Acetonyltriphenylphosphonium bromide in organic synthesis: A useful catalyst in the cyclotrimerization of aldehydes

Article abstract of DOI:10.1016/S0040-4020(01)00588-9

Acetonyltriphenylphosphonium bromide (ATPB) is a useful catalyst for the cyclotrimerization of the aliphatic aldehydes under solvent-free condition. The aldehydes tethered with a variety of functionality such as olefin, ether, ester, bromide, azide and diester could also be cyclotrimerized under the catalysis of ATPB.

Full text of DOI:10.1016/S0040-4020(01)00588-9

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 6181±6188
Acetonyltriphenylphosphonium bromide in organic synthesis:
a useful catalyst in the cyclotrimerization of aldehydes
Yung-Son Honp and Chia-Fu Lee
Department of Chemistry, National Chung Cheng University, Chia-Yi, Taiwan 621, Taiwan, R.O.C.
Received 30 March 2001; accepted 21 May 2001
AbstractÐAcetonyltriphenylphosphonium bromide (ATPB) is a useful catalyst for the cyclotrimerization of the aliphatic aldehydes under
solvent-free condition. The aldehydes tethered with a variety of functionality such as ole®n, ether, ester, bromide, azide and diester could also
be cyclotrimerized under the catalysis of ATPB. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
results of our efforts in this direction.
The common catalysts to prepare 1,3,5-trioxanes from alde-
hydes are protic acids,1 ZSM-5 zeolites,2 bentonitic earth,3
Lewis acids,4 heteropoly acids such as H3PMo12O40,5
organic metal oxides such as MeReO3,6 and ion exchange
resin.7 Most of these reports focused on the cyclotrimeri-
zation of a few simple aldehydes and the conversion yields
of the reactions were usually not high. Zhu and Espenson
did a more comprehensive study on this type of reaction.
However, methylrhenium trioxide (MTO) is a very effective
but expensive catalyst.6 Acetonyltriphenylphosphonium
bromide (ATPB) is a precursor to prepare the corresponding
phosphonium ylide, which is useful in the Wittig reaction.
Interestingly, we found that ATPB is an extremely ef®cient
catalyst for the protection and deprotection of alcohols as
alkyl vinyl ethers.8 ATPB (mp 221±2238C) can be easily
and economically prepared from triphenylphosphine and
bromoacetone in benzene at room temperature. It is soluble
in CH2Cl2, CHCl3, MeOH, EtOH and CH3CN but not in
THF, Et2O, benzene and EtOAc. When aldehyde 1 was
dissolved in a mixture of MeOH and CH2Cl2 in the presence
of ATPB, dimethylacetal 1b was formed in excellent yield
in 5 min. We also found that ATPB could catalyze the
cyclotrimerization of 3-phenylpropanal (1) in CH2Cl2 to
give the corresponding 1,3,5-trioxane 1a in 38% yield
(Eq. (1)). Since practical applications abound for 1,3,5-
trioxanes in different ®elds,9 to ®nd an economic and effec-
tive catalyst under mild preparation condition should be
attractive and useful in organic synthesis. Encouraged by
the result in Eq. (1), we tried to improve the reaction yield
and investigate the scope of ATPB catalyst in the cyclo-
trimerization of aldehydes. In this report, we describe the
ꢀ1†
2. Results and discussion
We tried to improve the chemical yield of the cyclotrimeri-
zation of the aldehyde by mixing and stirring the aldehyde
and ATPB together with or without solvent. In order to ®nd
the optimal yield for the reaction in Eq. (1), several reaction
conditions were investigated as shown in Table 1. The
conclusions of these ®ndings are described as follows:
(1) the substituent on the triphenylphosphonium salts
affected their catalytic activity signi®cantly. Replacing the
substituent from acetonyl (i.e. catalyst A) to methoxycarbo-
nylmethyl (i.e. catalyst B) on the phosphine resulted in no
reaction (entries 1 and 11, Table 1). Only ATPB is effective
to the cyclotrimerization. (2) The use of solvents such as
CH2Cl2 and CHCl3 led to a poor conversion yield of the
reaction even though the reaction time was extended to
48 h (entries 2±5, 7±10). (3) The reaction afforded a higher
yield of 1,3,5-trioxane under solvent-free condition, which
is a more environmentally friendly synthetic process
(entries 2±5, 7±10 vs entries 12±20).10 (4) Only 0.05±
0.1 mol equiv. of ATPB was enough to achieve good
Keywords: acetonyltriphenylphosphonium bromide; cyclotrimerization;
solvent-free synthesis.
p
Corresponding author. Tel.: 1886-5-2720411 ext. 66412; fax: 1886-5-
2721040; e-mail: cheysh@ccunix.ccu.edu.tw
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00588-9

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Y.-S. Hon, C.-F. Lee / Tetrahedron 57 (2001) 6181±6188
Table 1. Cyclotrimerization of aldehyde 1 catalyzed by the triphenylphosphonium salts
Entry
Catalyst (mol equiv.)
