Diastereoselective synthesis of 2,4-disubstituted tetrahydropyranols and ethers via a prins-type cyclization catalyzed by scandium triflate

Article abstract of DOI:10.1016/S0040-4020(00)00152-6

The reaction of aldehydes with homoallylic alcohols catalyzed by scandium triflate gives rise to the formation of 2-substituted tetrahydropyran-4-ols and ethers in good overall yields and with 'all-cis' configurations and high diastereoselectivities. The

Full text of DOI:10.1016/S0040-4020(00)00152-6

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2403–2411
Diastereoselective Synthesis of 2,4-Disubstituted
Tetrahydropyranols and Ethers via a Prins-Type Cyclization
Catalyzed by Scandium Triflate
*
Wen-Chun Zhang and Chao-Jun Li
Department of Chemistry, Tulane University, New Orleans, LA 70118, USA
Received 14 September 1999; accepted 15 February 2000
Abstract—The reaction of aldehydes with homoallylic alcohols catalyzed by scandium triflate gives rise to the formation of 2-substituted
tetrahydropyran-4-ols and ethers in good overall yields and with ‘all-cis’ configurations and high diastereoselectivities. The stereo-
chemistries of these products were assigned with the assistance of coupling constants and NOE. Factors affecting the reaction have been
examined in detail. The reaction was found to be most effective in chloroform. Various aromatic and aliphatic aldehydes underwent the
cyclization smoothly. A catalytic cycle for this reaction has been proposed. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
2,6-disubstituted 4-halotetrahydropyrans. The mechanism
of this reaction was postulated as a cyclization of the hemi-
acetal formed by condensation of an intermediate homoallyl
alcohol derivative with a second molecule of an aldehyde,
mediated by the halogenated Lewis acid. Coppi and co-
workers found that an analogous condensation could be
achieved by directly mixing aldehydes and unsaturated
The condensation of olefins with aldehydes, known as the
Prins reaction, is a fundamental reaction for forming
1
carbon–carbon bonds. Under the classical conditions, the
reaction was carried out in the presence of strong acids (e.g.
sulfuric acid) and at high reaction temperatures, which often
generated a mixture of products. The importance of pyrans
is exemplified by its presence in the backbone of various
5b
alcohols at 0ЊC in the presence of a Lewis acid. Subse-
quently, several groups have extended the scope of this
2
6
carbohydrates and natural products. This prompts extensive
reaction for various synthetic needs. On the other hand,
3
studies in forming these pyran structural derivatives.
the formation of oxygenated, instead of halogenated, tetra-
hydropyran derivatives would often be more desirable
synthetically. During our recent investigation of indium-
Recently, the potential of Prins-cyclization in forming tetra-
hydropyran derivatives has been recognized. In the litera-
4
5
7
ture, Chan as well as Coppi reported that the coupling
between allylsilanes and aldehydes could be used to prepare
mediated reactions under neat conditions, we accidentally
observed the formation of tetrahydropyran-4-ol and
Scheme 1.
Keywords: scandium and compounds; cyclization; diastereoselection; pyrans.
*
Corresponding author. Tel.: ϩ1-504-865-5573; fax: ϩ1-504-865-5596; e-mail: cjli@mailhost.tcs.tulane.edu
0
040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00152-6

2
404
W.-C. Zhang, C.-J. Li / Tetrahedron 56 (2000) 2403–2411
Table 1. Tetrahydropyran derivatives via scandium triflate catalyzed Prins-
8
4
-bromo derivatives. To explain the formation of the tetra-
type cyclization
hydropyran derivatives, we postulated that the product was
generated through a tandem carbonyl allylation–hemiacetal
formation—Prins reaction (Scheme 1).
Entry
RCHO
Product 8 Product 9 Overall yield
(%)
(%)
(%)
Subsequently, by controlling the reaction conditions,
various 4-chlorotetrahydropyrans were synthesized via the
reaction of homoallylic alcohols and aldehydes with indium
1
2
8a (14)
9a (63)
9a (58)
77
70
a
8a (12)
8
trichloride as the Lewis acid. From these results, we
conceived that by replacing the chloride ion with a non-
nucleophilic anion, the synthetically more valuable tetra-
hydropyranol or its ether would become the major product.
Herein, we describe such a reaction catalyzed by scandium
8b (19)
9b (50)
69
3
4
8c (12)
8d (16)
9c (57)
9d (69)
69
85
9
10
triflate (Eq. (1)). Independent of our work, Nishizawa and
1
1
Overman et al. recently reported preliminary results on
related cyclizations.
5
8e (13)
9e (71)
84
ꢀ1†
6
7
8f (11)
8g (15)
9f (65)
9g (68)
76
83
8
9
8h (17)
8i (14)
9h (49)
9i (72)
66
86
Results and Discussion
In light of the proposed mechanism, a Lewis acid with a
non-nucleophilic counterion is apparently required to
facilitate this ‘Prins-like’ carbonyl addition reaction. For
this purpose, it would appear that scandium triflate is an
appropriate candidate for forming the desired oxygenated
derivatives. When a mixture of benzaldehyde and 3-buten-
-ol was stirred with a catalytic amount of scandium triflate
in chloroform under a refluxing temperature, the formation
of products was observed by TLC. To ensure the completion
of the reaction, the refluxing was kept overnight. After a
regular work-up, column chromatography of the crude
materials on silica gel provided 2-phenyl-4-hydroxytetra-
hydropyran (8a) and 2-phenyl-4-(3-butenoxy)tetrahydro-
pyran (9a) in 14 and 63% yields, respectively.
10
8j (20)
8k (13)
9j (58)
9k (62)
78
75
1
2
1
11
12
8l (18)
9l (64)
82
66
1
3
4
8m (10)
9m (56)
It appears that the use of scandium triflate is important for
the success of the reaction. In the absence of scandium
triflate, no reaction was observed. When indium triflate
was used as the catalyst, nearly the same results were
1
8n (9)
9n (70)
79
1
3
obtained. With Yb(OTf)3 as the Lewis acid, the yield of
desired products diminished considerably. The results of
this scandium triflate catalyzed Prins-type cyclization
between a variety of aromatic aldehydes and 3-buten-1-ol
are summarized in Table 1. The uses of different aromatic
and aliphatic aldehydes (after further investigation) did not
affect the reaction significantly. By using the same standard
15
8o (17)
8p (12)
9o (54)
9p (60)
71
72
1
6
7
reaction conditions (CH Cl, cat. Sc(OTf)3, reflux),
b
3
1
8q (13)
9q (73)
86
compounds 1a–1p all reacted to give nearly the same yields
of products 8a–8p (ca. 20%) and 9a–9p (ca. 60%).
Decreasing the amount of alcohol being used did not affect
the reaction significantly. When equal equivalents of
a
Indium triflate was used as the catalyst.
9q was a dihydropyran product.
b

W.-C. Zhang, C.-J. Li / Tetrahedron 56 (2000) 2403–2411
2405
in all the products were found cis-related in all cases, which
was mostly likely due to a thermodynamic control of the
reaction. The assignment of the stereochemistry was based
on the coupling constants of the protons at the C-2 and C-4
positions. A splitting value of ca. 11 Hz was found for all
such protons, indicating the presence of an axial–axial
coupling. The two substituents are therefore in the
equatorial positions, in agreement with the all-cis stereo-
Figure 1.
1
chemistry. The assignment was also confirmed by the H
benzaldehyde and homoallylic alcohol were used for the
reaction, the ratio of products is nearly the same as the
one obtained under the standard reaction conditions.
Interestingly, the reaction of p-nitrobenzaldehyde mainly
generated a dihydropyran product 9q (entry 17).
NMR chemical shift of the 4-hydrogens in the range of 3.9–
14
4.2 ppm, a typical value for axial protons. The stereo-
chemistry was also corroborated by Nucleus Overhauser
Experiments (NOE). NOE measurements were performed
15
at room temperature using the NOESY pulse sequence.
The ROESY spectrum of compound 8a reveals that the
signal at 4.31 ppm (H-2) shows a large cross-peak with
the signal at 3.91 ppm (H-4) (Fig. 1).
The reaction temperature also has an effect on the yield of
the product. At an ambient temperature, the starting material
cannot be consumed completely even after reacting for 48 h;
whereas under refluxing conditions, no starting aldehyde
A possible mechanism for this Prins-type cyclization is
shown in Scheme 2. The reaction is initiated by scandium
1
could be detected either by TLC or H NMR after stirring
0
overnight. As a solvent chloroform is more effective than
tetrahydrofuran or diethyl ether for the reaction, which is
usually the case in Lewis acid catalyzed reactions. The
reaction also proceeds slowly in methylene chloride; however,
its low boiling point limits temperature changes. No
reaction was observed in either toluene or acetonitrile.
triflate (1 ) to generate the butenoxylated scandium agent
0
0
(2 ) which then reacts with the aldehyde to give 3 . Subse-
quently, the intermediates 4 and 4 could be formed
by losing [ScO(OTf) ] . The reaction of the latter with
0
00
Ϫ
2
3-buten-1-ol affords the corresponding tetrahydropyran
0
0
ethers (9). Alternatively, the intermediate 4 could also
Ϫ
0
pick up the [ScO(OTf) ] anion to afford 5 , which reacts
2
In forming multi-substituted tetrahydropyran derivatives,
stereochemistry is also important. In the present reaction,
only a single diastereomer was formed as judged by H
with HOTf to give rise to the formation of corresponding
tetrahydropyranols (8) and the catalyst (1 ) itself. A similar
0
1
mechanism has been used to explain a cross-allylation of
16
spectroscopy of the crude reaction mixture. The substituents
aldehyde by Nokami and co-workers very recently.
Scheme 2. Proposed mechanism for the scandium triflate catalyzed tetrahydropyran formations.

2
406
W.-C. Zhang, C.-J. Li / Tetrahedron 56 (2000) 2403–2411
ϩ
Conclusion
66.4, 42.3, 35.4; GC/MS: m/z (% base peak) 197 (M ϩ1, 1),
1
ϩ ϩ ϩ
96 (M , 7), 195 (M Ϫ1, 5), 179 (M ϪOH, 14), 178 (100),
In conclusion, the reaction of aldehydes with homoallylic
alcohol catalyzed by scandium triflate generates tetrahydro-
pyran-4-ols and ethers in good (overall) yield with cis dia-
stereoselectivity. Further investigation of this process and
its potential applications to natural product synthesis are
currently in progress.
