Direct synthesis of tetrahydropyrans via one-pot Babier-Prins cyclization of allylbromide with carbonyl compounds promoted by RTILs BPyX/SnX′2 or BBIMBr/SnBr2

Article abstract of DOI:10.1016/j.tet.2006.04.075

Tetrahydropyran compounds can be directly synthesized from allylbromide and carbonyl compounds by means of one-pot Babier-Prins cyclization promoted by BPyX/SnX′₂ or BBIMBr/SnBr₂ complex (functionalized RTILs) under solvent-free cond

Full text of DOI:10.1016/j.tet.2006.04.075

Tetrahedron 62 (2006) 7113–7120
Direct synthesis of tetrahydropyrans via one-pot Babier–Prins
cyclization of allylbromide with carbonyl compounds
promoted by RTILs BPyX/SnX02 or BBIMBr/SnBr2
*
Xian-Liang Zhao, Li Liu, Yong-Jun Chen and Dong Wang
*
Center for Molecular Science, Chinese Academy of Sciences, Institute of Chemistry, Beijing 100080, PR China
Received 9 February 2006; revised 11 April 2006; accepted 12 April 2006
Available online 19 May 2006
Abstract—Tetrahydropyran compounds can be directly synthesized from allylbromide and carbonyl compounds by means of one-pot
Babier–Prins cyclization promoted by BPyX/SnX02 or BBIMBr/SnBr2 complex (functionalized RTILs) under solvent-free conditions. 2,6-
Homo-bissubstituted- and 2,6,6-trisubstituted, especially 6-(spirocycloalkyl)-, tetrahydropyran compounds can be prepared in good yields.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
by Li,7a during investigation of indium-mediated reaction
of allylbromide with aldehyde under neat conditions, the for-
mation of a mixture of tetrahydropyran-4-ol and 4-bromo-
tetrahydropyran compounds was accidentally observed. It is
interesting to combine Babier reaction with Prins cyclization
into an one-pot tandem reaction system for direct formation
of tetrahydropyran (Eq. 4). Recently, noticeable progress in
the transformation under solvent-free condition has attracted
considerable attention.14 Herein, we report on the direct
synthesis of tetrahydropyran compounds through one-pot
Babier–Prins cyclization of allylbromide with carbonyl
compounds promoted by BPyX/SnX2 or BBIMBr/SnBr2
complex (functionalized RTILs) without the use of organic
solvent.
Tetrahydropyrans are common subunits in a variety of bio-
logically important natural products such as polyether anti-
biotics, marine toxins, pheromones, and pharmaceutical
agents.1 The Prins cyclization2 is one of the most effective
reaction for construction of the tetrahydropyran unit. In
most cases, the Prins cyclization involves the condensation
of homoallylic alcohol with carbonyl compounds (Eq. 2)
in the presence of protic acid3 or Lewis acid, such as
TiBr4,4 ZrCl4,5 AlCl3,6 InCl3,7 Sc(OTf)3,8 Ce(OTf)3$H2O
in ionic liquid,9 as well as TMSCl/NaI.10 The homoallylic
alcohols can be prepared by means of Babier reaction11
(Eq. 1), Grignard reaction (Eq. 2) or reaction of organo-
lithium reagents with aldehydes (Eq. 2). Alternatively, allyl
silyl12 and allyltin13 reagents can also react with aldehydes
in the presence of Lewis acid to give tetrahydropyran com-
pounds (Eq. 3). However, there are few examples of direct
formation of tetrahydropyran compounds via one-pot reac-
tion of allylhalide with carbonyl compounds. As reported
Babier Reaction
OH
M or MXn
(1)
X
RCHO
R
(M: Zn, In, Sn, Bi, Ga...)
Prins Cyclization
X
M' (Li, Mg)
R'CHO
Cat.