Solvent
Time (h)
Conversion (%)a
1
2
3
4
5
6
7
8
A (0.1)
B (0.1)
B (0.1)
B (0.1)
B (0.1)
B (0.1)
B (0.1)
B (0.1)
B (0.1)
B (0.1)
A (0.1)
B (0.05)
B (0.05)
B (0.05)
B (0.1)
B (0.1)
B (0.1)
B (0.2)
B (0.2)
B (0.2)
CH2Cl2 (2 M)
CH2Cl2 (2 M)
CH2Cl2 (2 M)
CH2Cl2 (2 M)
CH2Cl2 (2 M)
MeOH/CH2Cl2
CHCl3 (2 M)
CHCl3 (2 M)
CHCl3 (2 M)
CHCl3 (2 M)
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
1
1
5
24
48
1/12
1
0
36
44
43
44
95c
39
42
37
36
0
56
71
74d
64
73
80e
72
74
74
b
5
9
24
48
24
1
5
24
1
5
24
1
5
24
10
11
12
13
14
15
16
17
18
19
20
Neat
a
1
Determined by the integration of the 400 MHz H NMR at d 9.83 (for aldehyde 1) and d 4.82 (for trioxane ring protons 1a).
The volume ratio of MeOH and CH2Cl2 is 1:1.
b
c
d
e
The corresponding dimethyl acetal 1b is formed in 95% yield.
69% isolated yield and recovered 19% aldehyde 1.
74% isolated yield and recovered 15% aldehyde 1.
yield. The optimal conversion yield of the reaction was
about 80% in the presence of 0.1 mol equiv. of ATPB at rt
for 24 h (entry 17). More catalyst (0.2 mol equiv.) did not
improve the reaction in rate and chemical yield (entry 17 vs
entry 20). We could easily separate 1,3,5-trioxane 1a from
the remaining aldehyde 1 by silica gel column chroma-
tography. The characteristic peak from the trioxane ring
aldehyde) and a sterically hindered aldehyde (i.e. pival-
aldehyde).
Interestingly, under the same reaction conditions, 5,5-
dimethoxylpentanal (20)11 undergo the intramolecular
cyclization instead of cyclotrimerization. We isolated a dia-
stereomeric mixture of 2,6-dimethoxytetrahydropyran (20b)
and (20b0) (20b/20b0ˆ1:5) in 78% yield. The formation of
the tetrahydropyran products was explained as follows. The
pKa of ATPB is about 6.6.12 Therefore, ATPB is acidic
enough to protonate the dimethylacetal to give the oxonium
ion intermediate 20-A, which undergoes cyclization to give
the cyclic oxonium ion intermediate 20-B. The nucleophilic
addition of methanol to the intermediate 20-B to give two
diastereomers of 2,6-dimethoxytetrahydropyran (20b and
20b0) (Eq. (2)).
1
protons of the trimer 1a in 400 MHz H NMR appears at
d 4.82 (t, Jˆ5.2 Hz). All three substituents are oriented
equatorially, as con®rmed by X-ray crystallography.
Based on the results in Table 1, the following typical pro-
cedure was chosen for further study. Aldehyde (5 mmol)
and ATPB (0.5 mmol) were mixed together under N2 and
stirred at rt for 24 h. In general, the conversions of the
reactions in Table 2 ranged from modest to good. ATPB
is effective to the cyclotrimerization of the straight chain
and branched-chain aldehydes (entries 1±5 and 7, Table 2).
The aldehydes tethered with a variety of functionalities such
as ole®n (entries 8 and 9), ether (entry 10), ester (entries
11±15), bromide (entries 16±17), azide (entry 18) and
diester (entry 19) could also be trimerized under the
catalysis of ATPB. Interestingly, although dihydrocitro-
nellal (7) underwent cyclotrimerization in 65% yield, no
reaction occurred when citronellal (6) was used in the
reaction (entries 6 and 7). We recovered about 80% of
the starting material 6. However, the double bonds on
compounds 8 and 9 did not retard the reaction (entries
8±9). Comparison of the results in entries 6, 8, and 9
indicates that the spacer chain length between ole®n and
aldehyde is important to the cyclotrimerization. We do not
have a suitable explanation to their differences in reactivity.
In general, ATPB is effective to the reaction using uncoju-
gated aliphatic aldehydes. On the other hand, ATPB is
ineffective to the reactions using the conjugated aldehydes
(i.e. acrolein, crotonaldehyde, benzaldehyde and cinnam-
ꢀ2†
Alkaline hydrolysis of the triester 13a gave the correspond-
ing tricarboxylic acid 13b in 52% yield. Since the product is
very soluble in water, its isolation procedure is tedious. On
the other hand, Pd/C catalyzed hydrogenolysis of the tri-
benzyl ester 15a gave the corresponding tricarboxylic acid

Y.-S. Hon, C.-F. Lee / Tetrahedron 57 (2001) 6181±6188
6183
Table 2. Cyclotrimerization of aldehyde catalyzed by ATPB under solvent-free condition at rt
Entry
Reactant
Product
Yielda (%)
1
2
3
4
Ph(CH2)2CHO
MeCH2CHO
Me(CH2)7CHO
Me2CHCHO
1
2
3
4
1a
2a
3a
4a
78b
70
69
72c
5
6
7
5
6
7
5a
6a
7a
76d
0e
65
8
8
8a
77
9
9
9a
61
68
63
10
11
10
11
10a
11a
12
13
14
12
13
14
12a
13a
14a
74
73
71
15
16
15
16
15a
16a
74
72
17
18
17
18
17a
18a
70
68
19
19
19a
16
a
1
The isolated yields were reported. All products were characterized by H-, 13C-, MS, HRMS and/or elemental analysis.
Mp 65±668C.
Mp 59±608C.
Mp 196±1988C.
