Tetrahedron 59 (2003) 6739–6750

N-tert-Butylbenzenesulfenamide-catalyzed oxidation of alcohols to

the corresponding carbonyl compounds with N-chlorosuccinimide
Jun-ichi Matsuo,a,b Daisuke Iida,a,b Hiroyuki Yamanakaa,b and Teruaki Mukaiyamaa,b,*
a
Center for Basic Research, The Kitasato Institute, 6-15-5 (TCI), Toshima, Kita-ku, Tokyo, 114-0003, Japan
b
Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
Received 7 February 2003; revised 22 March 2003; accepted 22 March 2003
This paper is dedicated to Professor K. C. Nicolaou on the occasion of his receipt of the 2002 Tetrahedron Prize

Abstract—N-tert-Butylbenzenesulfenamide (1)-catalyzed oxidation of various primary and secondary alcohols to the corresponding
aldehydes and ketones was efficiently carried out by using N-chlorosuccinimide (NCS) in the coexistence of potassium carbonate and
molecular sieves 4 Å at easy-to-control temperatures ranging from 08C to room temperature. The present catalytic oxidation was performed
without giving any damage to the functional groups in alcohols, and was particularly effective in the oxidation of alcohols that formed labile
aldehydes because of its mild reaction conditions. Further, selective oxidation of primary hydroxy groups took place in 1-catalyzed oxidation
of several diols. Mechanistic investigation suggested that the chlorination of the sulfenamide 1 by NCS led to the formation of a key species,
N-tert-butylbenzenesulfinimidoyl chloride (2), which in turn oxidized alcohols in the presence of potassium carbonate to afford carbonyl
products by accompanying regeneration of the catalyst 1.
q 2003 Elsevier Ltd. All rights reserved.

1. Introduction doxol-3(1H)-one)7 were sometimes explosive on impact or

on heating to .2008C.
Oxidation of primary and secondary alcohols to the
corresponding aldehydes and ketones1 is one of the most For oxidation of alcohols, catalytic oxidation with a
important reactions in organic synthesis since the formed common oxidant is now considered most desirable
carbonyl compounds are quite useful synthetic inter- especially in large-scale synthesis, and numerous catalytic
mediates especially for the construction of carbon- methods1 using transition metal catalysts8,9 or non-metal
skeletons. There are many methods for stoichiometric organic catalysts10 – 12 have intensively been studied.
oxidation of alcohols by using following oxidants: e.g. Among them, tetrapropylammonium perruthenate (TPAP)-
chromium(VI)-based oxidants,2 manganese dioxide,3 acti- catalyzed oxidation9 and 2,2,6,6-tetramethylpiperidine-1-
vated dimethylsulfoxides, 4,5 hypervalent iodines.6,7 oxyl (TEMPO)-catalyzed oxidation10,11 are well known to
Although these methods are useful in organic synthesis, be versatile for oxidizing various primary and secondary
each contains problems to be solved: e.g. stoichiometric alcohols to the corresponding aldehydes and ketones under
oxidations using heavy metals or activated dimethyl- mild conditions. However, TPAP-catalyzed oxidation
sulfoxides accompany such co-products as poisonous sometimes turns unsuccessful when a substrate alcohol
heavy metal residues or bad-smelling dimethylsulfide, has a strong coordinating group though it is carried out in
respectively. In Swern oxidation,5 a commonly-employed simple procedures and has been utilized in the synthesis of
oxidation method using dimethylsulfoxide and oxalyl complex molecules.9 Also, the TEMPO-bleach oxidation10
chloride, the reaction temperature should be controlled which is the most useful for large-scale oxidation of
strictly in low temperature (,2208C) for the generation of a alcohols does not work well with unsaturated alcohols.11
key intermediate, chlorodimethylsulfonium chloride. Con- Therefore, it is worthwhile to develop a new and more
cerning hypervalent iodine oxidants, it was reported that practical method applicable to catalytic oxidation of various
Dess – Martin periodinane (1,1,1-triacetoxy-1,1-dihydro- alcohols to carbonyl compounds.
1,2-benziodo-3(1H)-one)6 and IBX (1-hydroxy-1,2-benzio-
Recently, a new method was reported from our laboratory
for the oxidation of primary and secondary alcohols to the
Keywords: oxidation; alcohols; catalysis. corresponding carbonyl compounds by using more than a
* Corresponding author. Address: Center for Basic Research, The Kitasato
Institute, 6-15-5 (TCI), Toshima, Kita-ku, Tokyo, 114-0003, Japan. Tel.:
stoichiometric amount of N-tert-butylbenzenesulfinimidoyl
þ81-3-3911-3111; fax: þ81-3-3911-3482; chloride (2) (Eq. (1)).13 It was further revealed that the new
e-mail: [email protected] oxidizing agent 2 was also applicable to other oxidation

0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00479-4
6740 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750

reactions such as oxidation of secondary amines to imines,14 Table 1. Effect of halogenating agent on 1-catalyzed oxidation of 3a to 4a
oxidation of N,N-dialkylhydroxylamines to nitrones,15 in the presence of DBU
one-pot dehydrogenation of saturated ketones to a,b-
unsaturated ketones.16 Despite its easy handling and
wide-applicability, a reduced product, N-tert-butylbenzene-
sulfenamide (1), and other co-products formed by decompo-
sition of 1 or by hydrolysis of 2 had to be removed during
purification procedures in the stoichiometric oxidation of
using 2. Therefore, a study on a catalytic oxidation mediated
by a catalytic amount of 2 with a suitable oxidant was tried Entry Halogenating agent Yield (%)
in order to establish a more useful oxidation method.
1a 61
2 86
3 87

ð1Þ

4 85

It was considered that the catalytic oxidation would be

established when in situ chlorination of sulfenamide 1 with
an appropriate chlorinating agent smoothly proceeded to
regenerate the oxidizing agent 2 (Fig. 1). This assumption 5 40
led us to study on a new method for the catalytic oxidation 6 9
of alcohols to the corresponding carbonyl compounds by
employing N-chlorosuccinimide (NCS) as a chlorinating
7 t-BuOCl 3
agent in the presence of a catalytic amount of 1, which had 8 Cl2 7
been reported briefly in our previous communication.17 In 9 Br2 30
this paper, we would like to describe the convenient a
NCS was added in one portion.
1-catalyzed oxidation of various alcohols with NCS to the
corresponding carbonyl compounds in detail.
aldehyde 4a was detected in 61% yield (entry 1). It was
further found that the slow addition of NCS improved the
yield of 4a up to 86% probably because the operation
suppressed the interaction of NCS with DBU. Investigations
on other halogenating agents proved that trichloroiso-
cyanuric acid and N-bromosuccinimide (NBS) were also
effective in the 1-catalyzed oxidation of 3a in the presence
of DBU while tert-butyl hypochlorite, chlorine, and
bromine were not (entries 3 –9).