177 (16), 163 (7), 150 (5), 149 (6), 126 (5), 125 (40), 124
(21), 123 (79), 122 (20), 121 (8), 109 (16), 105 (4), 97 (17),
ϩ
96 (12), 95 (10), 83 (3), 77 (Ph , 9), 75 (9), 57 (13), 55 (11),
44 (17), 43 (14), 39 (4); Anal. Calcd for C H O F: C,
11
13
2
67.33; H, 6.68. Found: C, 67.11; H, 6.68.
cis-2-(3-Fluorophenyl)-4-hydroxy-tetrahydropyran (8c).
FTIR(film): 3372, 1612, 1592, 1489, 1445, 1362, 1249,
1170, 1136, 1072, 989, 959, 935, 866, 783, 768,
Experimental
Ϫ1
1
6
89 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.28 (m,
3
All reactions were carried out under a nitrogen atmosphere.
Scandium triflate was purchased from Aldrich and was used
directly as received. All other chemicals were also used
without additional purification. Flash chromatography
1H), 7.08 (m, 2H), 6.96 (m, 1H), 4.30 (dd, Jˆ11.4, 2.0 Hz,
1H), 4.15 (ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.90 (tt, Jˆ10.6,
4.6 Hz, 1H), 3.56 (dt, Jˆ12.3, 2.1 Hz, 1H), 2.15 (m, 1H),
2.03 (br s, OH, 1H), 1.94 (m, 1H), 1.61 (m, 1H), 1.47 (m,
13
employed E. Merck silica gel (Kiesegel 60, 230–
1H); C NMR (CDCl , 100 MHz, ppm): dˆ164.1, 161.7,
3
1
4
00 mesh) purchased from Scientific Adsorbents. H and
144.5, 144.5, 130.0, 129.9, 121.4, 121.4, 114.5, 114.3,
1
3
C NMR measurements were conducted on a GE-400
113.0, 112.8, 77.6, 68.2, 66.3, 43.2, 35.3; GC/MS: m/z (%
ϩ
ϩ
ϩ
instrument in CDCl . GC–Mass spectra were obtained on
base peak) 197 (M ϩ1, 4), 196 (M , 29), 195 (M Ϫ1, 11),
3
ϩ
Hewlett Packard 5890. Elemental analyses were per-
formed at the Center of Instrumental Facility of Tulane
University.
179 (M ϪOH, 14), 178 (100), 177 (21), 163 (7), 150 (5),
149 (7), 126 (5), 125 (28), 124 (24), 123 (83), 122 (23), 121
(11), 109 (16), 105 (4), 101 (11), 97 (23), 96 (20), 95 (17),
ϩ
8
3 (5), 77 (Ph , 7), 75 (12), 57 (20), 56 (6), 55 (17), 44 (25),
General procedure for the scandium triflate catalyzed
cyclization
43 (19), 39 (5); Anal. Calcd for C11
6.68. Found: C, 67.44; H, 6.94.
H O F: C, 67.33; H,
13 2
A mixture of benzaldehyde (212 mg, 2 mmol), 3-buten-1-ol
cis-2-(4-Fluorophenyl)-4-hydroxy-tetrahydropyran (8d).
(
5
288 mg, 4 mmol) and scandium triflate (98 mg, 0.2 mmol,
mol% relative to the alcohol) in chloroform (5 mL) was
FTIR(film): 3382, 1602, 1509, 1362, 1293, 1244, 1219,
Ϫ1
1
1156, 1136, 1072, 984, 881, 832, 807, 777, 596 cm ; H
refluxed under nitrogen overnight. After concentrating in
vacuo, the crude reaction mixture was subjected to column
chromatography on silica gel eluting with hexane–ethyl
acetate (gradient eluent: hexane/EtOAcˆ27:1 to 3:1) to
give product 8a (50 mg, yield 14%) and product 9a
NMR (CDCl
3
, 400 MHz, ppm): dˆ7.31 (m, 2H), 7.02 (m,
2H), 4.29 (dd, Jˆ11.4, 1.8 Hz, 1H), 4.16 (ddd, Jˆ11.7, 5.0,
1.5 Hz, 1H), 3.93 (tt, Jˆ11.2, 4.4 Hz, 1H), 3.57 (dt, Jˆ12.3,
2.1 Hz, 1H), 2.15 (m, 1H), 1.96 (m, 1H), 1.73 (br s, OH,
13
1H), 1.64 (m, 1H), 1.50 (m, 1H); C NMR (CDCl
100 MHz, ppm): dˆ163.4, 161.0, 137.7, 137.7, 127.7,
27.6, 115.4, 115.2, 77.7, 68.3, 66.4, 43.3, 35.4; GC/MS:
,
3
(292 mg, yield 63%).
1
ϩ
ϩ
cis-2-Phenyl-4-hydroxy-tetrahydropyran (8a). FTIR(film):
m/z (% base peak) 197 (M ϩ1, 3), 196 (M , 21), 195
ϩ
ϩ
3
8
382, 1494, 1445, 1362, 1244, 1136, 1072, 1023, 979, 954,
(M Ϫ1, 12), 179 (M ϪOH, 13), 178 (93), 177 (21), 163
(6), 150 (6), 149 (6), 126 (3), 125 (33), 124 (28), 123 (100),
122 (21), 121 (12), 109 (18), 105 (3), 101 (10), 97 (20), 96
Ϫ1
1
81, 802, 753, 694, 636 cm ; H NMR (CDCl , 400 MHz,
3
ppm): dˆ7.30 (m, 5H), 4.31 (dd, Jˆ11.3, 2.2 Hz, 1H), 4.16
ϩ
(
ddd, Jˆ11.8, 4.7, 1.7 Hz, 1H), 3.91 (tt, Jˆ11.0, 4.7 Hz,
(17), 95 (18), 83 (4), 77 (Ph , 7), 75 (12), 57 (19), 56 (6), 55
1
H), 3.57 (dt, Jˆ12.6, 2.2 Hz, 1H), 2.15 (m, 1H), 2.09 (br
(24), 44 (30), 43 (21), 39 (6); Anal. Calcd for C11
67.33; H, 6.68. Found: C, 66.84; H, 6.79.
H O F: C,
13 2
13
s, OH, 1H), 1.95 (m, 1H), 1.62 (m, 1H), 1.55 (m, 1H);
C
NMR (CDCl , 100 MHz, ppm): dˆ141.8, 128.5, 127.7,
3
1
26.0, 78.4, 68.4, 66.4, 43.2, 35.4; GC/MS: m/z (% base
cis-2-(2-Chlorophenyl)-4-hydroxy-tetrahydropyran (8e).
ϩ
ϩ
ϩ
peak) 179 (M ϩ1, 3), 178 (M , 24), 177 (M Ϫ1, 19),
FTIR(film): 3382, 1472, 1433, 1368, 1283, 1244, 1204,
ϩ
Ϫ1
1
1
1
61 (M ϪOH, 9), 160 (77), 159 (27), 145 (5), 131 (8),
1178, 1125, 1068, 1024, 963, 870, 748 cm ; H NMR
(CDCl
ϩ
05 (100), 91 (17), 77 (Ph , 37), 44 (26), 43 (21), 39 (9);
3
, 400 MHz, ppm): dˆ7.48 (m, 1H), 7.24 (m, 1H),
Anal. Calcd for C H O : C, 74.13; H, 7.92. Found: C,
7.14 (m, 1H), 7.01 (m, 1H), 4.65 (dd, Jˆ11.5, 1.5 Hz, 1H),
1
1
14
2
73.70; H, 7.92.
4.17 (ddd, Jˆ11.7, 5.0, 1.5 Hz, 1H), 3.95 (tt, Jˆ10.6,
4
.7 Hz, 1H), 3.60 (dt, Jˆ12.3, 2.1 Hz, 1H), 2.20 (m, 1H),
cis-2-(2-Fluorophenyl)-4-hydroxy-tetrahydropyran (8b).
FTIR(film): 3372, 1587, 1494, 1455, 1362, 1229, 1185,
1.96 (m, 1H), 1.79 (br s, OH, 1H), 1.65 (m, 1H), 1.50 (m,
13
1H); C NMR (CDCl
129.2, 128.3, 127.2, 127.0, 70.7, 64.2, 63.1, 39.6, 32.5; GC/
, 100 MHz, ppm): dˆ140.5, 131.3,
3
1
136, 1077, 1024, 994, 989, 954, 886, 837, 807, 792, 753,
Ϫ1
1
37
ϩ
37
ϩ
6
90, 635 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.48
MS: m/z (% base peak) 215 ( Cl M ϩ1, 1), 214 ( Cl M ,
35 ϩ 35 ϩ
3
(
m, 1H), 7.24 (m, 1H), 7.14 (m, 1H), 7.01 (m, 1H), 4.64 (dd,
7), 213 (4), 212 ( Cl M , 22), 211 ( Cl M Ϫ1, 4), 196
ϩ
ϩ
Jˆ11.5, 1.5 Hz, 1H), 4.17 (ddd, Jˆ11.7, 5.0, 1.5 Hz, 1H),
(33), 195 (M ϪOH, 19), 194 (97), 193 (20), 177 (M ϪCl,
ϩ
3
2
1
1
1
.95 (tt, Jˆ11.1, 4.8 Hz, 1H), 3.60 (dt, Jˆ12.3, 2.1 Hz, 1H),
7), 160 (M ϪCl–OH, 3), 159 (26), 143 (16), 142 (14), 140
.20 (m, 1H), 1.96 (m, 1H), 1.79 (br s, OH, 1H), 1.65 (m,
(34), 139 (100), 138 (15), 137 (4), 131 (9), 127 (8), 125 (21),
1
3
ϩ
H), 1.50 (m, 1H), 1.55 (m, 1H); C NMR (CDCl3,
00 MHz, ppm): dˆ160.5, 158.1, 129.2, 129,0, 129.0,
28.9, 127.2, 127.2, 124.4, 124.3, 115.3, 115.1, 71.9, 68.2,
115 (6), 114 (5), 113 (14), 112 (ClPh , 11), 111 (9), 105 (7),
ϩ
103 (20), 102 (6), 91 (4), 89 (6), 77 (Ph , 41), 75 (13), 71
(4), 57 (17), 55 (21), 51 (14), 44 (26), 43 (25), 41 (4), 39 (7);

W.-C. Zhang, C.-J. Li / Tetrahedron 56 (2000) 2403–2411
2407
ϩ
Anal. Calcd for C H O Cl: C, 62.12; H, 6.16. Found: C,
(9), 111 (23), 102 (18), 101 (16), 85 (7), 77 (Ph , 7), 75 (29),
74 (14), 73 (10), 71 (13), 69 (12), 58 (29), 57 (66), 56 (26),
1
1
13
2
61.91; H, 6.24.