RCHO
OH
M'
(2)
(3)
R
R
O
R'
X
X
M" ( Si, Sn)
RCHO
M"
Lewis acid
R
O
R
Keywords: Babier–Prins cyclization; Allylbromide; Carbonyl compound; BBIMBr/SnBr2; Tetrahydropyran; Direct synthesis.
* Corresponding authors. Fax: +86 10 6255 4449; e-mail: dwang70118@yahoo.com
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.075

7114
X.-L. Zhao et al. / Tetrahedron 62 (2006) 7113–7120
Babier-Prins Cyclization (one pot, tandem reaction)
SnCl2$2H2O) was employed in the reaction of allylbromide
2 with benzaldehyde 1a (IA$2H2O:2:1a¼2:1.2:1) without
the use of any organic solvent at room temperature for
24 h (Scheme 1). The homoallylic alcohol 3a was obtained
in 93% yield, which is consistent with the observation of
Li.19 However, it is interesting to note that if complex IA de-
rived from anhydrous SnCl2 and BPyCl was used under the
same reaction conditions, a mixture of 3a (22%), 4-chloro-
(4b), and 4-bromo-2,6-diphenyltetrahydropyran (4a) (67%,
4a+4b) produced (Scheme 1). When the ratio of 2 to 1a
was changed to 1:2, only tetrahydropyran compounds (4a
and 4b) were obtained in 78% yield, but no homoallylic
alcohol 3a was detected (Scheme 2, Table 1, entry 1).
A series of RTILs (IA–IE) containing various tin halides
were synthesized and employed in the reaction of 1a with 2.
The results in Table 1 showed that the halide atom in the
4-position of the formed tetrahydropyran unit originates
from substrate 2 and complex BPyX/SnX02. The use of ID
(X and X0¼Br) provided a single product 4a in 80% yield
(entry 4). However, in most cases, the reaction system be-
came too sticky to be stirred during the course of the reaction
promoted by ID without using organic solvent. For improv-
ing the fluidity of the complex as a reaction medium, two
complexes of imidazole salts with SnBr2 (1:1.5, IIA and
IIB)18 were synthesized and also employed in the reaction
of 2 with 1a. As shown in Table 1 BBIMBr/SnBr2 (IIB) is
a better reaction system than ID and IIA (entry 4 vs 7 and
6 vs 7). Moreover, for most substrates used, the reaction sys-
tems employed IIB were in a liquid state during the course
of the reaction. If SnBr2 was used alone (without quaternary
ammoniumsalt), the reaction of 1awith 2didnot proceed and
starting materials were recovered, even after 24 h (entry 8).
X
M or MXn
RCHO
X
(4)
R
O
R
2. Results and discussion
2.1. Direct synthesis of 4-halo-2,6-homo-bissubstituted-
tetrahydropyrans
SnCl2-mediated Babier-type reaction of allylhalides with
carbonyl compounds yield homoallylic alcohol, though re-
quiring additional catalyst in most cases.15 Among the cata-
lysts suitable to this type of reaction, quaternary ammonium
salts are more convenient.16 It is also noteworthy that the
combination of quaternary ammonium salts with stannous
halides can generate a room temperature liquid state com-
plex (so-called room temperature ionic liquid: RTILs).17
Thus, it is expected that a complex of a quaternary ammo-
nium salt with SnCl2 can serve as both functionalized
reagent with Lewis acidity and reaction media.
SnX'2
SnBr2
+
+
N
N
R
Bu
X-
N
Br-
Bu
IA, X:Cl, X':Cl
IB, X:Cl, X':Br
IC, X:Br, X':Cl
ID, X:Br, X':Br
IE, X: I, X': Cl
IIA, R:CH3
IIB, R: Bu
Meanwhile, in order to examine solvent effects, various sol-
vents were used as reaction media in the reaction of 1a with 2
promoted by IIB (Scheme 3, Table 2). It was found that in
organic solvents the reactions gave homoallylic alcohol 3a
According to the authors,18 the complexes (IA–E) of N-
benzylpyridine halides (BPyX) with SnX02 (1:2) were easily
synthesized. At first, the complex IA$2H2O (BPyCl/
OH
CHO
3a
Br
+
OH
Cl
Br
1a
2
+
+
1a/2 = 1 : 1.2
Ph
O
Ph
Ph
O
Ph
3a
4a
4b
Scheme 1.
