Stereochemistry of PdII-Catalyzed THF Ring Formation of ?-Hydroxy Allylic Alcohols and Synthesis of 2,3,5-Trisubstituted and 2,3,4,5-Tetrasubstituted Tetrahydrofurans

Article abstract of DOI:10.1021/acs.joc.6b01154

Pd^II-catalyzed ring formation of 2,3,5-trisubstituted and 2,3,4,5-tetrasubstituted tetrahydrofurans is described. Oxypalladation of a chiral ?-hydroxy allylic alcohol provides a 5-alkenyltetrahydrofuran ring in excellent yields via a 5-exo-trigonal process. Nine substrates including six secondary allylic alcohols and three primary allylic alcohols with or without an additional secondary hydroxy substituent at the γ-position have been examined. Their structures are restricted by a 2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocane ring. The stereochemistry of the resulting tetrahydrofuran products was determined by chemical transformation. The reaction mechanism is discussed on the basis of the stereochemical results. The steps in the chiral allylic alcohol directed or the nucleophilic alcohol directed facial selection for the formation of the alkene-Pd^II-π-complex, the cis-oxypalladation, and a syn-elimination mechanism account for the observed stereochemistry of the reaction.

Full text of DOI:10.1021/acs.joc.6b01154

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Article
Stereochemistry of PdII-Catalyzed THF Ring Formation of
Epsilon-Hydroxy Allylic Alcohols and Synthesis of 2,3,5-
Trisubstituted and 2,3,4,5-Tetrasubstituted Tetrahydrofurans
Yuki Murata, and Jun'ichi Uenishi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01154 • Publication Date (Web): 19 Jul 2016
Downloaded from http://pubs.acs.org on July 20, 2016
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Stereochemistry of PdII-Catalyzed THF Ring Formation of ε-Hydroxy
Allylic Alcohols and Synthesis of 2,3,5-Trisubstituted and
2,3,4,5-Tetrasubstituted Tetrahydrofurans
Yuki Murata, and Jun’ichi Uenishi*
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Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, 607-8412, Japan
e-mail: juenishi@mb.kyoto-phu.ac.jp
Z
H
O
O
H X
cat.
H
5
O
iPr
iPr
O
iPr
iPr
OH
O
O
H
2
Si
Si
iPr
iPr
PdCl2(MeCN)2
H
X
X
Y
ε
Si
O
O
Si
H
Z
H
H
O
γ
H
THF, rt
– H2O
Y
δ
O
iPr
Si
Y
O
iPr
O
Z
iPr
Si
iPr
iPr
iPr
cis-oxypalladation
and
syn-elimination
5-exo-trigonal product
No 6-endo-trigonal product was formed.
X = H or OH
Y = H or OH
Z = H or Me
ABSTRACT: PdII-Catalyzed ring formation of 2,3,5-trisubstituted tetrahydrofuran is described.
Oxypalladation of a chiral ε−hydroxy allylic alcohol provides 5-alkenyl tetrahydrofuran ring in
excellent yields via a 5-exo-trigonal process. Nine substrates including six secondary allylic alcohols
and three primary allylic alcohols with or without an additional secondary hydroxy substituent at the
γ-position
have
been
examined.
Their
structures
are
restricted
by
a
2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocane ring. The stereochemistry of the resulting
tetrahydrofuran products was determined by chemical transformation. The reaction mechanism is
discussed based on the stereochemical results. The steps in the chiral allylic alcohol-directed or the
nucleophilic alcohol-directed facial selection for the formation of the alkene-PdII-π-complex, the
cis-oxypalladation, and a syn-elimination mechanism account for the observed stereochemistry of the
reaction.
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INTRODUCTION
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Oxypalladation is an addition reaction of an oxygen functional group to an alkene promoted by a
PdII-catalyst. The process has been utilized as a fundamental step in a variety of synthetically useful
O-C bond formations. Numerous PdII-catalyzed oxygenetive transformation reactions have been used
in organic synthesis.1 Particularly, the intramolecular oxypalladation reaction is important for the
formation of oxygen rings.2 With respect to the synthesis of chiral oxygen heterocycles, the
stereochemistry of oxypalladation becomes more important in enantioselective and diastereoselective
oxygen ring formation.3 Many arguments related to the mechanism for the oxypalladation and
aminopalladation have been proposed in the long history of the nucleopalladation reaction. Both cis-
and tran-additions have been proposed for inter- and intra-molecular nucleopalladation reactions
(Scheme 1).4
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SCHEME 1. Nucleopalladation to Alkene
PdII
Nu
H
trans (anti)
NuH
or Nu
H
PdII
NuH (from a front face)
PdII
PdII
H
NuH (from a back face)
PdII
H
Nu
NuH
or Nu
H
cis (syn)
PdII
H
Nucleopalladation Nu = O; oxypalladation
N; azapalladation
The process of the reaction involves three steps; i) coordination of an alkene to the PdII–catalyst to
form an alkene-PdII-π−complex; ii) oxypalladation to form the alkyl-PdII-σ-complex with a new O-C
bond formation; and iii) reductive elimination to produce an alkene product with the formation of a
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Pd 0 species which is oxidized to regenerate the PdII-catalyst. The reaction mechanism has been
discussed in terms of the results conducted under various reaction conditions with different
PdII-catalysts, solvents, temperatures and oxidants. When an allylic alcohol is used as a substrate, this
reaction becomes simpler. The dehydration reaction can proceed in the presence of a PdCl2(MeCN)2
catalyst at room temperature in THF without an oxidant, because the catalytic cycle works without
the formation of Pd0-species under these mild conditions. We have studied the reaction of various
allylic alcohol substrates and their stereochemistry.5 For example, as shown in Scheme 2, the
PdII-catalyzed reaction of ε-hydroxy allylic alcohol (1) gave a chiral 2,5-substituted THF product
bearing an alkenyl group at the 5-position in excellent yield with high diastereoselectivity (>20:1).6
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SCHEME 2. Intramolecular Oxypalladation to Allylic Alcohol
H
H
O
R
5
2
*
R
PdCl2(MeCN)2
(10 mol %)
(5S,E)-2
OH
ε
OH
*
20
1
δ
THF, 0 °C–rt
– H2O
γ
H
H
1
>99% ee
O
R
5
2
either R or S
*
*
(5R,E)-2
We have proposed a reaction mechanism (Scheme 3) that involves the chiral allylic alcohol-directed
formation7 of the alkene-PdII-π−complex followed by ligand exchange to form another
alkene-PdII-π−complex, which then undergoes cis-oxypalladation leading to the
alkyl-PdII-σ-complex. Dissociation of the PdII-species furnished the major stereoisomer
predominantly. The original chiral allylic hydroxy center was transmitted to the newly generated
chiral center at the C-5 carbon. On the other hand, the minor stereoisomer may be produced from the
initial alkene-PdII-π−complex via a trans-oxypalladation pathway.
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SCHEME 3. Proposed Mechanism of the Intramolecular Oxypalladation to Allylic Alcohol
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H
OH
H
O
cis-O-Pd
PdII
O
OH
PdII
– HX
PdII
OH
– PdX(OH)
syn-E
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(5S,E)-2
OH
major isomer
*
Ligand
exchange
(5R,E)-2
PdII
minor isomer
1
– PdX(OH)
syn-E
OH directed
coordination
H
OH
H
OH
O
PdII
O
trans-O-Pd
PdII
– HX
O-Pd = oxypalladation
syn-E = syn-elimination
SCHEME 4. Synthesis of Dihydrobenzofuran by the Intramolecular Oxypalladation
PdCl2(MeCN)2
(15 mol %)
O
OH
H
O
OH
H
THF, rt
44% 93% ee
33% >99% ee
>99% ee
(S,E)-4
(R,Z)-4
3
H
PdII
O
OH
H
O
OH
cis-O-Pd
PdII
– HX
PdII
OH
H
PdII
– PdX(OH)
syn-E
(S,E)-4
O
(>27:1)
OH
(R,Z)-4
PdII
3
syn-E
– PdX(OH)
OH
cis-O-Pd
H
O
OH
O
– HX
PdII
H
PdII
In contrast, the reaction of the phenol substrate 3 displayed quite different stereochemical results
(Scheme 4).8 The reaction afforded (S,E)-4 as a major isomer in 44% yield with 93% ee through the
same pathway as described in Scheme 3, while another isomer (R,Z)-4 was produced in 33% yield
with 99% ee. The latter product had an opposite stereocenter with a (Z)-alkene. The phenol-directed
opposite face recognition of the alkene-π-face, cis-oxypalladation and syn-elimination occurred.
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ε
X
OH
OH
OH
OH
δ
δ
6
7
γ
γ
8
9
Type A
Type B X = C or N
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21
sp2 atom at δ and ε position
H
O
H
O
OH
OH
γ
γ
OH
5-exo-trig. or
6-endo-trig.
5-exo-trig.
Type C
Figure 1. Type of Substrates in Oxypalladation of ε-Hydroxy allylic Alcohol
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Quite different stereochemical results were observed in 5-exo-trigonal cyclization for the two types
of substrates, termed Type A and Type B (Figure 1). Type A had saturated carbons from the γ− to
ε-positions and Type B had two sp2-hybridized atoms at the δ- and ε-positions. We were interested in
substrates like Type C (Figure 1). Configurational restriction in Type C substrates by a ring might
influence the stereochemical course of the cyclization reaction. Furthermore, if an additional
hydroxy group is placed at the γ-position, either 5-exo-trigonal cyclization leading to
2,3,4,5-tetrasubstituted tetrahydrofuran or 6-endo-trigonal cyclization leading to 2,3,6-trisubstituted
3,6-dihydro-2H-pyran would be expected.9 Both of the tetrahydrofuran and 3,6-dihydro-2H-pyran
are important moieties in biologically active natural products10,11 and C-nucleoside12. Based on this
idea, we report here an intramolecular oxypalladation reaction of nine substrates 5 to 13 (Figure 2)
and describe the stereochemistry of the products.