In order to establish more efficient catalytic oxidation, it is

Figure 1. Outline of the catalytic cycle of sulfenamide 1-catalyzed
oxidation of alcohol. important to choose a suitable base which is inert to NCS
and is effective in trapping hydrogen chloride. Then,
sterically hindered amine, diisopropylethylamine, was
employed instead of DBU, but the yield of 4a dropped
2. Results and discussion down unexpectedly to 35% (Table 2, entry 1). Solid bases
were next examined since they were insoluble and were thus
2.1. Optimization of reaction conditions (halogenating considered difficult to interact with NCS. Zinc oxide, an
agent, base, and additive) effective solid base in the 2-mediated stoichiometric
oxidation of alcohols,13b did not work well in the present
Oxidation of benzyl alcohol (3a) to benzaldehyde (4a) was catalytic oxidation. After screening other solid bases,
chosen as a model reaction to optimize the reaction potassium carbonate was found to be most effective, and
conditions for 1-catalyzed oxidation of alcohols. In the the slow addition of NCS was not required in this case
first place, several halogenating agents which in situ (entry 4).
chlorinated 1 to regenerate sulfinimidoyl halides were
screened (Table 1, entries 1 –9). NCS was then employed Addition of dehydrating agents such as molecular sieves and
as the chlorinating agent and 1.1 equiv. of 1,8-diazabicyclo- Drieritew improved the yield of oxidation product 4a while
[5.4.0]undec-7-ene (DBU) was used as a base to trap sodium or magnesium sulfate showed no effects (entries
hydrogen chloride. When one portion of NCS was added to 6– 11). All molecular sieves that were tested (MS3A, 4A
the dichloromethane solution of 5 mol% of the catalyst 1, and 5A) improved the yield of 4a, which worked to trap a
alcohol 3a, and DBU, the catalytic oxidation took place and trace amount of water involved in this reaction system.
 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750 6741

Table 2. Effect of base and additive on the 1-catalyzed oxidation of 3a to 4a with NCS

Entry Base (equiv.) Additive Reaction conditions GC-yield (%)

1a i-Pr2NEt (1.1) None 08C, 1 h 35

2 ZnO (5.0) None 08C, 1 h 24
3 Na2CO3 (10) None 08C, 1 h 56
4 K2CO3 (10) None 08C, 1 h 90
5 Cs2CO3 (10) None 08C, 1 h 44
6 K2CO3 (10) Na2SO4 (10 equiv.) 08C, 2 h 91
7 K2CO3 (10) Mg2SO4 (10 equiv.) 08C, 2 h 88
8 K2CO3 (10) Drierite (1 g/mmol) 08C, 1 h 94
9 K2CO3 (10) MS3A (1 g/mmol) 08C, 1 h 97
10 K2CO3 (10) MS4A (1 g/mmol) 08C, 1 h 98 (,1)b
11 K2CO3 (10) MS5A (1 g/mmol) 08C, 1 h 95
12 K2CO3 (10) MS4A (1 g/mmol) 2788C, 1 h 31
13 K2CO3 (10) MS4A (1 g/mmol) 2458C, 1 h 33
14 K2CO3 (10) MS4A (1 g/mmol) 2238C, 1 h 75
15 K2CO3 (10) MS4A (1 g/mmol) rt, 1 h 74
a i
Pr2NEt was added slowly.
b
The catalyst 1 was not used.

Therefore, catalytic oxidation was successfully carried out 2.2. Catalytic oxidation of various alcohols
by simply adding the catalyst 1 to the mixture of 3a, NCS,
potassium carbonate, and MS4A. Since the oxidation of 3a As shown in Tables 4 –8, various primary and secondary
with NCS18 did not take place in the absence of the catalyst alcohols involving simple allylic and benzylic alcohols were
1, the present catalytic oxidation was clearly mediated by 1. efficiently oxidized by using 5 mol% of the catalyst 1 and
1.1 equiv. of NCS in the coexistence of 10 equiv. of
Effects of solvents in the present catalytic oxidation of potassium carbonate and 1.0 g/mmol of MS4A in
alcohols were investigated taking oxidation of benzyl
alcohol (3a) and 1-octanol (3b) as a model. As shown in
Table 4. Catalytic oxidation of simple allylic and benzylic alcohols by
Table 3, both catalytic oxidations proceeded in the solvents using the catalyst 1 and NCS in the coexistence of K2CO3 and MS4A
other than dichloromethane such as dichloroethane, THF,
tert-butylmethylether, or toluene to afford the desired
carbonyl compounds in high yields. It was found that the
oxidation proceeded most rapidly in dichloromethane while
longer reaction time and more than 5 mol% of the catalyst 1
were required in other solvents.
Entry Alcohola Product GC-yield
(%)
Table 3. Effect of solvents

1 93

2 83

Entry Alcohol Solvent 1 (mol%) Conditions Yield (%)a 3 86

1 3a CH2Cl2 5 08C, 1 h 98
2 3a ClCH2CH2Cl 5 08C, 3 h 94
3 3a THF 10 08C, 6 h 97 4b 87
t
4 3a BuOMe 10 08C, 24 h 87
5 3a Toluene 10 08C, 24 h 90
6 3b CH2Cl2 5 rt, 1 h 94 5 .99
7 3b ClCH2CH2Cl 5 rt, 3 h 91
8 3b THF 10 rt, 3 h 93 6 80
t
9 3b BuOMe 10 rt, 10 h 93
10 3b Toluene 10 rt, 8 h 85 a
Alcohols (0.5 mmol) were used.
a b
Determined by GC-analysis using an internal standard. Conditions: 2788C,08C, 2 h.
6742 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750

Table 5. Catalytic oxidation of various primary alcohols to aldehydes Table 6. Catalytic oxidation of various secondary alcohols to ketones

Entry Alcohol Conditions Yield Entry Secondary alcohol Yield

(%)a (%)a

1 rt, 1 h 95b 1 96

2c rt, 3 h 99

2 .99
3 rt, 30 min .99b
3b 90
4 rt, 1 h 93
4 93
5 08C, 1 h .99b 5 99

6 rt, 1 h 88b
6 91
7 .99

7 08C, 1.5 h 94

8b 92
d
8 rt, 30 min 88

9d rt, 1 h 92 9b 96c

10 rt, 1 h 88e

10b 94c
11 08C, 1 h 80e

12f 2238C, 3 h 90
11 .99c

13f rt, 2 h 93 12 92c

a
Isolated yields unless otherwise noted. 13b,d 98
b
Determined by GC-analysis using an internal standard.
c
The catalyst 1 (0.5 mol%) was used.
d
The catalyst 1 (10 mol%) was used.
e
Isolated yield after Wittig reaction using (carbethoxymethylene)triphe-
nylphosphorane. 14b,d 92c
f
The catalyst 1 (20 mol%) was used.

a
dichloromethane. Simple allylic and benzylic alcohols were Determined by GC-analysis using an internal standard unless otherwise
noted.
smoothly oxidized at 08C (Table 4), and primary19 and b
The catalyst 1 (10 mol%) was used.
secondary20 alcohols were oxidized to aldehydes and c
Isolated yield.
d
ketones at 08C –room temperature (Tables 5 and 6). Since NBS was employed instead of NCS, and the reaction time was 24 h.
primary alcohols were more smoothly oxidized than the
 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750 6743

Table 7. Selective oxidation of primary hydroxy group of diol 13a–c oxidation, and no detectable loss of the geometric integrity
a of the carbon – carbon double bond was observed. There-
Entry Diol Product (yield (%))
fore, the 1-catalyzed catalytic oxidations proceeded without
giving any damage to the functional groups in alcohols and
the results shown in Tables 4– 7 suggest this method is
1b applicable to the preparation of various types of aldehydes
and ketones.

