A synthesis of optically active α-quaternary α-amino acids and esters by assembling three components, ketones, (R)-chloromethyl p-tolyl sulfoxide, and sodium azide, via sulfinyloxiranes

Article abstract of DOI:10.1016/j.tet.2006.06.112

Treatment of lithium α-sulfinyl carbanion of chloromethyl p-tolyl sulfoxides with ketones at low temperature afforded adducts in almost quantitative yields, which were exposed to t-BuOK to give sulfinyloxiranes in high yields. The sulfinyloxirane was reac

Full text of DOI:10.1016/j.tet.2006.06.112

Tetrahedron 62 (2006) 9268–9279
A synthesis of optically active a-quaternary a-amino acids and
esters by assembling three components, ketones, (R)-chloromethyl
p-tolyl sulfoxide, and sodium azide, via sulfinyloxiranes
*
Tsuyoshi Satoh, Mizue Hirano, Akio Kuroiwa and Youhei Kaneko
Department of Chemistry, Faculty of Science, Tokyo University of Science, Ichigaya-funagawara-machi 12,
Shinjuku-ku, Tokyo 162-0826, Japan
Received 5 June 2006; accepted 28 June 2006
Available online 1 August 2006
Abstract—Treatment of lithium a-sulfinyl carbanion of chloromethyl p-tolyl sulfoxides with ketones at low temperature afforded adducts in
almost quantitative yields, which were exposed to t-BuOK to give sulfinyloxiranes in high yields. The sulfinyloxirane was reacted with benzyl-
amine to give a-amino aldehyde, which was oxidized with iodine in methanol to afford a-amino carboxylic ester in moderate yield. The sul-
finyloxiranes were treated with sodium azide to afford a-azido aldehydes in good yields. Oxidation with NaClO2 followed by catalytic
hydrogenation of the azido group of the a-azido aldehydes gave a-quaternary a-amino acids in good overall yields. The oxidation of the azido
aldehydes with iodine in methanol in the presence of KOH followed by the catalytic hydrogenation resulted in a-quaternary a-amino acid
methyl esters in good yields. When these reactions were carried out starting from unsymmetrical ketones and optically pure (R)-chloromethyl
p-tolyl sulfoxide, a new method for a synthesis of optically active a-quaternary a-amino acids and esters in good overall yields was realized.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
We have also been interested in the synthesis of a-amino
acids, including optically active a-quaternary a-amino acids
and their derivatives, and cyclic a-amino acids.8 In continu-
ation of our investigation concerning the development of
new synthetic methods for a-amino acids, we recently real-
ized a new method for synthesis of a-quaternary a-amino
acids and cyclic a-amino acids 5 from ketones 1, chloro-
methyl p-tolyl sulfoxide 2, and nitrogen nucleophiles
(benzylamine or sodium azide). The key reaction is the
nucleophilic opening of sulfinyloxiranes 3 with the nitrogen
nucleophiles to afford aldehydes 4. This method was deve-
loped into an asymmetric synthesis by using unsymmetrical
ketones with optically active (R)-chloromethyl p-tolyl sulf-
oxide 2 (Scheme 1).9
Optically active a,a-disubstituted (a-quaternary) a-amino
acids and their derivatives, including cyclic a-amino acids
with the a-carbon embedded in the ring, have recently
received considerableattention. a-Quaternarya-aminoacids,
in some case, are found as antibiotics, for example, lacta-
cystin.1 Very interestingly, a-methylisoleucine, a-methyl-
alloisoleucine, and a-methylnorvaline have been found as
meteoritic a-amino acids form the Murchison meteorite.2
Cyclic a-quaternary a-amino acids are also quite interesting
compounds. For instance, 1-aminocyclopropane carboxylic
acid is known to be the biosynthetic precursor of the plant
hormone, ethylene.3 1-Aminocyclopentane-1,3-dicarbox-
ylic acid acts as a metabotropic glutamate receptor (mGluR)
agonist.4 Recently, a-quaternary a-amino acids and cyclic
a-amino acids are used in controlling peptide secondary
structures.5 Synthesis of a-quaternary a-amino acids6 and
cyclic a-amino acids7 are actively investigated recently
because of the importance of these compounds in molecular
biology and synthetic organic chemistry as mentioned
above.
2. Results and discussion
2.1. Synthesis of a-quaternary a-amino acid methyl
ester from a sulfinyloxirane with benzylamine as a
nitrogen nucleophile
We previously reported a method for synthesizing a-amino
ketones and a-amino aldehydes by nucleophilic opening of
sulfinyloxiranes with several amines.10 Based on these expe-
riences, at first, a synthesis of cyclic a-amino acid was inves-
tigated starting from cyclopentadecanone (Scheme 2).
Keywords: a-Amino acid; a-Quaternary a-amino acid; Cyclic a-amino acid;
Sulfinyloxirane; Asymmetric synthesis.
* Corresponding author. Tel.: +3 5228 8272; fax: +3 5261 4631; e-mail:
tsatoh@ch.kagu.tus.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.06.112

T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
9269
O
TolSCH2Cl
2
nitrogen
O
R1 COOR
R1
R2
R1 CHO
R1
R2
H
nucleophile
O
R2
R2
NH2
"N"
S(O)Tol
1
3
4
5
R= H, CH3
Scheme 1.
LDA
TolS(O)CH2Cl
O
H
OH
PhCH2NH2
t-BuOK
O
15
97%
70 °C, 24 h
t-BuOH - THF
0 °C, 10 min
S(O)Tol
CH(Cl)S(O)Tol
90%
3a
6
97%
CHO
COOCH3
NHCH2Ph
COOCH3
NH2
I2 / KOH
CH3OH
55%
H2 / Pd(OH)2
99%
NHCH2Ph
7
8
9
Scheme 2.
Lithium a-sulfinyl carbanion of chloromethyl p-tolyl sulf-
oxide at ꢀ78 ꢁC was treated with cyclopentadecanone to
give the adduct 6 in almost quantitative yield.11 Treatment
of 6 with 1.3 equiv of t-BuOK in a mixture of t-BuOH and
THF at 0 ꢁC resulted in the formation of sulfinyloxirane 3a
in 97% yield as crystals.12 The sulfinyloxirane 3a was
warmed at 70 ꢁC in 9 equiv of benzylamine without a solvent
for 24 h to give cleanly the desired a-amino aldehyde 7 as
crystals in 90% yield.
At first, we started to find the reaction conditions concerning
the ring-opening of sulfinyloxirane 3b with sodium azide
and the results of the investigation are summarized in
Table 1. Initially, sulfinyloxirane 3b was treated with NaN3
(3 equiv) in DMSO at the concentration of 0.1 mol/L at
65 ꢁC (entry 1). The starting material disappeared after
43 h and the desired azido aldehyde 10 was obtained; how-
ever, purification of 10 was found to be rather difficult and it
appeared that 10 was somewhat unstable. The crude 10,
without further purification, was oxidized with NaClO2 in
the presence of H2O2 in acetonitrile14 to afford the azido
carboxylic acid 11 in 65% overall yield from 3b (Table 1,
entry 1).
Next, we tried to oxidize the aldehyde group in 7 to a carbox-
ylic acid or an ester group in the presence of amino group in
the molecule, which is recognized to be rather difficult. After
some examinations of the oxidation, a somewhat old-
fashioned oxidation using iodine, reported by Inch,13 was
found to be successful. Thus, aldehyde 7 was treated with
a solution of KOH and iodine in methanol at room tempera-
ture for 20 min to give the desired methyl ester 8 in 55%
yield. However, the oxidation was found to be sensitive to
the reaction conditions and the yield of 8 was variable and
reproducibility was low. Finally, the benzyl group on the
nitrogen of the ester 8 was removed under hydrogenolysis
conditions using Pd(OH)2 as a catalyst to afford cyclic
a-amino acid methyl ester 9 in quantitative yield.
Improvement of the yield of 11 was studied (entries 2–6).
The reaction time could be reduced by addition of 15-
crown-5 in the reaction mixture; however, the yield was
not improved (entry 2). Using higher concentration of the
reaction mixture gave a worse result (entry 3). Using lower
concentration of the reaction mixture showed no effect
(entry 4). Finally, we changed the conditions of this reaction
from an aprotic solvent to a protic solvent reported by Caron
and Sharpless15 and Crotti and co-workers16 (entries 5 and
6). A solution of 3b with NaN3 (3 equiv) in methanol in
the presence of water and ammonium chloride was refluxed
for 16 h and the product 10 was oxidized to give 11 in much
higher yield (82%). The best yield of 11 was obtained when
5 equiv of NaN3 was used (entry 6).
2.2. Synthesis of a-quaternary a-amino acids and
methyl esters by the nucleophilic ring-opening of
the sulfinyloxiranes with azido anion as a nitrogen
nucleophile
Hydrogenation of the azido group in 11 was successfully
carried out in THF with 10% Pd–C to give the desired cyclic
quaternary a-amino acid 12 in quantitative yield (Scheme 3).
In the case of a synthesis of a-amino acid ester directly from
sulfinyloxirane 3b, the crude azido aldehyde 10 was oxi-
dized with iodine in methanol in the same way as described
above for the synthesis of 8 (see Scheme 2). This reaction
worked to afford the desired azido methyl ester 13 in 77%
overall yield from 3b. The same azido methyl ester 13 was
As mentioned above, because of the oxidation of the alde-
hyde group in the presence of an amino group in the same
molecule was found to be difficult, we next planned to use
the azido anion as the nitrogen nucleophile expecting forma-
tion of azido aldehydes. We used sulfinyloxirane 3b, synthe-
sized from 1,4-cyclohexanedione mono ethylene ketal in the
same way as described above, as a representative substrate of
the investigation (Scheme 3).