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H
O
H
O
O
O
O
OH
O
X
H
iPr
iPr
iPr
iPr
Si
Si
X
Y
H
OH
H
H
O
Y
O
iPr Si
iPr
iPr Si
iPr
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5
6
7
X = Y = H
8
X = Y = H
X = OH, Y = H
X = H, Y = OH
X = OH, Y = H
X = H, Y = OH
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10
H
O
O
OH
iPr
Si
X
Y
H
iPr
O
H
O
iPr Si
iPr
11 X = Y = H
12 X = OH, Y = H
13
X = H, Y = OH
Figure 2. Substrates for Oxypalladation
RESULTS AND DISCUSSION
Preparation of Precursors 5 to 13 for Cyclization
We started the synthesis of these ε-hydroxy allylic alcohols from commercial D-pentose. Two
hydroxy groups of D-2-deoxyribose, D-arabinose and D-ribose were protected with cyclic bis-silyl
ethers to give 14, 15, and 16 by the reported procedure.13 Wittig reaction of 14, 15, and 16 with
methyl (triphenylphosphoranylidene)acetate gave α,β−unsaturated esters 17, 18, and 19 in 74%, 81%,
and 73% yields, respectively. These esters were reduced with DIBAL-H in CH2Cl2 to give allylic
alcohols 5, 6, and 7 in 90%, 85%, and 88%, respectively (Scheme 5).
SCHEME 5. Preparation of Precursors 5-7 for Cyclization
O
O
iPr
iPr
Ph3PCHCOOMe
(2 equiv)
Si
H
O
X
Y
OH
D-2-deoxyribose
D-arabinose
D-ribose
O
H
Benzene
ref. 10
iPr Si
iPr
reflux, 1 h
14 X = Y = H
15
16
X = OH, Y = H
X = H, Y = OH
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H
H
O
O
O
O
O
iPr
iPr
iPr
DIBAL
(4 equiv)
Si
Si
X
Y
COOMe
H
X
Y
H
OH
iPr
O
H
H
CH2Cl2
O
O
iPr Si
iPr
iPr Si
iPr
–78 °C
30 min
X = Y = H
X = Y = H
5
90%
85%
17
18 X = OH, Y = H 81%
X = H, Y = OH
74%
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6
7
X = OH, Y = H
X = H, Y = OH
88%
19
73%
For the synthesis of compounds 8 to 13, a diastereomeric pair of three allylic alcohols was prepared
(Scheme 6). The first step was Wittig reaction of 14, 15, and 16 with
a
(triphenylphosphoranylidene)acetone which gave α,β−unsaturated ketones 20, 21, and 22 in 71%,
68%, and 70% yields, respectively. The resulting methyl ketones were reduced by NaBH4 in the
presence of CeCl3·7H2O to give diastereomeric mixture of the secondary alcohols 8 and 11, 9 and 12,
and 10 and 13, in 87%, 80%, and 91% yields, respectively. These diastereomeric alcohols were
differentiated by kinetic acetylation catalyzed with Cal-B (Candida antartica lipase B; Novozyme
435). A mixture of alcohols 8 and 11 were treated with vinyl acetate in the presence of Cal-B for 3
days to provide the (R)-acetate 23 in 48% yield along with recovery of the (S)-alcohol 11 in 47%
yield. Diastereomeric purities of both compounds were over >98%. (R)-Alcohol 8 was obtained in
91% yield by the reduction of 23 with LiAlH4. The same two steps afforded the diastereomeric
alcohols 9 and 12, and 10 and 13 effectively with satisfactory yields and purities in the same manner
described for the case of 8 and 11.
SCHEME 6. Preparation of Precursors 8-13 for Cyclization
H
Ph3PCHCOMe
(3 equiv)
O
O
O
O
iPr
iPr
Si
14, 15
X
Y
H
Benzene
H
and 16
reflux, 1 h
O
iPr Si
iPr
X = Y = H
20
71%
21 X = OH, Y = H 68%
X = H, Y = OH
22
70%
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H
O
O
O
OH Vinyl acetate
iPr
iPr
Si
.
CeCl3 7H2O
(5 equiv)
MS 4 Å
X
Y
H
(3 equiv)
H
7
8
9
O
iPr Si
iPr
Novozyme 435
(10 w/w%)
NaBH4
(1.5 equiv)
CH2Cl2, rt
iPr2O, rt, 2-3 d
8 and 11
X = Y = H
87%
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11
12
13
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15
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57
58
59
60
30 min
9 and 12 X = OH, Y = H 80%
X = H, Y = OH
10 and 13
91%
H
O
LiAlH4
O
O
OAc
iPr
Si
(4 equiv)
X
Y
H
iPr
(S)-alcohol
H
Et2O, 0 °C
1 h
O
iPr Si
iPr
11
12
13
47%
46%
X = Y = H
23
24 X = OH, Y = H 42%
X = H, Y = OH
48%
49%
25
46%
H
O
O
O
OH
iPr
iPr
X = Y = H
8
9
93%
Si
X
Y
H
X = OH, Y = H 90%
H
O
X = H, Y = OH
85%
10
iPr Si
iPr
PdII-Catalyzed Cyclization
First, we examined the cyclization of primary allylic alcohol 5. The reaction of 5 with 10 mol % of
PdCl2(CH3CN)2 in THF at rt gave a mixture of the 5-vinyl substituted THF products, 2,5-trans-26
and 2,5-cis-26 in 89% yield (Scheme 7 and Table 1, entry 1). Although the products were not
separable, the ratio was determined to be approximately 3:1 by the proton NMR spectrum. We
examined other reaction conditions using other PdII-catalysts, solvents, and additives, which are
summarized in Table 1. The reaction was completed after 2 h at 0 °C and in less than 1 min at 60 °C
(entries 2 and 3). However, the chemical yields decreased a little and while the selectivity did not
change much at 0 °C, but decrease at 60 °C. When 1 mol % of PdII-catalyst was employed, the
reaction took 3 h (entry 4). No influence was observed when acetic acid was added to the reaction
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(entry 5). On the other hand, when triethylamine or its hydrochloride was used as an additive, no
reaction occurred (entries 6 and 7). PdCl2 also catalyzed the reaction (entry 8). Other PdII-catalysts
such as Pd(OAc)2, or PdCl2(PPh3)2 were not effective at all (entries 9 and 10). The use of
Pd(OCOCF3)2 provided the cyclized product in 31% yield with a 2:1 ratio of isomers (entry 11).
Methylene chloride and toluene could be used as a solvent (entries 12 and 13), however their
chemical yields and selectivities were lower than those in THF. Polar solvents such as methanol or
acetonitrile gave the product with poor yield and selectivity (entries 14 and 15). In summary,
PdCl2(CH3CN)2 was found to be an appropriate catalyst for the reaction, and THF was the best
solvent for this reaction.
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11
12
13
14
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SCHEME 7. PdII-Catalyzed Cyclization of 5
O
H
O
iPr
iPr
Si
H
O
O
H
iPr
Si
H
O
2,5-trans-26
O
O
iPr
iPr
iPr
PdCl2(MeCN)2
(10 mol %)
Si
H
3
OH
H
89%
and
1
O
iPr Si
iPr
THF, rt, 10 min
O
O
iPr
iPr
Si
5
H
O
O
H
H
iPr Si
iPr
2,5-cis-26
Table 1. PdII-Catalyzed Cyclization of 5
a
b
entry
Pd-catalyst (mol %)
additive
solvent
temp (°C)
time
yield (%)
2,5-trans:2,5-cis
1
2
3
4
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
10
10
10
1
–
–
–
–
THF
THF
THF
THF
rt
0
10 min
2 h
89
84
84
87
77:23
79:21
69:31
79:21
60
rt
<1 min
3 h
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AcOH c
Et3N d
5
6
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2
10
10
10
10
10
10
10
10
10
10
10
THF
THF
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
2.5 h
3 d
85
0
78:22
–
Et3NHCl d
7
THF
3 d
0
–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
8
THF
15 min
1 d
87
0
72:29
–
9
Pd(OAc)2
–
–
–
–
–
–
–
THF
10
11
12
13
14
15
PdCl2(PPh3)2
Pd(OCOCF3)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
THF
1 d
0
–
THF
2 h
31
76
78
54
41
67:33
67:33
71:29
43:57
60:40
CH2Cl2
toluene
MeOH
CH3CN
10 min
20 min
15 h
2 h
a Isolated yield. b Ratio was calculated by the integration value of H-NMR spectrum, see experimental. c 3 equiv. d 1
1
equiv.
SCHEME 8. PdII-Catalyzed Cyclization of 6 and 7.