5
5 (88), 54 (25), 51 (18), 44 (100), 43 (87), 41 (22), 39 (16),
cis-2-(3-Chlorophenyl)-4-hydroxy-tetrahydropyran (8f).
38 (18); Anal. Calcd for C H O Cl : C, 53.47; H, 4.93.
11
12
2
2
FTIR(film): 3372, 1597, 1572, 1469, 1425, 1362, 1244,
Found: C, 53.54; H, 4.88.
1
6
1
1
4
1
1
1
3
2
170, 1136, 1072, 984, 954, 881, 851, 783, 714,
Ϫ1
1
85 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.35 (m,
cis-2-(3-Bromophenyl)-4-hydroxy-tetrahydropyran (8i).
FTIR(film): 3370, 1594, 1563, 1470, 1444, 1422, 1359,
1249, 1204, 1138, 1071, 987, 956, 881, 845, 779, 690,
3
H), 7.26 (m, 2H), 7.20 (m, 1H), 4.29 (dd, Jˆ11.5, 2.1 Hz,
H), 4.16 (ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.91 (tt, Jˆ11.3,
.5 Hz, 1H), 3.56 (dt, Jˆ12.3, 2.1 Hz, 1H), 2.16 (m, 1H),
.96 (m, 1H), 1.80 (br s, OH, 1H), 1.61 (m, 1H), 1.48 (m,
Ϫ1
1
681 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.51 (m,
3
1H), 7.40 (m, 1H), 7.22 (m, 2H), 4.27 (dd, Jˆ11.4, 1.8 Hz,
1H), 4.16 (ddd, Jˆ11.7, 5.0, 1.5 Hz, 1H), 3.91 (tt, Jˆ11.2,
4.4 Hz, 1H), 3.55 (dt, Jˆ12.3, 2.1 Hz, 1H), 2.15 (m, 1H),
1
3
H); C NMR (CDCl , 100 MHz, ppm): dˆ143.9, 134.3,
3
29.7, 127.7, 126.1, 124.0, 116.5, 77.6, 66.2, 66.3, 43.2,
3
7
ϩ
5.4; GC/MS: m/z (% base peak) 215 ( Cl M ϩ1, 2),
1.95 (m, 1H), 1.91 (br s, OH, 1H), 1.60 (m, 1H), 1.47 (m,
3
7
ϩ
35
ϩ
35
13
14 ( Cl M , 14), 213 (9), 212 ( Cl M , 41), 211 ( Cl
1H); C NMR (CDCl , 100 MHz, ppm): dˆ144.2, 130.7,
3
ϩ
ϩ
M Ϫ1, 11), 196 (35), 195 (M ϪOH, 21), 194 (100), 193
130.0, 129.0, 124.4, 122.5, 77.5, 77.6, 68.2, 66.3, 43.2, 35.3;
ϩ
ϩ
81
ϩ
81
(
1
1
21), 177 (M ϪCl, 18), 160 (M ϪCl–OH, 4), 159 (35),
43 (9), 142 (11), 141 (58), 140 (33), 139 (90), 138 (18),
37 (6), 131 (14), 127 (6), 125 (13), 115 (7), 114 (8), 113
GC/MS: m/z (% base peak) 259 ( Br M ϩ1, 6), 258 ( Br
ϩ 79 ϩ 79 ϩ
M , 46), 257 (14), 256 ( Br M , 48), 255 ( Br M Ϫ1, 8),
81 ϩ 79
241 (12), 240 ( Br M ϪOH, 93), 239 (28), 238 ( Br
ϩ
ϩ
(20), 112 (ClPh , 19), 111 (15), 105 (9), 103 (27), 102 (10),
M ϪOH, 93), 237 (17), 225 (5), 223 (5), 187 (23), 186
ϩ
9
1 (6), 89 (6), 77 (Ph , 39), 75 (17), 71 (5), 57 (22), 55 (20),
1 (15), 44 (29), 43 (27), 41 (5), 39 (8); Anal. Calcd for
(26), 185 (100), 184 (37), 183 (80), 182 (14), 178 (4), 177
ϩ
ϩ
5
(M ϪBr, 26), 171 (12), 169 (12), 159 (M ϪOH–Br, 61),
81
ϩ
79
ϩ
C H O Cl: C, 62.12; H, 6.16. Found: C, 62.16; H, 6.01.
158 ( BrPh , 21), 157 (22), 156 ( BrPh , 19), 155 (10),
31 (24), 120 (5), 105 (30), 104 (18), 103 (36), 102 (16), 101
11
13
2
1
ϩ
cis-2-(4-Chlorophenyl)-4-hydroxy-tetrahydropyran (8g).
FTIR(film): 3382, 2940, 2842, 1489, 1448, 1409, 1364,
1
8
(9), 91 (10), 89 (7), 78(18), 77 (Ph , 64), 76 (19), 75 (18), 71
(10), 58 (16), 57 (52), 56 (14), 55 (49), 54 (13), 51 (25), 50
(14), 45 (18), 44 (57), 43 (48), 41 (10), 39 (11); Anal. Calcd
for C H O Br: C, 51.38; H, 5.10. Found: C, 51.45; H, 5.12.
301, 1249, 1163, 1142, 1085, 1015, 987, 691, 885, 823,
Ϫ1 1
02, 717, 689, 594 cm ; H NMR (CDCl , 400 MHz,
3
11 13
2
ppm): dˆ7.30 (d, Jˆ8.8 Hz, 2H), 7.26 (d, Jˆ8.8 Hz, 2H),
4
.28 (dd, Jˆ11.4, 2.1 Hz, 1H), 4.16 (ddd, Jˆ12.0, 5.0,
.8 Hz, 1H), 3.92 (tt, Jˆ11.2, 4.4 Hz, 1H), 3.56 (dt,
cis-2-(2-Methylphenyl)-4-hydroxy-tetrahydropyran (8j).
FTIR(film): 3373, 1490, 1455, 1441, 1362, 1336, 1291,
1243, 1221, 1163, 1141, 1106, 1075, 982, 956, 880, 806,
1
Jˆ12.3, 2.1 Hz, 1H), 2.30 (br s, OH, 1H), 2.14 (m, 1H),
1
3
Ϫ1 1
1
.97 (m, 1H), 1.62 (m, 1H), 1.47 (m, 1H); C NMR
753, 722 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.43
3
(
7
2
(
(
CDCl , 100 MHz, ppm): dˆ140.4, 133.3, 128.6, 127.3,
(m, 1H), 7.19 (m, 3H), 4.48 (dd, Jˆ11.5, 1.8 Hz, 1H), 4.17
(ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.92 (tt, Jˆ11.0, 4.6 Hz,
1H), 3.58 (dt, Jˆ12.3, 2.1 Hz, 1H), 2.33 (s, 3H), 2.12 (m,
3
7.6, 68.2, 66.3, 43.2, 35.3; GC/MS: m/z (% base peak)
37 ϩ 37 ϩ
15 ( Cl M ϩ1, 1), 214 ( Cl M , 10), 213 (8), 212
3
5
ϩ
35
ϩ
Cl M , 32), 211 ( Cl M Ϫ1, 11), 196 (32), 195
1H), 2.02 (br s, OH, 1H), 1.97 (m, 1H), 1.65 (m, 1H), 1.53
ϩ
ϩ
13
M ϪOH, 19), 194 (95), 193 (20), 179 (6), 177 (M ϪCl,
8), 160 (M ϪCl–OH, 3), 159 (24), 143 (10), 142 (12), 141
(m, 1H); C NMR (CDCl , 100 MHz, ppm): dˆ139.8,
3
ϩ
1
134.5, 130.3, 127.5, 126.3, 125.5, 75.2, 68.5, 66.4, 41.8,
35.6, 19.0; GC/MS: m/z (% base peak) 193 (M ϩ1, 10),
192 (M , 65), 191 (M Ϫ1, 18), 177 (M ϪCH , 34), 175
(8), 174 (53), 173 (17), 160 (4), 159 (M ϪOH–CH , 31),
ϩ
(
61), 140 (33), 139 (100), 138 (17), 137 (8), 131 (8), 127 (6),
ϩ
ϩ
ϩ
ϩ
1
25 (16), 115 (5), 113 (15), 112 (ClPh , 19), 111 (13), 105
3
ϩ
ϩ
(
5
(
10), 103 (24), 89 (6), 77 (Ph , 40), 75 (16), 71 (5), 57 (25),
5 (36), 51 (16), 50 (9), 45 (10), 44 (37), 43 (30), 41 (8), 39
8); Anal. Calcd for C H O Cl: C, 62.12; H, 6.16. Found:
3
121 (28), 120 (28), 119 (100), 118 (18), 117 (19), 115 (8),
ϩ
105 (28), 103 (7), 93 (18), 92 (15), 91 (CH Ph , 35), 77
1
1
13
2
3
ϩ
C, 62.01; H, 5.95.
(Ph , 11), 65 (12), 57 (11), 55 (23), 44 (13), 43 (13), 41 (6),
3
9 (9); Anal. Calcd for C H O : C, 74.97; H, 8.39. Found:
12 16 2
cis-2-(3,4-Dichlorophenyl)-4-hydroxy-tetrahydropyran
C, 74.55; H, 8.46.
(
8h). FTIR(film): 3369, 1472, 1362, 1246, 1130, 1083,
030, 990, 962, 887, 821, 674, 611 cm ; H NMR
Ϫ1
1
1
cis-2-(3-Methylphenyl)-4-hydroxy-tetrahydropyran (8k).
