Regioselective reductive coupling of alkynes and aldehydes leading to allylic alcohols

Article abstract of DOI:10.1021/ol0272996

(Matrix presented) Treatment of a mixture of a terminal alkyne and an aldehyde with CrCl₂ and a catalytic amount of NiCl₂ and triphenylphosphine in the pre of water in DMF at 25°C gives a 1,2-disubstituted allylic alcohol regioselect

Full text of DOI:10.1021/ol0272996

ORGANIC
LETTERS
2
003
Vol. 5, No. 5
53-655
Regioselective Reductive Coupling of
Alkynes and Aldehydes Leading to
Allylic Alcohols
6
Kazuhiko Takai,* Shuji Sakamoto, and Takahiko Isshiki
Department of Applied Chemistry, Faculty of Engineering, Okayama UniVersity,
Tsushima, Okayama 700-8530, Japan
ktakai@cc.okayama-u.ac.jp
Received November 18, 2002
ABSTRACT
2 2
Treatment of a mixture of a terminal alkyne and an aldehyde with CrCl and a catalytic amount of NiCl and triphenylphosphine in the presence
of water in DMF at 25 °C gives a 1,2-disubstituted allylic alcohol regioselectively.
Addition of a metal-hydride species to a terminal alkyne
generates two regioisomeric alkenylmetal compounds, which
afford the corresponding allylic alcohols upon treatment with
an aldehyde. Because hydroboration, -alumination, and
In contrast, it is not easy to prepare the 2-alkyl-substituted
allylic alcohol 2 directly from a terminal alkyne and an
aldehyde (path B). Therefore, a two-step procedure via the
4
5
2-halo-1-alkene 3 usually has been employed (path C). We
report herein a direct method for the preparation of the
2-substituted allylic alcohol 2 from a terminal alkyne and
an aldehyde using chromium(II) under nickel catalysis.
Nucleophilic carbon-carbon bond formation with orga-
nometallic compounds, except organoboron and -indium
reagents, is usually conducted under water-free conditions.
Indeed, organochromium compounds hydrolyze with a lot
-zirconation of a terminal alkyne generate the corresponding
(E)-alkenylmetal compound, the 3-alkyl-substituted allylic
alcohol 1 is produced selectively via these hydrometalation
methods (Scheme 1, path A).1 Recent reports on intermo-
,2
Scheme 1
6
of water. On the other hand, the rate of hydrolysis is not so
fast among the early transition metal compounds.6c Thus,
the addition of an organochromium reagent can be ac-
complished without protecting the hydroxyl group of the
7
substrate aldehyde in some cases, and even a nucleophilic
organochromium species can be generated by addition of a
8
small aliquot of water. Water is a typical proton source,
lecular coupling reactions promoted with Et
amount of nickel also produce the alcohol 1 regioselectively.
3
B and a catalytic
(3) (a) Oblinger, E.; Montgomery, J. J. Am. Chem. Soc. 1997, 119, 9065.
(b) Huang, W.-S.; Chan, J.; Jamison, T. F. Org. Lett. 2000, 2, 4221.
3
(4) Kamiya, N.; Chikami, Y.; Ishii, Y. Synlett 1990, 675. See also: Takai,
K.; Sakogawa, K.; Kataoka, Y.; Oshima, K.; Utimoto, K. Org. Synth. 1995,
72, 180.
(5) For representative examples, see: Rowley, M.; Tsukamoto, M.; Kishi,
Y. J. Am. Chem. Soc. 1989, 111, 2735. MacMillan, D. W. C.; Overman, L.
E. J. Am. Chem. Soc. 1995, 117, 10391. Taylor, R. E.; Chen, Y. Org. Lett.
2001, 3, 2221.
(6) Hanson, J. R.; Premuzic, E. Angew. Chem., Int. Ed. Engl. 1968, 7,
247. (b) Espenson, J. H. Acc. Chem. Res. 1992, 25, 222. (c) Wessjohann,
L. A. Synthesis 1999, 1.
(7) Kauffmann, T.; Abeln, R.; Wingberm u¨ hle, D. Angew. Chem., Int.
Ed. Engl. 1984, 23, 729.
(
1) For representative examples using hydrozirconation, see: (a) Maeta,
H.; Hashimoto, T.; Hasegawa, T.; Suzuki, K. Tetrahedron Lett. 1992, 33,
965. (b) Wipf, P.; Xu, W. Tetrahedron Lett. 1994, 35, 5197.
2) The reactivity of the alkenylboron and -aluminum species toward
5
(
carbonyl compounds is low even when they are converted to the corre-
sponding ate complexes. Thus, the alkenylboron and -aluminum species
are usually converted to the corresponding halides with electrophilic sources
of halides (iodine or N-bromosuccinimide), and metalated. (a) Brown, H.
C.; Bowman, D. H.; Misumi, S.; Unni, M. K. J. Am. Chem. Soc. 1967, 89,
4
531. (b) Zweifel, G.; Whitney, C. C. J. Am. Chem. Soc. 1967, 89, 2753.
1
0.1021/ol0272996 CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/04/2003