H
O
PdCl2(MeCN)2
(10 mol %)
O
O
H
O
HO
O
iPr
iPr
iPr
iPr
Si
OH
H
Si
H
O
H
O
OH
H
H
THF, rt, 10 min
H
O
iPr Si
iPr
iPr Si
iPr
27
93%
OH
6
iPr
O
O
Si
iPr
O
O
Si
iPr
iPr
27'
O
H
O
HO
iPr
Si
H
O
iPr
O
H
H
H
iPr Si
iPr
O
O
PdCl2(MeCN)2
(10 mol %)
iPr
iPr
O
2,5-trans-28
Si
H
H
1
OH
H
and
THF, rt, 30 min
92%
OH
O
iPr Si
iPr
1
O
O
iPr
iPr
O
HO
Si
H
O
7
H
H
H
iPr
Si
iPr
2,5-cis-28
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The reaction of γ-(R)-hydroxy allylic alcohol 6 under the optimum reaction conditions for 5 afforded
a single stereoisomer 27 in 93% yield (Scheme 8). Neither the 2,5-cis stereoisomer nor the
3,6-dihydro-2H-pyran 27’ was produced in this reaction. The cyclization of 7 gave a mixture of
2,5-trans-28 and 2,5-cis-28 in 92% yield with a ratio of 1:1. In the cases of 6 and 7, the cyclization
proceeded in a 5-exo-trigonal fashion but not in a 6-endo-trigonal fashion.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Next, we examined secondary allylic alcohols. The reaction of (R)-allylic alcohols 8, 9, and 10 gave
the single 2,5-trans stereoisomers 29, 30, and 31 in 97, 95, and 95% yields, respectively (Scheme 9).
With or without the γ-hydroxyl group, the 2,5-trans products bearing the (E)-1-propenyl substituent
group were obtained. Each chemical yield was excellent over 95% with an exclusive
diastereoselectivity.
SCHEME 9. PdII-Catalyzed Cyclization of Secondary (R)-Allylic Alcohols 8, 9 and 10
H
O
O
O
H
iPr
iPr
O
PdCl2(MeCN)2
(10 mol %)
OH
O
O
Si
iPr
iPr
H
O
Si
H
H
H
THF, rt, 10 min
iPr Si
iPr
O
iPr Si
iPr
8
29
97%
O
H
O
O
O
H
PdCl2(MeCN)2
(10 mol %)
iPr
iPr
O
O
OH
iPr
iPr
Si
HO
H
OH
H
Si
H
H
H
THF, rt, 10 min
H
O
iPr Si
iPr
O
iPr Si
iPr
95%
9
30
H
O
O
O
H
O
iPr
iPr
PdCl2(MeCN)2
(10 mol %)
O
OH
iPr
iPr
Si
H
H
O
H
Si
O
H
H
H
THF, rt, 10 min
OH
iPr
Si
O
iPr
OH
Si
iPr
iPr
10
95%
31
In contrast to the result of (R)-allylic alcohols, cyclization of (S)-allylic alcohols was not simple
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8
9
(Scheme 10). The reaction of 11 gave a mixture of 2,5-trans-32 with the (Z)-propenyl substituent and
2,5-cis-33 with the (E)-propenyl substituent in 91% combined yield with a ratio of 1:5. The
formation of the (Z)-alkene was also found in the reaction of 12. An approximately 1:1 mixture of
2,5-trans-34 with the (Z)-propenyl substituent and 2,5-cis-35 with the (E)-propenyl substitutent was
formed in combined 93 % yield from 12. However, the reaction of diastereoisomer 13 afforded a
single stereoisomer 36 in 95% yield.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
SCHEME 10. PdII-Catalyzed Cyclization of Secondary (S)-Allylic Alcohols 11, 12 and 13
O
H
O
iPr
iPr
Si
H
O
O
H
iPr Si
iPr
H
O
PdCl2(MeCN)2
2,5-trans-32
O
O
OH
1
5
iPr
iPr
(10 mol %)
Si
91%
H
and
THF, rt, 10 min
H
O
O
iPr Si
O
iPr
Si
iPr
H
O
iPr
O
11
H
H
iPr Si
iPr
2,5-cis-33
O
H
O
HO
iPr
iPr
Si
O
H
O
H
H
iPr Si
iPr
H
O
PdCl2(MeCN)2
(10 mol %)
2,5-trans-34
O
O
OH
iPr
iPr
1
OH
H
Si
H
and
93%
THF, rt, 30 min
H
1
O
iPr Si
iPr
O
iPr
O
HO
Si
H
O
12
iPr
O
H
H
H
iPr
Si
iPr
2,5-cis-35
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5
6
7
8
H
O
O
O
OH
iPr
O
iPr
iPr
PdCl2(MeCN)2
(10 mol %)
O
Si
H
H
iPr
Si
H
H
O
H
O
H
H
OH
O
THF, rt, 30 min
iPr Si
iPr
OH
iPr Si
iPr
9
13
95%
36
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In all the cases, no dihydropyran via 6-endo-trigonal cyclization was detected. The stereochemistries
of these cyclized products were determined by their transformation to appropriate derivatives.
Determination of the Stereochemistry
The stereochemistries of 2,5-trans-26 and 2,5-cis-26 were determined by leading to the known
compounds 2,5-trans-39 and 2,5-cis-39 (Scheme 11).14 The cyclic bis-silyl ether of 26 was replaced
with a p-toluoyl ester, by desilylation with TBAF and acylation of the resulting diol 37 with toluoyl
chloride. A mixture of 2,5-trans-38 and 2,5-cis-38 was obtained in 79% yield in two steps.
Ozonolytic cleavage of the isomers followed by NaBH4 reduction gave 2,5-trans-39 and 2,5-cis-39 in
90% yield. They were separable by HPLC with a ratio of 74:26. The minor isomer was identified to
be 2,5-cis-39 and the major isomer to be 2,5-trans-39. In the same manner, product 29 lead to
2,5-trans-39 in 71% overall yields in four steps via compounds 40 and 41. This transformation
showed that compound 29 was a 2,5-trans isomer. Similarly, the stereochemistries of 2,5-trans-32
and 2,5-cis-33 were confirmed by the same four steps. The major isomer and minor isomer were
identified to be 2,5-cis-33 and 2,5-trans-32 by the transformation to 2,5-cis-39 via the intermediates
2,5-cis-43 and 2,5-cis-45 and 2,5-trans-39 via the intermediates 2,5-trans-42 and 2,5-trans-44,
respectively.
SCHEME 11. Assignment of Stereochemistry for Cyclized Products 26, 29, 32 and 33
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5
O
O
O
iPr
iPr
HO
TBAF
(3 equiv)
O
H
Si
H
O
H
6
7
8
9
H
THF
0 °C, 10 min
iPr Si
iPr
HO
2,5-trans-37
and 2,5-cis-37
2,5-trans-26
and 2,5-cis-26
3 : 1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3 : 1
93%
pTolCOO
O
H
(4 equiv)
pTolCOCl
Et N
(8 equiv)
H
pTolCOO
3
DMAP (0.04 equiv)
CH2Cl2, rt, 18 h
2,5-trans-38
and 2,5-cis-38
79%
pTol = para-tolyl
pTolCOO
H
O
HO
H
H
Ozone
OH
H
pTolCOO
CH2Cl2, –78 °C
2,5-trans-39
3
then NaBH4 (10 equiv)
MeOH, rt, 10 min
90%
1
pTolCOO
OH
O
H
H
H
pTolCOO
2,5-cis-39
TBAF
(3 equiv)
O
HO
H
O
iPr
iPr
H
O
Si
H
O
H
O
H
THF
0 °C, 10 min
H
iPr Si
iPr
HO
40
87%
29
pTolCOO
(4 equiv)
pTolCOCl
Et N
H
O
H
(8 equiv)
3
H
pTolCOO
DMAP (0.04 equiv)
CH2Cl2, rt, 18 h
91%
41
Ozone
CH2Cl2, –78 °C
trans-39
then NaBH4 (10 equiv)
MeOH, rt, 10 min
90%
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5
6
7
8
9
HO
H
O
H
H
O
O
O
iPr
HO
Si
TBAF
(3 equiv)
H
O
iPr
2,5-trans-42
H
iPr Si
iPr
97%
H
and
THF
0 °C, 10 min
HO
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
2,5-trans-32
and 2,5-cis-33
1 : 5
H
H
HO
2,5-cis-43
pTolCOO
H
O
H
H
(4 equiv)
pTolCOCl
Et N
pTolCOO
2,5-trans-44
(8 equiv)
3
1
5
DMAP (0.04 equiv)
CH2Cl2, rt, 18 h
and
98%
pTolCOO
O
H
H
pTolCOO
H
2,5-cis-45
Ozone
2,5-trans-39
90%
CH2Cl2, –78 °C
1
5
then
NaBH4 (10 equiv)
2,5-cis-39
MeOH, rt, 10 min
The stereochemistry of 27 was determined in two steps (Scheme 12). Ozonolysis of 27 and
successive NaBH4 reduction gave diol 46 in 89% yield. The resulting diol was transformed to the
cyclic bis-silyl ether with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane to give 47 in 80% yield, for
1
13
which H- and C-NMR spectra showed a simple pattern of the spectrum due to the molecular
symmetry. Based on this result, the structure of 27 with trans 2,5-substituents was determined.
Similarly, compound 30 was transformed to 2,5-trans-46 in 91% yield and it was assigned to be the
2,5-trans substituted structure. Ozonolysis of a mixture of 2,5-trans-34 and 2,5-cis-35 followed by
successive reduction with NaBH4 affording 2,5-trans-46 in 38% yield and another isomer in 36%
yield which was identified to be 2,5-cis-46.