I
Cl
Br
CHO
+
Br
+
+
BPyX /SnX'2, rt
Ph
O
Ph
Ph
O
Ph
Ph
O
Ph
4c
4a
1a
2
4b
1a/2 = 2 : 1
Scheme 2.

X.-L. Zhao et al. / Tetrahedron 62 (2006) 7113–7120
Table 1. The reaction of 1a with 2 promoted by complex I or IIa
7115
On the basis of the above experimental results, a variety of al-
dehydes were employed in the reactions with allylbromide 2
promoted by IIB without the use of organicsolvent, affording
the products of 4-bromo-2,6-homo-bissubstituted-tetrahy-
dropyrans (Scheme 3, Table 3). As shown in Table 3 both
aromatic and aliphatic aldehydes are able to react with 2 to
directly generate tetrahydropyran compounds 4a–l in moder-
ate to good yields (52–86%). The stereochemistry of 2,4,6-
trisubstituents of the tetrahydropyran ring was found to be
all-cis in all cases. The assignment was based on the coupling
constants of the protons at the C-2, C-4, and C-6 positions.
The coupling constants of 11.0–12.7 Hz were observed for
all such protons, indicating the presence of axial–axial cou-
pling. The three substituents are therefore all in equatorial
positions, in agreement with an all-cis stereochemistry.12b
Entry
Complexes (I and II)b
Yieldc (%) (4b:4a:4c)d
1
2
3
4
5
6
7
8
IA
IB
IC
ID
78 (5.3:1:0)
90 (1:1:0)
77 (3.2:1:0)
80 (0:1:0)
IE
89 (1.6:1:2.5)
81 (0:1:0)
86 (0:1:0)
IIA
IIB
SnBr2
e
—
a
Reaction time: 24 h at rt.
BPyX/SnX02¼1:2.
Determined by 1H NMR.
Starting materials were recovered.
b
c
d
e
Isolated yield.
2.2. A plausible reaction mechanism
solely or a mixture of 3a and tetrahydropyran compound 4a.
Only under solvent-free conditions the single product, tetra-
hydropyran compound 4a was obtained in 86% yield (Table
2, entry 5).
In the mechanism for the present reaction, it is assumed that
at the first is a Babier-type reaction of allylbromide with
SnBr2 in the presence of quaternary ammonium salt to pro-
duce allyltin compound A,15d which subsequently undergoes
reaction with aldehyde to generate the reactive intermediate
B. This intermediate exhibits high reactivity to give two dif-
ferent products (C and D) by two pathways (Scheme 4, path
a and b). In pathway (a), B could be hydrolyzed by the water
in the reaction system or during work-up procedure, giving
homoallylic alcohol C as product. However, under strict
anhydrous conditions the intermediate B was sufficiently
activated to react with another aldehyde molecule via path-
way (b) affording a Prins cyclization product, tetrahydro-
pyran compound D.8 It is interesting to note that when
homoallylic alcohol C was mixed with aldehyde in the pres-
ence of IIB, no reaction product D was detected.
Br
Br
+
RCHO
IIB(BBIMBr /SnBr2), rt
R
O
R
1a-j
2
4a-l
Scheme 3.
Table 2. The reaction of 1a with 2a
Entry
Solventb
Yieldc (%) (3a:4a)
1
2
3
4
5
THF
DMF
CH3CN
CH2Cl2
None
44 (44:0)
72 (72:0)
67 (13:54)
73 (8:65)
86 (0:86)
2.3. Direct synthesis of 4-bromo-2,6,6-trisubstituted-
tetrahydropyran
For preparing 2,6-cross-substituted-tetrahydropyran, two
different aromatic aldehydes were used in the reaction; a
mixture of the products containing 2,6-homo- and 2,6-
cross-bissubstituted-tetrahydropyrans was obtained. In view
a
1a:2:IIB¼2:1:2, 24 h at rt.