ð2Þ
3

Conditions: 1 (10 mol%), NCS (1.1 equiv.), K2CO3 (10 equiv.), MS4A
(1 g/mmol), CH2Cl2. 08C, 2 h.
a
Isolated yield.
b
Conditions: room temperature, 1.5 h. The exception is the oxidation of alcohols which form
stabilized carbocationes. In the cases of 1-catalyzed
secondary ones, selective oxidation of primary hydroxy oxidation of allylic and benzylic alcohols such as
group21 took place in the catalytic oxidation of diols which p-methoxybenzyl alcohol (17a), diphenylmethanol (17c),
had primary and secondary hydroxy groups within the same and 2-cyclohexenol (17d) under standard oxidation con-
molecule, and hydroxyaldehydes were obtained in moderate ditions where the corresponding carbonyl compounds were
yields (Table 7). In addition to small-scale oxidation, obtained in low yields (Table 9, entries 1 –4, yields shown in
preparative scale oxidation was successfully carried out as parentheses) while those oxidations were satisfactorily
well (Table 8),22 and oxidation products were isolated after improved by using DBU as a base.
purification by silica gel column chromatography or
distillation.
3. Mechanism
The catalytic oxidation of 2-phenylethanol (7d),13b highly
functionalized primary alcohol 7h which is a synthetic Figure 2 shows a proposed catalytic cycle in the present
intermediate for our total synthesis of Taxolw,23 and 7l24 catalytic oxidation of alcohols by using NCS, potassium
proceeded efficiently to give the corresponding aldehydes in carbonate, MS4A, and a catalytic amount of sulfenamide 1.
high yields. Also, the oxidation of N-Fmoc phenylglycinol 9 The key oxidant 2 is first formed by chlorination of the
(.99% ee) gave a highly epimerizable25 aldehyde 10 by catalyst 1 with NCS together with succinimide. It
keeping its high enantiomeric excess (98% ee, Eq. (2)). subsequently reacts with alcohol to form the key inter-
Double bonds in alcohols were not damaged during the mediate 19 in the presence of potassium carbonate.

Table 8. Gram-scale catalytic oxidation of various alcohols 15a –f and 7c to the corresponding carbonyl compounds 16a–f and 8c

Entry Alcohol (mmol) K2CO3 (equiv.) MS4A (g/mmol) Conditions Isolated yield (%)

1 10 0.1 08C, 3 h 98

2 10 0.1 rt, 1 h 91

3 10 0.1 rt, 1 h 91

4 5 0 rt, 3 h 95

5 10 0.1 rt, 1 h .99

6 5 0.1 rt, 2 h .99

7 5 0.1 rt, 2 h 98

The catalyst 1 (5 mol%) was used.

6744 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750

Table 9. Catalytic oxidation of allylic and benzylic alcohols by using the catalyst 1 and NCS in the coexistence of DBU

Entry Alcohol Product Yield (%)a

1 95 (24)

2 87 (31)

3b 94 (12)

4 79 (14)

5 92

6 88

a
Determined by GC-analysis using an internal standard except entry 3. Yields in entry 3 were isolated yields. Numbers in parentheses were yields which were
obtained under the standard conditions of using K2CO3 and MS4A instead of DBU.
b
Reaction temperature: 2238C.

Oxidation proceeds by intramolecular proton-transfer via NCS was suggested also by the change of color of the
five-membered transition state13c of 19 to give a carbonyl solution to yellow which corresponded to 2.
compound by accompanying regeneration of the catalyst 1.
Since 0.5 mol% of the catalyst 1 was enough to catalyze the Investigation on reaction temperature revealed that the
oxidation of octanol (3b), this catalytic cycle worked quite present catalytic oxidation of benzyl alcohol (3a) proceeded
efficiently (Table 5, entry 2). in good to exellent yields above 2238C (Table 2, entry 10
and entries 12– 15). It was then assumed that the rate-
Formation of sulfinimidoyl chloride 2 by the chlorination of determining step in the catalytic oxidation of 3b was the
sulfenamide 1 with NCS was confirmed by 1H NMR chlorination of 1 with NCS which took place smoothly
experiment. It was observed that an equimolar mixture of above 2238C because 2 oxidized 3a rapidly at 2788C.13
sulfenamide 1 and NCS in CDCl3 was quantitatively On the other hand, the rate-determining step in the
converted to 2 and succinimide at room temperature.26 catalytic oxidation of normal primary and secondary
The formation of sulfinimidoyl chloride 2 by mixing 1 and alcohols was the formation of 19 since the oxidation of
those alcohols proceeded at higher temperature (08C – room
temperature) than that required for chlorination of 1 with
NCS.

In order to clarify the reason for the unsuccessful oxidation

of p-methoxybenzyl alcohol (17a) under the standard
conditions (Table 9, entry 1), an equimolar amount of
sulfenamide 1 was used in the oxidation of 17a with NCS
(Eq. (3)). It was then found that the oxidation product,
p-methoxybenzaldehyde (18a), was formed in only 29%
yield together with 60% of p-methoxybenzyl chloride
(20).27 It was then considered that there were two reaction
pathways in the reaction of 17a with sulfinimidoyl chloride
2 (Scheme 1). When hydrogen chloride was trapped by a
base, alkyl sulfinimidate 21 immediately decomposed to
afford the oxidation product 18a and sulfenamide 1 (Path
A). On the other hand, sulfonium chloride intermediate 22
Figure 2. Assumed catalytic cycle of 1-catalyzed oxidation of alcohols with was formed when hydrogen chloride was insufficiently
NCS in the coexistence of K2CO3 and MS4A. trapped, and 22 decomposed to give sulfinamide 23 together
 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750 6745

Scheme 1. Possible two pathways in the oxidation of p-methoxybenzyl alcohol (17a). PMP: p-MeOC6H4.