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9
SCHEME 12. Assignment of Stereochemistry for Cyclized Product 27, 30, 34 and 35
O
H
O
O
O
HO
iPr
iPr
H
O
HO
iPr
iPr
Ozone
Si
H
O
Si
H
O
O
H
CH2Cl2, –78 °C
H
H
iPr Si
iPr
H
iPr Si
iPr
then NaBH4 (10 equiv)
MeOH, rt, 10 min
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
27
2,5-trans-46
89%
iPr
iPr
Si
H
[ClSiii-Pr)2O]2O
O
O
O
iPr
iPr
(3 equiv)
Si
Si
H
O
O
iPr
O
iPr
pyridine
rt, 19 h
H
O
H
iPr Si
iPr
80%
47
O
H
O
HO
Ozone
CH2Cl2, –78 °C
iPr
iPr
Si
H
O
O
2,5-trans-46
H
H
iPr Si
iPr
then NaBH4 (10 equiv)
MeOH, rt, 10 min
91%
30
O
H
O
HO
iPr
iPr
Si
O
H
O
H
H
iPr Si
iPr
38%
2,5-trans-46
Ozone
2,5-trans-34
CH2Cl2, –78 °C
and
O
then NaBH4 (10 equiv)
MeOH, rt, 10 min
OH
O
HO
iPr
iPr
Si
H
O
O
O
HO
iPr
H
H
Si
H
O
H
iPr
O
iPr Si
O
H
H
iPr
H
iPr Si
iPr
36%
2,5-cis-46
2,5-cis-35
Because a diastereomeric mixture of 28 was not separable, their secondary hydroxy groups were
once acylated as a benzoate (Scheme 13). The resulting benzoates were separable by HPLC to give
less polar isomer 2,5-cis-48 in 44% yield and polar isomer 2,5-trans-48 in 40% yield. The less polar
isomer was subjected to ozonolysis followed by the reduction with LiBH4 to give alcohol 2,5-cis-49
in 80% yield. Removal of silyl group and the resulting tetraol was acetylated with acetic anhydride to
1
give tetraacetate 2,5-cis-50 15 in 86% yield, whose symmetrical structure in the H-NMR spectrum
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5
confirmed a cis relation of the 2,5-substituents. On the other hand, the polar isomer led to the
6
7
1
corresponding tetraacetate 2,5-trans-5016 in the same steps via 2,5-trans-49, in which the H-NMR
8
9
spectrum showed four acetoxy groups due to the unsymmetrical structure. These results suggest that
the stereochemistry of the less polar product must be the 2,5-cis isomer and polar product the
2,5-trans isomer. The stereochemistry of compounds 31 and 36 were determined to be 2,5-trans and
2,5-cis in 2 steps. Ozonolysis of 31 and 36 followed by the reduction with NaBH4 afforded
2,5-trans-49 and 2,5-cis-49 in 80% and 70% yields, respectively.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
SCHEME 13. Assignment of Stereochemistry for Cyclized Product 28, 31 and 36
O
O
iPr
iPr
Si
H
H
O
O
H
H
OBz
iPr Si
iPr
O
O
O
iPr
iPr
BzCl (2 equiv)
Si
H
H
O
2,5-cis-48
Et3N (7.7 equiv)
H
44%
OH
iPr Si
iPr
DMAP (0.2 equiv)
CH2Cl2, rt, 11 h
O
H
O
iPr
iPr
Si
O
2,5-trans-28
H
H
O
and 2,5-cis-28
H
OBz
iPr Si
iPr
2,5-trans-48
40%
O
OH
H
O
iPr
TBAF
Ozone
Si
H
H
iPr
(3 equiv)
CH2Cl2, –78 °C
O
H
2,5-cis-48
OH
O
THF
0 °C, 10 min
then
iPr Si
iPr
LiBH4 (10 equiv)
2,5-cis-49
THF, rt, 10 min
80%
AcO
then
Ac2O (8 equiv)
OAc
O
H
H
H
2,5-cis-50
86%
H
pyridine, rt, 12 h
AcO OAc
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2
3
4
5
6
7
8
O
O
H
O
iPr
iPr
Ozone
TBAF
Si
H
H
O
(3 equiv)
CH2Cl2, –78 °C
H
OH
2,5-trans-48
OH
then
iPr Si
iPr
THF
LiBH4 (10 equiv)
THF, rt, 10 min
0 °C, 10 min
2,5-trans-49
9
94%
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
then
Ac2O (8 equiv)
AcO
H
O
H
H
H
pyridine, rt, 12 h
2,5-trans-50
OAc
AcO OAc
76%
O
O
Ozone
H
iPr
iPr
Si
H
CH2Cl2, –78 °C
H
O
2,5-trans-49
H
then
OH
O
iPr Si
iPr
80%
NaBH4 (10 equiv)
THF, rt, 10 min
31
O
Ozone
O
iPr
iPr
Si
O
H
CH2Cl2, –78 °C
H
O
2,5-cis-49
H
H
then
OH
70%
iPr Si
iPr
NaBH4 (10 equiv)
THF, rt, 10 min
36
Structures of all the cyclized products were assigned. Depending on the stereochemistry of the chiral
allylic alcohol, 2,5-trans- or 2,5-cis-5-alkenyltetrahydrofurans were synthesized. Particularly,
2,5-trans THF derivatives could be formed from (R)-allylic alcohols 8, 9 and 10, specifically. The
2,5-cis THF derivatives 27 and 36 were obtained from 6 and 13 exclusively.
Reaction Mechanism of PdII-Catalyzed Dehydrative Cyclization.
A new stereogenic carbon center arises by the O-C bond formation (Scheme 14). Facial selection
from the si-face on the alkene must afford the 2,5-trans isomer through the conformer-I, while, that
from the re-face afforded the 2,5-cis isomer through the conformer-II.
SCHEME 14. Facial Selection and Stereochemistry of the Products
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3
4
5
6
7
8
H
H
X
H
O
O
H
PdII
O
HO
H
O
X
5
– H2O
O
O
H
H
H
Conformer-I
9
from si-face
2,5-trans isomer
New
Stereogenic
Center
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
H
H
H
HO
O
O
H
PdII
O
O
X
5
X
– H2O
O
O
H
H
H
H
2,5-cis isomer
Conformer-II
from re-face
In the simple case of the reactions, precursors 8, 9, and 10 possess an (R)-allylic alcohol that
provided the single stereoisomer, 29, 30 or 31, respectively (Scheme 15). When either an additional
(R)- or (S)-secondary hydroxy group existed at the γ-position, 2,5-trans isomer with an (E)-propenyl
substituent was formed specifically. The product would be produced via the conformer-I, with either
the ally hydroxyl group or the nucleophilic hydroxyl group directing formation of this conformer-I.
Then, the conformer would undergo cis-oxypalladation to give the σ-Pd intermediate. A
syn-relationship of the Pd and the hydroxide would lead to the syn-elimination of PdCl(OH) that
dissociated to give the (E)-alkene stereospecifically. It is notable that neither cis-oxypalladation nor
trans-oxypalladation reactions through the conformer-II took place, because no 2,5-cis isomer was
detected in the reaction product. On the other hand, the results obtained with (S)-allylic alcohol 11,
12, and 13 were more complicate. Not only the (E)-alkene, but also the (Z)-alkene were formed. The
initial chiral allylic alcohol-directed the facial recognition of PdII-catalyst that could lead to the
conformer-II that is able to stabilize with the nucleophilic hydroxy group. Successive
cis-oxypalladation and syn-elimination reactions gave the 2,5-cis isomers, 2,5-cis-33, 2,5-cis-35, or
36 with an (E)-propenyl substituent. When the nucleophilic hydroxy group-directed formation of the
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Pd-π-complex in the conformer-I occurred cis-oxypalladation followed by syn-elimination provided
the 2,5-trans isomers, 2,5-trans-32 or 2.5-trans-34 bearing a (Z)-propenyl substituent. In the case of
the primary alcohols 5, 6, and 7, conformer-I derived by nucleophilic hydroxy group-directed or the
primary allylic alcohol-directed facial selection in coordination of alkene to PdCl2, afforded the
2,5-trans isomer predominantly. However, the other isomer through the conformer-II was also
produced with 5 and 7. In the case of compound 7, the secondary hydroxy group at the γ carbon
might influence the intermediate conformer-II to give 2,5-cis isomer, although the effect of the
γ-hydroxy group remains unclear.