9270
T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
O H
S(O)Tol
O
O
O
O
CHO
N3
O
O
COOH
N3
NaN3
NaClO2
see Table 1
NaH2PO4
H2O2 - CH3CN
3b
10
11 86% from 3b
I2, KOH
CH3OH
77% from 3b
CH2N2
ether
0 °C
H2, Pd-C THF
98%
86%
O
O
COOCH3
N3
O
O
COOH
NH2
13
12
O
O
COOCH3
NH2
H2, Pd-C
AcOEt
92%
14
Scheme 3.
Table 1. Reaction of sulfinyloxirane 3b with NaN3 followed by oxidation of
the resultant azido aldehyde 10 with NaClO2
In order to know the generality of this method for synthesis
of a-quaternary a-amino acids and esters, we carried out the
reactions using other ketones and the results are summarized
in Tables 2 and 3. Table 2 shows the synthesis of a-quater-
nary a-amino acids, 16a and 16b, starting from tert-butyl-
diphenylsilyloxy-2-propanone and 1-phenyl-2-butanone,
respectively. Sulfinyloxiranes 3c and 3d were synthesized
from the ketones in quantitative yields. Ring-opening of
the sulfinyloxiranes with NaN3 followed by oxidation of
the resultant aldehyde to azido carboxylic acids 15a and
15b proceeded quite smoothly. Finally, reduction of the
azido group took place without any problem to afford the
desired a-quaternary a-amino acids (16a and 16b) in quan-
titative yields. It is worth noting that 16a is an a-methyl-
serine derivative and 16b is an a-ethylphenylalanine.
Asymmetric synthesis of these amino acids is discussed later
(vide infra).
O
H
O
O
COOH
N3
O
O
O
O
CHO
N3
NaN3
S(O)Tol
NaClO2
NaH2PO4
H2O2 - CH3CN
11
3b
10
Entry NaN3/ Solvent
equiv
Concentration Conditions Yield
(mol/L)
of 11a/%
1
2
3
4
5
6
3
DMSO
DMSO
DMSO
DMSO
0.1
0.1
0.5
65 ꢁC, 43 h 65
60 ꢁC, 34 h 61
65 ꢁC, 36 h 24
65 ꢁC, 43 h 61
Reflux, 16 h 82
Reflux, 12 h 86
3b
3
3
3
5
0.05
MeOH–H2O (8:1)c 0.1
MeOH–H2O (8:1)c 0.1
a
b
c
Two-step overall yield from 3b.
15-Crown-5 of 3.6 equiv was added.
In the presence of NH4Cl.
obtained from the azido carboxylic acid 11 by ester forma-
tion with diazomethane in 86% yield. Finally, the azido
methyl ester 13 was catalytically reduced in ethyl acetate
with Pd–C as a catalyst to give the desired cyclic quaternary
a-amino acid methyl ester 14 in high yield.
The results for the synthesis of a-quaternary a-amino acid
methyl esters, including cyclic congeners, are summarized
in Table 3. Starting from cyclobutanone, cyclodecanone,
and cyclododecanone, the desired cyclic a-quaternary a-
amino acid methyl esters were synthesized in good overall
Table 2. Synthesis of a-quaternary a-amino acids 16 from sulfinyloxiranes 3 via a-azido carboxylic acids 15
R1
R2
COOH
NH2
R1
R2
H
O
R1 COOH
H2, Pd-C
1) NaN3, NH4Cl
R2
N3
THF
room temp.
2) NaClO2, H2PO4, H2O2
CH3CN, H2O
S(O)Tol
15
16
3
Entry
1
3
15
16
R1
R2
Yield/%a
Yield/%b
94
Yield/%
99
H3C
COOH
NH2
3c
CH3
TBDPSOCH2
98c
98d
15a
15b
16a
TBDPSO
CH3CH2
Ph
COOH
NH2
2
3d
CH3CH2
PhCH2
87
16b
99
a
Two-step overall yield from ketone.
Two-step overall yield from 3.
A mixture of two diastereomers (70:30).
A mixture of two diastereomers (65:35).
b
c
d

T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
Table 3. Synthesis of a-quaternary a-amino acid methyl esters 18 from sulfinyloxiranes 3
9271
R1
R2
R1
R2
H
H2, Pd-C
AcOEt
O
COOCH3
N3
R1 COOCH3
R2
NH2
1) NaN3, NH4Cl
2) I2, KOH, CH3OH
S(O)Tol
17
18
3
Entry
3
17
18
R1
R2
Yield/%a
92
Yield/%b
Yield/%
98
COOCH3
NH2
1
2
3e
3f
–(CH2)3–
–(CH2)9–
17a
17b
55
72
18a
18b
COOCH3
NH2
80
94
95
COOCH3
NH2
3
4
3a
3g
3d
–(CH2)14
–
17c
17d
17e
75
67
90
9
18c
18d
95
99
97
H3C COOCH3
NH2
CH3
PhCH2CH2
90c
98d
Ph
CH3CH2
Ph
COOCH3
NH2
5
CH3CH2
PhCH2
a
Two-step overall yield from ketone.
Two-step overall yield from 3.
A mixture of two diastereomers (59:41).
A mixture of two diastereomers (65:35).
b
c
d
yield (entries 1–3). In the case of 3e, the reaction of NaN3
followed by oxidation with iodine gave moderate yield
of azido ester 17a (entry 1). The reactions starting from
4-phenyl-2-butanone and 1-phenyl-2-butanone gave 18c
and a-ethylphenylalanine methyl ester 18d, respectively,
in good overall yields (entries 4 and 5).
enantiomeric excess of 20 and 21 was determined to be
over 99% by HPLC using CHIRALPAK AD as a chiral
stationary column.
The absolute configuration of sulfinyloxiranes 20 and 21
could easily be determined as shown in Scheme 4. Thus,
as we already reported, the addition reaction of the lithium
a-sulfinyl carbanion of (R)-chloromethyl p-tolyl sulfoxide
to carbonyl carbon was proved to induce R configuration
at the carbon bearing the chlorine atom.10b The whole stereo-
chemistry of the sulfinyloxiranes 20 and 21 was easily deter-
mined from the 1H NMR spectrum. As shown in Scheme 4,
the chemical shift of the benzylic hydrogens of the main
product 20 was markedly lowered compared with those of
21, which indicates that the benzylic carbon and the sulfinyl
group of 20 should be cis.10b
From the results described above, we concluded that the pro-
cedure mentioned above is highly applicable to many differ-
ent kinds of ketones and a variety of a-quaternary a-amino
acids and methyl esters could be synthesized.
2.3. Asymmetric synthesis of a-quaternary a-amino
acids and methyl esters including cyclic congeners by
using optically pure (R)-chloromethyl p-tolyl sulfoxide
As a further development of this investigation, we next
planned the asymmetric synthesis of a-quaternary a-amino
acids and methyl esters including cyclic congeners by using
optically pure (R)-chloromethyl p-tolyl sulfoxide. An asym-
metric synthesis of methyl 2-aminotetraline-2-carboxylate,
a-ethylphenylalanine and its methyl ester, and a-methyl-
serine methyl ester is discussed below.
The main product 20 was treated with NaN3 in the same way
as described above and the resulting azido aldehyde was
oxidized with I2 in methanol to give the desired azido methyl
ester (R)-(ꢀ)-22 in 82% overall yield from 20. The enantio-
meric excess of (R)-(ꢀ)-22 was determined to be over 99%
by HPLC using CHIRALCEL OD as a chiral stationary col-
umn. Finally, the catalytic hydrogenation of (R)-(ꢀ)-22 with
Pd–C/H2 in ethyl acetate gave the expected (R)-(+)-methyl
2-aminotetraline-2-carboxylate (R)-(+)-23 in a quantitative
yield. All the spectral data and the specific rotations were
highly consistent with the reported value.18 The minor sulfi-
nyloxirane 21 was treated with NaN3 followed by I2 in
methanol to give the enantiomer of the azido methyl ester
(S)-(+)-22 in 87% yield. Finally, the catalytic hydrogenation
of (S)-(+)-22 gave (S)-(ꢀ)-23 in a quantitative yield.
