Alkynes as activators in the nickel-catalysed addition of organoboronates to aldehydes

Article abstract of DOI:10.1039/b417353h

Alkynes act not as substrates but as co-catalysts in the presence of a nickel catalyst, an organoboronate and an aldehyde to promote the addition reaction between the substrates in combination with H₂O. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b417353h

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Alkynes as activators in the nickel-catalysed addition of
organoboronates to aldehydes{
Go Takahashi,a Eiji Shirakawa,*b Teruhisa Tsuchimotoa and Yusuke Kawakamia
Received (in Cambridge, UK) 17th November 2004, Accepted 23rd December 2004
First published as an Advance Article on the web 25th January 2005
DOI: 10.1039/b417353h
Alkynes act not as substrates but as co-catalysts in the presence
of a nickel catalyst, an organoboronate and an aldehyde to
promote the addition reaction between the substrates in
combination with H2O.
Table 1 Effect of additives in the nickel-catalysed addition of
2-(p-tolyl)-1,3,2-dioxaborinane to benzaldehydea
Entry
Additive
H2O
Yield of 3a (%)b
1
2
3
4
5
6
7
8
None
None
Ph3P (10 mol%)
Ph3P (10 mol%)
Pr–CMC–Pr (20 mol%)
Pr–CMC–Pr (20 mol%)
Pr–CMC–Pr (1.2 equiv)
Ph–CMC–Me (20 mol%)
Ph–CMC–Ph (20 mol%)
Pr–CMC–Pr (20 mol%)
2
+
0
0
0
0
28
Alkynes have long been representative substrates of transition
metal-catalysed reactions, accepting addition of various bonds1 or
undergoing diverse types of cyclization reactions.2 In particular,
late transition metals such as palladium and nickel, having a strong
affinity for alkynes, readily catalyse the transformation of alkynes.
In this context, we have been developing the palladium- or nickel-
catalysed addition of organotin3 or organoboron4 compounds to
alkynes, where alkynes are good reaction partners of the
organometallic compounds. Furthermore, alkynes are known to
undergo three-component coupling with aldehydes and organo-
metallics including organoboron compounds in the presence of a
nickel catalyst to give allylic alcohols.5,6 Here we report the
unusual behavior of alkynes in the presence of a transition metal
catalyst and an organometallic compound, where alkynes act not
as substrates but as activators. Thus, a catalytic amount of alkynes
assists a nickel catalyst to promote the addition of organoboron
compounds to aldehydes.7–9
2
+
2
+
99
79
+
+
52 (85)c
48 (72)d
0
9
+
10e
a
+
The reaction was carried out in 1,4-dioxane (0.45 mL) at 80 uC for
using 2-(p-tolyl)-1,3,2-dioxaborinane (1a: 0.30 mmol),
benzaldehyde (2a: 0.36 mmol) and Ni(cod)2 (15 mmol) in the
2
h
b
presence or absence of H2O (0.30 mmol). Isolated yield based on
arylboronate 1a. The isolated yield after 12 h. The isolated yield
c
d
e
after 24 h. Ni(acac)2 was used instead of Ni(cod)2.
changed the result to give 3a in 99% yield (entries 5 and 6),12,13
where three-component coupling product 4 between 1a, 2a and
4-octyne was not observed (entry 6). With an increased amount
(1.2 equiv) of 4-octyne, 4 (5% yield) and hydroarylation product 5
(4% yield) of the alkyne4 were generated14 but 3a still
predominated (entry 7). More electron-deficient alkynes also
mediated the addition but sluggishly (entries 8 and 9). A
nickel(II) complex did not catalyse the addition (entry 10).
We first examined the nickel-catalysed addition of 2-
(p-tolyl)-1,3,2-dioxaborinane (1a) to benzaldehyde (2a).
Treatment of 1a and 2a with bis(1,5-cyclooctadiene)nickel
(5 mol%) in 1,4-dioxane at 80 uC for 2 h did not afford even a
trace amount of the desired phenyl(p-tolyl)methanol (3a) (eqn. (1)
The Ni(cod)2–4-octyne catalyst was found to be applicable to
various combinations of organoboronates and aldehydes (Table 2).