Recovered 79% of the aldehyde 6.
b
c
d
e
15b in excellent yields. The spectroscopically pure
product can be obtained simply by ®ltration through
Celite to remove the catalyst and then subsequent concen-
tration. Similarly, the triol 10b can be formed from
compound 10a under the Pd/C catalyzed hydrogenolysis
in excellent yield. We believe that compounds 18b and
19b should be able to be prepared from their precursor
18a and 19a, respectively. Since these compounds are
easily prepared in two steps from the corresponding
aldehyde in good yields, we believe that they should be
the potential core structures for the preparation of the
dendritic molecules.13

6184
Y.-S. Hon, C.-F. Lee / Tetrahedron 57 (2001) 6181±6188
of aldehydes at room temperature under solvent-free
condition. Many functional groups on the aldehydes were
compatible with our reaction condition.
4. Experimental
All reactions were carried out under nitrogen. Unless other-
wise noted, materials were obtained from commercial
suppliers and used without further puri®cation. Melting
points were determined by using a Thomas±Hoover melting
1
point apparatus and were uncorrected. The H- and 13C
NMR spectra were recorded on a Bruker Avance APX-
400 and a Varian Gemini-200 spectrometers, and chemical
shifts were given in ppm down®eld from tetramethylsilane
(TMS). IR spectra were taken with a Perkin±Elmer 682
spectrophotometer and only noteworthy absorption was
listed. Mass spectra were measured on a VG-Trio-
2000GC/MS spectrometer by electronic impact at 70 eV
(unless otherwise indicated). High Resolution Mass Spec-
troscopy (HRMS) was measured on a JEOL JMS-HX 110
(National Hsing-Hua University) or VG-11-250J (Academia
Sinica) Mass Spectrometer. The elemental analyses were
measured on Heraeus NCH-RAPID and Perkin±Elmer
2400 CHN analyzer.
Scheme 1. Reagents: (i) Ac2O, Pyridine; (ii) NaH, PhCH2Br, THF, DMF;
(iii) (a) O3, CH2Cl2; (b) Et3N.
2-Allyl-1,3-propanediol (21)14 was protected as dibenzyl
ether 23, which was subjected to the ozonolysis and subse-
quently treated with Et3N15 to give the corresponding
aldehyde 24. Oxidation of aldehyde 24 with Jones reagent
gave the corresponding carboxylic acid 25 in 91% yield.
Compound 25 failed to react with oxalyl chloride to give
the corresponding acyl chloride 26. To our surprise, we
obtained g-butyrolactone 27 in 80% yield. Similar result
was obtained when thionyl chloride was used (Scheme 1).
Therefore, carboxylic acid 25 was used directly to react with
triol 10b by Mitsunobu reaction condition. Triol 10b reacted
with 3,5-dibenzyloxybenzoic acid (25) in the presence of
triphenylphosphine and diethyl azodicarboxylate (DEAD)
to give the corresponding tri-ester 28 in 25% yield (Eq.
(3)). There are six benzyl ethers at the periphery of
compound 28. These six benzyl ethers are the potential
useful precursors to buildup more complex dendritic
molecules. Further work to prepare the dendrimers from
our cyclotrimerization products is under investigation in
our laboratory now.
4.1. Typical procedure for the cyclotrimerization of
aldehyde
A mixture of the 3-phenylpropionaldehyde (1) (385 mg,
2.87 mmol) and ATPB (115 mg, 0.287 mmol) was stirred
at rt for 24 h. The crude mixtures were subjected to silica gel
column chromatography to isolate the desired product 1a
(300 mg) in 78% yield.
4.1.1. 2,4,6-Tri-(2-phenylethyl)-1,3,5-trioxane (1a). White
solid, mp 65±668C; H NMR (CDCl3, 400 MHz) d 2.00±
1
2.06 (m, 6H, ±CHCH2CH2Ph), 2.74±2.78 (m, 6H,
±CHCH2CH2Ph), 4.81 (t, Jˆ5.3 Hz, 3H, ±OCHO), 7.19±
7.30 (m, 15H, Ar±H); 13C NMR (CDCl3, 100 MHz) d 29.6,
35.6, 100.6, 125.9, 128.3, 128.4, 141.3; IR (KBr) 3022,
2930, 1604, 1498, 1457, 1365 cm21; MS m/z (relative
intensity): 402 (M1, 2), 134 (100), 117 (35), 91 (88);
Anal. Calcd for C27H30O3: C, 80.56; H, 7.51, found: C,
80.62; H, 7.55.
4.1.2. 2,4,6-Triethyl-1,3,5-trioxane (2a). 1H NMR (CDCl3,
400 MHz) d 0.95 (t, Jˆ7.6 Hz, 9H, ±CH3), 1.66±1.72 (m,
6H), 4.79 (t, Jˆ5.3 Hz, 3H, ±OCHO); 13C NMR (CDCl3,
100 MHz) d 7.8, 27.6, 102.4; IR (KBr) 2958, 1461, 1360,
1272 cm21; MS m/z (relative intensity): 174 (M1, 2), 145
(31), 117 (41), 58 (100).