FTIR(film): 3388, 1608, 1590, 1488, 1444, 1426, 1359,
1302, 1249, 1169, 1138, 1076, 1031, 983, 956, 881, 810,
(CDCl , 400 MHz, ppm): dˆ7.45 (m, 1H), 7.40 (m, 1H),
3
7
.15 (m, 1H), 4.28 (dd, Jˆ11.5, 2.0 Hz, 1H), 4.17 (ddd,
Ϫ1
1
Jˆ12.0, 5.0, 1.5 Hz, 1H), 3.93 (tt, Jˆ11.2, 4.4 Hz, 1H),
783, 756, 699 cm ; H NMR (CDCl , 400 MHz, ppm):
3
3
.55 (dt, Jˆ12.3, 2.0 Hz, 1H), 2.16 (m, 1H), 2.04 (br s,
dˆ7.24 (m, 1H), 7.18 (m, 1H), 7.11 (m, 2H), 4.27 (dd,
Jˆ11.5, 1.5 Hz, 1H), 4.16 (ddd, Jˆ11.6, 4.5, 1.5 Hz, 1H),
3.88 (tt, Jˆ11.2, 4.4 Hz, 1H), 3.56 (dt, Jˆ12.3, 2.1 Hz, 1H),
2.52 (br s, OH, 1H), 2.34 (s, 3H), 2.13 (m, 1H), 1.93 (m,
13
OH, 1H), 1.97 (m, 1H), 1.63 (m, 1H), 1.45 (m, 1H);
C
NMR (CDCl , 100 MHz, ppm): dˆ142.2, 132.5, 131.4,
3
1
30.4, 127.9, 125.1, 76.9, 68.1, 66.3, 43.2, 35.3; GC/MS:
37 ϩ 35
13
m/z (% base peak) 248 ( Cl M , 26), 247 (15), 246 ( Cl
1H), 1.63 (m, 1H), 1.53 (m, 1H); C NMR (CDCl3,
ϩ
35
ϩ
M , 38), 245 ( Cl M Ϫ1, 9), 232 (11), 231 (10), 230 (64),
2
2
(
(
1
100 MHz, ppm): dˆ141.6, 138.1, 128.5, 128.3, 126.7,
ϩ
29 (M ϪOH, 25), 228 (98), 227 (21), 215 (8), 213 (18),
123.0, 78.5, 68.3, 66.4, 43.2, 35.4, 21.5; GC/MS: m/z (%
ϩ
ϩ
ϩ
11 (27), 202 (6), 195 (11), 193 (32), 177 (27), 176
base peak) 193 (M ϩ1, 12), 192 (M , 78), 191 (M Ϫ1,
ϩ
ϩ
ϩ
M Ϫ2Cl 24), 175 (84), 174 (41), 173 (94), 172 (18), 165
21), 178 (4), 177 (M ϪCH , 33), 175 (M ϪOH, 11), 174
(63), 173 (20), 160 (4), 159 (M ϪOH–CH , 34), 145 (7),
3
ϩ
ϩ
13), 161 (11), 159 (M ϪOH–2Cl, 20), 149 (11), 148 (20),
3
ϩ
47 (ClPh , 23), 146 (27), 145 (11), 139 (23), 137 (24), 123
131 (7), 121 (24), 120 (29), 119 (100), 118 (20), 117 (21),

2
408
W.-C. Zhang, C.-J. Li / Tetrahedron 56 (2000) 2403–2411
ϩ
1
(
4
15 (10), 105 (28), 103 (8), 93 (26), 92 (CH Ph , 16), 91
cis-2-t-Butyl-4-hydroxy-tetrahydropyran (8o). FTIR-
(film): 3368, 2958, 2855, 1644, 1458, 1362, 1246, 1138,
1074, 1003, 952, 811, 600 cm ; H NMR (CDCl3,
3
ϩ
45), 77 (Ph , 14), 65 (16), 57 (13), 55 (20), 44 (17), 43 (17),
1 (7), 39 (11); Anal. Calcd for C H O : C, 74.97; H, 8.39.
Ϫ1
1
1
2
16
2
Found: C, 74.49; H, 8.56.
400 MHz, ppm): dˆ4.01 (ddd, Jˆ11.7, 5.0, 1.5 Hz, 1H),
3
.74 (m, 1H), 3.33 (dt, Jˆ12.3, 2.1 Hz, 1H), 2.85 (dd,
cis-2-(4-Methylphenyl)-4-hydroxy-tetrahydropyran (8l).
FTIR(film): 3381, 1609, 1514, 1444, 1414, 1361, 1309,
Jˆ11.2, 1.5 Hz, 1H), 2.20 (br s, OH, 1H), 1.95 (m, 1H),
1.85 (m, 1H), 1.46 (m, 1H), 1.18 (m, 1H), 0.89 (s, 9H);
1
3
1
7
244, 1204, 1161, 1139, 1074, 1030, 982, 956, 877, 812,
69, 712 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.23
C NMR (CDCl , 100 MHz, ppm): dˆ84.1, 69.1, 66.1,
3
Ϫ1
1
35.9, 35.8, 33.9, 26.0; GC/MS: m/z (% base peak) 157
(M Ϫ1, 0.4), 143 (3), 125 (8), 101 (100), 83 (21), 73 (9),
3
ϩ
(
d, Jˆ7.9 Hz, 2H), 7.15 (d, Jˆ7.9 Hz, 2H), 4.27 (dd,
Jˆ11.4, 1.8 Hz, 1H), 4.14 (ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H),
57 (90); Anal. Calcd for C H O : C, 68.31; H, 11.47.
9
18
2
3
2
1
1
6
.88 (tt, Jˆ10.9, 4.7 Hz, 1H), 3.56 (dt, Jˆ12.3, 2.1 Hz, 1H),
Found: C, 68.72; H, 11.34.
.34 (s, 3H), 2.32 (br s, OH, 1H), 2.12 (m, 1H), 1.93 (m,
1
3
H), 1.62 (m, 1H), 1.53 (m, 1H); C NMR (CDCl3,
00 MHz, ppm): dˆ138.9, 137.4, 129.1, 125.9, 78.3, 68.4,
6.4, 43.2, 35.4, 21.2; GC/MS: m/z (% base peak) 193
cis-2-n-Pentyl-4-hydroxy-tetrahydropyran (8p). FTIR-
(film): 3381, 2929, 2853, 1360, 1251, 1142, 1078, 1056,
Ϫ1
1
969, 860 cm ; H NMR (CDCl , 400 MHz, ppm):
3
ϩ
ϩ
ϩ
(
(
(
(
(
(
M ϩ1, 10), 192 (M , 69), 191 (M Ϫ1, 19), 178 (5), 177
M ϪCH , 35), 175 (M ϪOH, 8), 174 (57), 173 (17), 160
4), 159 (M ϪOH–CH , 33), 146 (4), 145 (6), 131 (5), 121
29), 120 (29), 119 (100), 118 (18), 117 (19), 105 (28), 93
18), 92 (CH Ph , 15), 91 (36), 77 (Ph , 13), 65 (12), 57
10), 55 (22), 44 (13), 43 (12), 41 (6), 39 (9); Anal. Calcd for
dˆ4.01 (ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.77 (m, 1H),
3.38 (dt, Jˆ12.0, 2.1 Hz, 1H), 3.25 (m, 1H), 1.95 (m, 1H),
1.88 (m, 1H), 1.71 (br s, OH, 1H), 1.57–1.15 (m, 10H), 0.90
ϩ
ϩ
3
ϩ
3
1
3
(t, Jˆ7.0 Hz, 3H); C NMR (CDCl , 100 MHz, ppm):
3
ϩ
ϩ
dˆ76.3, 68.3, 65.9, 41.6, 35.9, 35.8, 35.8, 27.7, 22.7,
3
ϩ
14.0; GC/MS: m/z (% base peak) 155 (M ϪOH, 0.4), 101
C H O : C, 74.97; H, 8.39. Found: C, 74.52; H, 8.37.
(100), 83 (6), 69 (9), 57 (33), 44 (20); Anal. Calcd for
C H O : C, 69.72; H, 11.70. Found: C, 69.22; H, 11.44.
12
16
2
10
20
2
cis-2-(4-Ethylphenyl)-4-hydroxy-tetrahydropyran (8m).
FTIR(film): 3366, 1616, 1512, 1463, 1412, 1368, 1247,
cis-2-(4-Nitrophenyl)-4-hydroxy-tetrahydropyran (8q).
Ϫ1
1
160, 1134, 1073, 1021, 986, 956, 878, 825, 804 cm ;
FTIR(film): 3368, 1599, 1516, 1343, 1247, 1138, 1073,
1
Ϫ1
1
H NMR (CDCl , 400 MHz, ppm): dˆ7.26 (d, Jˆ7.9 Hz,
984, 850, 747, 696, 587 cm ; H NMR (CDCl3,
400 MHz, ppm): dˆ8.19 (d, Jˆ8.2 Hz, 2H), 7.50 (d,
Jˆ8.2 Hz, 2H), 4.42 (dd, Jˆ11.4, 1.8 Hz, 1H), 4.20 (ddd,
Jˆ11.7, 4.7, 1.2 Hz, 1H), 3.95 (tt, Jˆ10.9, 4.7 Hz, 1H), 3.59
(dt, Jˆ12.0, 2.1 Hz, 1H), 2.21 (m, 1H), 2.07 (br s, OH, 1H),
3
2
4
4
H), 7.17 (d, Jˆ7.9 Hz, 2H), 4.28 (dd, Jˆ11.4, 1.8 Hz, 1H),
.15 (ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.90 (tt, Jˆ10.8,
.5 Hz, 1H), 3.56 (dt, Jˆ12.3, 2.3 Hz, 1H), 2.63 (q,
Jˆ7.6 Hz, 2H), 2.30 (br s, OH, 1H), 2.15 (m, 1H), 1.95
13
(
3
1
m, 1H), 1.64 (m, 1H), 1.56 (m, 1H), 1.22 (t, Jˆ7.6 Hz,
1.99 (m, 1H), 1.65 (m, 1H), 1.44 (m, 1H); C NMR (CDCl ,
3
1
3
H); C NMR (CDCl , 100 MHz, ppm): dˆ143.8, 139.1,
100 MHz, ppm): dˆ149.4, 147.2, 126.4, 123.7, 77.2, 68.0,
3
ϩ
27.9, 126.0, 78.3, 68.4, 66.4, 43.1, 35.5, 28.6, 15.7; GC/
66.4, 43.3, 35.3; GC/MS: m/z (% base peak) 205 (M ϪOH,
ϩ
ϩ
MS: m/z (% base peak) 207 (M ϩ1, 12), 206 (M , 74), 205
M Ϫ1, 18), 189 (M ϪOH, 8), 188 (48), 187 (15), 178
12), 177 (M ϪC H , 87), 173 (4), 160 (10), 159
M ϪOH–C H , 60), 135 (29), 134 (28), 133 (100), 132
14), 131 (16), 119 (27), 117 (24), 106 (12), 105 (46), 103
18), 91 (35), 79 (37), 77 (Ph , 19), 65 (7), 57 (15), 55 (31),
69), 188 (37), 150 (70), 107 (62), 77 (83), 57 (51), 44 (100);
ϩ
ϩ
(
(
(
(
(
Anal. Calcd for C H NO : C, 59.19; H, 5.87. Found: C,
11
13
4
ϩ
59.46; H, 6.26.