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SCHEME 15. Mechanism of 5-Exo-Trigonal Cyclization by PdII-Catalyst
(R)-allyl alcohol
H
X
H
O
H
H
PdII
O
O
O
O
cis (syn) O-Pd
O
Syn-E
PdII-cat
8, 9, 10
– HCl
O
– PdCl(OH)
H
XY
PdII
29, 30, 31
XY = H or OH
(E)-2,5-trans isomer
Conformer-I
H
O
H
H
O
H
X
PdII
O
O
H
O
OH
X
O
or
PdII
O
H
XY
H
XY
Conformer-II
Conformer-I
Leading to (Z)-2,5-cis isomer
Leading to (E)-2,5-cis isomer
(S)-allyl alcohol
H
H
O
OH
PdII-cat
cis (syn) O-Pd
O
PdII
Syn-E
O
O
11, 12, 13
H
X
O
– HCl
– PdCl(OH)
O
PdII
Major pathway
H
XY
2,5-cis-33
Conformer-II
2,5-cis-35, or 36
H
X
H
O
H
O
O
PdII
O
PdII-cat
O
Syn-E
cis (syn) O-Pd
11, 12
OH
O
– PdCl(OH)
– HCl
PdII
2,5-trans-32
or
XY
H
Conformer-I
2,5-trans-34
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Primary allyl alcohol
4
H
X
H
H
5
6
7
8
O
PdII-cat
Syn-E
O
H
cis (syn) O-Pd
O
PdII
O
O
5, 6, 7
– HCl
– PdCl(OH)
OH
O
2,5-trans-26, 27
or 2,5-trans-28
PdII
XY
9
Major pathway
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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26
27
28
29
30
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32
33
34
35
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Conformer-I
H
X
H
O
H
O
O
PdII
O
PdII-cat
O
cis (syn) O-Pd
Syn-E
5, 7
OH
O
– HCl
– PdCl(OH)
PdII
H
XY
2,5-cis-26
or 2,5-cis-28
Conformer-II
In our proposed reaction mechanism, none of the intermediates in the above models suffer from
allylic strain. Interestingly, no products assembled via 6-endo-trigonal cyclization were observed in
any of the cases. All the products were consistent with a cis-oxypalladation and syn-elimination
pathway via a 5-exo-trigonal cyclization. Our hypothesis provides a rationale for explaining the
stereochemical course of the reactions. Although Aponic et al. proposed an anti-oxypalladation and
anti-elimination pathway based on the DFT calculation studies in the case of a 6-exo-trigonal
cyclization for the formation of the simple tetrahydropyran,17 we were unable to account for the
current results according to their anti-oxypalladation and anti-elimination mechanism. Stabilization
of the five membered chelation intermediate by mean of the internal hydrogen bonding between the
nucleophilic hydroxy group and the allylic hydroxy group would not be operable in the presence of
multiple hydroxy groups with different stereochemistries.
CONCLUSION
In summary, we have disclosed the stereochemistry of oxypalladation for the chiral ε-hydroxy allylic
alcohols. This reaction proceeded via a 5-exo-trigonal fashion and effectively provided 5-alkenyl
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substituted tetrahydrofuran. In the case of the structurally restricted ε−hydroxy allylic alcohol with
an external ring, categorized as Type 3 (Figure 1), the stereochemical course was influenced by the
neighboring hydroxy groups of the alkene; (i) the chiral center of (R)-allylic alcohol was transmitted
to the C-5 position to give the 2,5-trans substituted THF ring product; (ii) in contrast, the chiral
center of the (S)-allylic alcohol was transmitted to give 2,5-cis substituted THF ring product, but
partially to give the 2,5-trans substituted THF ring product with a (Z)-alkenyl unit; and (iii) primary
allylic alcohols gave 2,5-trans and/or 2,5-cis substituted THF ring products with or without the
hydroxy group located at the γ-position. These results make it possible to explain by the hydroxy
group-directed facial recognition of alkene to the Pd-catalyst, cis-oxypalladation, and
syn-elimination mechanism.
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11
12
13
14
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16
17
18
19
20
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EXPERIMENTAL SECTION
General Information. The 1H NMR and 13C NMR spectra were recorded on 400 MHz
spectrometer. Proton chemical shifts were internally referenced to the residual proton signals in
CDCl3 (δ 7.26) and 13C NMR chemical shifts were internally referenced to the deuterated solvent
signals in CDCl3 (δ 77.00). THF was dried over sodium benzophenone ketyl. CH2Cl2 was dried over
P4O10. These solvents were distilled freshly before use. Low and high resolution mass spectra were
obtained on a double-focusing high resolution magnetic-sector mass analyzed operating in a fast
atom bombardment (FAB) mode or electron (EI) mode.
Preparation of the Precursors for Pd(II)-Catalyzed Cyclization.
General Procedure for the Preparation of Compounds 17, 18 and 19. A mixture of lactol
14,13a 15,13b or 1613c (20 mmol) and methyl (triphenylphosphoranylidene)acetate (14 g, 42 mmol) in
benzene (100 mL) was stirred for 15 h at room temperature. Hexane was added to the mixture and
resulting solid was removed by filtration. The filtrate was condensed and purified by
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chromatography on silica gel eluted with 25% EtOAc in hexane to give unsaturated esters 17, 18 or
19, respectively.
6
7
8
9
Methyl (E)-4-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)-but-2-
enoate (17). Compound 17 (6.40 g) was obtained in 74% yield from 14 (7.53 g). Colorless oil; Rf =
0.30 (15% EtOAc in hexane); [α]D20 +6.45 (c 1.29, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.07 (ddd,
J = 15.7, 8.6, 6.3 Hz, 1H), 5.93 (dt, J = 15.7, 1.2 Hz, 1H), 4.15 (dd, J = 11.6, 1.0 Hz, 1H), 3.82 (dt, J
= 9.2, 4.6 Hz, 1H), 3.77 (dd, J = 11.6, 2.2 Hz, 1H), 3.72 (s, 3H), 3.34 (brt, J = 7.4 Hz, 1H), 2.68
(dddd, J = 14.4, 6.3, 4.6, 1.2 Hz, 1H), 2.57 (dddd, J = 14.4, 8.6, 4.6, 1.0 Hz, 1H), 1.11-0.98 (m,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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26
27
28
29
30
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32
33
34
35
36
37
38
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40
41
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43
44
45
46
47
48
49
50
51
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53
54
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60
13
28H); C NMR (100 MHz, CDCl3) δ 167.0, 145.7, 123.7, 73.9, 69.9, 62.4, 51.6, 36.9, 17.6, 17.5,
17.48 (2C), 17.44 (2C), 17.43, 17.42, 13.5, 13.4, 12.8, 12.7; IR (film): 3445, 2945, 1728, 1464, 1029,
885 cm-1; MS (FAB): m/z = 455 [M+Na]+; HRMS (FAB): m/z [M+Na]+ calcd for C20H40O6Si2Na:
455.2261; Found 455.2267.
Methyl
(R,E)-
4-hydroxy-4-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)but-2-enoa
te (18). Compound 18 (7.26 g) was obtained in 81% yield from 15 (7.85 g). White solid; mp 81-83
1
ºC; Rf = 0.30 (40% EtOAc in hexane); [α]D20 +23.0 (c 1.12, CHCl3); H NMR (400 MHz, CDCl3) δ
7.12 (dd, J = 15.7, 3.4 Hz, 1H), 6.25 (dd, J = 15.7, 2.2 Hz, 1H), 4.59 (brs, 1H), 4.10 (dd, J = 12.0, 1.2
Hz, 1H), 3.89 (dd, J = 9.2, 2.8 Hz, 1H), 3.80 (dd, J = 12.0, 2.2 Hz, 1H), 3.75 (s, 3H), 3.66 (d, J = 9.2
13
Hz, 1H), 3.01 (brs, 1H), 2.37 (brs, 1H), 1.10-0.96 (m, 28H); C NMR (100 MHz, CDCl3) δ 166.9,
148.8, 121.6, 72.5, 72.4, 71.3, 62.5, 51.7, 17.6, 17.4 (2C), 17.39, 17.38, 17.36, 17.35, 17.31, 13.45,
13.40, 12.77, 12.76; IR (film): 3583, 2945, 2867, 1727, 1464, 1033, 885 cm-1; MS (FAB): m/z = 449
[M+H]+; HRMS (FAB): m/z [M+H]+ calcd for C20H41O7Si2: 449.2391; Found 449.2397; Anal. Calcd
for C20H40O7Si2: C, 53.54; H, 8.99. Found: C, 53.76 H, 9.08.
Methyl
(S,E)-
4-hydroxy-4-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)but-2-enoa
te (19). Compound 19 (6.54 g) was obtained in 73% yield from 16 (7.85 g). White solid; mp 77-79
1
ºC; Rf = 0.30 (30% EtOAc in hexane); [α]D20 +16.0 (c 0.93, CHCl3); H NMR (400 MHz, CDCl3) δ
7.11 (dd, J = 15.6, 3.2 Hz, 1H), 6.25 (dd, J = 15.6, 2.1 Hz, 1H), 4.58 (dd, J = 5.4, 2.9 Hz, 1H), 4.09
(dd, J = 11.9, 1.1 Hz, 1H), 3.88 (dd, J = 9.3, 2.7 Hz, 1H), 3.79 (dd, J = 11.9, 2.1 Hz, 1H), 3.75 (s,
3H), 3.65 (ddd, J = 9.3, 2.1, 1.1 Hz, 1H), 1.10-0.97 (m, 28H); 13C NMR (100 MHz, CDCl3) δ 166.9,
148.9, 121.6, 72.48, 72.45, 71.4, 62.4, 51.8, 17.6, 17.45 (2C), 17.43, 17.42, 17.40, 17.37, 17.33,
13.49, 13.44, 12.8, 12.7; IR (film): 3435, 2945, 1727, 1464, 1033, 885 cm-1; MS (FAB): m/z = 471
[M+Na]+; HRMS (FAB): m/z [M+Na]+ calcd for C20H40O7Si2Na: 471.2210; Found 471.2205; Anal.
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Calcd for C20H40O7Si2: C, 53.54; H, 8.99. Found: C, 53.43 H, 9.09.
5
6
7
8
General Procedure for the Preparation of Compounds 5, 6, and 7 by DIBALH Reduction.
To a solution of α,β-unsaturated ester 17, 18, or 19 (1.5 mmol) in CH2Cl2 (10 mL) was added
DIBALH (4.5 mL, 1 M in hexane solution) at –78 °C. The reaction mixture was stirred for 30 min at
the same temperature. Saturated potassium and sodium tartrate was added and stirred vigorously.