Asymmetric synthesis of both enantiomers of methyl
2-aminotetraline-2-carboxylate from b-tetralone is shown
in Scheme 4. Lithium a-sulfinyl carbanion generated from
optically pure (R)-chloromethyl p-tolyl sulfoxide10b with
LDA at ꢀ78 ꢁC was treated with b-tetralone to give the
adduct 19 as a mixture of two diastereomers in 82% yield
(99% yield calculated from the consumed sulfoxide).17
Without separation, the mixture was treated with t-BuOK
in a mixture of t-BuOH–THF at 0 ꢁC to afford a 3:1 mixture
of sulfinyloxiranes 20 and 21. These sulfinyloxiranes were
easily separated by silica gel column chromatography. The
In continuation of the asymmetric synthesis of a-quaternary
a-amino acids and their derivatives, an asymmetric synthesis

9272
T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
O
S
LDA
H2C
Cl
δ 2.87 and 3.13
δ 3.17 and 3.72
O
S
Tol
OH
H
H
H
H
H
O
O
*
t-BuOK
t-BuOH-THF
0 °C, 93%
H
S(O)Tol
Tol
+
THF, -78 °C
82% (99%)
Cl
O
S(O)Tol
*
H
19
21
20
(20:21=3:1)
1) NaN3, NH4Cl
2) I2, KOH, CH3OH
82%
H2, Pd-C
COOCH3
NH2
20
COOCH3
N3
AcOEt
98%
(R)-(+)-23
(R)-(-)-22
[α]D24 -38.1 (c 0.56, EtOH)
[α]D21 +19.6 (c 0.27, EtOH)
(Lit, [α]D20 +20 (c 1.26, EtOH))
1) NaN3, NH4Cl
2) I2, KOH, CH3OH
87%
H2, Pd-C
AcOEt
99%
NH2
21
N3
COOCH3
COOCH3
(S)-(-)-23
(S)-(+)-22
[α]D27 +39.2 (c 0.26, EtOH)
[α]D24 -19.3 (c 0.57, EtOH)
Scheme 4. Asymmetric synthesis of both enantiomers of methyl 2-aminotetraline-2-carboxylate 23 from b-tetralone and (R)-chloromethyl p-tolyl sulfoxide.
of both enantiomers of a-ethylphenylalanine methyl ester
29 and a-ethylphenylalanine 31 was investigated from
1-phenyl-2-butanone as shown in Schemes 5 and 6. At first,
lithium a-carbanion of (R)-chloromethyl p-tolyl sulfoxide
was reacted with 1-phenyl-2-butanone to give adducts 24
and 25 in quantitative yield. In this case, the ratio of the
main product 24 and minor product 25 was 2:1. These
adducts were separated by silica gel column chromato-
graphy and both were treated with t-BuOK to afford sulfinyl-
oxiranes 26 and 27, respectively, in quantitative yields.
column (CHIRALCEL OD). The main sulfinyloxirane 26
was treated with NaN3 followed by iodine in methanol to
give azido methyl ester (R)-28 in 90% overall yield. Finally,
the azido group in (R)-28 was hydrogenated in ethyl acetate
with Pd–C as a catalyst to give (R)-a-ethylphenylalanine
methyl ester (R)-(+)-29 in quantitative yield. All the spectral
data and the specific rotations were highly consistent with
the reported value.19 In the same way, the minor sulfinyl-
oxirane 27 gave (S)-a-ethylphenylalanine methyl ester (S)-
(ꢀ)-29 in good overall yield through azido methyl ester
(S)-28.
The absolute structure of sulfinyloxiranes 26 and 27 was
determined by the chemical shift of their 1H NMR, as men-
tioned above, as shown in Scheme 5. The optical purity was
determined to be over 99% by using HPLC with chiral
Synthesis of a-amino acid itself, not its ester, is also quite
important. We investigated the synthesis of both enantio-
mers of a-ethylphenylalanine 31 from the optically active
O
O
OH
H
OH
H
O
(R)-Chloromethyl p-tolyl sulfoxide
S
S
PhCH2
Et
Tol
Et
PhCH2
Tol
+
Ph
(24:25=2:1)
THF, -78 °C, 99%
Cl
Cl
25
24
δ 3.33
H
H
*
PhCH2
Et
Ph
O
S(O)Tol
COOCH3
NH2
PhCH2
Et
COOCH3
N3
t-BuOK
H2, Pd-C
AcOEt
97%
1) NaN3, NH4Cl
2) I2, KOH, CH3OH
90%
24
t-BuOH-THF
0 °C, 99%
Et
H
26
(R)-(+)-29
[α]D30 +22.1 (c 2.04, CHCl3)
(Lit, [α]D20 +20 (c 1.75, CHCl3), 80%ee)
(R)-(+)-28
[α]D29 +1.8 (c 0.95, EtOH)
*
Et
O
S(O)Tol
Et
COOCH3
Et
COOCH3
t-BuOK
t-BuOH-THF
0 °C, 99%
25
83%
97%
PhCH2 N3
PhCH2 NH2
Ph
H
H
H
(S)-(-)-29
(S)-(-)-28
27
[α]D30 -21.6 (c 0.53, CHCl3)
δ 2.89 and 3.07
[α]D29 +12.7 (c 2.63, EtOH)
Scheme 5. Asymmetric synthesis of both enantiomers of a-ethylphenylalanine methyl ester 29 from 1-phenyl-2-butanone and (R)-chloromethyl p-tolyl sulfoxide.

T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
9273
*
PhCH2
Et
Ph
O
S(O)Tol
COOH
NH2
PhCH2
Et
COOH
N3
1) NaN3, NH4Cl
2) NaClO2, NaH2PO4,
H2O2, CH3CN
H2, Pd-C
THF
99%
Et
Et
H
(R)-(+)-31
[α]D +21.1 (c 0.65, H2O)
26
(R)-(+)-30
83%
28
*
Et
COOH
N3
O
S(O)Tol
Et
COOH
NH2
PhCH2
87%
PhCH2
99%
Ph
H
(S)-(-)-31
(S)-(-)-30
27
[α]D30 -19.8 (c 0.36, H2O)
(Lit, [α]D -22.8 (c 2.0, H2O)
Scheme 6. Asymmetric synthesis of both enantiomers of a-ethylphenylalanine 31 from sulfinyloxiranes 26 and 27.
Table 4. Diastereoselective addition of chloromethyl p-tolyl sulfoxide to
O-protected acetols
sulfinyloxiranes 26 and 27 (Scheme 6). The main sulfinyl-
oxirane 26 was treated with NaN3 and the resultant azido
aldehyde was oxidized with NaClO2 to afford azido carbox-
ylic acid (R)-(+)-30 in 83% overall yield. The purified (R)-30
was hydrogenated in THF with Pd–C as a catalyst to give
the desired amino acid (R)-(+)-31 in quantitative yield.
Starting from the sulfinyloxirane 27 the enantiomer of
a-ethylphenylalanine (S)-(ꢀ)-31 was obtained in high over-
all yield and all the spectral data and the specific rotations
were consistent with the reported value.20 Purification of
the a-amino acid 31 was performed as follows: After the
hydrogenation, the catalyst was filtered off and the solvent
was evaporated. The residue was dissolved in a small amount
of water and the cloud was removed by passing the solution
slowly through a pad of Celite. Water was evaporated and
the residual crystals were recrystallized from methanol.
O
S
O
O
Tol
H2C
Cl
O
OH
H
OH
3 H
RO
S
S
CH3
RO
Tol
Tol
+
LDA, THF, -78 °C
CH
Cl
OR
Cl
32
33
Entry
R
LDA (equiv)
32:33
Yield/%
1
2
3
4
H
THP
TBDMS
TBDPS
2.5
1.2
1.5
1.5
1:1
82
99
94
99
1:1.5
1:2.0
1:2.3
Finally, asymmetric synthesis of the serine derivative, (R)-a-
methylserine methyl ester 38, was investigated starting from
hydroxyacetone (Scheme 7 and Table 4). First, diastereo-
selectivity of the addition reaction of lithium carbanion of
chloromethyl p-tolyl sulfoxide with hydroxyacetone and
its derivatives was studied and the results are summarized
in Table 4.
The addition reaction of lithium a-sulfinyl carbanion of
chloromethyl p-tolyl sulfoxide with hydroxyacetone itself
gave adducts 32 and 33 in good yields; however, no dia-
stereoselectivity was observed (entry 1). We synthesized
O-protected hydroxyacetones and performed the addition
reaction and found that the most bulky protecting group
(TBDPS) showed the highest diastereoselectivity (entry 4).
*
H3C O S(O)Tol
t-BuOK
32 (R=TBDPS)
t-BuOH-THF
0 °C, 99%
TBDPSO
H
34
H
H
δ 3.65 and 3.77
δ 4.00 and 4.16
H
H
*
TBDPSOCH2
H3C N3
COOCH3
TBDPSO
O
S(O)Tol
t-BuOK
t-BuOH-THF
1) NaN3, NH4Cl
2) I2, KOH, CH3OH
85%
33 (R=TBDPS)
H3C
H
0 °C, 99%
35
36
[α]D30 -11.9 (c 0.54, EtOH)
HOCH2
HOCH2
H3C N3
37
COOCH3
COOCH3
TBAF
THF
H2, Pd-C
AcOEt
91% from 36
H3C NH2
38
[α]D30 +6.9 (c 2.25, EtOH)
Scheme 7. Asymmetric synthesis of (R)-a-methylserine methyl ester 38 from the main adduct of TBDPS-protected acetol and (R)-chloromethyl p-tolyl
sulfoxide.

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T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
A synthesis of methylserine methyl ester 38 was investigated
starting from this main adduct (R¼TBDPS).
give 7 (340 mg; 90%) as colorless crystals; mp 56.5–58 ꢁC
(EtOH–H2O). IR (KBr) 3322 (NH), 2923, 2857, 2787,
1
2696, 1709 (CO), 1455, 694 cmꢀ1; H NMR d 1.21–1.63
First, the minor adduct 32 and the main adduct 33 were con-
verted to sulfinyloxiranes 34 and 35, respectively, and the
stereochemistry of these compounds was determined from
1H NMR as mentioned above. Sulfinyloxirane 35 was
treated with NaN3 followed by iodine to give azido methyl
ester 36 in good yield. The silyl protecting group of 36
was removed with TBAF to give the alcohol 37, which
was reduced with Pd–C as a catalyst in ethyl acetate to afford
the desired a-methylserine methyl ester 38 in 91% overall
yield from 36.
(29H, m), 3.55 (2H, s), 7.24–7.34 (5H, m), 9.39 (1H, s).
MS m/z (%) 343 (M+, 1), 272 (15), 202 (11), 146 (50), 133
(8), 91 (100). Calcd for C23H37NO: M, 343.2873. Found:
m/z 343.2878. Anal. Calcd for C23H37NO: C, 80.41; H,
10.86; N, 4.08. Found: C, 80.42; H, 10.80; N, 4.23.