with stabilized cation 24 which was in turn converted to 20 (500 MHz) spectrometer; chemical shifts (d) are reported in
(Path B). The use of DBU instead of potassium carbonate parts per million relative to tetramethylsilane. Splitting
improved the catalytic oxidation of 17a probably because patterns are designated as s, singlet; d, doublet; t, triplet; q,
DBU trapped hydrogen chloride more effectively than quartet; m, multiplet; br, broad. 13C NMR spectra were
potassium carbonate. recorded on a JEOL EX270 (68 MHz) spectrometer with
complete proton decoupling. Chemical shifts are reported in
parts per million relative to tetramethylsilane with the
solvent resonance as the internal standard (CDCl3; d
77.0 ppm). High resolution mass spectra (HRMS) were
ð3Þ
recorded on a HITACHI M-80B or a JEOL JMS-AX505HA
mass spectrometer. Analytical gas –liquid chromatography
(GLC) was performed on a Shimadzu GC-9A instrument
equipped with a flame ionizing detector and a capillary
column of OV-101 (0.25 mm£50 m) or CBP10
4. Conclusion (0.25 mm£25 m) using helium as carrier gas. Analytical
TLC was performed on Merk precoated TLC plates (silica
N-tert-Butylbenzenesulfenamide (1)-catalyzed oxidation of gel 60 GF254, 0.25 mm). Silica-gel column chromato-
various primary and secondary alcohols with NCS pro- graphy was carried out on Merk silica gel 60 (0.063 –
ceeded smoothly in the coexistence of potassium carbonate 0.200 mm). Preparative thin-layer chromatography (PTLC)
and MS4A to afford the corresponding aldehydes and was carried out on silica gel Wakogel B-5F. All reactions
ketones in high yields under mild conditions. Many were carried out under an argon atmosphere in anhydrous
functional groups in alcohols are tolerated under the solvents unless otherwise mentioned.
oxidation conditions, and labile aldehydes such as phenyl-
acetaldehyde (8d) and N-Fmoc phenylglycinal (10) were 5.2. Materials
prepared in high yields. The present oxidation is carried out
at easy-to-control reaction temperatures ranging from 08C to Potassium carbonate was purchased from Nakalai tesque
room temperature by using common reagents as NCS, and dried in vacuo with heating just before use. Molecular
potassium carbonate, and MS4A. Thus, the sulfenamide sieves 4 Å (powder, ,5 mm, activated) was purchased from
1-catalyzed oxidation would widely be employed in organic Aldrich Chemical Company, Inc. and dried in vacuo at
synthesis. 2508C for 8 h. Dry solvents were prepared by distillation
under appropriate drying agents. Organic bases, DBU and
diisopropylethylamine, were purified by distillation. The
5. Experimental primary alcohol 7f was prepared according to the reported
procedure. 23c Unless otherwise noted, commercially
5.1. General available reagents were used as received.

All melting points were determined on a Yanagimoto micro 5.2.1. N-tert-Butylbenzenesulfenamide (1).13c,28 To a
melting point apparatus (Yanaco MP-S3) and are uncor- stirred solution of tert-butylamine (13.6 g, 185 mmol) in
rected. Infrared (IR) spectra were recorded on a Horiba dry ether (150 mL), a solution of benzenesulfenyl chloride29
FT300 FT-IR spectrometer. 1H NMR spectra were recorded (12.2 g, 84.2 mmol) in dry ether (30 mL) was added
on a JEOL EX270 (270 MHz) or a JEOL JNM-LA500 dropwise during 30 min at 08C. After the reaction mixture
6746 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750

was stirred for 2 h at room temperature, the resulting white 0.60 mmol) and triphenylmehylchloride (167 mg,
suspension was filtered and the filtrate was concentrated. 0.60 mmol). After stirring the mixture at room temperature
The crude product was distilled (94 – 958C/7 mm Hg) to for 14 h, saturated NaHCO3 solution was added and the
give 1 (9.53 g, 62%) as a colorless oil; 1H NMR (270 MHz, mixture was extracted with dichloromethane. The combined
CDCl3) d¼1.18 (9H, s), 2.79 (1H, brs), 7.0 – 7.1 (1H, m), organic extracts were washed with water, dried over
7.2 – 7.3 (2H, m), 7.3 –7.4 (2H, m); 13C NMR (68 MHz, anhydrous Na2SO4, filtered, and concentrated in vacuo.
CDCl3) d¼29.1, 54.7, 122.4, 124.4, 128.3, 144.4. The residue was purified by preparative TLC (silica gel,
hexane/AcOEt¼2/1) to give 11k (169 mg, 82%) as a
5.2.2. Methyl (2R,3R,5R,6S)-2,6-dibenzyloxy-3-(tert- colorless amorphous; TLC Rf 0.36 (hexane/AcOEt¼2/1);
butyldimethylsiloxy)-5-(p-methoxybenxyloxy)-7- IR (neat, cm21) 3255, 1489; 1H NMR (270 MHz, CDCl3) d
hydroxy-4,4-dimethylheptanonate (7g). To a stirred 1.26– 1.87 (8H, m), 2.96 (1H, brs), 3.45 (1H, brs), 6.93 –
solution of methyl (2R,3R,5R,6S)-2,6-dibenzyloxy-3,7- 7.45 (15H, m); 13C NMR (68 MHz, CDCl3) d 35.3, 46.0,
bis(t-butyldimethylsiloxy)-5-(p-methoxybenxyloxy)-4,4- 69.2, 77.1, 125.9, 127.4, 128.2, 129.1; MS (EI) m/z 343
dimethylheptanonate23c (210 mg, 0.27 mmol) in THF (Mþ), 243 (Trþ).
(5.1 mL) was added 1 M hydrochloric acid (1.6 mL) at
08C. After the mixture was stirred for 11 h at room 5.2.5. Preparation of (3R)-4-benzyloxy-2,2-dimethyl-1,3-
temperature, hexane was added to the reaction mixture butanediol (13a). To a stirred suspension of NaH (55%,
until two layers were separated. The resulting mixture was 328 mg, 7.51 mmol) in DMF (15 mL) was added to a
neutralized with saturated aqueous NaHCO3 solution (ca. solution of 7f23c (1.58 g, 6.26 mmol) in DMF (10 mL). After
7 mL), extracted with CH2Cl2. The combined extracts were the mixture was stirred at 508C for 1 h, benzyl bromide
washed with saturated aqueous NaHCO3 solution and brine, (1.18 g, 6.89 mmol) was added to the mixture, and the
dried over anhydrous Na2SO4, filtered, and concentrated in reaction mixture was stirred at 508C for 2 h and 808C for 1 h.
vacuo. The crude product was purified by preparative TLC After cooling to room temperature, DMF was evaporated in
(hexane/ethyl acetate¼2/1) to give 7g (168 mg, 94%) as a vacuo, and saturated NaHCO3 solution (25 mL) was added
colorless oil: TLC Rf 0.57 (hexane/ethyl acetate¼2/1); to the residue. The mixture was extracted with AcOEt, and
21
[a]25
D ¼þ0.54 (c 1.0, EtOH); IR (neat, cm ) 2923, 1751, the combined organic extracts were washed with water and
1
1250, 1088; H NMR (500 MHz, CDCl3) d 0.05 (3H, s), brine, dried over anhydrous Na2SO4, filtered, and concen-
0.08 (3H, s), 0.92 (9H, s), 1.02 (3H, s), 1.04 (3H, s), 2.29 trated in vacuo. The obtained crude product was purified by
(1H, brs), 3.65 – 3.68 (1H, m), 3.68 (3H, s), 3.77 –3.87 (2H, column chromatography (silica gel, hexane/AcOEt¼10/
m), 3.80 (3H, s), 3.91 (1H, d, J¼4.3 Hz), 4.23 (1H, d, J¼ 1– 5/1) to give (2R,4R)-2-(4-methoxyphenyl)-5,5-dimethyl-
2.4 Hz), 4.29 (1H, d, J¼11.3 Hz), 4.33 (1H, d, J¼2.4 Hz), 4-benzyloxymethyl-1,3-dioxane (1.86 g, 87%) as a color-
4.50 (1H, d, J¼11.6 Hz), 4.52 (1H, d, J¼10.7 Hz), 4.56 (1H, less oil; TLC Rf 0.69 (hexane/AcOEt¼2/1); [a]20 D ¼228.1 (c
d, J¼11.6 Hz), 4.65 (1H, d, J¼11.3 Hz), 4.76 (1H, d, 1.0, EtOH); IR (neat, cm21) 1111, 1011; 1H NMR
J¼10.7 Hz), 6.86 (2H, d, J¼8.5 Hz), 7.26 –7.33 (12H, m); (270 MHz, CDCl3) d 0.83 (3H, s), 1.10 (3H, s), 3.50– 3.69
13
C NMR (125 MHz, CDCl3) d 24.4, 23.5, 18.4, 18.9, 21.2, (4H, m), 3.79 (3H, s), 3.79 –3.84 (1H, m), 4.51 (1H, d, J¼
26.1, 44.2, 51.5, 55.3, 61.8, 71.4, 72.6, 74.7, 77.3, 80.6, 82.2, 12.0 Hz), 4.63 (1H, d, J¼12.0 Hz), 5.48 (1H, s), 6.86 –6.90
83.0, 113.7, 127.7, 127.7, 127.8, 128.0, 128.2, 128.4, 129.1, (2H, m), 7.24 – 7.46 (7H, m); 13C NMR (68 MHz, CDCl3) d
130.8, 137.5, 138.0, 159.1, 171.4; MS (EI) m/z 665 (Mþ); 18.9, 21.6, 31.8, 55.3, 69.9, 73.4, 78.8, 84.5, 101.6, 113.5,
HRMS calcd for C38H53O8Si (M2H)þ: 665.3510, found m/z 127.5, 127.5, 127.6, 128.3, 131.1, 138.2, 159.9; HRMS
665.3521. calcd for C21H26O4 (Mþ): 342.1831, found m/z 342.1826.