ꢀ3†
4.1.3. 2,4,6-Trioctyl-1,3,5-trioxane (3a). 1H NMR (CDCl3,
400 MHz) d 0.88 (t, Jˆ7.0 Hz, 9H, ±CH3), 1.27±1.41 (m,
36H), 1.64±1.69 (m, 6H), 4.83 (t, Jˆ5.3 Hz, 3H, ±OCHO);
13C NMR (CDCl3, 100 MHz) d 14.1, 22.6, 23.6, 29.2, 29.4,
29.5, 31.9, 34.4, 101.7; IR (KBr) 2921, 2847, 1466, 1355,
1148 cm21; MS m/z (relative intensity): 409 (M12OH, 22),
267 (100), 141 (57), 83 (47); HRMS Calcd for C27H53O2
(M22OH): 409.4048, found: 409.4044.
3. Conclusions
In summary, ATPB is an economic, effective and easily
available catalyst, which is useful to the cyclotrimerization
4.1.4. 2,4,6-Triisopropyl-1,3,5-trioxane (4a). White solid,

Y.-S. Hon, C.-F. Lee / Tetrahedron 57 (2001) 6181±6188
6185
1
mp 59±608C; H NMR (CDCl3, 400 MHz) d 0.94 (d, Jˆ
were ®ltered through Celite and concentrated in vacuo to
give the desired product 10b in 87% yield. Needless to
purify, this product can be used for the further reaction.
1H NMR (CDCl3, 400 MHz) d 1.61±1.73 (m, 12H), 3.55±
3.58 (m, 6H), 4.98 (t, Jˆ4.8 Hz, 6H); 13C NMR (CDCl3,
100 MHz) d 27.6, 32.0, 62.6, 102.4; IR (KBr) 3372, 1447,
1360 cm21; MS m/z (relative intensity): 265 (M111, 2),
229 (22), 159 (43), 71 (100); HRMS Calcd for C12H25O6
(M11H): 265.1652, found: 265.1651.
6.8 Hz, 18H, ±CH3), 1.83±1.88 (m, 3H), 4.50 (d, Jˆ5.5 Hz,
3H, ±OCHO); 13C NMR (CDCl3, 100 MHz) d16.7, 32.4,
104.7; IR (KBr) 2958, 1470, 1355, 1263 cm21; MS m/z
(relative intensity): 216 (M1, 1), 199 (94), 127 (100), 98
(55), 81 (83); Anal. Calcd for C12H24O3: C, 66.63; H, 11.18,
found: C, 66.59; H, 11.14.
4.1.5. 2,4,6-Tricyclohexyl-1,3,5-trioxane (5a). White
solid, mp 196±1988C; 1H NMR (CDCl3, 400 MHz) d
1.01±1.24 (m, 15H), 1.58±1.83 (m, 18H), 4.49 (d,
Jˆ5.6 Hz, 3H, ±OCHO±); 13C NMR (CDCl3, 100 MHz)
d 25.6, 26.5, 27.0, 41.9, 104.3; IR (KBr) 2921, 1466,
1351, 1231 cm21; MS m/z (relative intensity): 336 (M1,
2), 225 (79), 113 (92), 95 (100); Anal. Calcd for
C21H36O3: C, 74.95; H, 10.78, found: C, 74.87; H, 10.78.
4.1.11. 2,4,6-Tri(4-benzoxybutyl)-1,3,5-trioxane (11a).
1H NMR (CDCl3, 400 MHz) d 1.55±1.60 (m, 6H), 1.72±
1.82 (m, 12H), 4.30±4.33 (m, 6H), 4.89 (t, Jˆ5.2 Hz, 3H,
±OCHO), 7.26±7.56 (m, 9H, Ar±H), 8.02±8.04 (m, 6H,
Ar±H); 13C NMR (CDCl3, 100 MHz) d 20.1, 28.5, 33.9,
64.7, 101.2, 128.3, 129.5, 130.4, 132.8, 166.6; IR (KBr)
3059, 2949, 1724, 1599, 1452, 1365 cm21; MS m/z (relative
intensity): 617 (M1, 5), 414 (17), 273 (10), 207 (100), 154
(16); HRMS Calcd for C36H41O9 (M12H): 617.2745,
found: 617.2751; Anal. Calcd for C36H42O9: C, 68.74; H,
6.29. Found: C, 68.77; H, 6.32
4.1.6. 2,4,6-Tri(2,6-dimethylheptyl)-1,3,5-trioxane (7a).
1H NMR (CDCl3, 400 MHz) d 0.86 (d, Jˆ6.6 Hz, 18H,
±CH3), 0.91 (d, Jˆ6.5 Hz, 9H, ±CH3), 1.12±1.31 (m,
18H), 1.47±1.53 (m, 6H), 1.68±1.69 (m, 6H), 4.94 (t, Jˆ
5.0 Hz, 3H, ±OCHO); 13C NMR (CDCl3, 100 MHz) d 19.8,
22.6, 22.7, 24.5, 28.2, 37.3, 39.2, 41.4, 100.8; IR (KBr)
2921, 1466, 1369 cm21; MS m/z (relative intensity): 468
(M1, 2), 313 (46), 155 (84), 83 (69), 69 (100); HRMS
Calcd for C30H60O3: 468.4545, found: 468.4533.
4.1.12.
2,4,6-Tri(3-methoxycarbonylpropyl)-1,3,5-tri-
1
oxane (12a). H NMR (CDCl3, 400 MHz) d 1.69±1.77
(m, 12H), 2.35 (t, Jˆ7.2 Hz, 6H), 3.67 (s, 9H, ±CH3),
4.87 (t, Jˆ4.8 Hz, 3H, ±OCHO); 13C NMR (CDCl3,
100 MHz) d 19.0, 33.5, 33.6, 51.5, 100.9, 173.8; IR (KBr)
2940, 1738, 1443, 1360 cm21; MS m/z (relative intensity):
391 (M111, 3), 261 (15), 131 (100), 99 (84).