2
5
ϩ
2
5
cis-2-Phenyl-4-(3-butenoxy)-tetrahydropyran (9a). FTIR-
(film): 1490, 1445, 1352, 1330, 1304, 1260, 1211, 1163.
1144, 1100, 1081, 1037, 1022, 988, 955, 906, 884,
ϩ
5
1 (7), 44 (15), 43 (16), 41 (7), 39 (8); Anal. Calcd for
Ϫ1
1
C H O : C, 75.69; H, 8.79. Found: C, 75.77; H, 9.06.
806 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.40–
13
18
2
3
7
.27 (m, 5H), 5.86 (m, 1H), 5.13–5.02 (m, 2H), 4.32 (dd,
(8n).
Jˆ11.5, 2.1 Hz, 1H), 4.20 (ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H),
3.63 (m, 1H), 3.59 (t, Jˆ6.8 Hz, 2H), 3.56 (m, 1H), 2.37 (q,
Jˆ6.8 Hz, 2H), 2.26 (m, 1H), 2.02 (m, 1H), 1.65 (m, 1H),
13
1.57 (m, 1H); C NMR (CDCl , 100 MHz, ppm): dˆ142.2,
3
135.3, 128.4, 127.6, 126.0, 116.4, 78.6, 75.5, 67.1, 66.5,
40.4, 34.6, 32.7; GC/MS: m/z (% base peak) 233 (M ϩ1,
2), 232 (M , 10), 177 (M ϪC H , 1), 161 (M ϪC H O,
ϩ
ϩ
ϩ
ϩ
4 7 4 7
16), 160(63), 159 (52), 131 (33), 117 (4), 105 (38), 91 (13),
ϩ
ϩ
ϩ
7
77 (Ph , 15), 71 (C H O , 3), 55 (C H , 100), 43 (10), 41
4
7
4
(10), 39 (13); Anal. Calcd for C H O : C, 77.55; H, 8.68.
15 20 2
dˆ137.3, 133.8, 130.4, 128.9, 128.2, 126.1, 125.5, 125.5,
Found: C, 77.93; H, 8.43.
1
23.2, 123.1, 75.3, 68.6, 66.6, 42.3, 35.7; GC/MS: m/z (%
ϩ
ϩ
ϩ
base peak) 229 (M ϩ1, 16), 228 (M , 100), 227 (M Ϫ1,
cis-2-(2-Fluorophenyl)-4-(3-butenoxy)-tetrahydropyran
(9b). FTIR(film): 1695, 1641, 1582, 1489, 1455, 1362,
1254, 1224, 1141, 1077, 1018, 989, 905, 812, 792,
ϩ
2
1
1
(
(
3), 211 (M ϪOH, 6), 210 (25), 209 (20), 182 (7), 181 (7),
57 (17), 156 (26), 155 (52), 154 (16), 153 (28), 152 (13),
51 (4), 142 (15), 141 (23), 129 (21), 128 (60), 127 (24), 126
6), 115 (5), 77 (Ph , 6), 76 (8), 75 (5), 57 (11), 55 (27), 44
10), 43 (4), 41 (5), 39 (5), 38 (5), 36 (13); Anal. Calcd for
Ϫ1
1
748 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.49 (m,
3
ϩ
1H), 7.23 (m, 1H), 7.14 (m, 1H), 7.01 (m, 1H), 5.83 (m, 1H),
5.12–5.02 (m, 2H), 4.65 (dd, Jˆ11.5, 2.0 Hz, 1H), 4.18
(ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.64 (m, 1H), 3.59 (m,
C H O : C, 78.92; H, 7.07. Found: C, 78.70; H, 6.72.
15
16
2

W.-C. Zhang, C.-J. Li / Tetrahedron 56 (2000) 2403–2411
2409
ϩ
35
ϩ
ϩ
1
H), 3.56 (t, Jˆ6.7 Hz, 2H), 2.35 (q, Jˆ6.7 Hz, 2H), 2.26
M , 14), 267 (7), 266 ( Cl M , 41), 231 (M ϪCl, 3),
13
ϩ
(m, 1H), 2.01 (m, 1H), 1.65 (m, 1H), 1.48 (m, 1H);
C
221 (4), 196 (5), 195 (M ϪC H O, 35), 194 (14), 193
(100), 177 (M ϪC H –Cl, 1), 163 (1), 141 (11), 140 (12),
139 (19), 138 (7), 128 (7), 127 (5), 125 (3), 112 (13), 111
(8), 110 (3), 105 (3), 99 (4), 98 (29), 97 (3), 83 (10), 77 (Ph ,
4
7
ϩ
NMR (CDCl , 100 MHz, ppm): dˆ160.5, 158.0, 135.2,
3
4 7
29.4, 129,3, 128.9, 128.8, 127.3, 127.3, 124.4, 124.3,
16.4, 115.2, 115.0, 75.2, 72.1, 67.1, 66.6, 39.4, 34.5,
2.7; GC/MS: m/z (% base peak) 251 (M ϩ1, 5), 250
ϩ
ϩ
ϩ
ϩ
7), 71 (C H O , 6), 70 (11), 56 (8), 55 (C H , 21), 54 (2), 53
4 7 4 7
ϩ
ϩ
ϩ
(5), 43 (16), 42 (9), 41 (13), 39 (5); Anal. Calcd for
C H O Cl: C, 67.54; H, 7.18. Found: C, 67.02; H, 7.19.
4
7
1
00), 149 (8), 125 (5), 124 (10), 123 (23), 112 (5), 109
15
19
2
ϩ ϩ
(5), 98 (20), 97 (5), 83 (9), 77 (Ph , 3), 71 (C H O , 5),
4
7
ϩ
7
7
0 (12), 55 (C H , 26), 43 (15), 41 (13), 39 (6); Anal. Calcd
cis-2-(3-Chlorophenyl)-4-(3-butenoxy)-tetrahydropyran
(9f). FTIR(film): 1641, 1597, 1573, 1474, 1425, 1362, 1244,
4
for C H O F: C, 71.98; H, 7.65. Found: C, 71.60; H, 7.97.
15
19
2
1
205, 1146, 1106, 1082, 1028, 989, 910, 778, 709,
Ϫ1
1
cis-2-(3-Fluorophenyl)-4-(3-butenoxy)-tetrahydropyran
9c). FTIR(film): 1636, 1612, 1587, 1484, 1440, 1361, 1254,
175, 1136, 1106, 1082, 1023, 994, 949, 915, 871, 783, 763,
685 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.36 (s,
3
(
1H), 7.28–7.20 (m, 3H), 5.82 (m, 1H), 5.12–5.02 (m, 2H),
4.27 (dd, Jˆ11.7, 1.8 Hz, 1H), 4.17 (ddd, Jˆ12.0, 5.0,
1.8 Hz, 1H), 3.60 (m, 1H), 3.55 (t, Jˆ7.0 Hz, 2H), 3.52
(m, 1H), 2.32 (q, Jˆ7.0 Hz, 2H), 2.22 (m, 1H), 2.00 (m,
1
6
1
2
1
1
1
Ϫ1
1
89 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.28 (m,
3
H), 7.09 (m, 2H), 6.95 (m, 1H), 5.82 (m, 1H), 5.12-5.02 (m,
H), 4.30 (dd, Jˆ11.7, 2.1 Hz, 1H), 4.18 (ddd, Jˆ11.7, 4.7,
.5 Hz, 1H), 3.61 (m, 1H), 3.55 (t, Jˆ6.8 Hz, 2H), 3.52 (m,
H), 2.33 (q, Jˆ6.8 Hz, 2H), 2.23 (m, 1H), 2.00 (m, 1H),
13
1H), 1.61 (m, 1H), 1.48 (m, 1H); C NMR (CDCl ,
3
100 MHz, ppm): dˆ144.2, 135.2, 134.3, 129.7, 127.7,
126.2, 124.0, 116.5, 77.7, 75.3, 67.1, 66.5, 40.3, 34.5,
1
3
37
ϩ
.62 (m, 1H), 1.47 (m, 1H); C NMR (CDCl , 100 MHz,
32.5; GC/MS: m/z (% base peak) 269 ( Cl M ϩ1, 4),
37 ϩ 35 ϩ
3
ppm): dˆ164.1, 161.7, 144.8, 144.8, 135.2, 129.9, 129.8,
268 ( Cl M , 11), 267 (9), 266 ( Cl M , 34), 196 (4),
ϩ
ϩ
1
6
21.4, 121.4, 116.4, 114.4, 114.2, 113.0, 112.8, 77.8, 75.3,
195 (M ϪC H O, 37), 194 (17), 193 (100), 175 (M , 4),
4 7
7.1, 66.5, 40.3, 34.5, 32.5; GC/MS: m/z (% base peak) 250
165 (12), 143 (5), 142 (9), 141 (9), 140 (15), 139 (16), 138
(10), 131(8), 128 (7), 127 (6), 125 (4), 112 (9), 111 (10), 110
(4), 105 (5), 103 (7), 98 (25), 97 (6), 83 (11), 81 (10), 77
ϩ
ϩ
ϩ
(
M , 2), 195 (M ϪC H , 1), 179 (M ϪC H O, 34), 178
4 7 4 7
ϩ
(
50), 177 (M ϪC H –F, 35), 163 (4), 150 (8), 149 (52), 125
4
7
ϩ
ϩ
(
8), 124 (9), 123 (28), 112 (11), 109 (16), 98 (1), 97 (5), 87
(Ph , 8), 71 (C H O , 6), 70 (13), 69 (24), 67 (11), 56 (11),
4 7
ϩ
ϩ
ϩ
ϩ
(10), 83 (4), 77 (Ph , 2), 71 (C H O , 2), 70 (5), 55 (C H ,
55 (C H , 48), 54 (8), 53 (11), 43 (23), 42 (16), 41 (24), 39
4 7
4
7
4
7
1
00), 53 (6), 43 (3), 41 (7), 39 (11); Anal. Calcd for
(12), 38 (17); Anal. Calcd for C H O Cl: C, 67.54; H,
7.18. Found: C, 67.40; H, 7.19.
15 19 2
C H O F: C, 71.98; H, 7.65. Found: C, 72.72; H, 8.01.