5.2.3. (5S,6R,8R,9S,10S)-6-(tert-Butyldimethylsiloxy)- To the solution of (2R,4R)-2-(4-methoxyphenyl)-5,5-

5,9-dibenzyloxy-7,7-dimethyl-10-(5-hydroxypent-1-en- dimethyl-4-benzyloxymethyl-1,3-dioxane (811 mg,
2-yl)-8-(4-methoxybenzyloxy)-1-oxa-4-oxospiro[2.7]- 2.37 mmol) in THF (15 mL) was added 1 M HCl solution
decane (7l). Colorless oil; TLC Rf 0.45 (20% EtOAc in (5 mL), and the mixture was stirred at room temperature for
benzene); IR (neat, cm21) 3247, 3062, 1712, 1095; 20 h. After neutralization with K2CO3 at 08C, the solvent
[a]15.4 1
D ¼224.0 (c 0.5, EtOH); H NMR (400 MHz, C6D6) was evaporated. The residue was extracted with CH2Cl2,
d 0.00 (3H, s) 0.03 (3H, s), 0.82 (9H, s), 1.01 (6H, s), 1.43– and the combined organic extracts were dried over
1.36 (2H, m), 2.00 –1.93 (1H, m), 2.19 –2.26 (2H, m), 2.53 anhydrous Na2SO4, filtered, and concentrated in vacuo.
(1H, d, J¼3.1 Hz), 2.92 (1H, d, J¼11.2 Hz), 3.08 (3H, s), The obtained crude product was purified by column
3.21 (2H, brs), 3.36 (1H, s), 3.86 (1H, d, J¼10.7 Hz), 4.04 chromatography (silica gel, hexane/AcOEt¼10/1 – 1/1) to
(1H, d, J¼11.2 Hz), 4.20 – 4.32 (4H, m), 4.45 (1H, d, give 13a (456 mg, 86%) as a colorless oil; TLC Rf 0.46
J¼11.2 Hz), 4.77 (1H, s), 4.83 (1H, d, J¼10.7 Hz), 5.16 (hexane/AcOEt¼1/1); [a]20 D ¼215.4 (c 1.0, EtOH); IR
(1H, s), 6.61 (2H, d, J¼8.8 Hz), 6.88 –7.28 (12H, m); 13C (neat, cm21) 3471, 1088; 1H NMR (270 MHz, CDCl3) d
NMR (75 MHz, C6D6) d 24.6, 23.8, 18.5, 26.4, 31.0, 32.6, 0.90 (3H, s), 0.91 (3H, s), 2.82 (1H, brs), 2.86 (1H, brs), 3.46
44.5, 51.1, 52.2, 54.7, 62.3, 63.0, 72.8, 74.1, 75.3, 80.9, (2H, s), 3.48 (1H, dd, J¼8.4, 9.4 Hz), 3.62 (1H, dd, J¼3.0,
89.2, 112.9, 113.9, 127.8, 127.9, 128.1, 128.3, 128.5, 130.2, 9.4 Hz), 3.75 (1H, dd, J¼3.0, 8.4 Hz), 4.56 (2H, s), 7.30–7.37
130.9, 138.8, 149.3, 159.7, 206.3; HRMS calcd for C44H60- (5H, m); 13C NMR (68 MHz, CDCl3) d 19.4, 22.4, 37.4, 71.1,
NaO8Si (MþNaþ): 767.3955, found m/z 767.3986. 71.7, 73.5, 77.1, 127.7, 127.9, 128.5, 137.7; HRMS calcd for
C13H20O3 (Mþ): 224.1412, found m/z 224.1415.
5.2.4. N-Triphenylmethyl-4-hydroxypiperidine (11k). To
the solution of 4-hydroxypiperidine (61 mg, 0.60 mmol) in 5.2.6. Preparation of tridecane-1,9-diol (13b). 13-Benzy-
dichloromethane was added triethylamine (61 mg, loxy-5-tridecanol was prepared in 64% yield by using 8c
 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750 6747