Table 2 Nickel-catalysed addition of organoboronates to aldehydesa
Entry
R1
R2
Yield of 3 (%)b
1
2
3
4
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-CF3C6H4
4-AcC6H4
3-HOCH2C6H4
4-MeC6H4
4-MeOC6H4
4-CF3C6H4
4-AcC6H4
3-HOCH2C6H4
styryl
4-MeOC6H4
4-CF3C6H4
Ph
Ph
Ph
80
93
88
93
90
84
96
80
77
82
74
70
85
ð1Þ
5
6
Ph
7c
8
pentyl
pentyl
pentyl
pentyl
pentyl
Ph
and entry 1 of Table 1). Addition of H2O (1.0 equiv) as an
activator10 of 1a and/or triphenylphosphine (10 mol%) as a ligand
did not promote the reaction at all (entries 2–4). Other ligands such
as tributylphosphine, 1,3-bis(diphenylphosphino)propane and
2,29-bipyridyl were equally ineffective. In sharp contrast, use of a
catalytic amount of 4-octyne in conjunction with H2O11 drastically
9
10
11
12
13d
a
styryl
Ph
The reaction was carried out in 1,4-dioxane (0.45 mL) at 80 uC for
12 h using an organoboronate (0.30 mmol), an aldehyde (0.36 mmol)
and Ni(cod)2 (15 mmol) in the presence of 4-octyne (60 mmol) and
b
H2O (0.30 mmol). Isolated yield based on the arylboronate.
c
d
{ Electronic supplementary information (ESI) available: Experimental
details. See http://www.rsc.org/suppdata/cc/b4/b417353h/
*shirakawa@kuchem.kyoto-u.ac.jp
Reaction time 5 2 h. 1-Phenylpropyne was used instead of
4-octyne.
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Go Takahashi,a Eiji Shirakawa,*b Teruhisa Tsuchimotoa and
p-Tolylboronate 1a added to both electron-rich and -poor
aromatic aldehydes (entries 1 and 2). Benzaldehyde (2a) accepted
the addition of phenylboronates having a methoxy, trifluoro-
methyl, acetyl or hydroxymethyl group (entries 3–6). In contrast to
more nucleophilic arylmetals such as arylmagnesium halides
and aryllithiums, organoboronates are compatible with electro-
philic functional groups such as ketone and hydroxy. Hexanal,
an aliphatic aldehyde, also underwent the reaction with diverse
types of arylboronates to give a-pentylbenzyl alcohols with an
electron-donating or -withdrawing group at their para or meta
position (entries 7–11). Ketone moieties were unaffected,
showing a strong preference for aldehydes (entries 5 and 10).
For the addition of an alkenylboronate, 1-phenylpropyne was
found to be more effective than 4-octyne as an additive, affording
an increased yield of the corresponding allylic alcohol (entries
12 and 13).
Yusuke Kawakamia
aGraduate School of Materials Science, Japan Advanced Institute of
Science and Technology, Tatsunokuchi, Ishikawa, 923-1292, Japan
bDepartment of Chemistry, Graduate School of Science, Kyoto
University, Sakyo, Kyoto, 606-8502, Japan.
E-mail: shirakawa@kuchem.kyoto-u.ac.jp; Fax: 81 75 753 3988
Notes and references
1 For recent reviews, see: F. Alonso, I. P. Beletskaya and M. Yus, Chem.
Rev., 2004, 104, 3079–3159; M. Beller, J. Seayad, A. Tillack and H. Jiao,
Angew. Chem. Int. Ed., 2004, 43, 3368–3398.
2 For recent reviews, see: S. Saito and Y. Yamamoto, Chem. Rev., 2000,
100, 2901–2915; M. Rubin, A. W. Sromek and V. Gevorgyan, Synlett,
2003, 2265–2291.