15
19
2
cis-2-(4-Fluorophenyl)-4-(3-butenoxy)-tetrahydropyran
cis-2-(4-Chlorophenyl)-4-(3-butenoxy)-tetrahydropyran
(9g). FTIR(film): 1636, 1489, 1361, 1244, 1151, 1106,
(
1
9d). FTIR(film): 1636, 1597, 1509, 1411, 1362, 1219,
151, 1106, 1082, 1023, 999, 910, 832, 778 cm ; H
Ϫ1
1
Ϫ1
1
1082, 1008, 989, 910, 822 cm ; H NMR (CDCl3,
400 MHz, ppm): dˆ7.31 (d, Jˆ8.5 Hz, 2H), 7.27 (d,
Jˆ8.5 Hz, 2H), 5.81 (m, 1H), 5.12–5.02 (m, 2H), 4.28
(dd, Jˆ11.7, 2.1 Hz, 1H), 4.17 (ddd, Jˆ11.7, 5.0, 1.8 Hz,
1H), 3.59 (m, 1H), 3.55 (t, Jˆ6.8 Hz, 2H), 3.53 (m, 1H),
NMR (CDCl , 400 MHz, ppm): dˆ7.32 (d, Jˆ8.5 Hz,
3
2
2
1
1
1
H), 7.02 (d, Jˆ8.5 Hz, 2H), 5.82 (m, 1H), 5.12–5.02 (m,
H), 4.28 (dd, Jˆ11.7, 2.0 Hz, 1H), 4.17 (ddd, Jˆ11.7, 4.7,
.5 Hz, 1H), 3.61 (m, 1H), 3.55 (t, Jˆ6.8 Hz, 2H), 3.52 (m,
H), 2.33 (q, Jˆ6.8 Hz, 2H), 2.20 (m, 1H), 2.01 (m, 1H),
2.32 (q, Jˆ6.8 Hz, 2H), 2.20 (m, 1H), 2.00 (m, 1H), 1.60 (m,
1
3
13
.61 (m, 1H), 1.50 (m, 1H); C NMR (CDCl , 100 MHz,
1H), 1.48 (m, 1H); C NMR (CDCl , 100 MHz, ppm):
3
3
ppm): dˆ163.4, 161.0, 137.9, 137.9, 135.2, 127.7, 127.6,
dˆ140.7, 135.2, 133.2, 128.5, 127.3, 116.5, 77.8, 75.3,
1
16.4, 115.3, 115.1, 77.9, 75.4, 67.1, 66.5, 40.3, 34.5, 32.5;
67.1, 66.5, 40.3, 34.5, 32.5; GC/MS: m/z (% base peak)
ϩ
ϩ
37
ϩ
37
ϩ
35
GC/MS: m/z (% base peak) 250 (M , 2), 249 (M Ϫ1, 1),
269 ( Cl M ϩ1, 1), 268 ( Cl M , 6), 267 (3), 266 ( Cl
ϩ
ϩ
ϩ ϩ ϩ
1
95 (M ϪC H , 1), 179 (M ϪC H O, 29), 178 (100), 177
M , 20), 231 (M ϪCl, 1), 196 (6), 195 (M ϪC H O, 37),
4 7
ϩ
4
7
4
7
ϩ
(
(
(
(
M ϪC H –F, 29), 163 (5), 150 (9), 149 (35), 135 (5), 125
194 (17), 193 (100), 175 (M , 1), 165 (2), 143 (1), 142 (3),
141 (8), 140 (10), 139 (17), 138 (6), 131(1), 128 (3), 127 (3),
125 (4), 112 (4), 111 (8), 109 (3), 105 (2), 103 (4), 98 (15),
4
7
13), 124 (10), 123 (40), 122(14), 109 (15), 97 (5), 96 (5), 95
7), 87 (4), 83 (4), 77 (Ph , 3), 71 (C H O , 1), 70 (5), 55
C H , 78), 54 (8), 53 (5), 43 (3), 41 (6), 39 (11); Anal.
ϩ
ϩ
4
7
ϩ
7
ϩ
ϩ
97 (2), 83 (7), 81 (5), 77 (Ph , 7), 71 (C H O , 4), 70 (9), 69
4 7
ϩ
4
Calcd for C H O F: C, 71.98; H, 7.65. Found: C, 71.90; H,
(5), 67 (6), 56 (9), 55 (C H , 28), 54 (6), 53 (6), 43 (19), 42
4 7
1
5
19
2
7.87.
(13), 41 (17), 39 (9); Anal. Calcd for C H O Cl: C, 67.54;
H, 7.18. Found: C, 67.38; H, 7.13.
15 19 2
cis-2-(2-Chlorophenyl)-4-(3-butenoxy)-tetrahydropyran
9e). FTIR(film): 1636, 1568, 1469, 1435, 1357, 1249, 1205,
(
cis-2-(3,4-Dichlorophenyl)-4-(3-butenoxy)-tetrahydro-
pyran (9h). FTIR(film): 1720, 1639, 1469, 1356, 1244,
1158, 1145, 1127, 1110, 1087, 1024, 993, 961, 916, 899,
1
6
146, 1106, 1082, 1053, 1028, 989, 954, 910, 807, 753,
Ϫ1
1
99 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.55
3
Ϫ1
1
(
5
(
1
dd, Jˆ7.6, 1.8 Hz, 1H), 7.34–7.17 (m, 3H), 5.82 (m, 1H),
818, 759, 732, 701, 669 cm ; H NMR (CDCl , 400 MHz,
3
.12–5.01 (m, 2H), 4.70 (dd, Jˆ11.7, 2.0 Hz, 1H), 4.20
ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.65 (m, 1H), 3.60 (m,
H), 3.56 (t, Jˆ6.8 Hz, 2H), 2.38 (m, 1H), 2.33 (q,
ppm): dˆ7.45 (s, 1H), 7.39 (d, Jˆ8.5 Hz, 1H), 7.15 (dd,
Jˆ8.5, 1.8 Hz, 1H), 5.81 (m, 1H), 5.11–5.02 (m, 2H), 4.25
(dd, Jˆ11.7, 2.0 Hz, 1H), 4.16 (ddd, Jˆ11.7, 4.7, 1.5 Hz,
1H), 3.59 (m, 1H), 3.54 (t, Jˆ6.8 Hz, 2H), 3.50 (m, 1H),
2.30 (q, Jˆ6.8 Hz, 2H), 2.20 (m, 1H), 2.00 (m, 1H), 1.58 (m,
Jˆ6.8 Hz, 2H), 2.01 (m, 1H), 1.64 (m, 1H), 1.32 (m, 1H);
1
3
C NMR (CDCl , 100 MHz, ppm): dˆ139.8, 135.2, 131.3,
3
13
1
3
29.2, 128.5, 127.2, 127.2, 116.4, 75.2, 75.1, 67.1, 66.5,
1H), 1.43 (m, 1H); C NMR (CDCl , 100 MHz, ppm):
3
37
8.9, 34.5, 32.7; GC/MS: m/z (% base peak) 268 ( Cl
dˆ142.5, 135.1, 132.4, 131.3, 130.3, 128.0, 125.2, 116.5,

2
410
W.-C. Zhang, C.-J. Li / Tetrahedron 56 (2000) 2403–2411
ϩ
7
7.4, 75.1, 67.2, 66.5, 40.3, 34.5, 32.4; GC/MS: m/z (% base
(M ϪC H O, 27), 174 (100), 173 (33), 160 (4), 159
4
7
3
7
ϩ
35
ϩ
35
ϩ
ϩ
peak) 302 ( Cl M , 14), 301 ( Cl M ϩ1, 4), 300 ( Cl M ,
(M ϪC H O–CH , 33), 146 (7), 145 (33), 131 (8), 121
4 7 3
ϩ
ϩ
2
2
1
7
3), 231 (11), 230 (M Ϫ2Cl, 10), 229 (M ϪC H O, 67),
28 (17), 227 (100), 175 (10), 174 (10), 173 (13), 172 (4),
12 (6), 111 (8), 98 (26), 97 (4), 83 (12), 81 (6), 77 (Ph , 2),
5 (4), 71 (C H O , 10), 70 (15), 55 (C H , 48), 43 (29), 42
(13), 120 (11), 119 (42), 118 (11), 117 (8), 115 (5), 105
ϩ ϩ ϩ
4
7
(13), 91 (CH Ph , 17), 77 (Ph , 5), 71 (C H O , 2), 55
3 4 7
ϩ
ϩ
(C H , 75), 43 (3), 41 (6), 39 (10); Anal. Calcd for
4 7
ϩ
ϩ
7
C H O : C, 78.01; H, 9.00. Found: C, 77.67; H, 9.18.
16 22 2
4
7
4
(
5
19), 41 (26), 39 (10); Anal. Calcd for C H O Cl : C,
9.82; H, 6.02. Found: C, 59.46; H, 5.80.