All solvents are anhydrate.
Isolated yield.
b
c
OH
H2O
(a)
R
C
OSnX3
BBIMX/SnX2
X
RCHO
X
SnX3
+
BBIMX/SnX2
R'CHO
R
B
A
R'CHO
SnO
(b)
R'
O
R
-[SnO]
X
X-
R'
O
R
R'
O
R
R'
O
R
D
Scheme 4.

7116
X.-L. Zhao et al. / Tetrahedron 62 (2006) 7113–7120
Table 3. Direct synthesis of 4 via reaction of 2 with 1 promoted by IIBa
Entry
1
Aldehyde
Product
Yield (%)b
Br
4a
CHO
1a
86
O
Br
4d
CHO
Cl
1b
2
3
4
5
6
7
78
78
82
75
54
60
O
Cl Cl
Br
4e
CHO
1c
O
Cl
Cl
4f
Cl
Br
1d
CHO
Br
O
Br Br
Br
4g
1e
CHO
F
O
F
F
Br
4h
1f
CHO
O
F3C
F3C
CF3
Br
O
4i
CHO
1g
H3C
H3C
CH3
Br
4j
1h
CHO
8
9
82
72
O
Br
4k
1i
CHO
O
Br
4l
CHO
1j
10
79
O
BnO
BnO
OBn
a
Reaction time: 24 h at rt, 1:2¼2:1.
b
Isolated yield.
of the plausible reaction mechanism discussed above, for-
mation of 2,6-homo-bissubstituted product may be retarded
by use of a relatively less reactive carbonyl compound in the
first step. Thus, the reaction could stop at intermediate B and
not go on to generate homo-bissubstituted-tetrahydropyran
compound. Then, more active aldehyde may be added to
continue the reaction with B to give 2,6-cross-bissubsti-
tuted-tetrahydropyran. Interestingly, when cyclic ketones
with less reactivity were used, 6-(spirocycloalkyl)-2-
substituted-tetrahydropyran compounds were obtained

X.-L. Zhao et al. / Tetrahedron 62 (2006) 7113–7120
7117
Table 4. Direct synthesis of cross-bissubstituted tetrahydropyrans 6 via reaction of 2 with carbonyl compounds
Entry
Ketone
Timea (h)
Aldehyde
Timeb (h)
Product
Yieldc (%)
Br
6a
O
5a
CHO
1a
1
6
10
85
O
Br
6b
CHO
1k
2
6
10
76
MeO
O
Br
O
OMe
CN
6c
CHO
1l
3
4
6
6
10
10
78
72
NC
Br
6d
1h
CHO
O
Br
6e
O
5b
5
6
5
5
1a
10
10
74
68
O
Br
6f
CHO
Cl
1b
O
Cl
Br
6g
CHO
1c
7
8
5
5
10
10
70
64
O
Br
O
Cl
Cl
6h
CHO
1g
Me
Me
Br
6i
5c
O
9
8
8
1a
10
10
67
54
O
Br
6j
1i
10
CHO
O
Br
6k
O
5d
11
8
1a
10
64
O
a
Reaction time with ketone in the first step.
Reaction time with aldehyde in the second step.
Isolated yield.
b
c

7118
X.-L. Zhao et al. / Tetrahedron 62 (2006) 7113–7120
(Scheme 5). For example, cyclohexanone 5a was allowed to
react with allylbromide 2 in the presence of IIB for 6 h.
Then, benzaldehyde 1a was added, followed by stirring for
10 h to give the product, 4-bromo-2-phenyl-6-(spirocyclo-
hexyl)tetrahydropyran 6a in 85% yield (Table 4, entry 1).