3.1.3. Methyl 1-(benzylamino)cyclopentadecanecarb-
oxylate (8). A solution of KOH (80 mg; 1.43 mmol) in
methanol (2 mL) was added to a solution of iodine (155 mg;
0.61 mmol) in 2 mL of methanol at room temperature with
stirring. After 10 min, the solution was added dropwise to
a solution of the aldehyde 7 (30 mg; 0.087 mmol) in metha-
nol. The reaction mixture was stirred at room temperature
for 20 min. The reaction was quenched by adding satd aq
Na2S2O3 and the whole was extracted with CHCl3. The
extract was washed with satd aq NH4Cl and dried over
MgSO4. The product was purified by silica gel column chro-
matography to give 8 (17.8 mg; 55%) as colorless needles;
mp 106–107.5 ꢁC (EtOH–hexane). IR (KBr) 3338 (NH),
In conclusion, a new method for the synthesis of a-quater-
nary a-amino acids and their methyl esters was realized
starting from unsymmetrical ketones and chloromethyl
p-tolyl sulfoxides through sulfinyloxiranes in good overall
yields in relatively short steps. Asymmetric synthesis of
a-quaternary a-amino acids and their methyl esters was also
developed by using optically active chloromethyl p-tolyl
sulfoxide. The absolute stereochemistry of the sulfinyloxi-
ranes, at the same time absolute configuration of the amino
1
2928, 2855, 1716 (CO), 1459, 1218, 701 cmꢀ1; H NMR
1
acids or their esters, was easily determined from H NMR
of the optically active sulfinyloxiranes, which is one of the
most striking characteristics of this method.
d 1.20–1.40 (25H, m), 1.57–1.65 (2H, m), 1.73–1.79 (2H,
m), 3.51 (2H, s), 3.73 (3H, s), 7.22–7.32 (5H, m). MS m/z
(%) 373 (M+, 0.5), 315 (23), 314 (100), 91 (27). Calcd for
C24H39NO2: M, 373.2981. Found: m/z 373.2964. Anal.
Calcd for C24H39NO2: C, 77.16; H, 10.52; N, 3.75. Found:
C, 77.32; H, 10.52; N, 3.94.
3. Experimental
3.1. General
3.1.4. Methyl 1-aminocyclopentadecanecarboxylate (9).
Palladium hydroxide (20 wt % Pd on carbon; 18 mg) was
added to a solution of 8 (17.5 mg) in ethyl acetate
(0.5 mL) and the reaction mixture was stirred at room tem-
perature under hydrogen atmosphere for 12 h. The catalyst
was filtered off and the solvent was evaporated to give a resi-
due, which was purified by short silica gel column to afford
9 (13.1 mg; 99%) as a colorless oil; IR (neat) 3381(NH),
1
All melting points are uncorrected. H NMR spectra were
measured in a CDCl3 solution with JEOL JNM-LA 500
spectrometer. Electron-impact mass spectra (MS) were
obtained at 70 eV by direct insertion. Silica gel 60 (Merck)
containing 0.5% fluorescence reagent 254 and a quartz col-
umn were used for column chromatography and the products
having UV absorption were detected by UV irradiation. In
experiments requiring a dry solvent and reagent, benzyl-
amine, DMSO, DMF, and acetonitrile were distilled from
CaH2 and THF was distilled from diphenylketyl. Methanol,
t-BuOH, and ethyl acetate were distilled before use.
1
3314 (NH), 2929, 2857, 1732 (CO), 1460, 1222 cmꢀ1; H
NMR d 1.25–1.37 (26H, m), 1.53–1.59 (2H, m), 1.69–1.75
(2H, m), 3.71 (3H, s). MS m/z (%) 283 (M+, trace), 268
(2), 225 (16), 224 (100). Calcd for C17H33NO2: M,
283.2511. Found: m/z 283.2504.
3.1.1. 20-(p-Tolylsulfinyl)spiro[cyclopentadecane-1,10-
oxirane] (3a). This sulfinyloxirane was synthesized from
cyclopendadecanone and chloromethyl p-tolyl sulfoxide
through the adduct 610 in almost quantitative yield in a sim-
ilar way as described before.11 Colorless crystals; mp 71–
72 ꢁC (AcOEt–hexane). IR (KBr) 2928, 2848, 1464, 1444,
3.1.5. 200-(p-Tolylsulfinyl)dispiro[1,3-dioxolane-2,10-
cyclohexane-40,100-oxirane] (3b). Colorless crystals; mp
88–89 ꢁC (AcOEt–hexane). IR (KBr) 2964, 2891, 1092,
1031 (SO), 931 cmꢀ1; 1H NMR d 1.56–1.64 (1H, m), 1.79–
2.12 (6H, m), 2.31–2.37 (1H, m), 2.43 (3H, s), 3.73 (1H, s),
3.96–4.02 (4H, m), 7.37, 7.60 (each 2H, d, J¼8.0 Hz). MS
m/z (%) 308 (M+, 0.8), 169 (100), 140 (36), 125 (26), 99
(76), 86 (50). Calcd for C16H20O4S: M, 308.1082. Found:
m/z 308.1084. Anal. Calcd for C16H20O4S: C, 62.31; H,
6.54; S, 10.40. Found: C, 62.32; H, 6.52; S, 10.40.
1
1086, 1049 (SO), 810, 756 cmꢀ1; H NMR d 1.33–1.74
(26H, m), 1.87–1.93 (1H, m), 2.02–2.08 (1H, m), 2.42
(3H, s), 3.62 (1H, s), 7.35, 7.58 (each 2H, d, J¼8.0 Hz).
MS m/z (%) 236 (M+, 32), 140 (100), 139 (24), 91 (45), 81
(33). Calcd for C23H36O2S: M, 376.2436. Found: m/z
376.2432. Anal. Calcd for C23H36O2S: C, 73.35; H, 9.64;
S, 8.51. Found: C, 73.35; H, 9.59; S, 8.54.
3.1.6. 2-(tert-Butyldiphenylsilanyloxy)methyl-2-methyl-
3-(p-tolylsulfinyl)oxirane (3c). Less polar isomer (Z)-3c:
Colorless crystals; mp 122.0–123.0 ꢁC (AcOEt–hexane).
IR (KBr) 3050, 2932, 2858, 1493, 1472, 1428, 1112, 1048
3.1.2. 1-(Benzylamino)cyclopentadecanecarbaldehyde
(7). A solution of 3a (414 mg; 1.1 mmol) in dry benzylamine
(1.08 mL; 9.9 mmol) was warmed at 70 ꢁC for 24 h. The
benzylamine was evaporated under vacuum to give a residue,
which was purified by silica gel column chromatography to
1
(SO), 811, 743, 702 cmꢀ1; H NMR d 1.12 (9H, s), 1.53
(3H, s), 2.40 (3H, s), 3.71 (1H, s), 4.00 (1H, d, J¼
11.6 Hz), 4.16 (1H, d, J¼11.6 Hz), 7.32 (2H, d, J¼7.9 Hz),
7.40–7.49 (8H, m), 7.71–7.75 (4H, m). MS m/z (%) 464

T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
9275
(M+, trace), 407 (20), 268 (24), 267 (100), 243 (18), 239 (20),
199 (61), 197 (33), 140 (37), 135 (64), 129 (28), 91 (20).
Calcd for C27H32O3SSi: M, 464.1841. Found: m/z
464.1844. Anal. Calcd for C27H32O3SSi: C, 69.79; H, 6.94;
S, 6.90. Found: C, 69.54; H, 6.93; S, 7.15.
d, J¼7.3 Hz), 7.36 (2H, d, J¼8.0 Hz), 7.58 (2H, d,
J¼8.0 Hz). MS m/z (%) 300 (M+, trace), 140 (20), 92 (19),
91 (100). Calcd for C18H20O2S: M, 300.1184. Found: m/z
300.1185.
More polar isomer (E)-3g: Colorless oil; IR (neat) 3027,
2927, 1599, 1495, 1455, 1395, 1208, 1087, 1047 (SO),
More polar isomer (E)-3c: Colorless oil; IR (neat) 2931,
2859, 1493, 1472, 1428, 1113, 1088, 1048 (SO),
1016, 701 cmꢀ1 1H NMR d 1.76 (3H, s), 1.94 (2H, t,
;
1
703 cmꢀ1; H NMR d 1.01 (9H, s), 1.72 (3H, s), 2.43 (3H,
J¼8.3 Hz), 2.42 (3H, s), 2.68–2.72 (2H, m), 3.71 (1H, s),
7.12–7.15 (2H, m), 7.17–7.20 (1H, m), 7.24–7.29 (2H, m),
7.36 (2H, d, J¼8.0 Hz), 7.60 (2H, d, J¼8.0 Hz). MS m/z
(%) 300 (M+, trace), 140 (28), 92 (18), 91 (100). Calcd for
C18H20O2S: M, 300.1184. Found: m/z 300.1192.
s), 3.65 (1H, d, J¼11.9 Hz), 3.77 (1H, d, J¼11.9 Hz), 3.90
(1H, s), 7.35–7.38 (6H, m), 7.40–7.43 (2H, m), 7.59–7.64
(6H, m). MS m/z (%) 464 (M+, trace), 268 (24), 267 (100),
239 (20), 199 (57), 197 (32), 183 (22), 139 (38), 135 (66),
129 (31), 91 (22). Calcd for C27H32O3SSi: M, 464.1841.
Found: m/z 464.1836.