1
4.1.7. 2,4,6-Tri(9-decenyl)-1,3,5-trioxane (8a). H NMR
(CDCl3, 400 MHz) d 1.28±1.39 (m, 36H), 1.63±1.69 (m,
6H), 2.01±2.06 (m, 6H), 4.83 (t, Jˆ5.3 Hz, 3H, ±OCHO),
4.91±5.01 (m, 6H, ±CHCH2), 5.77±5.86 (m, 3H,
±CHCH2); 13C NMR (CDCl3, 100 MHz) d 23.5, 28.9,
29.1, 29.3, 29.4, 29.5, 33.8, 34.4, 101.7, 114.1, 139.2; IR
(KBr) 3068, 2921, 1641, 1466, 1355 cm21; MS m/z (relative
intensity): 504 (M1, 1), 335 (12), 149 (43), 95 (100); Anal.
Calcd for C33H60O3: C, 78.51; H, 11.98. Found: C, 78.56; H,
12.06.
4.1.13. 2,4,6-Tri(4-methoxycarbonylbutyl)-1,3,5-trioxane
(13a). H NMR (CDCl3, 400 MHz) d 1.40±1.46 (m, 6H),
1
1.61±1.69 (m, 12H), 2.31 (t, Jˆ7.6 Hz, 6H), 3.66 (s, 9H,
±CH3), 4.83 (t, Jˆ5.2 Hz, 3H, ±OCHO); 13C NMR (CDCl3,
100 MHz) d 23.0, 24.6, 33.8, 33.9, 51.4, 101.2, 174.0; IR
(KBr) 2940, 1738, 1438, 1365 cm21; MS m/z (relative inten-
sity): 432 (M1, 1), 289 (14), 145 (100), 113 (56); HRMS
Calcd for C21H37O9 (M11H): 433.2438, found: 433.2443.
1
4.1.8. 2,4,6-Tri(4-pentenyl)-1,3,5-trioxane (9a). H NMR
(CDCl3, 400 MHz) d 1.49±1.53 (m, 6H), 1.66±1.71 (m,
6H), 2.05±2.10 (m, 6H), 4.85 (t, Jˆ5.3 Hz, 3H, ±OCHO),
4.94±5.03 (m, 6H, ±CHCH2), 5.76±5.80 (m, 3H, ±
CHCH2); 13C NMR (CDCl3, 100 MHz) d 22.8, 33.4, 33.8,
101.4, 114.7, 138.4; IR (KBr) 3068, 2930, 1641, 1443,
1355 cm21; MS m/z (relative intensity): 294 (M1, 10), 252
(22), 197 (100), 154 (50), 137 (57); HRMS Calcd for
C18H30O3: 294.2196, found: 294.2192.
4.1.14. 2,4,6-Tri(4-carboxybutyl)-1,3,5-trioxane (13b). A
solution of compound 13a (261 mg, 0.603 mmol) in 6 mL of
MeOH was added to a solution of KOH (118 mg,
2.11 mmol) in 3 mL of water. The reaction mixtures were
heated up to re¯ux for 30 min. Subsequently, the reaction
mixture was cooled down to room temperature, neutralized
by 1N HCl until the pH was between 4±5 and then extracted
with CH2Cl2 three times. The organic layer was dried over
MgSO4 and concentrated to give compound 13b (123 mg) in
52% yield. 1H NMR (D2O, 400 MHz) d 1.46±1.48 (m, 6H),
1.62±1.73 (m, 12H), 2.29 (t, Jˆ7.4 Hz, 6H), 5.18 (t, Jˆ
5.1 Hz, 3H); 13C NMR (D2O, 100 MHz) d 22.8, 25.2,
33.3, 36.5, 1.2.2, 182.3; IR (KBr) 2949, 1710, 1415, 1369,
1300 cm21
4.1.9. 2,4,6-Tri(3-benzyloxypropyl)-1,3,5-trioxane (10a).
1H NMR (CDCl3, 400 MHz) d 1.72±1.77 (m, 12H), 3.48 (t,
Jˆ5.6 Hz, 6H, ±OCH2±), 4.49 (s, 6H, ±OCH2Ph), 4.83 (t,
Jˆ4.8 Hz, 3H, ±OCHO), 7.26±7.33 (m, 15H, Ar±H); 13C
NMR (CDCl3, 100 MHz) d 23.8, 31.1, 69.9, 72.8, 101.1,
127.4, 127.5, 128.3, 138.5; IR (KBr) 3032, 2857, 1682,
1447, 1360 cm21; MS m/z (relative intensity): 534 (M1,
39), 358 (10), 249 (10), 179 (100); HRMS Calcd for
C32H41O6 (M12H): 533.2903, found: 533.2909.
4.1.15.