3 For the palladium- or nickel-catalysed carbostannylation of alkynes, see:
E. Shirakawa, H. Yoshida, T. Kurahashi, Y. Nakao and T. Hiyama,
J. Am. Chem. Soc., 1998, 120, 2975–2976; E. Shirakawa, H. Yoshida,
Y. Nakao and T. Hiyama, J. Am. Chem. Soc., 1999, 121, 4290–4291;
E. Shirakawa, K. Yamasaki, H. Yoshida and T. Hiyama, J. Am. Chem.
Soc., 1999, 121, 10221–10222; E. Shirakawa, H. Yoshida, Y. Nakao and
T. Hiyama, Org. Lett., 2000, 2, 2209–2211; H. Yoshida, E. Shirakawa,
T. Kurahashi, Y. Nakao and T. Hiyama, Organometallics, 2000, 19,
5671–5678; E. Shirakawa, Y. Yamamoto, Y. Nakao, T. Tsuchimoto
and T. Hiyama, Chem. Commun., 2001, 1926–1927; H. Yoshida,
E. Shirakawa, Y. Nakao, Y. Honda and T. Hiyama, Bull. Chem. Soc.
Jpn., 2001, 74, 637–647.
Use of water as a solvent should be favorable for environmental
and safety reasons.15 Because H2O was found to be a crucial
activator in the addition (entries 5 and 6 of Table 1), we expected
that the reaction should be accelerated in the presence of a
substantial excess of the activator. Actually, the addition of 1a to
2a in water proceeded at a much lower temperature (40 uC, 2 h) to
afford 3a in 97% yield, though it required an excess amount
(1.5 equiv with respect to 2a) of 1a because of competitive
hydrolysis of 1a to toluene.16 Furthermore, glutaraldehyde (6),17
which is usually available only as an aqueous solution, successfully
reacted with organoboronates in a mixed solvent consisting of 1,4-
dioxane and H2O to provide diastereoisomeric mixtures18 of
lactols 7a or 7b (eqn. (2)).The lactols were easily oxidized to the
corresponding lactones 8a or 8b.19
4 For the nickel-catalysed addition of arylboron compounds to alkynes,
see: E. Shirakawa, G. Takahashi, T. Tsuchimoto and Y. Kawakami,
Chem. Commun., 2001, 2688–2689.
5 E. Oblinger and J. Montgomery, J. Am. Chem. Soc., 1997, 119,
9065–9066; X.-Q. Tang and J. Montgomery, J. Am. Chem. Soc., 1999,
121, 6098–6099; X.-Q. Tang and J. Montgomery, J. Am. Chem. Soc.,
2000, 122, 6950–6954; W.-S. Huang, J. Chan and T. F. Jamison, Org.
Lett., 2000, 2, 4221–4223; E. A. Colby and T. F. Jamison, J. Org.
Chem., 2003, 68, 156–166; K. M. Miller, W.-S. Huang and
T. F. Jamison, J. Am. Chem. Soc., 2003, 125, 3442–3443;
K. M. Miller, T. Luanphaisarnnont, C. Molinaro and T. F. Jamison,
J. Am. Chem. Soc., 2004, 126, 4130–4131.
6 The three-component coupling between phenylboronic acid, 1-phenyl-
propyne and an imine derived from benzaldehyde has been reported.
S. J. Patel and T. F. Jamison, Angew. Chem. Int. Ed., 2003, 42,
1364–1367.
7 To the best of our knowledge, there has been no report on the transition
metal-catalysed addition of organoboron compounds to aldehydes
except for the rhodium-catalysed reaction. M. Sakai, M. Ueda and
N. Miyaura, Angew. Chem. Int. Ed., 1998, 37, 3279–3281; M. Ueda
and N. Miyaura, J. Org. Chem., 2000, 65, 4450–4452; A. Fu¨rstner and
H. Krause, Adv. Synth. Catal., 2001, 343, 343–350; C. Moreau,
C. Hague, A. S. Weller and C. G. Frost, Tetrahedron Lett., 2001, 42,
6957–6960. See also ref. 9.
ð2Þ
8 Asymmetric addition of arylboronates to aromatic aldehydes mediated
by an excess amount of diethylzinc in the presence of a chiral
oxazolylalcohol has been reported. C. Bolm and J. Rudolph, J. Am.
Chem. Soc., 2002, 124, 14850–14851.
9 Addition products of triphenylborane to aldehydes were produced as
by-products (yield ¡ 22%) in the nickel-catalysed three-component
coupling between triphenylborane, isoprene and aldehydes. K. Shibata,
M. Kimura, K. Kojima, S. Tanaka and Y. Tamaru, J. Organomet.
Chem., 2001, 624, 348–353.