and n-butyllithium according to the preparation of 10- 5.0 mmol), molecular sieves 4 Å (500 mg), and N-chloro-
benzyloxy-2-decanol (vide infra); TLC Rf 0.43 (hexane/ succinimide (73 mg, 0.55 mmol) in dichloromethane
AcOEt¼4/1); IR (neat, cm21) 3325, 1103; 1H NMR (1 mL) were added a solution of 9-benzyloxy-1-nonanol
(270 MHz, CDCl3) d 0.90 (3H, t, J¼6.6 Hz), 1.30 –1.64 (7c) (125 mg, 0.50 mmol) in dichloromethane (1.5 mL) and
(21H, m), 3.46 (2H, t, J¼6.6 Hz), 3.54 – 3.58 (1H, m), 4.50 a solution of 1 (4.5 mg, 25 mmol) in dichloromethane
(2H, s), 7.25– 7.34 (5H, m); 13C NMR (68 MHz, CDCl3) d (1.5 mL) at 08C. After the reaction mixture was stirred at
14.0, 22.7, 25.6, 26.1, 27.8, 29.4, 29.5, 29.6, 29.7, 37.1, 08C for 1 h, the mixture was filtered through Celite-pad, and
37.4, 70.4, 71.9, 72.8, 127.4, 127.5, 128.3, 138.6; MS (EI) 10% sodium carbonate solution was added to the filtrate.
m/z 306 (Mþ); HRMS calcd for C20H34O2 (Mþ): 306.2559, The mixture was then extracted with dichloromethane, and
found m/z 306.2567. the combined organic extracts were dried over anhydrous
Na2SO4, filtered, and concentrated. The crude product was
Tridecane-1,9-diol (13b) was then prepared in 87% yield by purified by column chromatography (silica gel, hexanes/
deprotection of 13-benzyloxy-5-tridecanol according to the ethyl acetate¼15/1 – 5/1) to give 9-benzyloxy-1-nonanal
preparation of decane-1,9-diol (13c) (vide infra); TLC Rf (8c) (116 mg, 93%) as a colorless oil: 1H NMR (270 MHz,
0.40 (hexane/AcOEt¼1/1); IR (KBr, cm21) 3363, 3248; 1H CDCl3) d 1.26 –1.31 (8H, m), 1.50 –1.68 (4H, m), 2.40 (2H,
NMR (270 MHz, CDCl3) d 0.91 (3H, t, J¼6.8 Hz), 1.26 – td, J¼7.0, 1.6 Hz), 3.46 (2H, t, J¼6.5 Hz), 4.50 (2H, s),
1.59 (22H, m), 3.56 –3.61 (1H, m), 3.64 (2H, t, J¼6.6 Hz); 7.25 – 7.37 (5H, m), 9.75 (1H, t, J¼1.6 Hz); 13C NMR
13
C NMR (68 MHz, CDCl3) d 14.0, 22.7, 25.6, 25.7, 27.8, (68 MHz, CDCl3) d 22.0, 26.0, 29.0, 29.2, 29.2, 29.6, 43.8,
29.3, 29.5, 29.6, 32.7, 37.1, 37.4. 62.8, 71.9; MS (EI) m/z 70.4, 72.8, 127.4, 127.5, 128.3, 138.6, 202.8.
215 (Mþ); HRMS calcd for C13H28O2 (Mþ): 216.2089,
found m/z 216.2076. 5.3.1. Methyl (2R,3R,5R,6S)-2,6-dibenzyloxy-3-(tert-
butyldimethylsiloxy)-5-(p-methoxybenzyloxy)-6-formyl-
5.2.7. Preparation of decane-1,9-diol (13c).30 To the 4,4-dimethylhexanoate (8g). Colorless oil: TLC Rf 0.50
solution of MeLi (1.04 M in ether, 1.55 mL, 1.61 mmol) in (hexane/ethyl acetate 4/1); [a]24
D ¼þ4.18 (c 1.4, EtOH); IR
ether (5 mL) was added a solution of 8c (400 mg, (neat, cm21) 1736, 1250, 1095; 1H NMR (270 MHz,
1.61 mmol) in ether (5 mL) at 2788C. After stirring the CDCl3) d 0.06 (3H, s), 0.91 (9H, s), 0.98 (3H, s), 1.05
mixture at 2788C for 30 min, the reaction was quenched by (3H, s), 3.68 (3H, s), 3.78 (3H, s), 3.88 (1H, s), 4.11 – 4.12
adding saturated NH4Cl solution. The mixture was extracted (1H, m), 4.21 – 4.27 (2H, m), 4.30 (1H, d, J¼11.8 Hz), 4.42
with ether, and the combined organic extracts were washed (1H, d, J¼11.8 Hz), 4.44 (1H, d, J¼10.9 Hz), 4.62 – 4.69
with water and brine, dried over anhydrous Na2SO4, filtered, (3H, m), 6.84 –6.87 (2H, m), 7.21– 7.32 (12H, m), 9.71 (1H,
and concentrated in vacuo. The crude product was purified d, J¼1.7 Hz); 13C NMR (68 MHz, CDCl3) d 24.5, 23.6,
by column chromatography (silica gel, hexane/AcOEt) to 18.3, 19.0, 20.8, 26.1, 44.0, 51.5, 55.2, 72.3, 72.7, 73.4,
give 10-benzyloxy-2-decanol (321 mg, 75%) as a colorless 77.2, 82.0, 84.2, 85.5, 113.6, 127.7, 127.8, 127.8, 127.9,
oil; TLC Rf 0.54 (hexane/AcOEt¼2/1); IR (neat, cm21) 128.2, 128.4, 129.1, 130.3, 137.3, 137.4, 159.0, 171.1,
3340, 1110; 1H NMR (270 MHz, CDCl3) d 1.17 (3H, d, 201.4; MS (FAB) m/z 688 (MþNa)þ; HRMS calcd
J¼6.3 Hz), 1.22 –1.66 (15H, m), 3.46 (2H, t, J¼6.6 Hz), for C38H52O8SiNa (MþNa)þ: 687.3329, found m/z
3.74 –3.81 (1H, m), 4.50 (2H, s), 7.23– 7.39 (5H, m); 13C 687.3327.
NMR (68 MHz, CDCl3) d 23.4, 25.7, 26.1, 29.3, 29.5, 29.5,
29.7, 39.3, 68.1, 70.4, 72.8, 127.4, 127.6, 128.3, 138.6; MS 5.3.2. (2R,3R,5R,6R)-2,6-Bis(benzyloxy)-5-(tert-butyl-
(EI) m/z 264 (Mþ); HRMS calcd for C17H28O2 (Mþ): dimethylsilyloxy)-8-chloro-3-(4-methoxybenzyloxy)-4,4-
264.2089, found m/z 264.2095. demethyl-7-oxo-nonanal (8h).23c 13C NMR (68 MHz,
CDCl3) d 25.1, 22.9, 18.5, 18.9, 19.0, 20.8, 26.2, 44.1,
Under a hydrogen atmosphere (balloon, 1 atm), a suspen- 51.2, 55.2, 72.5, 73.1, 75.1, 78.1, 83.9, 84.6, 86.6, 113.7,
sion of 10-benzyloxy-2-decanol (310 mg, 1.17 mmol) and 127.8, 127.9, 128.0, 128.2, 128.4, 128.4, 129.0, 130.1,
10% Pd/C in acetic acid (10 mL) was stirred at room 137.1, 137.3, 159.1, 201.5, 205.7.
temperature for 15 h. After the mixture was filtered through
Celite pad, the filtrate was concentrated in vacuo. 10% 5.3.3. Ethyl (methyl 2,3,4-tri-O-benzyl-6,7-dideoxy-a-D -
NaOH solution was added to the residue, and the mixture gluco-octo-6(Z)-enopyranosid)uronate. Alcohol (7l)31
was extracted with ether. The combined organic extracts was oxidized according to the general procedure. (Car-
were washed with water and brine, dried over anhydrous bethoxymethylene)triphenylphosphorane (241 mg, 0.69
Na2SO4, filtered, and concentrated in vacuo. The obtained mmol) was added to the solution of crude product in
crude product was purified by column chromatography benzene, and the mixture was stirred at room temperature
(silica gel, hexane/AcOEt¼2/1 –1/1) to give 13c (184 mg, for 11.5 h. After evaporation of the solvent, the residue was
90%) as a colorless oil; 1H NMR (270 MHz, CDCl3) d 1.18 purified by column chromatography (silica gel,
(3H, d, J¼6.3 Hz), 1.21– 1.58 (14H, m), 2.05 –2.23 (2H, m), hexane/AcOEt¼7/1 – 3/1) to give ethyl (methyl 2,3,4-tri-
3.61 (2H, t, J¼6.8 Hz), 3.72– 3.81 (1H, m); 13C NMR O-benzyl-6,7-dideoxy-a-D -gluco-octo-6(Z)-enopyranosid)-
(68 MHz, CDCl3) d 23.3, 25.6, 29.3, 29.5, 32.6, 39.1, 62.7, uronate (234 mg, 88%) as a colorless solid; mp 608C (lit.
68.0. 698C);32 1H NMR (500 MHz, CDCl3) d 1.29 (3H, t,
J¼7.3 Hz), 3.24 (1H, dd, J¼9.8, 9.8 Hz), 3.35 (3H, s),
5.3. Typical procedure for the catalytic oxidation of 3.52 (1H, dd, J¼3.7, 9.8 Hz), 4.01 (1H, dd, J¼9.2, 9.2 Hz),
alcohols (Table 5, entry 4) 4.20 (2H, q, J¼7.0 Hz), 4.25 (1H, ddd, J¼1.6, 4.9, 10.1 Hz),
4.56 (1H, d, J¼10.7 Hz), 4.60 (1H, d, J¼3.7 Hz), 4.67
To a stirred mixture of potassium carbonate (691 mg, (1H, d, J¼10.7 Hz), 4.80 (1H, J¼12.2 Hz), 4.82 (1H,
6748 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750