2,4,6-Tri(5-methoxycarbonylpentyl)-1,3,5-tri-
1
oxane (14a). H NMR (CDCl3, 400 MHz) d 1.27±1.39
(m, 12H), 1.55±1.64 (m, 12H), 2.26 (t, Jˆ7.6 Hz, 6H),
3.61 (s, 9H, ±CH3), 4.78 (t, Jˆ5.3 Hz, 3H, ±OCHO); 13C
NMR (CDCl3, 100 MHz) d 23.0, 24.7, 28.7, 33.8, 34.1,
51.3, 101.3, 174.0; IR (KBr) 2930, 2857, 1738, 1438,
1360 cm21; MS m/z (relative intensity): 475 (M111, 1),
285 (20), 159 (100), 81 (43); HRMS Calcd for C24H41O9
(M1-H): 473.2751, found: 473.2758
4.1.10. 2,4,6-Tri(3-hydroxypropyl)-1,3,5-trioxane (10b).
Compound 10a (471 mg, 0.88 mmol) in 20 mL of EtOAc
was added 10% Pd/C (9.3 mg, 0.088 mmol). The reaction
mixtures were shaked under the Parr hydrogenation appa-
ratus under 50 psi H2 at rt for 24 h. The reaction mixtures

6186
Y.-S. Hon, C.-F. Lee / Tetrahedron 57 (2001) 6181±6188
4.1.16. 2,4,6-Tri(2-benzoxycarbonylethyl)-1,3,5-trioxane
(15a). H NMR (CDCl3, 400 MHz) d 1.96±2.01 (m, 6H),
4.1.22. 2,6-Dimethoxytetrahydropyran. A mixture of
aldehyde 20 (532 mg, 3.64 mmol) and ATPB (145 mg,
0.364 mmol) was stirred at rt for 24 h. The crude mixture
was subjected to silica gel column chromatography to
isolate compounds 20b (353 mg, 66% yield; Rfˆ0.52
(Hexane/EtOAcˆ5:1)) and 20b0 (62 mg, 12% yield; Rfˆ
0.45 (Hexane/EtOAcˆ2:1)).
4.1.23. trans-2,6-Dimethoxytetrahydropyran (20b). 1H
NMR (CDCl3, 400 MHz) d 1.51±1.57 (m, 2H), 1.70±1.73
(m, 4H), 3.45 (s, 6H), 4.76 (2H, t, Jˆ4.5 Hz); 13C NMR
(CDCl3, 100 MHz) d 17.2, 29.9, 55.2, 98.4; IR (KBr)
2930, 1457, 1392, 1171 cm21; MS m/z (relative intensity):
146 (M1, 5), 145 (29), 115 (63), 86 (60), 58 (100).
1
2.48 (t, Jˆ7.5 Hz, 6H), 4.91 (t, Jˆ4.8 Hz, 3H, ±OCHO),
5.11 (s, 6H), 7.26±7.35 (m, 15H); 13C NMR (CDCl3,
100 MHz) d 27.9, 29.2, 66.3, 99.5, 128.2, 128.5, 135.9,
172.8; IR (KBr) 3022, 2930, 1728, 1503, 1452,
1355 cm21; MS m/z (relative intensity): 577 (M111, 4),
385 (12), 193 (47), 91 (100); HRMS Calcd for C33H37O9
(M11H): 577.2438, found: 473.2469
4.1.17. 2,4,6-Tri (2-carboxylethyl)-1,3,5-trioxane (15b).
Compound 10a (273 mg, 0.47 mmol) in 20 mL of EtOAc
was mixed with 10% Pd/C (5 mg, 0.05 mmol). The reaction
mixture was shaked under the Parr hydrogenation apparatus
under 50 psi H2 at rt for 10 h. The reaction mixture was
®ltered through Celite and concentrated in vacuo to give
the desired product 15b in 81% yield. Needless to purify,
4.1.24. cis-2,6-Dimethoxytetrahydropyran (20b0). 1H
NMR (CDCl3, 400 MHz) d 1.46±1.49 (m, 3H), 1.72±1.77
(m, 2H), 1.85±1.86 (m, 1H), 3.50 (s, 6H), 4.45 (2H, t, Jˆ
2.5 Hz); 13C NMR (CDCl3, 100 MHz) d 18.2, 30.2, 55.8,
100.9; IR (KBr) 2940, 1452, 1392 cm21; MS m/z (relative
intensity): 146 (M1, 0.1), 145 (1), 115 (4), 86 (13), 71 (20),
58 (100).
1
this product can be used for the further reaction. H NMR
(CD3OD, 400 MHz) d 1.92±1.95 (m, 6H), 2.41 (t, Jˆ
7.5 Hz, 6H), 5.02 (t, Jˆ5.4 Hz, 3H, ±OCHO); 13C NMR
(CD3OD, 100 MHz) d 28.7, 30.6, 101.1, 176.9; IR (KBr)
3032, 2930, 1705, 1438, 1365 cm21; MS m/z (relative
intensity): 307 (M111, 15), 205 (56), 154 (51), 85 (96);
Anal. Calcd for C12H18O6: C, 47.06; H, 5.92. Found: C,
46.59; H, 6.00
4.1.25. 2-Allyl-propane-1,3-diol (21). It was prepared
according to the literature procedure in 88% yield.14 1H
NMR (CDCl3, 400 MHz) d 1.78±1.82 (m, 1H), 2.01 (t,
2H, Jˆ7.1 Hz), 3.57±3.61 (m, 4H), 3.70±3.74 (m, 2H),
5.00±5.06 (m, 2H), 5.70±4.79 (m, 1H); 13C NMR (CDCl3,
100 MHz) d 32.4, 41.7, 64.9, 116.5, 136.1; IR (KBr) cm21
3326, 2921, 1645, 1443.
