J. Am. Chem. Soc. 2000, 122, 4817-4818
Chelation Control through the Coordination of Lewis
4817
Acids to an Acetylenic π-Bond
Naoki Asao, Toru Asano, Takeshi Ohishi, and
Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science
Tohoku UniVersity, Sendai 980-8578, Japan
ReceiVed NoVember 15, 1999
The Lewis acid-mediated chelation control is one of the most
fundamental and practically important concepts in modern organic
chemistry. It is well accepted that the chelating controlled reaction
are summarized in Table 1. High chemoselectivity was observed
in the Bu SnH reduction of 1a and 3a with GaCl ; 4a was obtained
3 3
in 63% yield along with the recovered 1a (32% yield), and 5a
1
proceeds through the coordination of a Lewis acid to a lone pair
of heteroatoms, such as an oxygen of aldehydes and a nitrogen
atom of imines. To the best of our knowledge, there is no
precedent for a synthetically useful level of the chelation-
controlled reaction which proceeds via the coordination of Lewis
was obtained only in 2% yield along with the recovered 3a (92%)
3
(entry 1). Utilization of Ph
3
SnH instead of Bu
3
SnH elevated the
selectivity up to 43:1 (entry 2). The reactions promoted by
aluminum Lewis acids also tended to afford 4a as a major product
though the selectivities were lower than those of the GaCl
3
2
4
acids to π-electrons of C-C multiple bonds. We wish to report
mediated reactions (entries 3-7). The selective reductions were
also observed with the starting materials having other alkynyl
groups (entries 8-12). In all the above reactions, the material
balance of substrates was high; large amounts of 3 (98∼60%)
were recovered, and small amounts (38∼8%) of 1 was recovered
in the case where the yields of 4 were not necessary high (for
example, entries 3-11). Accordingly, the selective activation of
the first example for the regio- and chemoselective reactions which
are most probably controlled by the chelation to π-electrons of
alkynes (eq 1).
1
is ascribed most probably to the preferred formation of the
bidentate chelation 6 rather than the monodentate coordination
5-8
7.
However, all of the reactivity data might be explained by a
strong electron-withdrawing effect of the alkyne: the ortho-isomer
(
3) It was difficult to obtain the product ratio at lower conversion, since
The reaction of a 1:1 mixture of 1a (1 equiv) and 2 (1 equiv)
the reduction was very rapid. Accordingly, the reduction using smaller amounts
3
of Bu SnH (0.2 and 0.4 equiv) was carried out. The ratios of 4a/5a, determined
with Bu
Cl at -78 °C gave 4a in 73% yield along with the 2-(phenyl-
3 3 2
SnH (1 equiv) in the presence of GaCl (1 equiv) in CH -
both by NMR and by GC analysis, were essentially identical with those shown
in entry 1.
2
ethyl)benzyl alcohol in 19%. The remarkable chemoselectivity
suggested that the bidentate chelation between the carbonyl
oxygen and alkyne of 1a, as shown in eq 1, would enhance the
reactivity of the aldehyde of 1a in comparison with that of 2.
However, there is a possibility that the chemoselectivity is due
to the electronic effect of the alkyne group, since it is less sterically
demanding and more electron-withdrawing than the phenylethyl
group of 2. Accordingly, we next examined the reaction of an
(4) The BF
3 2
‚OEt -promoted reduction of a 1:1 mixture of 1a and 3a gave
a 62:38 mixture of 4a and 5a in 52% combined yield.
(
5) Several examples of aluminum pentacoordinate complexes have been
isolated and characterized, see: (a) Heitsch, C. W.; Nordman, C. E.; Parry,
P. W. Inorg. Chem. 1963, 2, 508. (b) Palenick, G. Acta Crystallogr. 1964,
1
2
7, 1573-1580. (c) Beattie, I. R.; Ozin, G. A. J. Chem. Soc. A 1968, 2373-
377. (d) von Vliet, M. R. P.; Buysingh, P.; von Koten, G.; Vrieze, K.; Kojic-
Prodic, B.; Spek, A. L. Organometallics 1985, 4, 1701-1707. (e) Bennett, F.