Table 1. Coupling Reactions between Terminal Alkynes and Aldehydesa
a
b
Reaction was conducted on a 1.0-mmol scale. See typical procedure. 3 mol of an alkyne, 6 mol of CrCl2, 0.3 mol of NiCl2, 0.6 mol of PPh3, and 6
c
d
mol of water were used per mole of aldehyde. E/Z ) 98/2. 3 mol of water was used per mole of aldehyde.
but in some cases it acts formally as a hydride anion or a
hydrogen radical source by reaction with low-valent metals.
markedly.11 In addition, the yield was improved by slow
9
addition of a mixture of the alkyne and water to a mixture
of the aldehyde, chromium(II) chloride, nickel(II) chloride,
and triphenylphosphine in DMF. For example, when a
mixture of 4-phenyl-1-butyne (2 equiv) and water (2 equiv)
in DMF was added at 25 °C over a period of 2 h to a mixture
of nonanal (1 equiv), chromium(II) chloride (4 equiv), nickel-
(II) chloride (0.2 equiv), and triphenylphosphine (0.4 equiv)
in DMF, a mixture of the two allylic alcohols was obtained
in 78% yield (4/5 ) 91/9, Scheme 2). The 2-alkyl-substituted
allylic alcohol 4 was produced selectively. Although the
addition of water to the mixture was indispensable for the
reaction, the yield of allylic alcohols decreased when an
excess amount (16 equiv) of water was added.
Therefore, we examined the addition of a small amount of
water to a mixture of an alkyne, chromium(II) chloride, and
a catalytic amount of nickel(II) chloride in the presence of
1
0
an aldehyde to generate an alkenylchromium species by
formal hydrochromation of an alkyne.
To a stirred solution of chromium(II) chloride (4 equiv)
and a catalytic amount of nickel(II) chloride (0.2 equiv) in
DMF was added a solution of 4-phenyl-1-butyne (2 equiv)
and nonanal (1 equiv) at 25 °C. A 1 M solution of water (2
equiv) in DMF was added slowly to the mixture at 25 °C,
and the mixture was stirred at the same temperature for 6 h.
Most of the alkyne and the aldehyde were recovered;
however, the two desired allylic alcohols, 2-(2-phenylethyl)-
The results obtained with several kinds of alkynes and
aldehydes are summarized in Table 1. Cyclotrimerization of
1-undecen-3-ol (4) and (E)-1-phenyl-3-tridecen-5-ol (5), were
detected after hydrolysis, though the combined yield was less
than 3%. During the reaction, a deposition of nickel(0) was
observed. Therefore, phosphine ligands were added to the
mixture to prevent this deposition. Among those examined,
triphenylphosphine was found to accelerate the reaction
Scheme 2
(8) Takai, K.; Toratsu, C. J. Org. Chem. 1998, 63, 6450. See also a review
on water-accelerated organic transformations: Ribe, S.; Wipf, P. Chem.
Commun. 2001, 299.
(
9) (a) Tolman, C. A. J. Am. Chem. Soc. 1970, 92, 6777. (b) Trost, B.
M. Chem. Eur. J. 1998, 2405.
10) (a) Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.;
(
Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048. (b) Jin, H.; Uenishi, J.-i.;
Christ, W. J.; Kishi, Y. J. Am. Chem. Soc. 1986, 108, 5644. (c) Hodgson,
D. M.; Wells, C. Tetrahedron Lett. 1994, 35, 1601.
654
Org. Lett., Vol. 5, No. 5, 2003

Scheme 3
Scheme 4
the alkynes was observed as a side reaction, thus, 2-3 equiv
of the alkyne was employed to obtain good yields. 2-Sub-
stituted allylic alcohols were obtained in a selective manner
except in the case of phenyl acetylene (entry 5). An internal
alkyne, 6-dodecyne, also reacted with an aldehyde to give
the corresponding allylic alcohols in 60% yield though the
reaction proceeded slowly (entry 6). The alcohol 6 was
produced almost exclusively, and the stereochemistry of the
double bond of 6 proved to be the E configuration. Since
the coupling reaction is insensitive to a proton source,
carbon-carbon bond formation could be accomplished
without protecting the hydroxyl group (entry 7). In this case,
one regioisomer 7 was produced exclusively, probably due
to the coordination of the hydroxyl group to the nickel. A
typical feature of the nucleophilic addition of organochro-
There are two possibilities for the formation of the
alkenylnickel species 8 from terminal alkynes (Scheme 4).
In path A, a terminal alkyne coordinates to nickel(0)
generated by the reduction of nickel(II) with 2 equiv of
chromium(II), and a nickel-alkyne complex 10 is produced.
A reaction of the complex 10 with water gives the alk-
1
3
enylnickel species 8, which transmetalates to yield the
alkenylchromium reagent 9. In path B, nickel(0) reacts
immediately with water to give a nickel-hydride species.9
Addition of the nickel-hydride species to the terminal alkyne
9
a
gives the alkenylnickel species 8.
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research on Priority Areas from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy of Japan and by the Nagase Science and Technology
Foundation.
mium reagents is their selective addition to aldehydes prior
to ketone carbonyl groups.6
c,12
This was also observed in
the reaction with a keto aldehyde (entry 8).
Similar to the reported alkenylchromium reagents (Scheme
10
3
), we assume that the alkenylchromium reagent 9 reported
Supporting Information Available: General experimen-
tal procedure and characterization data for all compounds
in Table 1. This material is available free of charge via the
Internet at http://pubs.acs.org.
here is generated by transmetalation from the alkenylnickel
species 8.
(
11) Effects of additives on the yields and regioselectivities of the
reactions between 4-phenyl-1-butyne and nonanal are as follows: PBu3,
4% (4/5 ) 0/100); P(o-tolyl)3, 16% (64/36); P(2-franyl)3, 18% (78/22);
P[3,5-(CF3)2C6H3]3, 30% (90/10); P[2,6-(MeO)2C6H3]3, <5%.
12) Takai, K.; Utimoto, K. J. Synth. Org. Chem., Jpn. 1988, 46, 66.
F u¨ rstner, A. Chem. ReV. 1999, 99, 991.
1
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(
(13) Bennett, M. A.; Castro, J.; Edwards, A. J.; Kopp, M. R.; Wenger,
E.; Willis, A. C. Organometallics 2001, 20, 980.
Org. Lett., Vol. 5, No. 5, 2003
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