4.1.18. 2,4,6-Tri(5-bromopentyl)-1,3,5-trioxane (16a). 1H
NMR (CDCl3, 400 MHz) d 1.39±1.48 (m, 12H), 1.63±1.68
(m, 6H), 1.81±1.88 (m, 6H), 3.38 (t, Jˆ6.8 Hz, 6H), 4.83 (t,
Jˆ5.2 Hz, 3H, ±OCHO); 13C NMR (CDCl3, 100 MHz) d
22.5, 27.8, 32.5, 33.7, 34.0, 101.2; IR (KBr) 2930, 2857,
1457, 1360 cm21; MS m/z (relative intensity): 535 (M111,
0.3), 359 (34), 137 (32), 69 (100); HRMS Calcd for
C18H33O3 79Br2 81Br: 534.9862, found: 534.9881
4.1.26. 1,3-Diacetoxy-2-allylpropane (22). It was prepared
according to the literature procedure in 88% yield.14 1H
NMR (CDCl3, 400 MHz) d 2.02 (s, 6H), 2.05±2.13 (m,
3H), 3.97±4.07 (m, 4H), 5.02±5.06 (m, 2H), 5.67±5.75
(m, 2H); 13C NMR (CDCl3, 100 MHz) d 20.7, 32.6, 36.9,
63.8, 117.4, 134.8, 170.8; IR (KBr) 2940, 1738, 1443, 1369,
4.1.19. 2,4,6-Tri(5-bromo-3-methylpentyl)-1,3,5-trioxane
1
(17a). H NMR (CDCl3, 400 MHz) d 0.91 (d, Jˆ6.3 Hz,
9H, ±CH3), 1.25±1.28 (m, 3H), 1.43±1.45 (m, 3H), 1.65±
1.74 (m, 12H), 1.86±1.90 (m, 3H), 3.39±3.47 (m, 6H), 4.84
(t, Jˆ5.3 Hz, 3H, ±OCHO); 13C NMR (CDCl3, 100 MHz) d
18.7, 29.7, 31.2, 31.6, 31.9, 39.7, 101.5; IR (KBr) 2940,
1461, 1360, 1259 cm21; MS m/z (relative intensity): 578
(M112, 2), 387 (9), 193 (100), 154 (39), 113 (94);
HRMS Calcd for C21H38O3Br3 (M12H): 575.0371, found:
575.0408.
1245 cm21
.
4.1.27. 2-Allyl-1,3-benzyloxypropane (23). To a suspen-
sion solution of NaH (312 mg, 130 mg) in a mixture of
THF (10 mL) and DMF (2 mL) was added a solution of
2-allyl-propane-1,3-diol (21) (503 mg, 4.34 mmol) in
5 mL of THF at 08C. To the resulted mixture was added a
solution of benzyl bromide (1.63 g, 9.54 mmol) in 3 mL of
THF at room temperature and the reaction was stirred at rt
for 24 h. The reaction was quenched with water and
extracted with ether. The organic layer was dried over
MgSO4 and concentrated to give the crude residue. It was
puri®ed by silica gel column chromatography to give
compound 23 (1.12 g) in 87% yield. Rfˆ0.6 (Hexane/
1
4.1.20. 2,4,6-Tri(5-azidopentyl)-1,3,5-trioxane (18a). H
NMR (CDCl3, 400 MHz) d 1.37±1.43 (m, 12H), 1.57±
1.66 (m, 12H), 3.24 (t, Jˆ7.0 Hz, 6H), 4.82 (t, Jˆ5.2 Hz,
3H, ±OCHO); 13C NMR (CDCl3, 100 MHz) d 22.9, 26.3,
28.6, 34.0, 51.2, 101.2; IR (KBr) 2930, 2101, 1457, 1351,
1254 cm21; MS m/z (relative intensity): 423 (M1, 0.3), 409
(16), 267 (77), 238 (9), 141 (100); HRMS Calcd for
C18H33O3N9 (M11H): 424.2785, found: 424.2783.
1
EtOAcˆ10:1). H NMR (CDCl3, 400 MHz) d 2.09±2.12
(m, 1H), 2.26±2.30 (m, 2H), 3.52±3.60 (m, 4H), 4.55 (s,
2H), 5.05±5.12 (m, 2H), 5.82±5.86 (m, 1H), 7.31±7.41 (m,
10H); 13C NMR (CDCl3, 100 MHz) d 33.1, 39.3, 70.4, 73.0,
116.2, 127.4, 127.5, 128.2, 136.6, 138.6; IR (KBr) 3068,
2857, 1641, 1457, 1365 cm21; MS m/z (relative intensity):
205 (8), 107 (34), 91 (100).
4.1.21. 2,4,6-Tri[(1,1-diacetoxymethyl)ethyl]-1,3,5-tri-
oxane (19a). H NMR (CDCl3, 400 MHz) d 1.71±1.74
1
(m, 6H), 2.02 (s, 18H, ±CH3), 2.03±2.06 (m, 3H), 3.99±
4.09 (m, 12H), 4.98 (t, Jˆ5.2 Hz, 3H, ±OCHO); 13C NMR
(CDCl3, 100 MHz) d 20.7, 32.6, 63.9, 99.6, 170.8; IR (KBr)
2949, 1742, 1443, 1378 cm21; MS m/z (relative intensity):
607 (M111, 1), 405 (10), 279 (42), 143 (100); HRMS Calcd
for C27H43O15 (M11H): 607.2602, found: 607.2602.