No 2,6-diphenyltetrahydropyran 4a and 2,6-bis(spirocyclo-
hexyl)tetrahydropyran were observed in the reaction mix-
ture. It is indicated in Table 4 that either cyclic or acyclic
ketones, and aromatic or aliphatic aldehydes can be em-
ployed in the one-pot Babier–Prins cyclization, affording
the products of 4-bromo-2,6,6-trisubstituted-tetrahydro-
pyrans 6a–i in good yields of 64–85%. The stereochemistry
of the substituents at C-4 and C-2 positions was deduced as
cis in consideration of the coupling constants for the
protons (Jw11 Hz). The method of one-pot Babier–Prins
cyclization provided a direct and convenient synthesis of
2,6,6-trisubstituted-tetrahydropyran compounds, especially
for constructing a structural unit of 6-(spirocycloalkyl)-
2-substituted-tetrahydropyran, which is of importance in
organic synthesis and not easily prepared by conventional
methods.20
from BBIMBr (522 mg, 2.0 mmol), and SnCl2 (1100 mg,
4.0 mmol) was stirred at ambient temperature for 24 h.
The reaction mixture was extracted with diethyl ether. The
combined ether phases were washed by 2 mL aqueous
HCl, and dried over Na2SO4. The solvent was removed in
vacuum and the crude product was purified by flash chroma-
tography on silica gel (eluent: ethyl acetate/petroleum ether,
1:40) to afford a white solid 4a (273 mg, 86%).
4.3. Typical experimental procedure for the synthesis of
4-bromo-2,6,6-trisubstituted-tetrahydropyrans
A mixture of cyclohexanone (294 mg, 3.0 mmol), allylbro-
mide (120 mg, 1.0 mmol) and complex IIB derived from
BBIMBr (522 mg, 2.0 mmol), and SnBr2 (840 mg,
3.0 mmol) was stirred at ambient temperature for 6 h.
Then benzaldehyde 1a (106 mg, 1.0 mmol) was added,
followed by stirring for 10 h. The reaction mixture was
extracted with diethyl ether. The combined ether phases
were washed by 2 M aqueous HCl, and dried over
Na2SO4. The solvent was removed in vacuum and the crude
product was purified by flash chromatography on silica gel
(eluent: ethyl acetate/petroleum ether, 1:40) to afford
a pale-yellow oil 6a (260 mg, 85%).
Br
R
R
R'CHO
Br
O
+
R
R
IIB(BBIMBr) /SnBr2, rt
O
R'
4.3.1. 2-Phenyl-4-bromo-1-oxaspiro[5.5]undecane 6a. 1H
NMR (CDCl3) d 7.28–7.58 (m, 5H), 4.65 (d, J¼10.1 Hz,
1H), 4.45–4.58 (m, 1H), 2.49–2.58 (dm, J¼10.7 Hz, 1H),
2.26–2.36 (dm, J¼11.8 Hz, 1H), 1.73–2.10 (m, 5H), 1.37–
1.57 (m, 7H); 13C NMR (CDCl3) d 142.2, 128.4, 127.5,
125.8, 75.2, 71.6, 47.1, 45.6, 45.5, 40.0, 30.3, 26.0, 21.7,
21.3. FTIR (film): 2931, 1494, 1447, 1331, 1172,
1060 cmꢀ1. HRMS (EI): m/z calcd for C16H21OBr:
308.0775, found: 308.0776.
2
6a-k
5a-d
Scheme 5.
3. Conclusion
Babier and Prins reactions can be combined into an one-pot
tandem reaction system promoted by functionalized RTILs
derived from quaternary ammonium salt and Sn(II) halides.
By utilizing this method, either 2,6-homo-bissubstituted
or 2,6,6-trisubstituted-tetrahydropyran, especially 6-(spiro-
cycloalkyl)-2-substituted-tetrahydropyran compounds can
be directly synthesized from allylbromide and carbonyl
compounds. The study on scope of the reaction and applica-
tion in the synthesis of natural compounds is in process.