3.1.11. 8-Azido-1,4-dioxaspiro[4,5]decane-8-carboxylic
acid (11). A solution of 3b (20.1 mg; 0.065 mmol) in meth-
anol (0.56 mL) and water (0.07 mL) was heated with NaN3
(21.2 mg; 0.33 mmol) in the presence of NH4Cl (7.7 mg;
0.15 mmol) for 12 h under reflux. The reaction mixture
was diluted with water, and the whole was extracted with
CHCl3. The organic layer was dried over MgSO4 and the sol-
vent was evaporated under vacuum to afford the azido alde-
hyde 10. Without further purification, NaClO2 (74.3 mg;
0.82 mmol) was added to a solution of azido aldehyde 10
in acetonitrile (0.13 mL), NaH2PO4 (95.3 mg) in water and
35% H2O2 (71 mg; 0.65 mmol). The reaction mixture was
stirred at room temperature for 16 h. A small amount of
Na2SO3 was added to destroy the unreacted NaClO2 and
H2O2 at 0 ꢁC. Acidification with 10% aqueous HCl afforded
11 (12.7 mg; 86% from 3b) as colorless prisms; mp 60–
62 ꢁC (AcOEt–hexane). IR (KBr) 2935, 2890, 2111 (N3),
1719 (CO), 1265, 1152, 1106, 954 cmꢀ1; 1H NMR d 1.70–
1.73 (2H, m), 1.83 (2H, ddd, J¼13.0, 12.8, 4.0 Hz), 1.96
(2H, d, J¼13.8 Hz), 2.17 (2H, ddd, J¼13.3, 13.1, 4.0 Hz),
3.94–4.00 (4H, m). MS m/z (%) 227 (M+, trace), 185 (2),
155 (3), 126 (46), 99 (100), 82 (25). Anal. Calcd for
C9H13N3O4: C, 47.57; H, 5.77; N, 18.49. Found: C, 47.62;
H, 5.79; N, 18.04.
3.1.7. 2-Benzyl-2-ethyl-3-(p-tolylsulfinyl)oxirane (3d).
Less polar isomer (Z)-3d: Colorless oil; IR (neat) 3029,
2973, 2939, 1598, 1495, 1455, 1401, 1085, 1045 (SO),
1
1016, 704 cmꢀ1; H NMR d 0.87 (3H, t, J¼7.9 Hz), 1.53
(1H, sextet, J¼7.4 Hz), 1.61 (1H, sextet, J¼7.4 Hz), 2.45
(3H, s), 3.33 (2H, s), 3.78 (1H, s), 7.25–7.31 (1H, m),
7.34–7.41 (6H, m), 7.64 (2H, d, J¼8.3 Hz). MS m/z (%)
300 (M+, trace), 161 (25), 140 (34), 139 (15), 92 (20), 91
(100). Calcd for C18H20O2S: M, 300.1184. Found: m/z
300.1186.
More polar isomer (E)-3d: Colorless crystals; mp 77.5–
78.5 ꢁC (AcOEt–hexane). IR (KBr) 3029, 2972, 2925,
1
1598, 1495, 1454, 1085, 1049 (SO), 703 cmꢀ1; H NMR
d 1.23 (3H, t, J¼7.6 Hz), 1.86 (1H, sextet, J¼7.1 Hz), 2.01
(1H, sextet, J¼7.1 Hz), 2.42 (3H, s), 2.89 (1H, d,
J¼14.7 Hz), 3.07 (1H, d, J¼14.7 Hz), 3.67 (1H, s), 7.18–
7.31 (5H, m), 7.35 (2H, d, J¼8.3 Hz), 7.57 (2H, d,
J¼8.3 Hz). Anal. Calcd for C18H20O2S: C, 71.97; H, 6.71;
S, 10.67. Found: C, 72.02; H, 6.69; S, 10.68.
3.1.8. 20-(p-Tolylsulfinyl)spiro[cyclobutane-1,10-oxirane]
(3e). Colorless oil; IR (neat) 2942, 1493, 1416, 1086, 1051
1
(SO), 815 cmꢀ1; H NMR d 1.97–2.04 (2H, m), 2.41–2.47
3.1.12. 8-Amino-1,4-dioxaspiro[4,5]decane-8-carboxylic
acid (12). Palladium carbon 10% (54 mg) was added to a
solution of 11 (54 mg; 0.24 mmol) in THF (2.4 mL). The
reaction mixture was stirred at room temperature for 13 h
under hydrogen atmosphere. The catalyst was filtered off
and the solvent was evaporated under vacuum to afford 12
(47 mg; 98%) as colorless crystals; dec 193 ꢁC. IR (KBr)
2954, 2931, 2883, 2598, 1616 (CO), 1560, 1400, 1333,
(1H, m), 2.43 (3H, s), 2.55–2.62 (1H, m), 2.66–2.72 (1H,
m), 2.84–2.90 (1H, m), 3.77 (1H, s), 7.36, 7.59 (each 2H,
d, J¼8.2 Hz). MS m/z (%) 222 (M+, 0.3), 206 (2), 140
(43), 139 (45), 123 (16), 92 (57), 91 (42), 83 (100). Calcd
for C12H14O2S: M, 222.0714. Found: m/z 222.0712.
3.1.9. 20-(p-Tolylsulfinyl)spiro[cyclodecane-1,10-oxirane]
(3f). Colorless crystals; mp 61.5–62.5 ꢁC (AcOEt–hexane).
1
1273, 1129, 1095, 880 cmꢀ1; H NMR (D2O) d 1.61 (2H,
IR (KBr) 2936, 2906, 1483, 1085, 1045 (SO), 809 cmꢀ1
;
t, J¼11.0 Hz), 1.69–1.81 (4H, m), 2.05–2.10 (2H, m), 3.89
(4H, s). MS (FAB) m/z (%) 202 ([M+H]+, 43), 185 (92),
154 (49), 138 (23), 137 (52), 136 (31), 93 (100). Calcd for
C9H16NO4: M, 202.1079. Found: m/z 202.1081.
1H NMR d 1.55–1.93 (16H, m), 2.00–2.10 (1H, m), 2.17–
2.31 (1H, m), 2.42 (3H, s), 3.63 (1H, s), 7.35, 7.58 (each
2H, d, J¼8.1 Hz). MS (FAB) m/z (%) 307 ([M+H]+, 55),
289 (10), 167 (100), 154 (51), 149 (52), 141 (63), 140
(51), 81 (39). Calcd for C18H27O2S: [M+H] 307.1732.
Found: m/z 307.1737. Anal. Calcd for C18H27O2S: C,
70.55; H, 8.55; S, 10.46. Found: C, 70.54; H, 8.57; S, 10.45.
3.1.13. Methyl 8-Azido-1,4-dioxaspiro[4,5]decane-8-car-
boxylate (13). CH2N2 in Et2O was added dropwise to a solu-
tion of 11 (37.5 mg; 0.17 mmol) in Et2O at 0 ꢁC until the
light yellow color of excess CH2N2 appeared. The reaction
mixture was stirred for 10 min. After concentration, the res-
idue was purified by silica gel flash chromatography to give
13 (34.1 mg; 86%) as a colorless oil. IR (neat) 2959, 2935,
2884, 2109 (N3), 1739 (CO), 1440, 1277, 1249, 1151,
3.1.10. 2-Methyl-2-(2-phenylethyl)-3-(p-tolylsulfinyl)-
oxirane (3g). Less polar isomer (Z)-3g: Colorless oil; IR
(neat) 3005, 1599, 1494, 1455, 1381, 1218, 1086, 1040
1
(SO), 1016, 771 cmꢀ1; H NMR d 1.46 (3H, s), 2.21–2.35
1
(2H, m), 2.42 (3H, s), 2.85–2.91 (1H, m), 2.98–3.04
(1H, m), 3.70 (1H, s), 7.21–7.28 (3H, m), 7.32 (2H,
1105, 938 cmꢀ1; H NMR d 1.66–1.70 (2H, m), 1.82 (2H,
ddd, J¼12.9, 12.7, 4.0 Hz), 1.89–1.95 (2H, m), 2.13 (2H,

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T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
ddd, J¼13.2, 13.0, 4.0 Hz), 3.80 (3H, s), 3.92–3.99 (4H, m).
MS m/z (%) 241 (M+, trace), 126 (61), 99 (100), 82 (25).
d 1.00 (3H, t, J¼7.6 Hz), 1.68–1.72 (1H, m), 2.01–2.05
(1H, m), 2.95 (1H, d, J¼14.1 Hz), 3.27 (1H, d,
J¼14.1 Hz), 7.24–7.35 (5H, m). MS (FAB) m/z (%) 194
([M+H]+, 100), 154 (22), 148 (31), 137 (18), 93 (18). Calcd
for C11H16NO2: 194.1181. Found: m/z 194.1181.
3.1.14. Direct oxidation of 3b to 13 using iodine in meth-
anol. A solution of 3b (20 mg; 0.065 mmol) in methanol
(0.58 mL) and water (0.072 mL) was heated under reflux
with NaN3 (21.1 mg; 0.33 mmol) in the presence of
NH4Cl (7.6 mg; 0.14 mmol) for 11 h. The reaction mixture
was diluted with water, and the whole was extracted with
CHCl3. The solution was dried over MgSO4 and the solvent
was evaporated under vacuum to afford the azido aldehyde
10. A solution of iodine (115 mg; 0.45 mmol) and a
4% (w/w) solution of potassium hydroxide (59.2 mg;
0.91 mmol) in methanol (1.4 g) was stirred at room temper-
ature for 10 min. This solution was added dropwise to a solu-
tion of the azido aldehyde 10 in methanol (1 mL). The
reaction mixture was stirred at room temperature for
20 min. The reaction was quenched by satd aq Na2S2O3.
The whole was extracted with CHCl3 and the organic layer
was washed with brine, and dried over MgSO4. After
concentration, the residue was purified by silica gel flash
chromatography to give 13 (12.1 mg; 77% from 3b) as a
colorless oil.
