carbon bearing the hydroxy group (J = 4.6 and 11.0 Hz) of the
tetrahydropyranol 4a indicated a structure where the hydroxy
and the phenyl groups are in a cis relationship and are equatorial
(
J = 2.2, 11.3Hz) (J = 4.6, 11.0 Hz)
H
H
(
Fig. 1). The formation of other stereoisomers is negligible as
Ph
OH
Fig. 1 Coupling constants in 4a.
1
shown by the H NMR measurement of the crude reaction
mixture. A variety of other aromatic aldehydes reacted similarly
generating the corresponding products (Table 1) in good
isolated (overall) yields. Aliphatic aldehydes were less effective
for the reactions. Other solvents that we have tested (such as
O
corresponding tetrahydropyran derivatives. Subsequently, by
controlling the reaction conditions, we have developed an
efficient synthesis of 4-chlorotetrahydropyrans 3 mediated by
CH
as CHCl
2
Cl
2
, hexane, toluene,THF and Et
2
O) were not as effective
3
for the reaction. The catalytic cycle of this Prins-type
5
indium trichloride [Scheme 1, route (a)]. We also conceived
reaction is postulated in Scheme 2. A similar mechanism has
been used to explain a cross-allylation of aldehydes by Nokami
and co-workers very recently. In conclusion, we have devel-
that if we replaced the chloride ion with a non-nucleophilic
anion, then the tetrahydropyranol 4 or its ether 5 would become
the major products [route (b)]. However, to do so we would
need a Lewis acid to facilitate the Prins reaction. It appears that
the scandium triflate chemistry developed by Kobayashi and
8
3
oped an effective Sc(OTf) -catalyzed Prins-type reaction to
form tetrahydropyranols and related ether derivatives. The
conditions for the catalyzed reaction are much milder than the
classical Prins reaction using strong acids. Presently, we are
evaluating a range of synthetic potentials of this catalyzed
reaction.
We are grateful to US NSF-EPA, LEQSF and the NSF Early
CAREER Award program for partial support of this research.
6
others would be the best choice for this reaction. Here, we
report that the reaction of aldehydes with homoallyl alcohols
catalyzed by scandium triflate generates the corresponding
desired products readily (Scheme 1).7
When a mixture of benzaldehyde and but-3-en-1-ol was
stirred with Sc(OTf) in CHCl under a refluxing temperature
3 3
overnight, 63% of a tetrahydropyran ether 5a was isolated
together with 14% of the corresponding tetrahydropyranol 4a.†
Measurement of the coupling constants of the benzylic
hydrogen (J = 2.2 and 11.3 Hz) as well as the hydrogen on the
Notes and references
† Typical experimental procedure: A mixture of 1 (2 mmol), but-3-en-1-ol
3
2 (4 mmol) and scandium triflate (5 mol%) was mixed in CHCl (5 ml). The
reaction mixture was refluxed under nitrogen overnight. After concentrated
in vacuo, the crude reaction mixture was subjected to column chromatog-
raphy on silica gel eluting with hexane–EtOAc (gradient eluent: 27:1 to
OH
3
:1) to yield products 4 and 5.
1
For reviews, see: E. Arundale and L. A. Mikeska, Chem. Rev., 1952, 51,
5
05; D. R. Adams and S. P. Bhatnagar, Synthesis, 1977, 661.
2
3
K. C. Nicolaou and E. J. Sorensen, Classics in Total Synthesis, VCH,
Weinheim, 1996.
The best known method in this regard is probably the hetero-Diels–Alder
reaction with Danishefsky’s diene; for examples, see: S. J. Danishefsky,
W. H. Pearson and D. F. Harvey, J. Am. Chem. Soc., 1984, 106, 2456;
S. J. Danishefsky and C. J. Maring, J. Am. Chem. Soc., 1989, 111,
OSc(OTf)2
OH
O
Sc(OTf)3
–HOTf
R
H
R
O
2
193.
X. H. Yi, J. X. Haberman and C. J. Li, Synth. Commun., 1998, 28,
999.
J.Yang, G. S. Viswanathan and C. J. Li, Tetrahedron Lett., in the press.
Such compounds were also accessible through TiCl and AlCl catalyzed
4
5
2
HOTf
OSc(OTf)2
4
3
allylsilane reactions of aldehydes and cross2coupling between homo-
allyl alcohols and aldehydes, however, when both substituents are
aromatic, the reaction provided no or a low yield of the product, see: Z. Y.
Wei, J. S. Li, D.Wang and T. H. Chan, Tetrahedron Lett., 1987, 28, 3441;
F. Perron and K. F. Albizati, J. Org. Chem., 1987, 52, 4130; Z. Y. Wei,
D. Wang, J. S. Li and T. H. Chan, J. Org. Chem., 1989, 54, 5768; L.
Coppi, A. Ricci and M. Taddei, J. Org. Chem., 1988, 53, 913. Very
(
OTf)2ScO
R
O
R
O
+
4
recently, Rychnovsky and co-workers reported an interesting SnBr -
mediated segment-coupling Prins cyclization, see: S. D. Rychnovsky, Y.
Hu and B. Ellsworth, Tetrahedron Lett., 1998, 39, 7271.
For a leading reference, see: S. Kobayashi and I. Hachiya, J. Org. Chem.,
+ [ScO(OTf)2]–
+
OH
6
7
R
O
R
O
1
6
994, 59, 3590; For a related review, see: S. Kobayashi, Synlett, 1994,
89.
1
All products have been fully characterized and produced satisfactory H
and 13C NMR, IR and elemental analysis results. For a Yb(OTf)
O
O
3
catalyzed allylation of aldehydes with allylsilane to generate homoallyl
alcohols, see: Y. Yang, M. Wang and D. Wang, Chem. Commun., 1997,
1
651.
J. Nokami, K. Yoshizane, H. Matsuura and S. Sumida, J. Am. Chem. Soc.,
998, 120, 6609.
8
R
1
3
Scheme 2 Proposed mechanism for the Sc(OTf) catalyzed tetrahydropyran
formations.
Communication 8/08960D
292
Chem. Commun., 1999, 291–292
Zhang, Wen-Chun