4.3.2. 2-(40-Methoxyphenyl)-4-bromo-1-oxaspiro[5.5]un-
decane 6b. A yellow oil. 1H NMR (CDCl3) d 7.33 (d,
J¼8.7 Hz, 2H), 6.9 (d, J¼8.8 Hz, 2H), 4.46–4.58 (m, 2H),
3.82 (s, 3H), 2.43–2.51 (dm, J¼11.4 Hz, 1H), 2.23–2.32
(dm, 12.6 Hz, 1H), 1.99–2.10 (m, 1H), 1.60–1.90 (m, 3H),
1.31–1.59 (m, 8H); 13C NMR (CDCl3) d 158.9, 134.3,
127.1, 113.7, 75.2, 71.2, 55.3, 45.6, 45.3, 40.0, 30.3, 26.0,
21.7, 21.3. FTIR (film): 2932, 2856, 1613, 1513, 1446,
4. Experimental
4.1. General
1246, 987, 829 cmꢀ1
. HRMS (EI): m/z calcd for
C17H23O2Br: 338.0881, found: 338.0887.
IR spectra were recorded on a Bruker Tensor 27 infra-red
4.3.3. 2-(40-Nitrilphenyl)-4-bromo-1-oxaspiro[5.5]un-
decane 6c. A yellow oil. 1H NMR (CDCl3) d 7.60 (d,
J¼7.9 Hz, 2H), 7.52 (d, J¼7.9 Hz, 2H), 4.63 (d, J¼
11.2 Hz, 1H), 4.39–4.54 (m, 1H), 2.45–2.55 (dm, J¼
11.9 Hz, 1H), 2.24–2.33 (dm, J¼12.0 Hz, 1H), 1.99–2.10
(m, 1H), 1.67–1.84 (m, 4H), 1.36–1.52 (m, 7H); 13C NMR
(CDCl3) d 147.4, 132.2, 126.4, 118.8, 111.1, 75.5, 70.9,
46.8, 45.1, 44.4, 39.8, 30.1, 25.8, 21.6, 21.2. FTIR (film):
1
spectrometer. H and 13C NMR spectra were measured by
Bruker AV-300 spectrometers in CDCl3 with tetramethyl-
silane as an internal standard. Mass spectra were recorded
on a GCT–MS Micromass spectrometer. Elemental analyses
were performed on a Carlo Flash 1112 Element Analysis in-
strument. Melting points were measured by a Beijing-Tike
X-4 apparatus and were uncorrected. Common reagents
and materials were purchased from commercial sources
and purified before used. Complexes IA–IE and IIA–IIB
were synthesized according to literature procedures.18
2932, 2851, 2227, 1609, 1447, 1172, 1071, 986, 831 cmꢀ1
.
HRMS (EI): m/z calcd for C17H20OBr: 333.0728, found:
333.0726.
4.2. Typical experimental procedure for the synthesis of
4-bromo-2,6-homo-bissubstituted-tetrahydropyrans
4.3.4. 2-(Isopropyl)-4-bromo-1-oxaspiro[5.5]undecane
6d. A light-yellow oil. H NMR (CDCl3) d 4.31–4.42 (m,
1
A mixture of benzaldehyde (1a, 212 mg, 2.0 mmol), allyl-
bromide (2, 120 mg, 1.0 mmol) and complex IIB derived
1H), 3.17–3.08 (m, 1H), 2.34–2.25 (m, 1H), 2.17–2.10 (m,
1H), 1.99–2.07 (m, 1H), 1.58–1.76 (m, 7H); 13C NMR

X.-L. Zhao et al. / Tetrahedron 62 (2006) 7113–7120
7119
(CDCl3) d 74.8, 74.1, 48.0, 46.7, 41.4, 39.9, 33.5, 33.1, 30.0,
26.0, 21.6, 20.9, 18.8, 18.5. FTIR (film): 2933, 2857, 1447,
1384, 1167, 1065 cmꢀ1. HRMS (EI): m/z calcd for
C13H23OBr: 274.0932, found: 274.0929.