10 H2O has played a crucial role in the nickel-catalysed hydroarylation of
alkynes or 1,3-dienes using arylboronates. For alkynes, see ref. 4. For
1,3-dienes, see: E. Shirakawa, G. Takahashi, T. Tsuchimoto and
Y. Kawakami, Chem. Commun., 2002, 2210–2211.
11 Although the role of water is not clear at present, it may act as a Lewis
base that coordinates to the boron atom and promotes the attack of the
aryl groups on the aldehyde carbons.
12 Arylboronate 1a was found to be relatively stable to water, not being
hydrolysed on treatment of 1 equiv of H2O in 1,4-dioxane at 80 uC for
6 h.
In conclusion, we have disclosed that a catalytic amount of
alkynes in combination with a nickel catalyst promotes the
addition of organoboronates to aldehydes. Alkynes, one of the
most representative substrates in transition metal catalysis, do not
react with organoboron compounds or aldehydes but activate
them. Although the reaction mechanism including the role of the
alkynes is not clear at present, the complete inability of usual
ligands such as triphenylphosphine and 2,29-bipyridyl might imply
that the alkynes do not behave as conventional ligands.20,21 Studies
on the mechanistic details as well as application of the system to
other substrates are in progress.
13 p-Tolylboronic acid did not add to 2a at all under the conditions
identical to entry 6 in Table 1.
14 Yields of 4 and 5 were determined by isolation with SiO2
chromatography and 1H NMR, respectively.
We thank Professor Tamio Hayashi (Kyoto University) for
helpful discussions. This work was supported in part by Daicel
Chemical Industries, Ltd.
1460 | Chem. Commun., 2005, 1459–1461
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15 For reviews of transition metal-catalysed reactions in aqueous media,
see: C.-J. Li and T.-H. Chan, Organic Reactions in Aqueous Media, John
Wiley, New York, 1997, pp. 115–160; B. Cornils and W. A. Herrmann,
Aqueous-Phase Organometallic Chemistry, Wiley-VCH, Weinheim,
1998; D. Sinou, in Modern Solvents in Organic Synthesis, ed.
P. Knochel, Springer, Berlin, 1999, pp. 41–59.
rhodium(I) catalyst at their terminal acetylenic C–H bond. R. Grigg,
P. Stevenson and T. Worakun, Tetrahedron, 1988, 44, 4967–4972.
Furthermore, in the rhodium–bisphosphine-catalysed successive clea-
vage of carbon–carbon and carbon–oxygen bonds of 2-(alkoxymethyl)-
cyclobutanones, diphenylacetylene was used as an effective co-ligand,
which is thought to coordinate to a rhodium–bisphosphine complex
inhibiting unfavorable coordination of the olefinic moiety of the
substrates. M. Murakami, T. Itahashi, A. Amii, K. Takahashi and
Y. Ito, J. Am. Chem. Soc., 1998, 120, 9949–9950.
16 The reaction of 1a with 2a in water in a ratio of 1 to 1.2 gave 3a only in
ca. 60% yield (determined by 1H NMR).
17 The triethylborane-promoted, nickel-catalysed homoallylation of glutar-
aldehyde in an aqueous media has been reported. M. Kimura, A. Ezoe,
S. Tanaka and Y. Tamaru, Angew. Chem. Int. Ed., 2001, 40, 3600–3602.
18 Although we have not determined the stereochemistry of each
compound, the observation that the isomers were transformed to a
single lactone after oxidation should show that they are diastereomers.
19 E. J. Corey and J. W. Suggs, Tetrahedron Lett., 1975, 31, 2647–2650.
20 Grigg and co-workers proposed the potentiality of alkynes as activators
in the rhodium-catalysed cyclization of unconjugated enynes, where the
enynes act both as substrates and co-catalysts adding oxidatively to a
21 Considering the significant number of examples of an alkyne and an
aldehyde undergoing oxidative cyclization with a nickel(0) complex to
give a 2-oxanickellacyclopent-4-ene, there might be some possibility that
the reaction proceeds through the nickellacycles, which react with
organoboronates with cleavage of the C(3)–C(4) bond to afford addition
product 3, the nickel(0) complex and 4-octyne. See ref. 5. Oxidative
cyclization of enals to nickel(0) complexes to afford 2-oxanickellacyclo-
pentanes also has recently been reported. S. Ogoshi, M. Oka and
H. Kurosawa, J. Am. Chem. Soc., 2004, 126, 11802–11803.
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