3.1.20. Methyl 1-azidocyclobutanecarboxylate (17a). Col-
orless oil; IR (neat) 2957, 2108 (N3), 1739 (CO), 1250,
1
1138 cmꢀ1; H NMR d 1.96–2.11 (2H, m), 2.25–2.31 (2H,
m), 2.58–2.64 (2H, m), 3.82 (3H, s).
3.1.21. Methyl 1-azidocyclodecanecarboxylate (17b).
Colorless oil; IR (neat) 2927, 2106 (N3), 1743 (CO), 1251,
1202 cmꢀ1 1H NMR d 1.45–1.66 (14H, m), 1.84–2.04
;
(4H, m), 3.81 (3H, s).
3.1.22. Methyl 1-azidocyclopentadecanecarboxylate
(17c). Colorless oil; IR (neat) 2930, 2858, 2107 (N3), 1743
1
(CO), 1460, 1255 cmꢀ1; H NMR d 1.24–1.42 (24H, m),
1.66–1.73 (2H, m), 1.82–1.88 (2H, m), 3.79 (3H, s).
3.1.23. Methyl 2-azido-2-methyl-4-phenylbutyrate (17d).
Colorless oil; IR (neat) 3028, 2955, 2105 (N3), 1741 (CO),
1604, 1498, 1457, 1380, 1251, 1174, 1113, 1068,
1
3.1.15. Methyl 8-amino-1,4-dioxaspiro[4,5]decane-8-car-
boxylate (14). Colorless oil; IR (neat) 3376 (NH), 3310
700 cmꢀ1; H NMR d 1.55 (3H, s), 1.93–1.99 (1H, m),
2.10–2.16 (1H, m), 2.53–2.59 (1H, m), 2.69–2.75 (1H, m),
3.76 (3H, m), 7.16–7.21 (3H, m), 7.26–7.30 (2H, m). MS
(FAB) m/z (%) 234 ([M+H]+, 3), 197 (54), 149 (30), 135
(100), 105 (40), 91 (51). Calcd for C12H16N3O2: 234.1243.
Found: m/z 234.1243.
1
(NH), 2953, 2885, 1729 (CO), 1440, 1241, 1108 cmꢀ1; H
NMR d 1.55–1.69 (6H, m), 1.83–1.95 (2H, m), 2.05–2.16
(2H, m), 3.72 (3H, s), 3.95 (4H, s). MS m/z (%) 215 (M+,
3), 187 (8), 168 (12), 156 (100), 99 (31), 94 (45), 86 (33).
Calcd for C10H17NO4: M, 215.1158. Found: m/z 215.1156.
3.1.24. Methyl 2-azido-2-benzylbutyrate (17e). Colorless
oil; IR (neat) 3032, 2976, 2954, 2106 (N3), 1739 (CO),
3.1.16. 2-Azido-3-(tert-butyldiphenylsilanyloxy)-2-methyl-
propionic acid (15a). Colorless amorphous; IR (KBr) 3072,
2933, 2860, 2651, 2103 (N3), 1719 (CO), 1428, 1259, 1113,
1
1497, 1456, 1243, 1199, 1122, 1003, 701 cmꢀ1; H NMR
d 0.97 (3H, t, J¼7.3 Hz), 1.75 (1H, sextet, J¼7.0 Hz), 1.92
(1H, sextet, J¼7.0 Hz), 3.01 (1H, d, J¼14.1 Hz), 3.16 (1H,
d, J¼14.1 Hz), 3.76 (3H, s), 7.20 (2H, d, J¼7.6 Hz), 7.24–
7.32 (3H, m). MS m/z (%) 233 (M+, trace), 145 (10), 91
(100). Calcd for C12H15N3O2: M, 233.1164. Found: m/z
233.1166.
1
824, 702 cmꢀ1; H NMR d 1.05 (9H, s), 1.36 (1H, s), 3.80
(1H, d, J¼10.4 Hz), 3.98 (1H, d, J¼10.4 Hz), 7.39–7.44
(6H, m), 7.66–7.70 (4H, m). MS (FAB) m/z (%) 429
([M+H+Na2]+, 30), 428 (100), 406 ([M+H+Na]+, 30), 301
(30), 199 (21), 197 (20), 135 (43), 123 (68). Calcd for
C20H25N3O3SiNa: M, 406.1563. Found: m/z 406.1559.
3.1.25. Methyl 1-aminocyclobutanecarboxylate (18a).
Colorless oil; IR (neat) 3370 (NH), 2927, 2856, 1733
3.1.17. 2-Azido-2-benzylbutyric acid (15b). Yellow amor-
phous; IR (neat) 2977, 2109 (N3), 1714 (CO), 1454, 1260,
1
(CO), 1275, 1122 cmꢀ1; H NMR d 1.91–2.04 (4H, m),
1
701 cmꢀ1; H NMR d 1.03 (3H, t, J¼7.5 Hz), 1.76–1.85
2.53–2.58 (2H, m), 3.76 (3H, s). MS (FAB) m/z (%) 130
([M+H]+, 13), 93 (100), 75 (52). Calcd for C6H12NO2:
130.0868. Found: m/z 130.0865.
(1H, m), 1.97–2.05 (1H, m), 3.04 (1H, d, J¼14.0 Hz),
3.22 (1H, d, J¼14.0 Hz), 7.24–7.34 (5H, m). MS m/z (%)
219 (M+, 1), 147 (12), 92 (50), 91 (100). Calcd for
C11H13N3O2: M, 219.1007. Found: m/z 219.1009.
3.1.26. Methyl 1-aminocyclodecanecarboxylate (18b).
Colorless oil; IR (neat) 3377 (NH), 2925, 1732 (CO),
3.1.18. 2-Amino-3-(tert-butyldiphenylsilanyloxy)-2-
methylpropionic acid (16a). Colorless crystals; dec 195 ꢁC
(MeOH). IR (KBr) 3049, 2931, 2857, 1645 (CO), 1589,
1196 cmꢀ1 1H NMR d 1.47–1.75 (18H, m), 1.85–1.91
;
(2H, m), 3.70 (3H, s). MS (FAB) m/z (%) 214 ([M+H]+,
34), 185 (25), 154 (100), 137 (83), 136 (86), 107 (29), 93
(53), 89 (23). Calcd for C12H24NO2: 214.1808. Found: m/z
214.1814.
1
1509, 1428, 1400, 1362, 1113, 1088, 701 cmꢀ1; H NMR
(CD3OD) d 1.08 (9H, s), 1.39 (3H, s), 3.68 (1H, d,
J¼10.7 Hz), 4.00, (1H, d, J¼10.7 Hz), 7.34–7.47 (6H, m),
7.65–7.72 (4H, m). MS (FAB) m/z (%) 358 ([M+H]+,
100), 234 (36), 199 (20), 174 (37), 135 (30). Calcd for
C20H28NO3Si: 358.1838. Found: m/z 358.1834.
3.1.27. Methyl 2-amino-2-methyl-4-phenylbutyrate
(18c). Colorless oil; IR (neat) 3377 (NH), 3311 (NH),
3027, 2926, 2856, 1731 (CO), 1603, 1497, 1454, 1199,
1
1117, 700 cmꢀ1; H NMR d 1.38 (3H, s), 1.77 (2H, s),
3.1.19. 2-Amino-2-benzylbutyric acid (16b). Colorless
crystals; dec 218 ꢁC (MeOH). IR (KBr) 3411, 2970, 1619
1.86–1.92 (1H, m), 2.01–2.07 (1H, m), 2.49–2.55 (1H, m),
2.63–2.69 (1H, m), 3.71 (3H, s), 7.16–7.20 (3H, m), 7.27
(2H, d, J¼6.7 Hz). MS m/z (%) 207 (M+, 3), 149 (11), 148
(CO), 1522, 1497, 1397, 703 cmꢀ1 1H NMR (CD3OD)
;

T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
9277
(100), 102 (21), 91 (67). Calcd for C12H17NO2: M,
207.1260. Found: m/z 207.1262.
3.1.33. (1R,2S,Rs)-(L)-2-Benzyl-1-chloro-1-(p-tolylsul-
finyl)-2-butanol (24). Colorless oil; [a]3D0 ꢀ131.9 (c 0.53,
EtOH). Racemic-24: Colorless crystals; mp 161–162 ꢁC
(AcOEt–hexane). IR (KBr) 3368, 2964, 1495, 1454, 1086,
1045 (SO), 1032, 701 cmꢀ1; 1H NMR d 1.06 (3H, t, J¼7.3
Hz), 1.78 (1H, sextet, J¼7.4 Hz), 2.02 (1H, sextet, J¼7.4
Hz), 2.41 (3H, s), 2.52 (1H, s), 3.19 (1H, d, J¼14.1 Hz),
3.26 (1H, d, J¼14.1 Hz), 4.31 (1H, s), 7.27–7.37 (9H, m).
Anal. Calcd for C18H21ClO2S: C, 64.18; H, 6.28; Cl, 10.52;
S, 9.52. Found: C, 64.18; H, 6.23; Cl, 10.45; S, 9.50.
3.1.28. Methyl 2-amino-2-benzylbutyrate (18d). Colorless
oil; IR (neat) 3379 (NH), 3316 (NH), 3030, 2967, 1732
(CO), 1604, 1495, 1455, 1196, 1117, 997, 757, 703 cmꢀ1
;
1H NMR d 0.89 (3H, t, J¼7.7 Hz), 1.59–1.66 (3H, m),
1.95 (1H, sextet, J¼7.7 Hz), 2.76 (1H, d, J¼13.1 Hz), 3.17
(1H, d, J¼13.1 Hz), 3.70 (3H, s), 7.13 (2H, d, J¼6.7 Hz),
7.20–7.30 (3H, m). MS (FAB) m/z (%) 208 ([M+H]+,
100), 149 (18), 148 (60), 116 (26), 91 (38). Calcd for
C12H18NO2: 208.1337. Found: m/z 208.1337.