d, J¼10.7 Hz), 4.83 (1H, d, J¼10.7 Hz), 4.97 (1H, 5.3.9. 5a-Lanosta-8,24-dien-3-one (12j). Mp 87– 898C.
d, J¼11.0 Hz), 6.11 (1H, dd, J¼1.5, 15.6 Hz), 7.02 (1H, (lit.36 87– 898C).
dd, J¼4.9, 15.9 Hz), 7.26 – 7.37 (15H, m); 13C NMR
(68 MHz, CDCl3) d 14.2, 55.3, 60.4, 69.2, 73.4, 75.4, 5.3.10. N-Triphenylmethyl-4-piperidone (12k). Colorless
75.9, 79.7, 81.6, 81.8, 98.1, 122.0, 127.7, 127.9, 128.0, solid; mp .2008C; IR (KBr, cm21) 1705, 1219; 1H NMR
128.1, 128.1, 128.4, 128.4, 128.5, 137.6, 138.0, 138.5, (270 MHz, CDCl3) d 2.43 – 2.71 (8H, m), 7.15 –7.53 (15H,
143.8, 166.2. m); 13C NMR (68 MHz, CDCl3) d 42.1, 47.7, 77.3, 126.3,
127.7, 128.8, 142.4, 209.1.
5.3.4. (4R,5R)-Ethyl 4,5-epoxy-5-phenylpent-2-enoate.
After alcohol (7l)33 was oxidized according to the general 5.3.11. Methyl N a-Boc-4-keto-prolinate (12l).37 1H NMR
procedure, (carbethoxymethylene)triphenylphosphorane (270 MHz, CDCl3) d 1.42 –1.47 (9H, m), 2.54– 2.62 (1H,
(241 mg, 0.69 mmol) was added to the solution of the m), 2.88 – 3.02 (1H, m), 3.77 (3H, s), 3.83– 3.90 (2H, m),
crude product in benzene. The reaction mixture was stirred 4.70– 4.82 (1H, m); 13C NMR (68 MHz, CDCl3) d 28.1,
at room temperature for 2 h, and the solvent was evaporated. 40.7, 41.1, 52.4, 52.7, 55.5, 56.2, 81.2, 153.4, 154.3, 172.2,
The residue was purified by column chromatography (silica 207.5, 208.3.
gel, hexane/AcOEt¼3/1) to give (4R,5R)-ethyl 4,5-epoxy-
5-phenylpent-2-enoate (E/Z¼76/24, 87 mg, 80%) as a 5.3.12. (3R)-4-Benzyloxy-2,2-dimethyl-3-hydroxy-1-
colorless oil; TLC Rf 0.71 (hexane/AcOEt¼2/1); 1H NMR butanal (14a). Colorless oil; TLC Rf 0.71 (hexane/
(270 MHz, CDCl3) d 1.23 (0.72H, t, J¼7.3 Hz), 1.30 AcOEt¼1/1); [a]17 D ¼21.29 (c 0.5, EtOH); IR (neat,
(2.28H, t, J¼7.3 Hz), 3.46 (0.76H, ddd, J¼0.66, 1.8, cm21) 3417, 1720, 1095; 1H NMR (270 MHz, CDCl3) d
6.9 Hz), 3.82– 3.83 (1H, m), 4.16 (0.48H, q, J¼7.3 Hz), 1.08 (3H, s), 1.09 (3H, s), 2.75 (1H, brs), 3.46 (1H, dd,
4.22 (1.52 Hz, q, J¼7.3 Hz), 4.63 (0.24H, ddd, J¼0.66, 1.8, J¼7.4, 9.6 Hz), 3.57 (1H, dd, J¼3.1, 9.6 Hz), 3.92 (1H, dd,
7.9 Hz), 5.91 (0.24H, dd, J¼7.9, 11.5 Hz), 6.04 (0.24H, dd, J¼3.1, 7.4 Hz), 4.53 (2H, s), 7.26 – 7.39 (5H, m), 9.59 (1H,
J¼0.66, 11.5 Hz), 6.18 (0.76H, dd, J¼0.66, 15.8 Hz), 6.81 s); 13C NMR (68 MHz, CDCl3) d 17.6, 18.9, 48.6, 70.5,
(0.76H, dd, J¼6.9, 15.8 Hz) 7.26– 7.40 (5H, m); 13C NMR 73.4, 74.2, 127.7, 127.8, 128.4, 137.5, 205.3; HRMS calcd
(68 MHz, CDCl3) d 14.0, 14.2, 58.2, 59.7, 60.4, 60.5, 60.6, for C13H18O3 (Mþ): 222.1256, found m/z 222.1257.
61.0, 124.0, 124.2, 125.5, 125.8, 128.4, 128.5, 128.6, 136.1,
136.2, 143.5, 145.5, 165.5, 165.7. 5.3.13. 9-Hydroxy-1-tridecanal (14b). Colorless oil; TLC
Rf 0.70 (hexane/AcOEt¼1/1); IR (neat, cm21) 3340, 1720;
1
5.3.5. (2R,3R)-2,3-Epoxyundecanal (8k). Colorless oil; H NMR (270 MHz, CDCl3) d 0.91 (3H, t, J¼6.8 Hz),
TLC Rf 0.50 (hexane/ethyl acetate¼6/1); [a]17 D ¼221.4 (c 1.32– 1.66 (19H, m), 2.43 (2H, td, J¼1.8, 7.3 Hz),
1.0, EtOH); IR (neat, cm21) 1728, 1450; 1H NMR 3.57– 3.60 (1H, m), 9.77 (1H, t, J¼1.8 Hz); 13C NMR
(270 MHz, CDCl3) d 0.88 (3H, t, J¼6.4 Hz), 1.20– 1.60 (68 MHz, CDCl3) d 14.1, 22.0, 22.7, 25.5, 27.8, 29.1, 29.3,
(12H, m), 1.62– 1.71 (2H, m), 3.13 (1H, dd, J¼2.0, 6.3 Hz), 29.4, 37.2, 37.4, 43.9, 71.9, 202.9; MS (EI) m/z 213 (Mþ);
3.23 (1H, td, J¼5.3, 2.0 Hz), 9.01 (1H, d, J¼6.3 Hz); 13C HRMS calcd for C13H26O2 (M2H)þ: 213.1855, found m/z