Then, the mixture was extracted with ether. The extract was washed with water and brine, dried over
MgSO4. The crude product was chromatographed on silica gel eluted with 20 to 40% EtOAc in
hexane to give allylic alcohols 5, 6 or 7, respectively.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
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26
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28
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(7S)-6-((E)-4-Hydroxybut-2-en-1-yl)-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-7-ol (5).
The reaction of 17 (649 mg) gave 5 (546 mg) in 90% yield. Colorless oil; Rf = 0.30 (25% EtOAc in
hexane); [α]D20 +14.7 (c 1.26, CHCl3); 1H NMR (400 MHz, CDCl3) δ 5.86-5.72 (m, 2H), 4.14 (dd, J
= 11.7, 1.0 Hz, 1H), 4.11 (d, J = 5.3 Hz, 2H), 3.77 (dd, J = 11.7, 1.9 Hz, 1H), 3.76 (dd, J = 9.2, 4.2
Hz, 1H), 3.54 (ddd, J = 9.2, 1.9, 1.0 Hz, 1H), 2.54 (dt, J = 14.2, 4.2 Hz, 1H), 2.43 (ddd, J = 14.2, 7.1,
4.2 Hz, 1H), 1.10-0.97 (m, 28H); 13C NMR (100 MHz, CDCl3) δ 132.2, 128.7, 73.7, 70.2, 63.9, 62.7,
36.8, 17.6, 17.59, 17.52, 17.49 (2C), 17.48, 17.45, 17.44, 13.55, 13.52, 12.87, 12.80; IR (film): 3359,
2944, 2867, 1464, 1028, 885 cm-1; MS (FAB): m/z = 427 [M+Na]+; HRMS (FAB): m/z [M+Na]+
calcd for C19H40O5Si2Na: 427.2312; Found 427.2317.
(R,E)-1-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)but-2-ene-
1,4-diol (6). The reaction of 18 (673 mg) gave 6 (536 mg) in 85% yield. Colorless oil; Rf = 0.30
1
(60% EtOAc in hexane); [α]D20 +22.4 (c 1.27, CHCl3); H NMR (400 MHz, CDCl3) δ 6.03 (dtd, J =
15.7, 5.3, 1.5 Hz, 1H), 5.89 (ddt, J = 15.7, 4.3, 1.5 Hz, 1H), 4.45 (brs, 1H), 4.21 (dt, J = 5.2, 1.5 Hz,
2H), 4.16 (dd, J = 11.9, 1.1 Hz, 1H), 3.81 (dd, J = 8.7, 2.3 Hz, 1H), 3.80 (dd, J = 11.9, 1.1 Hz, 1H),
3.71 (brd, J = 8.6 Hz, 1H), 3.07 (brs, 1H), 2.70 (brs, 1H), 1.10-0.97 (m, 28H); 13C NMR (100 MHz,
CDCl3) δ 131.5, 130.4, 72.7, 72.2, 71.6, 63.3, 62,8, 17.6, 17.47, 17.46, 17.44, 17.43 (2C), 17.39,
17.37, 13.5, 13.4, 12.8, 12.7; IR (film): 3361, 2943, 2867, 1464, 885 cm-1; MS (FAB): m/z = 443
[M+Na]+; HRMS (FAB): m/z [M+Na]+ calcd for C19H40O6Si2Na: 443.2261; Found 443.2266.
(S,E)-1-{(6S,7R)-7-Hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl}but-2-ene-
1,4-diol (7). The reaction of 19 (673 mg) gave 7 (555 mg) in 88% yield. Colorless oil; Rf = 0.30
1
(60% EtOAc in hexane); [α]D20 +15.7 (c 1.22, CHCl3); H NMR (400 MHz, CDCl3) δ 6.03 (dtd, J =
15.7, 5.2, 1.6 Hz, 1H), 5.89 (ddt, J = 15.7, 2.9, 1.3 Hz, 1H), 4.54 (m, 1H), 4.20 (dt, J = 5.1, 1.3 Hz,
2H), 4.10 (dd, J = 11.9, 0.9 Hz, 1H), 3.81 (dd, J = 11.9, 2.3 Hz, 1H), 3.80 (t, J = 3.3 Hz, 1H), 3.71
(m, 1H) 1.01-0.99 (m, 28H); 13C NMR (100 MHz, CDCl3) δ 131.6, 130.4, 72.5, 72.1, 71.9, 63.4, 62,6,
17.6, 17.48 (5C), 17.42, 17.40, 13.55, 13.52, 12.89, 12.82; IR (film): 3353, 2943, 2867, 1464, 885
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cm-1; MS (FAB): m/z = 443 [M+Na]+; HRMS (FAB): m/z [M+Na]+ calcd for C19H40O6Si2Na:
443.2261; Found 443.2266.
6
7
8
9
General Procedure for the Preparation of Compounds 20, 21, and 22 by Wittig reaction. A
mixture of lactol 14, 15 or 16 (5 mmol) and (triphenylphosphoranylidene)acetone (2.4 g, 7.5 mmol)
in benzene (25 mL) was stirred for 2 h at refluxing temperature. Hexane was added and resulted
solid was removed by filtration. The filtrate was condensed and purified by chromatography on silica
gel eluted with 20 to 40% EtOAc in hexane to give unsaturated ketones 20, 21 or 22, respectively.
(E)-5-((7S)-7-Hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)pent-3-en-2-one
(20). Compound 20 (1.48 g) was obtained in 71% yield from 14 (1.88 g). Colorless oil; Rf = 0.30
(25% EtOAc in hexane); [α]D20 +4.56 (c 1.21, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.91 (ddd, J =
15.8, 8.5, 6.4 Hz, 1H), 6.18 (dt, J = 15.8, 1.1 Hz, 1H), 4.15 (dd, J = 11.7, 1.1 Hz, 1H), 3.84 (dt, J =
9.3, 4.6 Hz, 1H), 3.78 (dd, J = 11.7, 2.2 Hz, 1H), 3.34 (brt, J = 9.3 Hz, 1H), 2.71 (dddd, J = 14.4, 6.4,
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14
15
16
17
18
19
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13
4.6, 1.1 Hz, 1H), 2.60 (dddd, J = 14.4, 8.5, 4.6, 1.1 Hz, 1H), 2.25 (s, 3H), 1.10-0.96 (m, 28H); C
NMR (100 MHz, CDCl3) δ 198.6, 144.5, 133.9, 73.9, 70.0, 62.4, 37.3, 27.1, 17.6, 17.5, 17.48, 17.47,
17.43 (2C), 17.41 (2C), 13.55, 13.51, 12.84, 12.79; IR (film): 3446, 2944, 2867, 1675, 1464, 1031,
885 cm-1; MS (FAB): m/z = 439 [M+Na]+; HRMS (FAB): m/z [M+Na]+ calcd for C20H40O5Si2Na:
439.2312; Found 439.2309.
(5R,E)-5-Hydroxy-5-[(7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl]-
pent-3-en-2-one (21). Compound 21 (1.47 g) was obtained in 68% yield from 15 (1.96 g). White
1
solid; mp 64-66 ºC; Rf = 0.30 (30% EtOAc in hexane); [α]D20 +12.6 (c 1.07, CHCl3); H NMR (400
MHz, CDCl3) δ 6.94 (dd, J = 15.9, 3.5 Hz, 1H), 6.50 (dd, J = 15.9, 2.0 Hz, 1H), 4.61 (d, J = 1.9 Hz,
1H), 4.10 (dd, J = 11.9, 1.2 Hz, 1H), 3.86 (dd, J = 9.3, 2.8 Hz, 1H), 3.80 (dd, J = 11.9, 2.2 Hz, 1H),
13
3.65 (d, J = 9.2 Hz, 1H), 3.16 (brs, 1H), 2.28 (s, 3H), 1.10-0.96 (m, 28H); C NMR (100 MHz,
CDCl3) δ 198.1, 147.1, 130.5, 72.5 (2C), 71.5, 62.5, 28.1, 17.5, 17.44 (2C), 17.42 (2C), 17.39 (2C),
17.36, 13.5, 13.4, 12.8, 12.7; IR (film): 3399, 2944, 2867, 1676, 1464, 1032, 885 cm-1; MS (FAB):
m/z = 455 [M+Na]+; HRMS (FAB): m/z [M+Na]+ calcd for C20H40O6Si2Na: 455.2261; Found
455.2267; Anal. Calcd for C20H40O6Si2: C, 55.52; H, 9.32. Found: C, 55.23 H, 9.29.
(5S,E)-5-Hydroxy-5-((7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)pent-3
-en-2-one (22). Compound 22 (1.52 g) was obtained in 70% yield from 16 (1.96 g). White solid; mp
1
126-129 ºC; Rf = 0.30 (30% EtOAc in hexane); [α]D20 +16.2 (c 1.18, CHCl3); H NMR (400 MHz,
CDCl3) δ 6.89 (dd, J = 16.0, 5.4 Hz, 1H), 6.35 (dd, J = 16.0, 1.7 Hz, 1H), 4.57 (brs, 1H), 4.13 (d, J =
11.6 Hz, 1H), 3.81 (dd, J = 9.2, 4.1 Hz, 1H), 3.80 (dd, J = 11.6, 2.4 Hz, 1H), 3.61 (t, J = 10.1 Hz,
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1H), 2.98 (brs, 1H), 2.28 (s, 3H), 1.10-0.97 (m, 28H); C NMR (100 MHz, CDCl3) δ 198.8, 145.2,
130.1, 74.1, 73.6, 72.5, 62.6, 27.5, 17.6, 17.48, 17.42, 17.38, 17.37, 17.36, 17.34, 17.32, 13.49, 13.43,
12.8, 12.7; IR (film): 3400, 2944, 2867, 1676, 1464, 1032, 885 cm-1; MS (FAB): m/z = 455 [M+Na]+;
HRMS (FAB): m/z [M+Na]+ calcd for C20H40O6Si2Na: 455.2261; Found 455.2258; Anal. Calcd for
C20H40O6Si2: C, 55.52; H, 9.32. Found: C, 55.33 H, 9.06.