3.1.34. (1R,2R,Rs)-(L)-2-Benzyl-1-chloro-1-(p-tolylsul-
finyl)-2-butanol (25). Colorless crystals; [a]3D0 ꢀ50.8 (c
0.53, EtOH). Racemic-25: Colorless crystals; mp 120.5–
121.5 ꢁC (AcOEt–hexane); IR (KBr) 3324, 2970, 1456,
3.1.29. (2S,3R,Rs)-(D)-2-Tetralin-2-yl-3-(p-tolylsulfi-
nyl)oxirane (20). Colorless crystals; mp 78–79.5 ꢁC
(AcOEt–hexane). IR (KBr) 2925, 1495, 1086, 1046 (SO),
1
1084, 1042 (SO), 1017, 703 cmꢀ1; H NMR d 1.06 (3H,
1
750 cmꢀ1; H NMR d 1.69–1.74 (1H, m), 2.18 (1H, ddd,
t, J¼7.6 Hz), 1.90 (1H, sextet, J¼7.3 Hz), 1.99 (1H, sextet,
J¼7.3 Hz), 2.41 (3H, s), 2.61 (1H, s), 3.09 (1H, d,
J¼14.0 Hz), 3.26 (1H, d, J¼14.0 Hz), 4.22 (1H, s), 7.24–
7.34 (7H, m), 7.40 (2H, d, J¼8.0 Hz). Anal. Calcd for
C18H21ClO2S: C, 64.18; H, 6.28; Cl, 10.52; S, 9.52. Found:
C, 63.89; H, 6.24; Cl, 10.36; S, 9.42.
J¼13.5, 10.6, 5.5 Hz), 2.43 (3H, s), 2.87–2.95 (1H, m),
2.96–3.05 (1H, m), 3.17 (1H, d, J¼18.0 Hz), 3.72 (1H, d,
J¼18.0 Hz), 3.86 (1H, s), 7.13–7.21 (4H, m), 7.37 (2H, d,
J¼8.0 Hz), 7.62 (2H, d, J¼8.0 Hz). [a]2D4 +61.8 (c 0.40,
CHCl3). Racemic-20: Colorless prisms; mp 104–105 ꢁC
(AcOEt–hexane). MS m/z (%) 298 (M+, trace), 154 (48),
129 (100), 128 (47), 91 (39). Calcd for C18H18O2S:
M, 298.1028. Found: m/z 298.1034. Anal. Calcd for
C18H18O2S: C, 72.45; H, 6.08; S, 10.75. Found: C, 72.35;
H, 6.00; S, 10.67.
3.1.35. (2S,3R,Rs)-(D)-2-Benzyl-2-ethyl-3-(p-tolylsulfi-
nyl)oxirane (26). Colorless oil; [a]2D9 +1.8 (c 0.95, EtOH).
Spectral data see (Z)-3d.
3.1.36. (2R,3R,R)-(D)-2-Benzyl-2-ethyl-3-(p-tolylsulfi-
nyl)oxirane (27). Colorless crystals; mp 82–83 ꢁC (AcOEt–
hexane); [a]2D9 +12.7 (c 2.63, EtOH). Spectral data see
(E)-3d.
3.1.30. (2R,3R,Rs)-(L)-2-Tetralin-2-yl-3-(p-tolylsulfi-
nyl)oxirane (21). Colorless crystals; mp 81.5–83.5 ꢁC
(AcOEt–hexane). IR (KBr) 2925, 1495, 1455, 1086, 1048
1
(SO), 754 cmꢀ1; H NMR d 2.28–2.33 (1H, m), 2.39–2.47
(1H, m), 2.44 (3H, s), 2.87 (1H, d, J¼17.4 Hz), 3.07–3.17
(2H, m), 3.13 (1H, d, J¼17.4 Hz), 3.88 (1H, s), 7.02 (1H,
d, J¼6.7 Hz), 7.12–7.20 (3H, m), 7.38, 7.62 (each 2H, d,
J¼8.6 Hz). [a]2D3 ꢀ60.7 (c 0.47, CHCl3). Racemic-21:
Colorless crystals; mp 133–135 ꢁC (AcOEt–hexane). MS
m/z (%) 298 (M+, trace), 158 (48), 140 (23), 129 (100), 91
(41). Calcd for C18H18O2S: M, 298.1027. Found: m/z
298.1027. Anal. Calcd for C18H18O2S: C, 72.45; H, 6.08;
S, 10.75. Found: C, 72.45; H, 6.09; S, 10.79.
3.1.37. (R)-(D)-Methyl 2-azido-2-benzylbutyrate (28).
Colorless oil; [a]3D0 +41.8 (c 1.52, EtOH). Spectral data see
17e.
3.1.38. (S)-(L)-Methyl 2-azido-2-benzylbutyrate (28).
Colorless oil; [a]2D9 ꢀ40.8 (c 1.03, EtOH). Spectral data
see 17e.
3.1.39. (R)-(D)-Methyl 2-amino-2-benzylbutyrate (29).
Colorless oil; [a]3D0 +22.1 (c 2.04, CHCl3). Spectral data
see 18d.
3.1.31. (R)-(L)-Methyl 2-azidotetraline-2-carboxylate
(22). Colorless oil; [a]D24 ꢀ38.1 (c 0.56, EtOH). IR (neat)
3022, 2954, 2108 (N3), 1743 (CO), 1455, 1435, 1282,
3.1.40. (S)-(L)-Methyl 2-amino-2-benzylbutyrate (29).
Colorless oil; [a]3D0 ꢀ21.6 (c 0.53, CHCl3). Spectral data
see 18d.
1
1256 cmꢀ1; H NMR d 2.17–2.20 (2H, m), 2.87 (1H, dt,
J¼17.4, 4.9 Hz), 2.95–3.04 (1H, m), 3.00 (1H, d,
J¼16.8 Hz), 3.31 (1H, d, J¼16.8 Hz), 3.84 (3H, s), 7.08–
7.17 (4H, m). MS m/z (%) 231 (M+, trace), 188 (25),
144 (100), 129 (31), 117 (73), 115 (25). Calcd for
C12H13N3O2: M, 231.1008. Found: m/z 231.1008. (S)-(+)-
22: Colorless oil; [a]2D6 +39.2 (c 0.26, EtOH).
3.1.41. (R)-(D)-2-Azido-2-benzylbutyric acid (30). Color-
less oil; [a]2D9 +38.9 (c 0.99, EtOH). Spectral data see 15b.
3.1.42. (S)-(L)-2-Azido-2-benzylbutyric acid (30). Color-
less oil; [a]2D7 ꢀ43.4 (c 0.43, EtOH). Spectral data see 15b.
3.1.32. (R)-(D)-Methyl 2-aminotetraline-2-carboxylate
(23). Colorless oil; [a]D21 +19.6 (c 0.27, EtOH). IR (neat)
3375 (NH), 3302 (NH), 2950, 2848, 1731 (CO),
3.1.43. (R)-(D)-2-Amino-2-benzylbutyric acid (31). Color-
less oil; [a]3D0 +21.1 (c 0.65, H2O). Spectral data see 16b.
1
1215 cmꢀ1; H NMR d 1.87–1.94 (1H, m), 2.13–2.20 (1H,
m), 2.75 (1H, d, J¼16.5 Hz), 2.83 (1H, dt, J¼17.1,
5.5 Hz), 3.00 (1H, ddd, J¼17.1, 10.1, 6.1 Hz), 3.30 (1H, d,
J¼16.5 Hz), 3.74 (3H, s), 7.06–7.14 (4H, m). MS m/z (%)
205 (M+, 12), 146 (100), 129 (43), 128 (12), 104 (15). Calcd
for C12H15NO2: M, 205.1103. Found: m/z 205.1103. (S)-
(ꢀ)-23: Colorless oil; [a]2D4 ꢀ19.3 (c 0.57, EtOH).
3.1.44. (S)-(L)-2-Amino-2-benzylbutyric acid (31). Col-
orless oil; [a]3D0 ꢀ19.8 (c 0.36, H2O). Spectral data see 16b.
3.1.45. (1R,2R,Rs)-(L)-3-(tert-Butyldiphenylsilanyloxy)-
1-chloro-2-methyl-1-(p-tolylsulfinyl)-2-propanol (32).
Colorless oil; [a]3D1 ꢀ124.2 (c 0.66, EtOH). IR (neat) 3369,

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T. Satoh et al. / Tetrahedron 62 (2006) 9268–9279
3072, 2932, 2859, 1494, 1472, 1392, 1217, 1087 (SO) cmꢀ1
;
4. Knopfel, T.;Kuhn, R.;Allgeier, H.J. Med.Chem. 1995, 38, 1417.
5. (a) Tanaka, M. J. Synth. Org. Chem. Jpn. 2002, 60, 125; (b)
Tanaka, M.; Demizu, Y.; Doi, M.; Kurihara, M.; Suemune, H.
Angew. Chem., Int. Ed. 2004, 43, 5360; (c) Oba, M.; Tanaka,
M.; Takano, Y.; Suemune, H. Tetrahedron 2005, 61, 593; (d)
Tanaka, M.; Anan, K.; Demizu, Y.; Kurihara, M.; Doi, M.;
Suemune, H. J. Am. Chem. Soc. 2005, 127, 11570 and the
reference cited therein.