NMR (68 MHz, CDCl3) d 14.0, 22.6, 25.7, 29.1, 29.2, 29.3, 213.1857.
31.2, 31.8, 56.7, 59.1, 198.4; MS (EI) m/z 184 (Mþ).
5.3.14. 9-Hydroxy-1-decanal (14c).38 1H NMR (270 MHz,
5.3.6. (5S,6R,8R,9S,10S)-6-(tert-Butyldimethylsiloxy)- CDCl3) d 1.18 (3H, d, J¼6.1 Hz), 1.21 –1.80 (13H, m), 2.43
5,9-dibenzyloxy-7,7-dimethyl-10-(4-formylbut-1-en-2- (2H, td, J¼7.3, 1.5 Hz), 3.75 –3.82 (1H, m), 9.76 (1H, t,
yl)-8-(4-methoxybenzyloxy)-1-oxa-4-oxospiro[2.7]- J¼1.5 Hz); 13C NMR (68 MHz, CDCl3) d 22.0, 23.4, 25.6,
decane (8l). Colorless oil; TLC Rf 0.51 (30% EtOAc in 29.0, 29.2, 29.3, 39.2, 43.8, 68.0, 202.9.
21
hexanes); [a]15.7
D ¼ – 33.0 (c 1.0, EtOH); IR (neat, cm )
1
3424, 3070, 2954, 2892, 1720, 1087; H NMR (270 MHz, 5.4. Large-scale catalytic oxidation of 1-decanol (15c)
C6D6) d 20.03 (3H, s), 0.00 (3H, s), 0.79 (9H, s), 0.99 (6H, (Table 8, entry 3)
s), 1.74 – 1.83 (2H, m), 1.90 –2.01 (1H, m), 2.14 (1H, d,
J¼4.8 Hz), 2.29– 2.40 (1H, m), 2.47 (1H, d, J¼4.8 Hz), To a mechanically stirred suspension of potassium carbonate
2.82 (1H, d, J¼11.1 Hz), 3.05 (3H, s), 3.31 (1H, s), 3.79 (138.2 g, 1.0 mol), molecular sieves 4 Å (10 g), and NCS
(1H, d, J¼10.9 Hz), 3.90 (1H, d, J¼11.2 Hz), 4.16– 4.29 (14.7 g, 110 mmol) in dichloromethane (400 mL) was added a
(4H, m), 4.41 (1H, d, J¼10.9 Hz), 4.50 (1H, s), 4.76 (1H, d, solution of 1-decanol (15c) (15.8 g, 100 mmol) in dichloro-
J¼11.4 Hz), 4.84 (1H, brs), 5.07 (1H, s), 6.59 (1H, d, J¼ methane (70 mL) at room temperature. After 1 h at room
8.7 Hz), 6.79 –7.27 (12H, m), 9.04 (1H, t, J¼1.3 Hz); 13C temperature, the reaction mixture was filtered through Celite
NMR (75 MHz, C6D6) d 24.6, 23.8, 18.5, 26.4, 28.8, 41.4, pad, and the filtrate was concentrated by a rotary evaporator.
44.5, 51.0, 52.0, 54.7, 62.7, 72.7, 74.1, 75.4, 80.8, 89.1, 113.3, Ether (200 mL) was added to the residue, and the ether layer
114.1 127.7, 127.8, 127.8, 128.1, 128.3, 128.6, 129.8, 130.9, was washed with 20% KOH solution (50 mL£2), 1 M HCl
138.6, 138.7, 147.9, 159.7, 200.4, 206.1; HRMS calcd for solution (50 mL£2), H2O (50 mL£2), and brine (50 mL£2),
C44H58NaO8Si (MþNaþ): 765.3799, found m/z 765.3834. dried over anhydrous Na2SO4, filtered, and concentrated. The
crude product was purified by distillation (658C, 2 mm Hg) to
5.3.7. 5-Cholesten-3-one (12h). Mp 125– 1268C. (lit.34 give 1-decanal (16c) (14.2 g, 91%) as a colorless oil.
124– 1298C).
5.5. Synthesis of N-Fmoc phenylglycinal (10) (Eq. (2))25
5.3.8. 5a-Androstane-3,17-dione (12i). Mp 129– 1308C.
(lit.35 1308C). N-Fmoc-(S)-phenylglycinol (9)39 (.99% ee, 108 mg,
 J. Matsuo et al. / Tetrahedron 59 (2003) 6739–6750 6749

0.30 mmol) was added to a suspension of powdered Academic: New York, 1981. (e) Wiberg, W. B. Oxidation in
molecular sieves 4 Å (300 mg), powdered potassium Organic Chemistry; Academic: New York, 1965.
carbonate (415 mg, 3.0 mmol), and NCS (44 mg, 2. (a) Cainelli, G.; Cardillo, G. Chromium Oxidations in Organic
0.33 mmol) in dichloromethane (2 mL) at 2108C. A Chemistry; Springer: New York, 1984. (b) Ley, S. V.; Madin,
solution of 1 (11 mg, 0.06 mmol) in dichloromethane A. Comprehensive Organic Synthesis; Trost, B. M., Fleming,
(2 mL) was added successively to the above suspension I., Eds.; Pergamon: Oxford, 1991; Vol. 7, p 251. (c) Bowden,
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