CHART 1. Alk yn es, Keton es, Ald eh yd es, a n d Ba se
Ca ta lytic Alk yn yla tion of Keton es a n d
Ald eh yd es Usin g Qu a ter n a r y Am m on iu m
Hyd r oxid e Ba se
Teruhiko Ishikawa,*,† Tomohiro Mizuta,‡
Kumiko Hagiwara,‡ Toshiaki Aikawa,‡
Takayuki Kudo,‡ and Seiki Saito*,‡
Department of Bioscience and Biotechnology,
School of Engineering, and Department of Chemistry,
School of Education, Okayama University, Tsushima,
Okayama, 700-8530, J apan
seisaito@biotech.okayama-u.ac.jp
Received October 22, 2002
Abstr a ct: Catalytic alkynylation of diverse ketones and
aldehydes using nonmetallic benzyltrimethylammonium
hydroxide or a basic resin of the hydroxide type in DMSO is
described. Aliphatic or alicyclic carbonyl partners gave
satisfactory results, whereas aromatic ones afforded products
with low yields. When aromatic aldehydes were reacted with
phenylacetylene, enones such as chalcone derivatives were
obtained in place of ynols. These organobase-catalyzed
systems provide a practical nonmetallic protocol for C-C
bond formation.
aldehydes or ketones and aromatic carbonyl compounds,
is highly desirable.
In our continuing interest in the development of
practical methods for C-C bond formation,6 we have
investigated catalytic alkynylation using a nonmetallic
ammonium acetylide anion.7 Since no effort has been
made toward examining the potential of such a cabanion
in a catalytic alkynylation process so far, we hoped that
there still remains a possibility for the nonmetallic
acetylide anion of this class to become a more tolerable
alkynylide. In this report, we describe the catalytic
alkynylation of diverse ketones and aldehydes (2) with
a variety of alkynes (1) using commercially available
benzyltrimethylammonium hydroxide (3) as a base (eq
1 and Chart 1). This provided a promising nonmetallic
protocol for alkynylation in a practical sense. Some
interesting transformations from phenylacetylene (1a )
and aromatic aldehydes to chalcone derivatives under the
given reaction conditions are also presented.
Propargylic alcohols are well-known as versatile build-
ing blocks in organic synthesis. Their traditional syn-
thesis through alkynylation of ketones and aldehydes
using a stoichiometric amount of bases such as Grignard
reagents or alkyllithiums has recently been replaced with
a catalytic system. Babler,1 Knochel,2 Carreira,3 Pu,4 and
Chan5 have made a significant contribution to this
important achievement in organic synthesis. They used
alkynylides containing potassium,1 cesium,2 or zinc3-5
playing a key role as a nucleophile in C-C bond forma-
tion. However, t-BuOK-catalyzed alkynylation of enoliz-
able aldehydes led to a complex mixture of products.1 A
CsOH-catalyzed system gave a solution to this problem
by means of a syringe pump technique but did not effect
alkynylation of aromatic carbonyl compounds.2 On the
other hand, zinc alkynylides are required for asymmetric
alkynylation in combination with appropriate chiral
ligands to result in a high level of enantiocontrol, but only
aldehydes were employed as an electrophile in these
cases.3-5 Therefore, a more general alkynylide with a
higher tolerance for substrates, including both enolizable
Catalytic alkynylation reactions between alkynes (1a -
e) and carbonyl compounds (2a -n ) were examined by
employing method A or B. A typical experimental pro-
cedure for method A is as follows. To a solution of 1 (5.0
mmol) and 2 (1.2 equiv) in DMSO (2.5 mL) was added a
solution of 3 (10 mol %) in DMSO (2.5 mL) over 10 min
at room temperature. The reaction was stirred until the
* To whom correspondence should be addressed. Phone (Fax): +81-
86-251-8209.
(6) Ishikawa, T.; Kadoya, R.; Arai, M.; Takahashi, H.; Kaisi, Y.;
Mizuta, T.; Yoshikai, K.; Saito, S. J . Org. Chem. 2001, 66, 8000-8009.
(7) For quaternary ammonium hydroxide-catalyzed reactions, see:
(a) O’Donnell, M. J .; Bennett, W. D.; Wu, S. J . Am. Chem. Soc. 1989,
111, 2353-2355. (b) Arai, S.; Shirai, Y. Ishida, T.; Shioiri, T. Chem.
Commun. 1999, 49-50. (c) Corey, E. J .; Bo, Y.; Petersen, J . B. J . Am.
Chem. Soc. 1998, 120, 13000-13001. (d) Ooi, T.; Takeuchi, M.;
Kameda, M.; Maruoka, K. J . Am. Chem. Soc. 2000, 122, 5228-5229.
For other nonmetal organo-catalytic processes, see: (e) Hajos, Z. G.;
Parrish, D. R. J . Org. Chem. 1974, 39, 1615-1621. (f) List, B.; Lerner,
R. A.; Barbas, C. F., III. J . Am. Chem. Soc. 2000, 122, 2395-2396. (g)
Paras, N. A.; MacMillan, D. W. C. J . Am. Chem. Soc. 2001, 123, 4370-
4371.
† Department of Chemistry, School of Education.
‡ Department of Bioscience and Biotechnology, School of Engineer-
ing.
(1) Babler, J . H.; Liptak, V. P.; Phan, N. J . Org. Chem. 1996, 61,
416-417.
(2) Tzalis, D.; Knochel, P. Angew. Chem., Int. Ed. 1999, 38, 1463-
1465.
(3) Anand, N. K.; Carreira, E. M. J . Am. Chem. Soc. 2001, 123,
9687-9688.
(4) Moor, D.; Pu, Lin. Org. Lett. 2002, 4, 1855-1857.
(5) Li, X.; Lu, G.; Kwok, W. H.; Chan, A. S. C. J . Am. Chem. Soc.
2002, 124, 12636-12637.
10.1021/jo026592g CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/04/2003
3702
J . Org. Chem. 2003, 68, 3702-3705