1H NMR d 1.07 (9H, s), 1.42 (3H, s), 2.44 (3H, s), 3.30 (1H,
s), 3.70 (1H, d, J¼10.4 Hz), 3.86 (1H, d, J¼10.4 Hz), 4.60
(1H, s), 7.34–7.50 (10H, m), 7.59–7.65 (4H, m). MS m/z
(%) 499 (M+, trace), 445 (33), 444 (23), 443 (75), 199
(75), 198 (28), 139 (100), 135 (47), 91 (21). Calcd for
C27H32O3ClSSi: M, 499.1530. Found: m/z 499.1535.
6. Some recent reviews and papers concerning a-quaternary
a-amino acids: (a) Cativiela, C.; Diaz-de-Villegas, M. D.
Tetrahedron: Asymmetry 1998, 9, 3517; (b) Sano, S.; Nagao,
Y. J. Synth. Org. Chem. Jpn. 2000, 58, 756; (c) Ma, D.; Ding,
K. Org. Lett. 2000, 2, 2515; (d) Tanaka, M.; Oba, M.; Tamai,
K.; Suemune, H. J. Org. Chem. 2001, 66, 2667; (e) Ooi, T.;
Takeuchi, M.; Ohara, D.; Maruoka, K. Synlett 2001, 1185; (f)
Grogner, H. Chem. Rev. 2003, 103, 2795; (g) Belokon, Y. N.;
Bhave, D.; D’Addario, D.; Groaz, E.; North, M.; Tagliazucca,
V. Tetrahedron 2004, 60, 1849; (h) Ooi, T.; Uematsu, Y.;
Maruoka, K. Tetrahedron Lett. 2004, 45, 1675; (i) Kato, N.;
Suzuki, M.; Kanai, M.; Shibasaki, M. Tetrahedron Lett. 2004,
45, 3147.
3.1.46. (1R,2S,Rs)-(L)-3-(tert-Butyldiphenylsilanyloxy)-
1-chloro-2-methyl-1-(p-tolylsulfinyl)-2-propanol (33).
Colorless oil; [a]3D1 ꢀ91.5 (c 1.29, EtOH). IR (neat) 3401,
3011, 2932, 2859, 1494, 1472, 1463, 1428, 1217, 1088
1
(SO), 760 cmꢀ1; H NMR d 1.10 (9H, s), 1.57 (3H, s),
2.44 (3H, s), 3.15 (1H, s), 3.80 (1H, d, J¼10.4 Hz), 3.92
(1H, d, J¼10.4 Hz), 4.68 (1H, s), 7.34 (2H, d, J¼8.0 Hz),
7.36–7.49 (8H, m), 7.65–7.71 (4H, m). MS m/z (%) 499
(M+, trace), 445 (32), 444 (22), 443 (74), 199 (75), 197
(27), 139 (100), 135 (47), 91 (20). Calcd for C27H32O3ClSSi:
M, 499.1530. Found: m/z 499.1521.
3.1.47. (2R,3R,Rs)-(L)-34. Colorless oil; [a]3D0 ꢀ22.8 (c
1.16, EtOH). Spectral data see (E)-3c.
7. Some recent reviews and papers concerning cyclic a-quater-
nary a-amino acids: (a) Cativiela, C.; Diaz-de-Villegas,
M. D. Tetrahedron: Asymmetry 2000, 11, 645; (b) Czombos,
J.; Aelterman, W.; Tkachev, A.; Martins, J. C.; Tourwe, D.;
Peter, A.; Toth, G.; Fulop, F.; Kimpe, N. D. J. Org. Chem.
2000, 65, 5469; (c) Kabalka, G. W.; Das, B. C.; Das, S.
Tetrahedron Lett. 2001, 42, 7145; (d) Park, K.-H.; Kurth,
M. J. Tetrahedron 2002, 58, 8629; (e) Bradley, D. M.;
Mapitse, R.; Thomson, N. M.; Hayes, C. J. J. Org. Chem.
2002, 67, 7613; (f) Volk, F.-J.; Wagner, M.; Frahm, A. W.
Tetrahedron: Asymmetry 2003, 14, 497; (g) Truong, M.;
Lecornue, F.; Fadel, A. Tetrahedron: Asymmetry 2003, 14,
1063; (h) Kotha, S. Acc. Chem. Res. 2003, 36, 342; (i)
Andrei, M.; Undheim, K. Tetrahedron: Asymmetry 2004, 15,
53; (j) Meyer, U.; Breitling, E.; Bisel, P.; Frahm, A. W.
Tetrahedron: Asymmetry 2004, 15, 2029; (k) Kabalka, G. W.;
Yao, M.-L. J. Org. Chem. 2004, 69, 8286; (l) Ung, A. T.;
Pyne, S. G.; Batenburg-Nguyen, U.; Davis, A. S.; Sherif, A.;
Bischoff, F.; Lesage, S. J. Tetrahedron 2005, 61, 1803; (m)
Avenoza, A.; Busto, J. H.; Canal, N.; Peregrina, J. M.; Perez-
Fernandez, M. Org. Lett. 2005, 7, 3597; (n) Suri, J. T.;
Steiner, D. D.; Barbas, C. F., III. Org. Lett. 2005, 7, 3885.
8. (a) Satoh, T.; Ozawa, M.; Takano, K.; Kudo, M. Tetrahedron
Lett. 1998, 39, 2345; (b) Satoh, T.; Ozawa, M.; Takano, K.;
Chyouma, T.; Okawa, A. Tetrahedron 2000, 56, 4415; (c)
Satoh, T.; Fukuda, Y. Tetrahedron 2003, 59, 9803; (d) Ota,
H.; Chyouma, T.; Iso, S.; Satoh, T. Tetrahedron Lett. 2004,
45, 3903; (e) Satoh, T.; Osawa, A.; Kondo, A. Tetrahedron
Lett. 2004, 45, 6703; (f) Satoh, T.; Miura, M.; Sakai, K.;
Yokoyama, Y. Tetrahedron 2006, 62, 4253.
3.1.48. (2S,3R,Rs)-(D)-35. Colorless crystals, mp 80–81 ꢁC
(AcOEt–hexane); [a]3D0 +30.3 (c 2.51, EtOH). Spectral data
see (Z)-3c.
3.1.49. (R)-(L)-Methyl 2-azido-3-(tert-butyldiphenylsila-
nyloxy)-2-methylpropionate (36). Colorless oil; [a]D27
ꢀ11.9 (c 0.54, EtOH). IR (neat) 2933, 2859, 2106 (N3),
1745 (CO), 1473, 1460, 1428, 1299, 1236, 1113, 825,
1
702 cmꢀ1; H NMR d 1.04 (9H, s), 1.32 (3H, s), 3.76 (1H,
d, J¼10.0 Hz), 3.79 (3H, s), 3.94 (1H, d, J¼10.0 Hz),
7.38–7.47 (6H, m), 7.64–7.68 (4H, m). MS (FAB) m/z (%)
398 ([M+H]+, 1), 340 (100), 320 (59), 213 (75), 197 (24),
135 (42). Calcd for C21H28O3N3Si: M, 398.1900. Found:
m/z 398.1894.
3.1.50. (R)-(D)-Methyl 2-amino-3-hydroxy-2-methylpro-
pionate (38). Colorless oil; [a]3D0 +6.9 (c 2.25, EtOH); IR
(neat) 3366 (NH), 2957, 1732 (CO), 1651, 1460, 1235,
1
1139, 1054 cmꢀ1; H NMR d 1.29 (3H, s), 2.45 (3H, s,
NH2, OH), 3.46 (1H, d, J¼10.7 Hz), 3.75 (3H, s), 3.78
(1H, d, J¼10.7 Hz). MS (FAB) m/z (%) 134 ([M+H]+,
100), 74 (25), 57 (14), 55 (12). Calcd for C5H12O3N: M,
134.0818. Found: m/z 134.0818.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science, and Technology of Japan to promote multi-disci-
plinary research project, which is gratefully acknowledged.
9. Preliminary results of this study were reported as a communica-
tion: Satoh, T.; Hirano, M.; Kuroiwa, A. Tetrahedron Lett.
2005, 46, 2659.
10. (a) Satoh, T.; Kaneko, Y.; Sakata, K.; Yamakawa, K. Bull.
Chem. Soc. Jpn. 1986, 59, 457; (b) Satoh, T.; Oohara, T.;
Ueda, Y.; Yamakawa, K. J. Org. Chem. 1989, 54, 3130; (c)
Satoh, T.; Yamakawa, K. Synlett 1992, 455.
References and notes
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Koyama, M. Tetrahedron 1998, 54, 5557.
1. Fenteany, G.; Standaert, R. F.; Lane, W. S.; Choi, S.; Corey,
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13. Inch, T. D.; Ley, R. V.; Rich, P. J. Chem. Soc. C 1968, 1693.
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9279
14. Dalcanale, E.; Montanari, F. J. Org. Chem. 1986, 51, 567.
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18. Solladie-Cavallo, A.; Martin-Cabrejas, L. M.; Caravatti, G.;
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19. Belokon, Y. N.; Bhave, D.; D’Addario, D.; Groaz, E.; North,
M.; Tagliazucca, V. Tetrahedron 2004, 60, 1849.
17. One equivalent of (R)-chloromethyl p-tolyl sulfoxide was
reacted with 1.4 equiv of b-tetralone. The yield was calculated
based on the sulfoxide.
20. Kruizinga, W. H.; Bolster, J.; Kellogg, R. M.; Kamphuis, J.;
Boesten, W. H. J.; Meijer, E. M.; Schoemaker, H. E. J. Org.
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