4.1.28. 4-Acetoxy-4-acetoxymethylbutanal (19). In a
250 mL of two-neck ¯ask, which was equipped with a
magnetic stirrer, a drying tube and a gas dispersing tube
(with porous fritted tip), were placed 100 mL of CH2Cl2

Y.-S. Hon, C.-F. Lee / Tetrahedron 57 (2001) 6181±6188
6187
and
1,3-diacetoxy-2-allylpropane
(22)
(571 mg,
200 MHz) d 2.37 (dd, Jˆ17.6 and 6.4 Hz, 1H), 2.61 (dd,
Jˆ17.6, 8.8 Hz, 1H), 2.77±2.91 (m, 1H), 3.41±3.51 (m,
2H), 4.18 (dd, Jˆ9.4 and 5.4 Hz, 1H), 4.40 (dd, Jˆ9.4
and 7.4 Hz, 1H), 4.52 (s, 2H), 7.26±7.40 (m, 5H); 13C
NMR (CDCl3, 50 MHz) d 31.0, 35.3, 70.3, 70.7, 73.2,
127.5, 127.8, 128.4, 137.5, 176.7; IR (KBr) 3022, 2847,
2.86 mmol). A stream of ozone was bubbled through the
solution at 2788C. Ozone treatment was terminated when
the mixture assumed a blue color. A stream of nitrogen was
used to remove excess ozone. Et3N (0.52 mL, 3.72 mmol)
was added to the solution at 2788C. The reaction was
warmed slowly to room temperature and stirred for 12 h.
The reaction mixture was concentrated and chromato-
graphed on a silica gel column to give compound 19
(421 mg) as a colorless oil in 73% yield.15 1H NMR
(CDCl3, 400 MHz) d 1.97 (s, 6H), 2.47±2.49 (m, 2H),
2.61±2.64 (m, 1H), 3.96±4.06 (m, 4H), 9.69 (s, 1H);
13C NMR (CDCl3, 100 MHz) d 20.5, 31.9, 42.6, 63.6,
170.6, 199.7; IR (KBr) 2949, 2893, 2829, 2718, 1742,
1774, 1456, 1369, 1175 cm21
.
4.1.32. 1,3,5-Trioxane[3]:(4-oxa-3-oxo-heptylidene):2-oxa-
1-phenylpropane (28). To a stirring solution of triol 10b
(91 mg, 0.36 mmol), 3,5-dibenzyloxybenzoic acid (25)
(392 mg, 1.25 mmol) and Ph3P (327 mg, 1.25 mmol) in
5 mL of THF, a solution of 40% of DEAD in THF was
added dropwise until the yellow color persisted. The reac-
tion was then stirred at room temperature for 24 h. The
reaction mixture was concentrated and the crude products
were separated by silica gel column chromatography to give
the desired product 28 (397 mg) in 25% yield. Rfˆ0.71
(Hexane:EtOAcˆ2:1); 1H NMR (CDCl3, 400 MHz) d
1.70±1.78 (m, 9H), 2.45±2.52 (m, 12H), 3.48±3.57 (m,
12H), 4.01±4.08 (m, 6H), 4.49 (s, 12H), 4.84 (s, 3H),
7.26±7.36 (m, 30H); 13C NMR (CDCl3, 100 MHz) d 22.7,
30.8, 33.9, 36.5, 63.9, 70.5, 73.1, 100.7, 127.5, 128.3, 138.5,
172.8; IR (KBr) 3031, 1733, 1457, 1365 cm21; MS m/z
(relative intensity): 1152 (M1, 10), 475 (100), 475 (100),
405 (38); HRMS Calcd for C69H84O15: 1152.5896; found:
1152.5818.
1369 cm21
.
4.1.29. 4-Benzyloxy-3-benzyloxymethylbutyraldehyde
(24). In a 250 mL of two-neck ¯ask, which was equipped
with a magnetic stirrer, a drying tube and a gas dispersing
tube (with porous fritted tip), were placed 150 mL of
CH2Cl2 and 2-allyl-1,3-benzyloxypropane (23) (972 mg,
3.28 mmol). A stream of ozone was bubbled through the
solution at 2788C. Ozone treatment was terminated when
the mixtures assumed a blue color. A stream of nitrogen was
used to remove excess ozone. Et3N (0.60 mL, 4.24 mmol)
was added to the solution at 2788C. The reaction was
warmed slowly to room temperature and stirred for 12 h.
The reaction mixture was concentrated and chromato-
graphed on a silica gel column to give compound 24
(421 mg) as a colorless oil in 87% yield.15 Rfˆ0.19
(Hexane/EtOAcˆ10:1). The spectral data is identical to
that reported in the literature.16 1H NMR (CDCl3,
400 MHz) d 2.53±2.55 (m, 2H), 2.62±2.65 (m, 1H),
3.43±3.57 (m, 4H), 4.48 (s, 4H), 7.25±7.36 (m, 10H),
9.77 (t, 1H, Jˆ1.3 Hz); 13C NMR (CDCl3, 100 MHz) d
43.9, 70.6, 73.1, 127.5, 127.6, 128.4, 138.1, 201.9; IR
Acknowledgements
We are grateful to the National Science Council and
National Chung Cheng University, Republic of China for
®nancial support.
(KBr) 3032, 2857, 2718, 1724, 1452, 1365 cm21
.
References
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layer was dried over MgSO4, concentrated and chromato-
graphed on a silica gel column to give the desired product 25
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