R.; Elms, F. M.; Gardiner, M. G.; Koutsantonis, G. A.; Raston, C. L.; Roberts,
N. K. Organometallics 1992, 11, 1457-1459. (f) Muller, G.; Lachmann, J.;
Rufinska, A. Organometallics 1992, 11, 2970-2972. (g) Fryzuk, M. D.;
Giesbrecht, G. R.; Olovsson, G.; Rettig, S. J. Organometallics 1996, 15, 4832-
4841.
3
equimolar mixture of 1 and its para-isomer 3 with Bu SnH (1
equiv) in the presence of Lewis acids (1 equiv). It was thought
that the electronic effect of the alkyne groups upon the aldehyde
group of 1 would be nearly equal to that of 3 and sterically the
aldehyde of 1 is more crowded than that of 3 (eq 2). The results
(6) Aluminum and gallium Lewis acids are known to act as bidntate Lewis
acids. For aluminum Lewis acid, see: (a) Maruoka, K.; Ooi, T. Chem. Eur.
J. 1999, 5, 829-833. (b) Ooi, T.; Kagoshima, N.; Ichikawa, H.; Maruoka, K.
J. Am. Chem. Soc. 1999, 121, 3328-3333. (c) Evans, D. A.; Allison, B. D.;
Yang, M. G. Tetrahedron Lett. 1999, 40, 4457-4460. (d) Evans, D. A.;
Chapman, K. T.; Bisaha, J. J. Am. Chem. Soc. 1988, 110, 1238-1256. For
gallium Lewis acid, see: (e) Ooi, T.; Morikawa, J.; Ichikawa, H.; Maruoka,
K. Tetrahedron Lett. 1999, 40, 5881-5884.
(1) For reviews, see: (a) Yamamoto, H. Lewis Acid Chemistry: A Practical
Approach; Oxford University Press: Oxford, 1999. (b) Mahrwald, R. Chem.
ReV. 1999, 99, 1095-1120. (c) Santelli, M.; Pons, J. M. Lewis Acids and
SelectiVity in Organic Synthesis; CRC Press: Boca Raton, 1996. (d)
Shambayati, S.; Schreiber, S. L. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming I., Eds.; Pergamon Press: Oxford, 1991; Vol. 1, pp 283-
(7) The hypercoodinated aluminum Lewis acids have been used for
asymmetric reactions; see: (a) Heller, D. P.; Goldberg, D. R.; Wulff, W. D.
J. Am. Chem. Soc. 1997, 119, 10551-10552. (b) Murakata, M.; Jono, T.;
Mizuno, Y.; Hoshino, O. J. Am. Chem. Soc. 1997, 119, 11713-11714. (c)
Arai, T.; Sasai, H.; Yamaguchi, K.; Shibasaki, M. J. Am. Chem. Soc. 1998,
120, 441-442.
3
24.
2) The Lewis basicity of the lone pair of imine’s nitrogen and aldehyde’s
(
oxygen atom is, in general, stronger than that of the π-electron of C-C double
and triple bonds. Accordingly it is reasonable that all the previous examples
for the synthetically useful chelation controlled reactions are concerning the
coordination to lone pair electrons. The interaction of alkynes with Lewis
acids was studied by NMR and IR spectroscopy, see: (a) Hogeveen, H.; Kok,
D. M. Tetrahedron Lett. 1980, 21, 659-662. (b) Perkampus, H. H.; Weiss,
W. Z. Naturforsch. 1974, 29b, 61-64.
3
(8) Recently, the GaCl -mediated carbogallation of alkynes was reported,
see: (a) Yamaguchi, M.; Tsukagoshi, T.; Arisawa, M. J. Am. Chem. Soc.
1999, 121, 4074-4075. (b) Yamaguchi, M.; Sotokawa, T.; Hirama, M. J.
Chem. Soc., Chem. Commun. 1997, 743-744. (c) Yamaguchi, M.; Kido, Y.;
Hayashi, A.; Hirama, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 1313-1315.
(d) Yamaguchi, M.; Hayashi, A.; Hirama, M. Chem. Lett. 1995, 1093-1094.
1
0.1021/ja994000e CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/29/2000