4.3.11. 2-Phenyl-6,6-diethyl-tetrahydropyran 6k. A yel-
low oil. H NMR (CDCl3) d 7.28–7.41 (m, 5H), 4.50–4.60
1
(m, 2H), 2.42–2.50 (dm, J¼12.6 Hz, 1H), 2.17–2.26 (dm,
J¼12.9 Hz, 1H), 1.87–2.02 (m, 3H), 1.55–1.64 (m, 3H),
0.92 (t, J¼7.5 Hz, 6H); 13C NMR (CDCl3) d 142.1, 128.4,
127.6, 125.9, 78.5, 72.4, 45.9, 45.5, 43.5, 31.8, 24.0, 7.5,
7.1. FTIR (film): 2968, 2936, 2878, 1452, 1335, 1058,
987, 757, 699 cmꢀ1. HRMS: m/z calcd for C15H21OBr:
296.0776, found: 296.0772.
4.3.5. 2-Phenyl-4-bromo-1-oxaspiro[5.4]decane 6e. A
yellow oil. H NMR (CDCl3) d 7.25–7.45 (m, 5H), 4.5
1
(d, J¼11.4 Hz, 1H), 4.33–4.45 (m, 1H), 2.43–2.52 (dm,
J¼12.7 Hz, 1H), 2.11–2.23 (m, 2H), 1.90–2.04 (m, 3H),
1.27–1.69 (m, 6H); 13C NMR (CDCl3) d 141.9, 128.4,
127.6, 125.9, 85.8, 73.9, 46.6, 46.1, 45.3, 41.5, 33.0, 24.6,
23.1. FTIR (film): 2958, 2868, 1448, 1335, 1059, 995,
753, 699 cmꢀ1. HRMS (EI): m/z calcd for C15H19OBr:
294.0619, found: 294.0615.
Acknowledgements
We are grateful to the National Natural Foundation of China
and Chinese Academy of Sciences for their financial
support.
4.3.6. 2-(20-Chlorophenyl)-4-bromo-1-oxaspiro[5.4]-
decane 6f. A yellow oil. 1H NMR (CDCl3) d 7.69 (d,
J¼7.2 Hz, 1H), 7.35–7.21 (m, 3H), 4.90 (d, J¼11.2 Hz,
1H), 4.45–4.34 (m, 1H), 2.63–2.55 (dm, J¼12.6 Hz, 1H),
2.24–2.10 (m, 2H), 1.94–1.83 (m, 2H), 1.60–1.26 (m, 7H);
13C NMR (CDCl3) d 139.3, 131.6, 129.2, 128.5, 127.4,
127.2, 86.0, 70.7, 46.7, 45.7, 43.5, 41.6, 32.9, 24.7, 23.1.
References and notes
1. (a) Ohuchida, S.; Hamanaka, N.; Hayashi, M. Tetrahedron
1983, 39, 4257–4261; (b) Kale, V. N. D.; Clive, L. J. J. Org.
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2. For reviews of the Prins reaction, see: (a) Arundale, E.;
Mikeska, L. A. Chem. Rev. 1952, 51, 505–555; (b) Adams,
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1493–1501.
FTIR (film): 2956, 2870, 1474, 1438, 1067, 994 cmꢀ1
.
HRMS (EI): m/z calcd for C15H18OClBr: 328.0230, found:
328.0234.