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General Procedure for the Preparation of Compounds 11, 12, and 13 by NaBH4 Reduction
of Ketones 20, 21, and 22 and Lipase Catalyzed Kinetic Acetylation of the Alcohols. To a
solution of ketone (1 mmol) in CH2Cl2 (5 mL) was added cerium chloride (3 mmol) at -78 °C. The
mixture was stirred for 30 min at the same temperature and NaBH4 (57 mg, 1.5 mmol) was added in
several portions. The reaction was warmed up to room temperature. Water and CH2Cl2 was added to
the mixture and organic layer was washed with water and brine. The solvent was evaporated and the
residue was purified by column chromatography on silica gel to give diastereomeric mixture of
alcohol. Reduction of 20 (417 mg), 21 (432 mg), and 22 (432 mg) gave a mixture of 8 and 11 (364
mg) in 87% yield, 9 and 12 (348 mg) in 80% yield and 10 and 13 (396 mg) in 91% yield,
respectively. They were able to separate by the following lipase catalyzed kinetic acetylation and
reductive deacetylation. To a mixture of allylic alcohols (0.5 mmol) in iPr2O (3 mL) was added
molecular sieves 4Å (215 mg), vinyl acetate (154 µL, 215 mg, 2.5 mmol), and Novozyme 435 (22
mg, 10 w/v%). The mixture was stirred for 1 day at room temperature. Solid was filterd through
celite pad and the filtrate was condensed. The residue was purified by chromatography on silica gel
eluted with 20% EtOAc in hexane to give (R)-acetate and with 60% EtOAc in hexane recovery of
(S)-alcohol.
Reaction of a mixture of 8 and 11 (209 mg) gave acetate 23 (110 mg) in 48% yield with recovery
of 11 (98 mg) in 47% yield.
(R,E)-2-Acetoxy-5-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)-pent
-3-ene (23). Colorless oil; Rf = 0.80 (30% EtOAc in hexane); [α]D20 +18.2 (c 0.95, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 5.81 (dddd, J = 15.4, 8.1, 4.5, 1.0 Hz, 1H), 5.58 (ddt, J = 15.4, 6.4 1.2 Hz, 1H),
5.33 (qd, J = 6.4. 6.3, 1H), 4.14 (dd, J = 11.6, 1.2 Hz, 1H), 3.77 (dd, J = 11.6, 2.1 Hz, 1H), 3.75 (q, J
= 4.5 Hz, 1H), 3.34 (brt, J = 7.5 Hz, 1H), 2.52 (dt, J = 14.2, 4.5 Hz, 1H), 2.39 (ddd, J = 14.2, 8.1, 4.5
Hz, 1H), 2.02 (s, 3H), 1.29 (d, J = 6.4 Hz, 3H), 1.10-1.00 (m, 28H); 13C NMR (100 MHz, CDCl3) δ
170.5, 132.6, 128.6, 73.6, 71.2, 70.3, 62.7, 36.7, 21.6, 20.5, 17.69, 17.66, 17.5, 17.49, 17.48, 17.47,
17.46, 17.44, 13.55, 13.50, 12.9, 12.8; IR (film): 3471, 2944, 2867, 1740, 1464, 1028, 885 cm-1; MS
(FAB): m/z = 483 [M+Na]+; HRMS (FAB): m/z [M+Na]+ calcd for C22H44O6Si2Na: 483.2574; Found
483.2565.
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(S,E)-5-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)pent-3-en-2-ol
(11). White solid; mp 99-101 ºC; Rf = 0.30 (30% EtOAc in hexane); [α]D20 +3.36 (c 1.10, CHCl3); 1H
NMR (400 MHz, CDCl3) δ 5.76 (ddd, J = 15.2, 7.7, 0.7 Hz, 1H), 5.64 (ddd, J = 15.4, 6.4, 1.0 Hz,
1H), 4.28 (dq, J = 6.4, 6.3 Hz, 1H), 4.14 (dd, J = 11.6, 1.2 Hz, 1H), 3.76 (dd, J = 11.6, 2.1 Hz, 1H),
3.75 (dt, J = 8.6, 4.5 Hz, 1H), 3.38 (brd, J = 8.7 Hz, 1H), 2.50 (dt, J = 14.2, 4.5 Hz, 1H), 2.43 (ddd, J
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= 14.2, 7.7, 4.5 Hz, 1H), 1.26 (d, J = 6.4 Hz, 3H), 1.10-0.96 (m, 28H); C NMR (100 MHz,
CDCl3) δ 137.3, 126.5, 73.7, 70.4, 69.2, 62.7, 36.6, 23.5, 17.7, 17.6, 17.54, 17.51 (2C), 17.49, 17.47,
17.45, 13.56, 13.53, 12.9, 12.8; IR (film): 3326, 2944, 2867, 1512, 1464, 1062, 884 cm-1; MS (FAB):
m/z = 441 [M+Na]+; HRMS (FAB): m/z [M+Na]+ calcd for C20H42O5Si2Na: 441.2469; Found
441.2474; Anal. Calcd for C20H42O5Si2: C, 57.37; H, 10.11. Found: C, 57.63 H, 10.07.
Reaction of a mixture of 9 and 12 (217 mg) gave 24 (100 mg) in 42% yield with recovery of 12
(100 mg) in 46% yield.
(1R,4R,E)-4-Acetoxy-2-hydroxy-1-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisi
locan-6-yl)pent-2-ene (24). Colorless oil; Rf = 0.80 (60% EtOAc in hexane); [α]D20 +36.6 (c 1.07,
1
CHCl3); H NMR (400 MHz, CDCl3) δ 5.90-5.81 (m, 2H), 5.41 (m, 1H), 4.43 (d, J = 7.1 Hz, 1H),
4.08 (dd, J = 11.8, 1.0 Hz, 1H), 3.83 (dd, J = 9.3, 2.5 Hz, 1H), 3.80 (dd, J = 11.8, 1.8 Hz, 1H), 3.66 (t,
J = 5.0 Hz, 1H), 2.95 (brd, J = 9.1 Hz, 1H), 2.42 (brd, J = 8.3 Hz, 1H), 2.03 (s, 3H), 1.32 (d, J = 6.5
13
Hz, 3H), 1.10-0.97 (m, 28H); C NMR (100 MHz, CDCl3) δ 170.5, 131.9, 130.7, 72.5, 72.1, 71.7,
70.5, 62.7, 21.5, 20.4, 17.59, 17.54, 17.44, 17.43 (2C), 17.41, 17.38, 17.35, 13.49, 13.47, 12.8, 12.7;
IR (film): 3421, 2944, 2867, 1739, 1465, 1035, 885 cm-1; MS (FAB): m/z = 499 [M+Na]+; HRMS
(FAB): m/z [M+Na]+ calcd for C22H44O7Si2Na: 499.2523; Found 499.2520.
(1R,4S,E)-5-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)pent-2-en-1
,4-diol (12). White solid; mp 131-132 ºC; Rf = 0.30 (60% EtOAc in hexane); [α]D20 +20.8 (c 1.01,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 5.91 (ddd, J = 15.6, 6.0, 1.3 Hz, 1H), 5.82 (ddd, J = 15.6, 4.3,
0.7 Hz, 1H), 4.39 (brs, 1H), 4.35 (qd, J = 6.3, 6.0 Hz, 1H), 4.09 (dd, J = 11.6, 1.1 Hz, 1H), 3.83 (dd,
J = 9.3. 2.7 Hz, 1H), 3.80 (dd, J = 11.6, 2.2 Hz, 1H), 3.70 (t, J = 8.3 Hz, 1H), 3.02 (brd, J = 9.2 Hz,
13
1H), 2.60 (brs, 1H), 1.29 (d, J = 6.3 Hz, 3H), 1.10-0.97 (m, 28H); C NMR (100 MHz, CDCl3) δ
135.5, 129.7, 73.1, 72.2, 71.1, 68.6, 63.1, 23.3, 17.55, 17.52, 17.4, 17.3 (4C), 17.2, 13.4, 13.3, 12.74,
12.71; IR (film): 2944, 2867, 1733, 1456, 1042 cm-1; MS (FAB): m/z = 457 [M+Na]+; HRMS (FAB):
m/z [M+Na]+ calcd for C20H42O6Si2Na: 457.2418; Found 457.2411; Anal. Calcd for C20H42O6Si2: C,
55.26; H, 9.74. Found: C, 55.03 H, 9.86.
Reaction of a mixture of 10 and 13 (240 mg) gave 25 (121.4 mg) in 46% yield with recovery of
13 (116.8 mg) in 49% yield.