15 18 2 2
cis-2-(4-Methylphenyl)-4-(3-butenoxy)-tetrahydropyran
9l). FTIR(film): 1637, 1541, 1439, 1365, 1308, 1246, 1162,
1145, 1110, 1083, 1022, 991, 960, 912, 890, 815, 767,
(
cis-2-(3-Bromophenyl)-4-(3-butenoxy)-tetrahydropyran
9i). FTIR(film): 1634, 1594, 1563, 1470, 1422, 1359, 1249,
Ϫ1
1
(
714 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.26 (d,
3
1
8
200, 1164, 1147, 1107, 1080, 1023, 991, 960, 912, 885,
Jˆ8.2 Hz, 2H), 7.17 (d, Jˆ8.2 Hz, 2H), 5.86 (m, 1H), 5.16-
5.05 (m, 2H), 4.30 (dd, Jˆ11.4, 1.8 Hz, 1H), 4.20 (ddd,
Jˆ11.7, 4.7, 1.8 Hz, 1H), 3.63 (m, 1H), 3.58 (t, Jˆ7.0 Hz,
2H), 3.55 (m, 1H), 2.37 (q, Jˆ7.0 Hz, 2H), 2.36 (s, 3H),
Ϫ1
1
45, 810, 779, 694, 681 cm ; H NMR (CDCl , 400 MHz,
3
ppm): dˆ7.52 (s, 1H), 7.38 (d, Jˆ7.6 Hz, 1H), 7.25 (d,
Jˆ7.6 Hz, 1H), 7.18 (t, Jˆ7.6 Hz, 1H), 5.82 (m, 1H),
13
5
.11–5.02 (m, 2H), 4.26 (dd, Jˆ11.7, 2.1 Hz, 1H), 4.16
2.24 (m, 1H), 2.01 (m, 1H), 1.66 (m, 1H), 1.58 (m, 1H); C
(
ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.59 (m, 1H), 3.54 (t,
NMR (CDCl , 100 MHz, ppm): dˆ139.2, 137.2, 135.3,
3
Jˆ6.7 Hz, 2H), 3.50 (m, 1H), 2.32 (q, Jˆ6.7 Hz, 2H),
129.1, 126.0, 116.4, 78.5, 75.6, 67.1, 66.5, 40.3, 34.6,
ϩ
2
.22 (m, 1H), 1.99 (m, 1H), 1.59 (m, 1H), 1.46 (m, 1H);
32.7, 21.2; GC/MS: m/z (% base peak) 247 (M ϩ1, 2),
1
3
ϩ
ϩ
ϩ
C NMR (CDCl , 100 MHz, ppm): dˆ144.5, 135.2, 130.6,
246 (M , 10), 245 (M Ϫ1, 1), 175 (M ϪC H O, 24),
4 7
ϩ
3
1
4
30.0, 129.1, 124.5, 122.5, 116.5, 77.6, 75.2, 67.1, 66.5,
0.3, 34.5, 32.5; GC/MS: m/z (% base peak) 312 ( Br
174 (100), 173 (32), 160 (7), 159 (M ϪC H O–CH , 51),
4 7 3
81
146 (7), 145 (25), 131 (7), 121 (18), 120 (12), 119 (49), 118
ϩ
79
ϩ
79
ϩ
ϩ ϩ
M , 2), 311 (1), 310 ( Br M , 2), 241 ( Br M ϪC H ,
1
(11), 117 (8), 115 (4), 105 (13), 91 (CH Ph , 16), 77 (Ph ,
3
ϩ ϩ
4
7
7), 240 (23), 239 (31), 238 (21), 237 (16), 211 (17), 209
5), 71 (C H O , 2), 70 (5), 55 (C H , 79), 43 (4), 41 (6), 39
4 7 4 7
(
1
17), 185 (12), 184 (7), 182 (10), 159 (11), 131 (5), 130 (8),
(9); Anal. Calcd for C H O : C, 78.01; H, 9.00. Found: C,
78.25; H, 8.95.
16 22 2
ϩ
ϩ
ϩ
27 (7), 87 (14), 77 (Ph , 8), 71 (C H O , 4), 55 (C H ,
4
7
4
7
1
00), 54 (8), 43 (3), 41 (5), 39 (9); Anal. Calcd for
C H O Br: C, 57.89; H, 6.15. Found: C, 58.01; H, 6.27.
cis-2-(4-Ethylphenyl)-4-(3-butenoxy)-tetrahydropyran
9m). FTIR(film): 1712, 1642, 1514, 1457, 1444, 1413,
1365, 1246, 1158, 1145, 1105, 1083, 1021, 991, 956, 912,
15
19
2
(
cis-2-(2-Methylphenyl)-4-(3-butenoxy)-tetrahydropyran
9j). FTIR(film): 1639, 1487, 1460, 1442, 1428, 1357, 1249,
Ϫ1
1
(
1
890, 824 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.29
3
222, 1163, 1141, 1105, 1078, 1020, 988, 957, 912, 809,
(d, Jˆ8.2 Hz, 2H), 7.25 (d, Jˆ8.2 Hz, 2H), 5.84 (m, 1H),
5.14–5.04 (m, 2H), 4.30 (dd, Jˆ11.5, 1.8 Hz, 1H), 4.19
(ddd, Jˆ11.7, 4.7, 1.5 Hz, 1H), 3.63 (m, 1H), 3.57 (t,
Jˆ6.8 Hz, 2H), 3.55 (m, 1H), 2.65 (q, Jˆ7.6 Hz, 2H),
2.38 (q, Jˆ6.8 Hz, 2H), 2.25 (m, 1H), 2.03 (m, 1H), 1.67
Ϫ1
1
7
50, 719, 638 cm ; H NMR (CDCl , 400 MHz, ppm):
3
dˆ7.48 (m, 1H), 7.26–7.15 (m, 3H), 5.85 (m, 1H), 5.16–
5
.02 (m, 2H), 4.50 (dd, Jˆ11.4, 1.8 Hz, 1H), 4.21 (ddd,
Jˆ11.7, 4.7, 1.2 Hz, 1H), 3.66 (m, 1H), 3.59 (t, Jˆ6.8 Hz,
13
2
2
H), 3.57 (m, 1H), 2.38 (q, Jˆ6.8 Hz, 2H), 2.37 (s, 3H),
(m, 1H), 1.58 (m, 1H), 1.26 (t, Jˆ7.6 Hz, 3H); C NMR
13
.22 (m, 1H), 2.05 (m, 1H), 1.68 (m, 1H), 1.59 (m, 1H);
C
(CDCl , 100 MHz, ppm): dˆ143.7, 139.4, 135.2, 127.9,
3
NMR (CDCl , 100 MHz, ppm): dˆ140.0, 135.3, 134.5,
126.1, 116.4, 78.5, 75.6, 67.1, 66.5, 40.2, 34.5, 32.7, 28.6,
3
ϩ
ϩ
1
3
30.3, 127.4, 126.3, 125.7, 116.5, 75.7, 75.4, 67.1, 66.6,
15.7; GC/MS: m/z (% base peak) 261 (M ϩ1, 2), 260 (M ,
ϩ ϩ ϩ
8.9, 34.6, 32.7, 19.1; GC/MS: m/z (% base peak) 247
12), 259 (M Ϫ1, 2), 231 (M ϪC H , 5), 189 (M ϪC H O,
2 5 4 7
ϩ
ϩ
ϩ
ϩ
ϩ
(M ϩ1, 1), 246 (M , 3), 245 (M Ϫ1, 1), 231 (M ϪCH ,
27), 188 (100), 173 (5), 160 (M ϪC H O–C H , 17), 159
4 7 2 5
3
ϩ
1
), 205 (15), 175 (M ϪC H O, 25), 174 (83), 173 (19), 160
(100), 145 (4), 135 (18), 134 (13), 133 (50), 131 (10), 119
(12), 117 (15), 115 (5), 105 (13), 103 (5), 91 (14), 79 (13),
4
7
ϩ
(5), 159 (M ϪC H O–CH , 35), 146 (12), 145 (32), 131
4 7 3
ϩ
ϩ
ϩ
(7), 129 (16), 121 (15), 120 (15), 119 (36), 118 (10), 117
77 (Ph , 8), 71 (C H O , 3), 70 (5), 55 (C H , 84), 54 (9),
4 7 4 7
10), 111 (6), 105 (13), 93 (8), 91 (18), 87 (6), 81 (7), 77
43 (4), 41 (6), 39 (9); Anal. Calcd for C H O : C, 78.42; H,
17 24 2
9.29. Found: C, 78.41; H, 9.40.
ϩ
ϩ
ϩ
4
7
4
7
4
1 (6), 39 (11); Anal. Calcd for C H O : C, 78.01; H, 9.00.
16 22 2
Found: C, 77.93; H, 9.37.
cis-2-(1-Naphthyl)-4-(3-butenoxy)-tetrahydropyran (9n).
FTIR(film): 1637, 1593, 1505, 1444, 1426, 1356, 1250,
1233, 1176, 1140, 1110, 1079, 1053, 1017, 987, 912, 855,
cis-2-(3-Methylphenyl)-4-(3-butenoxy)-tetrahydropyran
9k). FTIR(film): 1636, 1605, 1484, 1439, 1359, 1252,
Ϫ1
1
(
798, 771, 732 cm ; H NMR (CDCl , 400 MHz, ppm):
3
1
6
7
171, 1144, 1109, 1082, 1028, 992, 956, 912, 885, 782,
dˆ8.10 (d, Jˆ8.2 Hz, 1H), 7.89 (d, Jˆ7.9 Hz, 1H), 7.81
(d, Jˆ7.9 Hz, 1H), 7.68 (d, Jˆ7.0 Hz, 1H), 7.57–7.49 (m,
3H), 5.87 (m, 1H), 5.17–5.07 (m, 2H), 5.06 (dd, Jˆ11.4,
1.2 Hz, 1H), 4.31 (ddd, Jˆ11.7, 4.7, 1.2 Hz, 1H), 3.76 (m,
1H), 3.72 (m, 1H), 3.60 (t, Jˆ6.7 Hz, 2H), 2.46 (m, 1H),
Ϫ1
1
97 cm ; H NMR (CDCl , 400 MHz, ppm): dˆ7.26–
3
.20 (m, 2H), 7.15–7.09 (m, 2H), 5.83 (m, 1H), 5.13–5.03
(
4
(
2
1
1
3
2
m, 2H), 4.28 (dd, Jˆ11.4, 1.8 Hz, 1H), 4.19 (ddd, Jˆ11.7,
.7, 1.5 Hz, 1H), 3.61 (m, 1H), 3.57 (t, Jˆ7.0 Hz, 2H), 3.54
m, 1H), 2.36 (s, 3H), 2.34 (q, Jˆ7.0 Hz, 2H), 2.23 (m, 1H),
2.38 (q, Jˆ6.7 Hz, 2H), 2.11 (m, 1H), 1.82 (m, 1H), 1.77 (m,
1
3
13
.01 (m, 1H), 1.65 (m, 1H), 1.56 (m, 1H); C NMR (CDCl ,
1H); C NMR (CDCl , 100 MHz, ppm): dˆ137.7, 135.3,
3
3
00 MHz, ppm): dˆ142.0, 138.1, 135.2, 128.4, 128.3,
133.9, 130.5, 129.0, 128.2, 126.1, 125.7, 125.5, 123.4,
123.4, 116.5, 75.7, 75.6, 67.2, 66.8, 39.4, 34.7, 32.9; GC/
26.7, 123.1, 116.4, 78.7, 75.5, 67.1, 66.6, 40.2, 34.5,
ϩ
ϩ
ϩ
2.7, 21.5; GC/MS: m/z (% base peak) 247 (M ϩ1, 1),
MS: m/z (% base peak) 283 (M ϩ1, 12), 282 (M , 59), 281
ϩ
ϩ
ϩ
ϩ ϩ
46 (M , 7), 245 (M Ϫ1, 1), 231 (M ϪCH , 1), 175
(M Ϫ1, 2), 211 (M ϪC H O, 21), 210 (81), 209 (80), 182
4 7
3

W.-C. Zhang, C.-J. Li / Tetrahedron 56 (2000) 2403–2411
2411
(
12), 181 (18), 167 (7), 166 (5), 157 (12), 156 (23), 155 (40),
661. (c) Snider, B. B. The Prins and Carbonyl Ene Reactions. In
Comprehesive Organic Synthesis; Trost, B. M., Ed.; Pergamon:
Oxford, 1991; Vol. 2, pp 527–561. Overman has used cation-
alkene cyclization extensively in natural product synthesis, for
an example, see: Overman, L. E.; Thompson, A. S. J. Am. Chem.