4.3.7. 2-(40-Chlorophenyl)-4-bromo-1-oxaspiro[5.4]-
decane 6g. A yellow oil. H NMR (CDCl3) d 7.28–7.34
1
(m, 5H), 4.51 (d, J¼11.4 Hz, 1H), 4.32–4.44 (m, 1H),
2.40–2.50 (dm, J¼12.7 Hz, 1H), 2.15–2.21 (m, 2H), 1.90–
1.98 (m, 3H), 1.57–1.77 (m, 6H); 13C NMR (CDCl3)
d 140.4, 133.2, 128.5, 127.3, 85.9, 73.2, 46.5, 45.6, 45.3,
41.4, 32.9, 24.6, 23.0. FTIR (film): 2959, 2868, 1490,
1335, 1207, 1066, 822, 729 cmꢀ1. HRMS (EI): m/z calcd
for C15H18OClBr: 328.0230, found: 328.0233.
3. Hart, D. J.; Bennett, C. E. Org. Lett. 2003, 5, 1499–1502 and
references cited therein.
4. Patterson, B.; Marumoto, S.; Rychnovsky, S. D. Org. Lett.
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hedron 2000, 56, 2403–2411.
4.3.8. 2-(40-Methylphenyl)-4-bromo-1-oxaspiro[5.4]-
decane 6h. A yellow oil. H NMR (CDCl3)n d 7.23 (d,
1
J¼7.1 Hz, 2H), 7.13 (d, J¼7.7 Hz, 2H), 4.48 (d,
J¼11.4 Hz, 1H), 4.31–4.43 (m, 1H), 2.39–2.48 (dm,
J¼12.6 Hz, 1H), 2.17 (s, 3H), 1.98–2.04 (m, 2H), 1.75–
1.87 (m, 3H), 1.39–1.52 (m, 6H). FTIR (film): 2957, 2867,
1514, 1445, 1288, 1063, 996, 812 cmꢀ1. HRMS (EI): m/z
calcd for C16H21OBr: 308.0776, found: 308.0777.
4.3.9. 2-Phenyl-6,6-dimethyl-tetrahydropyran 6i. A yel-
low oil. H NMR (CDCl3) d 7.21–7.55 (m, 5H), 4.59 (d,
9. Keh, C. C. K.; Namboodiri, V. V.; Varma, R. S.; Li, C.-J.
Tetrahedron Lett. 2002, 43, 4993–4996.
1
J¼11.2 Hz, 1H), 4.39–4.55 (m, 1H), 2.40–2.50 (dm,
J¼12.7 Hz, 1H), 2.18–2.28 (dm, J¼12.7 Hz, 1H), 1.87–
2.02 (m, 2H), 1.30 (s, 6H); 13C NMR (CDCl3) d 141.9,
128.5, 127.8, 126.0, 79.7, 74.4, 73.3, 47.8, 45.4, 31.6,
22.4. FTIR (film): 2975, 2924, 2876, 1450, 1190, 1061,
973, 754 cmꢀ1. HRMS (EI): m/z calcd for C13H17OBr:
268.0464, found: 268.0463.
10. Sabitha, G.; Reddy, K. B.; Kiran Kumar Reddy, G. S.; Fatima,
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13. (a) Gambaro, A.; Boaretto, A.; Marton, D.; Tagliavini, G.
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Boaretto, A.; Marton, D.; Tagliavini, G. J. Organomet. Chem.
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4.3.10. 2-Ethyl-6,6-dimethyl-tetrahydropyran 6j. A light-
yellow oil. H NMR (CDCl3) d 4.28–4.38 (m, 1H), 3.42–
1
3.46 (m, 1H), 2.16–2.22 (dm, J¼10.6 Hz, 1H), 1.82 (t,
J¼12.5 Hz, 1H), 1.46–1.65 (m, 4H), 1.24 (s, 3H), 1.18 (s,
3H), 0.94 (t, J¼7.4 Hz, 3H); 13C NMR (CDCl3) d 73.6,
72.2, 48.0, 46.0, 43.5, 31.4, 29.1, 22.3, 9.7. FTIR (film):
2974, 2877, 1464, 1381, 1195, 1084 cmꢀ1. HRMS (EI):
m/z calcd for C9H17BrO: 220.0460, found: 220.0463.

7120
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659–666 and references cited therein.