Substitution of hydroxyl groups with alkynyl moieties using alkynylboron dihalides: An efficient approach to secondary alkylacetylene derivatives

Article abstract of DOI:10.1021/ol052957i

The reaction of alkynylboron dihalides with benzylic, allylic, and propargylic alcohols provides an efficient route to internal acetylenes. Isomerization of the product alkynes does not occur under the reaction conditions.

Full text of DOI:10.1021/ol052957i

ORGANIC
LETTERS
2006
Vol. 8, No. 5
879-881
Substitution of Hydroxyl Groups with
Alkynyl Moieties Using Alkynylboron
Dihalides: An Efficient Approach to
Secondary Alkylacetylene Derivatives
George W. Kabalka,* Min-Liang Yao, and Scott Borella
Departments of Chemistry and Radiology, The UniVersity of Tennessee, KnoxVille,
Tennessee 37996-1600
kabalka@utk.edu
Received December 6, 2005
ABSTRACT
The reaction of alkynylboron dihalides with benzylic, allylic, and propargylic alcohols provides an efficient route to internal acetylenes.
Isomerization of the product alkynes does not occur under the reaction conditions.
Alkynes are important building blocks in materials science1
and organic synthesis.2 They are also a common structural
unit in natural products and drugs.3 Among the synthetic
approaches to internal alkynes, the palladium-catalyzed
Sonogashira cross-coupling reaction between terminal alkynes
and aryl/alkenyl halides is widely utilized.4 Recent modifica-
tions include the use of more efficient palladium catalysts5
and more active alkynylmetal coupling partners (e.g., Sn,6
Zn,7 Mg,8 Al,9 and B10). However, the palladium-catalyzed
alkynylation of allylic, benzylic, and propargylic electrophiles
(4) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
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* To whom all correspondence should be addressed. Phone: (865) 974-
2160. Fax: (865) 974-2297.
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M.; Meijer, E. M. Chem. Eur. J. 2003, 9, 5597. (d) Collings, J. C.; Parsons,
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10.1021/ol052957i CCC: $33.50
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has not been well developed;11 only a few examples have
appeared in the literature.7a,12 As a result, preparations of
secondary alkylacetylene derivatives still rely on traditional
methods such as substitution reactions of secondary halides
or elimination reactions involving 1,2-dihalides.13 Since these
reactions often require the use of strong bases or high
temperatures, in most cases the desired products are con-
taminated by allene byproducts that are difficult to remove.14
Therefore, an alternative route to these important reagents
would be desirable.
Scheme 2. Preparation of 1,3,3-Triphenyl-1-propyne
Fortunately, the reaction proceeded smoothly using alky-
nylboron dichloride 1a in the presence of n-BuLi at room
temperature.19 The desired product 3a was isolated in 68%
yield. The NMR resonances observed at 90.2 and 84.9 ppm
in the 13C NMR spectrum clearly demonstrate the existence
Our research has focused on the chemistry of boron halide
derivatives for many years, and several novel reactions have
been developed.15 Very recently, we reported the substitution
of hydroxyl groups with alkenyl moieties using alkenylboron
dihalides.16 The particularly appealing features of this novel
reaction are the mild reaction conditions and the absence of
1
of the alkynyl group. In the H NMR, a resonance at 5.19
ppm (singlet) was observed. To evaluate the scope and
limitations of the new reaction, alcohols 2a-j were prepared
a transition metal. A mechanistic study revealed that the
2
reaction involves a migration of the halovinyl group (Csp
)
Table 1. Coupling of Alkynylboron Dichloride 1 with 2a
from boron to the carbon attached to oxygen. Encouraged
by these results, we postulated that an alkynyl group (Csp)
migration from boron to carbon might also occur. This would
provide a novel route to secondary alkylacetylene derivatives
from readily available alcohols. In this paper, we describe
the results of our study.
Unlike alkenylboron dihalides, the chemistry of alkynyl-
boron dihalides has not drawn much attention. Only one
method is currently available to generate alkynylboron
dihalides based on the boron-tin exchange reaction of boron
halides with alkynylstannanes at -78 °C.17 Considering the
toxicity of tin compounds, we examined the possibility of
generating alkynylboron dihalides by the sequential in situ
treatment of terminal alkynes with n-BuLi followed by boron
trichloride at 0 °C (Scheme 1).18 Using this procedure, both
Scheme 1. Preparation of Alkynylboron Dihalides
aryl and aliphatic alkynes can be converted to the corre-
sponding alkynylboron dihalides 1a-e.
Due to its ready availability, diphenylmethanol, 2a, was
chosen as a model substrate to investigate alkynyl group
migration (Scheme 2).
(11) (a) Negishi, E.-i.; Anastasia, L. Chem. ReV. 2003, 103, 1979.
(12) (a) Pe´rez, I.; Sestelo, J. P.; Sarandeses, L. A. J. Am. Chem. Soc.
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1999, 1, 1267.
(13) (a) Brandsma, L. PreparatiVe Acetylenic Chemistry; Elsevier: New
York, 1988. (b) Nicholas, K. M.; Siegel, J. J. Am. Chem. Soc. 1985, 107,
4999. (c) Marcuzzi, F.; Modena, G.; Melloni, G. J. Org. Chem. 1982, 47,
4577.
a Reaction carried out at room temperature on a 1.5 mmol scale in dry
methylene chloride (for the detailed procedure, see ref 19). b Yield of
isolated product based on the alkynylboron dichloride (alkyne).
(14) (a) March’s AdVanced Organic Chemistry: Reactions, Mechanism,
and Structure, 5th ed.; Smith, M. B., March, J., Eds.; Wiley Interscience:
New York, 2001. (b) Ma, S.; He, Q.; Zhang, X. J. Org. Chem. 2005, 70,
3336. (c) Enomoto, M.; Katsuki, T.; Yamaguchi, M. Tetrahedron Lett. 1986,
27, 4599.
and subjected to the reaction conditions (Table 1). The
reactions proceeded smoothly with benzylic, allylic, and
880
Org. Lett., Vol. 8, No. 5, 2006