Soc. 1988, 110, 2248. For an excellent account on cation-alkene
cyclizations, see: Overman, L. E. Acc. Chem. Res. 1992, 25, 352.
2. Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis,
VCH: Weinheim, 1996.
1
54 (13), 153 (17), 152 (7), 141 (16), 129 (13), 128 (31), 127
ϩ
ϩ
ϩ
(15), 83 (9), 77 (Ph , 3), 71 (C H O , 4), 55 (C H , 100),
4 7 4 7
5
4 (10), 53 (6), 43 (6), 41 (5), 39 (8); Anal. Calcd for
C H O : C, 80.82; H, 7.85. Found: C, 80.71; H, 7.73.
19
22
2
cis-2-t-Butyl-4-(3-butenoxy)-tetrahydropyran (9o). FTIR-
(film): 2955, 2852, 1645, 1467, 1359, 1166, 1142, 1113,
Ϫ1
1
1
093, 1058, 999, 911 cm ; H NMR (CDCl , 400 MHz,
3
ppm): dˆ5.85 (m, 1H), 5.07 (m, 2H), 4.06 (ddd, Jˆ12.9,
3
. The best known method in this regard is probably the hetero-
5
1
1
1
3
1
.0, 1.5 Hz, 1H), 3.60-3.30 (m, 4H), 2.87 (dd, Jˆ11.4,
Diels–Alder reaction with Danishefsky’s Diene, for examples: (a)
Danishefsky, S. J.; Pearson, W. H.; Harvey, D. F. J. Am. Chem.
Soc. 1984, 106, 2456. (b) Danishefsky, S. J.; Maring, C. J. J. Am.
Chem. Soc. 1989, 111, 2193.
.2 Hz, 1H), 2.35 (m, 2H), 2.01–1.91 (m, 2H), 1.43 (m,
1
3
H), 1.20 (m, 1H), 0.91 (s, 9H);
C NMR (CDCl3,
00 MHz, ppm): dˆ135.3, 116.4, 84.3, 76.2, 67.0, 66.2,
4.6, 34.0, 32.9, 32.8, 26.1; GC/MS: m/z (% base peak)
4
. (a) Wei, Z. Y.; Li, J. S.; Wang, D.; Chan, T. H. Tetrahedron
ϩ
ϩ
57 (M ϪC H , 16), 155 (M ϪC H , 16), 141 (20), 85
4
7
4
9
Lett. 1987, 28, 3441. (b) Wei, Z. Y.; Wang, D.; Li, J. S.; Chan, T. H.
J. Org. Chem. 1989, 54, 5768.
(100), 57 (48), 55 (92), 41 (52); Anal. Calcd for
C H O : C, 73.54; H, 11.39. Found: C, 74.02; H, 11.01.
13
24
2
5
9
9
6
1
. (a) Coppi, L.; Ricci, A.; Taddei, M. Tetrahedron Lett. 1987, 28,
73. (b) Coppi, L.; Ricci, A.; Taddei, M. J. Org. Chem. 1988, 53,
13.
. Rychnovsky, S. D.; Hu, Y.; Ellsworth, B. Tetrahedron Lett.
998, 39, 7271. For some other related recent examples of Prins-
cis-2-n-Pentyl-4-(3-butenoxy)-tetrahydropyran
FTIR(film): 3072, 2936, 2854, 1639, 1459, 1355, 1252,
(9p).
Ϫ1
1
1
154, 1104, 1083, 990, 914, 865, 625 cm ; H NMR
(CDCl , 400 MHz, ppm): dˆ5.84 (m, Jˆ7.0 Hz, 1H),
3
cyclization in forming tetrahydropyrans, see: Petasis, N. A.; Lu,
S.-P. Tetrahedron Lett. 1996, 37, 141; Marko, I. E.; Chelle, F.
Tetrahedron Lett. 1997, 38, 2895; Marko, I. E.; Dobbs, A. P.;
Bayston, D. J. Tetrahedron Lett. 1997, 38, 2899; Chan, T. H.;
Arya, P. Tetrahedron Lett. 1989, 30, 4065; Marko, I. E. In Novel
Trends in Electrorganic Synthesis; Torii, S., Ed.; Springer: Berlin,
1998; Metzger, J. O.; Biermann, U. Bull. Soc. Chim. Belg. 1994,
5
.07 (m, 2H), 4.03 (ddd, Jˆ11.7, 5.0, 1.8 Hz, 1H), 3.53
(
(
(
dt, Jˆ12.0, 2.1 Hz, 2H), 3.41 (m, 2H), 3.23 (m, 1H), 2.33
q, Jˆ6.8 Hz, 2H), 1.98 (m, 1H), 1.91 (m, 1H), 1.57–1.14
1
3
m, 10), 0.90 (t, Jˆ7.0 Hz, 3H); C NMR (CDCl ,
3
1
00 MHz, ppm): dˆ135.3, 116.3, 76.4, 75.4, 67.0, 66.0,
3
8.5, 36.0, 34.5, 32.8, 31.6, 27.7, 22.7, 14.1; GC/MS: m/z
ϩ
(% base peak) 171 (M ϪC H , 0.4), 170 (0.6), 155 (5), 141
4
7
1
03, 393; Semeyn, C.; Blaauw, R. H.; Hiemstra, H.; Speckamp, W.
(
31), 111 (10), 85 (15), 69 (18), 55 (100), 41 (49); Anal.
N. J. Org. Chem. 1997, 62, 3426; Rychnovsky, S. D.; Yang, G.;
Hu, Y.; Khire, U. R. J. Org. Chem. 1997, 62, 3022; Lolkema, L.;
Hiemstra, H.; Semeyn, C.; Speckamp, W. N. Tetrahedron 1994,
Calcd for C H O : C, 74.29; H, 11.58. Found: C, 73.90; H,
1
4
26
2
1
1.52.
5
0, 7115; Masuyama, Y.; Gotoh, S.-Y.; Kurusu, Y. Synth.
cis-2-(4-Nitrophenyl)-2,3-dihydropyran (9q). FTIR(film):
Commun. 1995, 25, 1989; Samoshin, V. V.; Gremyachinskiy,
D. E.; Gross, P. H. Mendeleev Commun. 1999, 53.
3
1
035, 2932, 2894, 2829, 1599, 1516, 1343, 1234, 1176,
Ϫ1 1
086, 1022, 920, 843, 741, 690, 657, 517 cm ; H NMR
7
2
8
4
9
. Yi, X. H.; Haberman, J. X.; Li, C. J. Synth. Commun. 1998, 28,
999.
. Yang, J.; Viswanathan, G. S.; Li, C. J. Tetrahedron Lett. 1999,
0, 1627.
. Zhang, W. C.; Viswanathan, G. S.; Li, C. J. Chem. Commun.
(
CDCl , 400 MHz, ppm): dˆ8.20 (d, Jˆ8.2 Hz, 2H), 7.50
3
(
d, Jˆ8.2 Hz, 2H), 5.92 (m, 1H), 5.85 (m, 1H), 4.66 (dd,
1
3
Jˆ10, 4.4 Hz, 1H), 4.39 (m, 2H), 2.35 (m, 2H); C NMR
(CDCl , 100 MHz, ppm): dˆ150.1, 147.2, 126.5, 126.4,
3
1
23.8, 123.6, 74.5, 66.5, 32.9; GC/MS: m/z (% base peak)
ϩ
205 (M , 5), 150 (3), 128 (4), 116 (2), 91 (3), 77 (10), 54
1999, 291.
(
5
100), 39 (20); Anal. Calcd for C H NO : C, 64.38; H,
.40. Found: C, 64.53; H, 5.44.
10. Nishizawa, M.; Shigaraki, T.; Takao, H.; Imagawa, H.;
Sugihara, T. Tetrahedron Lett. 1999, 40, 1153.
1
1
11
3
1
1
1
1. Cloninger, M. J.; Overman, L. E. J. Am. Chem. Soc. 1999, 121,
092.
2. For a leading reference, see: (a) Kobayashi, S.; Hachiya, I.
Acknowledgements
J. Org. Chem. 1994, 59, 3590. For a related review, see: (b)
Kobayashi, S. Synlett 1994, 689; Kobayashi, S. In Organic
Synthesis in Water; Grieco, P. A., Ed., Thomson Science: Glasgow
We are grateful to the support provided by the NSF–EPA
joint program for a Sustainable Environment. Acknowledg-
ment is also made to LEQSF and the NSF Early Career
Award program for partial support of this research. We
also thank Profs M. Karol and S. Andrew for their help on
NOE experiments.
1
1
998; Xie, W.; Jin, Y.; Wang, G. P. Chemtech 1999, 29 (2), 23.
3. For a Yb(OTf) catalyzed allylation of aldehydes with
3
allylsilane, see: Yang, Y.; Wang, M.; Wang, D. Chem. Commun.
1
997, 1651.
1
4. Wigfield, D. C.; Feiner, S. Can. J. Chem. 1978, 56, 789.
References
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