car-
bon–carbon bond. For an example of nickelacycle formation,
see: S. Ogoshi, M. Oka, H. Kurosawa, J. Am. Chem. Soc.
2004, 126, 11802, and references cited therein.
3
4
G. Takahashi, E. Shirakawa, T. Tsuchimoto, Y. Kawakami,
Chem. Commun. 2005, 1459.
Dienes 1c and 1d in combination with a catalytic amount of
a nickel complex were found to catalyze the addition of 2-
(p-tolyl)-1,3,2-dioxaborinane to hexanal in comparable effi-
ciencies (97 and 80% yields, respectively) to 4-octyne (96%
yield) under the identical conditions described in Ref. 3.
Rhodium complexes coordinated with a C2-symmetric che-
lating diene show high enantioselectivities and high catalytic
activities in the conjugate addition of arylboronic acids to
enones. T. Hayashi, K. Ueyama, N. Tokunaga, K. Yoshida,
J. Am. Chem. Soc. 2003, 125, 11508.
11 Optically pure alkyne 1e was prepared as follows. The
reaction of (R)-styrene oxide with phenylethynyllithium
5
6
.
(2.8 equiv.) in the presence of BF3 Et2O (2.8 equiv.) in
THF at À78 ꢀC for 10 min gave (R)-1,4-diphenylbut-3-yn-
1-ol (45% yield) and 2,4-diphenylbut-3-yn-1-ol (24% yield).
The former was treated with sodium hydride (1.5 equiv.) and
iodomethane (4.0 equiv.) in THF at room temperature for 2 h
to give 1e in 88% yield.
Alkynes as well as 1,3- and 1,2-dienes accept addition of
arylboron reagents in the presence of a nickel catalyst.
Published on the web (Advance View) June 10, 2006; doi:10.1246/cl.2006.768