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(1S,4R,E)-4-Acetoxy-1-hydroxy-1-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisil
ocan-6-yl)pent-2-ene (25). Colorless oil; Rf = 0.80 (60% EtOAc in hexane); [α]D20 +14.6 (c 0.92,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 5.88-5.74 (m, 2H), 5.33 (qd, J = 6.5, 6.4 Hz, 1H), 4.36 (dd, J
= 5.9, 3.6 Hz, 1H), 4.08 (dd, J = 11.7, 1.1 Hz, 1H), 3.80 (dd, J = 9.9, 3.6 Hz, 1H), 3.79 (dd, J = 11.7,
2.3 Hz, 1H), 3.47 (brt, J = 8.2 Hz, 1H), 2.65 (brs, 1H), 2.55 (brd, J = 8.2 Hz, 1H), 2.04 (s, 3H), 1.32
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(d, J = 6.5 Hz, 3H), 1.10-0.97 (m, 28H); C NMR (100 MHz, CDCl3) δ 170.6, 132.0, 129.9, 74.4,
73.8, 72.4, 70.7, 62.8, 21.5, 20.4, 17.7, 17.58, 17.50, 17.49, 17.48, 17.45, 17.44, 17.41, 13.54, 13.51,
13.0, 12.8; IR (film): 3445, 2944, 2867, 1738, 1464, 1030, 885 cm-1; MS (FAB): m/z = 499 [M+Na]+;
HRMS (FAB): m/z [M+Na]+ calcd for C22H44O7Si2Na: 499.2523; Found 499.2518.
(1S,4S,E)-5-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)pent-2-en-1,
4-diol (13). White solid; mp 92-95 ºC; Rf = 0.30 (60% EtOAc in hexane); [α]D20 −10.3 (c 1.08,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 5.94-5.78 (m, 2H), 4.40 (brs, 1H), 4.35 (qd, J = 6.4, 5.9 Hz,
1H), 4.12 (d, J = 10.9 Hz, 1H), 3.79 (dd, J = 8.2, 3.2 Hz, 1H), 3.78 (dd, J = 10.9, 3.2 Hz, 1H), 3.55
(brt, J = 8.2 Hz, 1H), 2.91 (brs, 1H), 2.47 (brs, 1H), 2.35 (brd, J = 9.2 Hz, 1H), 1.29 (d, J = 6.4 Hz,
13
3H), 1.10-0.98 (m, 28H); C NMR (100 MHz, CDCl3) δ 136.9, 128.2, 74.7, 73.7, 72.6, 68.4, 62.7,
23.4, 17.7, 17.58, 17.50 (2C), 17.49, 17.46, 17.42, 17.41, 13.55, 13.52, 13.0, 12.8; IR (film): 3352,
2944, 2867, 1652, 1464, 1058, 885 cm-1; MS (FAB): m/z = 457 [M+Na]+; HRMS (FAB): m/z
[M+Na]+ calcd for C20H42O6Si2Na: 457.2418; Found 457.2422; Anal. Calcd for C20H42O6Si2: C,
55.26; H, 9.74. Found: C, 55.37 H, 9.55.
General Procedure for the Preparation of Compounds 8, 9, and 10 from 23, 24 and 25. To a
solution of acetate 23, 24 or 25 (1 mmol) in anhydrous ether (30 mL) was added LiAlH4 (4 mmol) at
0 °C. The mixture was stirred for 1 h at the same temperature and quenched with acetone. Aq.
potassium sodium tartrate was added to the mixture and stirred vigorously. The mixture was
extracted with ether and the extract was dried over MgSO4. Solvent was removed and the residue
was purified by chromatography on silica gel eluted with 30% EtOAc in hexane.
(R,E)-5-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)pent-3-en-2-ol
(8). LiAlH4 reduction of 23 (99 mg) gave 8 (83.5 mg) in 93% yield. Colorless oil; Rf = 0.30 (30%
EtOAc in hexane); [α]D20 +11.3 (c 1.70, CHCl3); 1H NMR (400 MHz, CDCl3) δ 5.77 (dddd, J = 15.2,
7.9, 5.3, 0.8 Hz, 1H), 5.64 (ddt, J = 15.5, 6.2, 1.2 Hz, 1H), 4.29 (qd, J = 6.3, 6.2 Hz, 1H), 4.14 (dd, J
= 11.6, 1.2 Hz, 1H), 3.76 (dd, J = 11.6, 2.2 Hz, 1H), 3.75 (dt, J = 9.1, 5.3 Hz, 1H), 3.36 (t, J = 9.1 Hz,
1H), 2.51 (dt, J = 14.3, 5.3 Hz, 1H), 2.41 (ddd, J = 14.3, 7.9, 5.3 Hz, 1H), 2.05 (brd, J = 10.4 Hz,
1H), 1.26 (d, J = 6.3 Hz, 3H), 1.10-0.98 (m, 28H); 13C NMR (100 MHz, CDCl3) δ 137.3, 126.5, 73.7,
70.3, 69.1, 62.7, 36.7, 23.5, 17.7, 17.6, 17.55, 17.51 (2C), 17.49, 17.46, 17.45, 13.55, 13.53, 12.9,
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12.8; IR (film): 3367, 2944, 2867, 1464, 1058, 885 cm-1; MS (FAB): m/z = 441 [M+Na]+; HRMS
(FAB): m/z [M+Na]+ calcd for C20H42O5Si2Na: 441.2469; Found 441.2471.
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(1R,4R,E)-5-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)pent-2-en-1
,4-diol (9). LiAlH4 reduction of 24 (114 mg) gave 9 (93.7 mg) in 90% yield. White solid; mp
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127-130 ºC; Rf = 0.30 (60% EtOAc in hexane); [α]D20 +18.8 (c 1.19, CHCl3); H NMR (400 MHz,
CDCl3) δ 5.93 (ddd, J = 15.6, 5.3, 1.3 Hz, 1H), 5.84 (ddd, J = 15.6, 4.3, 3.3 Hz, 1H), 4.57 (brs, 1H),
4.36 (qd, J = 6.3, 5.3 Hz, 1H), 4.09 (dd, J = 11.8, 1.1 Hz, 1H), 3.82 (dd, J = 9.0. 2.7 Hz, 1H), 3.80
(dd, J = 11.8, 2.1 Hz, 1H), 3.68 (t, J = 7.7 Hz, 1H), 2.90 (brd, J = 9.0 Hz, 1H), 2.44 (brd, J = 7.6Hz,
1H), 1.29 (d, J = 6.3 Hz, 3H), 1.10-0.97 (m, 28H); 13C NMR (100 MHz, CDCl3) δ 135.5, 129.7, 72.7,
72.2, 71.9, 68.4, 62.7, 23.5, 17.6, 17.5, 17.47, 17.46, 17.45 (2C), 17.399, 17.395, 13.5, 13.4, 12.89,
12.81; IR (film): 2944, 2867, 1733, 1456, 1040 cm-1; MS (FAB): m/z = 457 [M+Na]+; HRMS (FAB):
m/z [M+Na]+ calcd for C20H42O6Si2Na: 457.2418; Found 457.2411; Anal. Calcd for C20H42O6Si2: C,
55.26; H, 9.74. Found: C, 55.07 H, 9.62.
(1S,4R,E)-5-((6S,7R)-7-hydroxy-2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocan-6-yl)pent-2-en-1
,4-diol (10). LiAlH4 reduction of 25 (60.7 mg) gave 10 (46.9 mg) in 85% yield. White solid; mp
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115-117 ºC; Rf = 0.30 (60% EtOAc in hexane); [α]D20 −12.1 (c 1.19, CHCl3); H NMR (400 MHz,
CDCl3) δ 5.88-5.78 (m, 2H), 4.38 (t, J = 4.1 Hz, 1H), 4.32 (qd, J = 6.4, 5.9 Hz, 1H), 4.11 (d, J = 11.0
Hz, 1H), 3.79 (dd, J = 10.5, 2.3 Hz, 2H), 3.53 (brd, J = 8.7 Hz, 1H), 2.61 (brs, 1H), 1.29 (d, J = 6.4
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Hz, 3H), 1.10-0.96 (m, 28H); C NMR (100 MHz, CDCl3) δ 136.8, 128.3, 74.6, 73.7, 72.4, 68.5,
62.7, 23.4, 17.7, 17.58, 17.51 (2C), 17.49, 17.46, 17.423, 17.420, 13.56, 13.53, 13.0, 12.8; IR (film):
3358, 2944, 2867, 1464, 1058, 886 cm-1; MS (FAB): m/z = 457 [M+Na]+; HRMS (FAB): m/z
[M+Na]+ calcd for C20H42O6Si2Na: 457.2418; Found 457.2412; Anal. Calcd for C20H42O6Si2: C,
55.26; H, 9.74. Found: C, 55.09 H, 9.50.
PdCl2(MeCN)2-Catalyzed Cyclization
General Method. To a solution of allylic alcohol (0.1 mmol) in THF (0.5 mL) was added
PdCl2(MeCN)2 (2.6 mg, 10 mol %) and the mixture was stirred for 5 to 20 min at room temperature.
The mixture was diluted with ether (10 mL) and washed with water and brine. The extract was
condensed and the residue was purified by column chromatography on silica gel eluted with 5% to
10% EtOAc in hexane. The chemical yields, products ratio, physical and spectroscopic data are
following.
A mixture of 2,5-trans-26 and 2,5-cis-26 (3:1). Diol 5 (26.8 mg) gave a mixture of 2,5-trans-26
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and 2,5-cis-26 (22.8 mg) in 89% yield. Colorless oil; Rf = 0.30 (5% EtOAc in hexane); H NMR
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