propargylic alcohols and produced the desired products in
good to high yields. Although alkynylation of benzylic
halides has been reported,7a,11 alkynylation of benzylic
alcohols had not yet been achieved. The successful alkynyl-
ation of allylic and propargylic alcohols provides a new route
to 1,4-enynes 3l-n and 1,4-diynes 3o-r which are suitable
for further elaboration.
Scheme 3. A Tandem Reaction to Internal Alkynes
In recent years, much effort has been devoted to tandem
reactions due to their potential utility in converting simple
starting materials into relatively complex molecules in a rapid
and efficient manner.20 Therefore, the in situ generation of
benzylic alkoxides from aryl aldehydes followed by treatment
with an alkynylboron dihalide was also examined (Scheme
3). The reaction is quite efficient and produces the anticipated
products in good yield.
In summary, we report a novel method for generating
alkynylboron dichlorides and their subsequent reaction with
secondary alcohols. The migration of the alkynyl group from
boron to carbon occurs under very mild reaction conditions.
The reaction provides an alternative route to secondary
alkylacetylene derivatives from readily available secondary
alcohols (the precursor of the alkoxides) and alkynes. The
new procedure obviates the difficulties associated with the
Pd-catalyzed alkynylation syntheses. Notably, the method
successfully overcomes the isomerizations that often occur
in the preparation of internal alkynes.
(15) (a) Kabalka, G. W.; Wu, Z.; Trotman, S. E.; Gao, X. Org. Lett.
2000, 2, 255. (b) Kabalka, G. W.; Wu, Z. Tetrahedron Lett. 2000, 41, 579.
(c) Kabalka, G. W.; Wu, Z.; Ju. Y. Tetrahedron Lett. 2001, 42, 5793. (d)
Kabalka, G. W.; Wu, Z.; Ju. Y. Org. Lett. 2002, 4, 1491. (e) Kabalka, G.
W.; Wu, Z.; Ju. Y. J. Organomet. Chem. 2003, 680 (1-2), 12.
(16) (a) Kabalka, G. W.; Yao, M.-L.; Borella, S.; Wu, Z.-Z. Org. Lett.
2005, 7, 2865. (b) Kabalka, G. W.; Yao, M.-L.; Borella, S.; Wu, Z.-Z. Chem.
Commun. 2005, 2492. (c) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2004,
6, 3929.
Acknowledgment. We thank the U.S. Department of
Energy and the Robert H. Cole Foundation for support of
this research. Acknowledgment is made to the donors of the
Petroleum Research Fund for support of this research.
(17) Leung, S.-W.; Singleton, D. A. J. Org. Chem. 1997, 62, 1955.
(18) A similar procedure to alkynylzinic derivatives has been reported
by Negishi. See ref 7b.
(19) Typical Experimental Procedure. A solution of alkyne (1.5 mmol)
in dry hexane (8 mL) was treated with n-butyllithium (1.0 mL of a 1.6 M
solution in hexane) at 0 °C. After the reaction mixture was stirred at room
temperature for 30 min, boron trihalide (1.5 mmol) was added. In a separate
flask, the benzylic alcohol (1.6 mmol) in dry dichloromethane (8 mL) was
treated with n-butyllithium (1.0 mL of a 1.6 M solution in hexane) at 0 °C
and warmed to room temperature. After being stirred at room temperature
for 30 min, this solution was transferred to the first flask and the mixture
was allowed to stir overnight. Water (20 mL) was added to quench the
reaction. The mixture was extracted with ethyl acetate and dried over
anhydrous MgSO4. The solvent was removed in vacuo and the product
purified by silica gel column chromatography using hexane as an eluent to
provide 3a in 68% yield.
Supporting Information Available: Experimental pro-
cedures for synthesis and full characterization for compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL052957I
(20) (a) Tietze, L. F. Chem. ReV. 1996, 96, 115. (b) Parsons, P. J.; Penkett,
C. S.; Shell, A. J. Chem. ReV. 1996, 96, 195.
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