Catalytic Mannich-type reactions of Sulfonylimidates

Article abstract of DOI:10.1246/bcsj.82.1083

A novel nucleophile, sulfonylimidate, has been successfully employed in Mannich-type reactions. Due to electronwithdrawing property of sulfonyl group of sulfonylimidate, the acidity of α-proton is enhanced so that sulfonylimidate bearing no activating functional group at α-position is deprotonated by relatively weak base. DBU-catalyzed reactions of sulfonylimidates with protected imines in DMF provided the adducts in high yields with high anti selectivity. This reaction represents a wide substrate scope and a high catalytic turnover. A thorough kinetic study revealed that ratedetermining step is most likely deprotonation step in case of Ts-imidate. Alkali earth metal alkoxide and its HMDS salt also catalyze Mannich-type reactions of sulfonylimidates. The reactions catalyzed by Mg(O ^tBu)₂ in DMF provided the adducts with high anti selectivity, while those catalyzed by [Sr(HMDS)₂]₂ gave syn selectivity. The asymmetric variant of Mannich-type reaction of sulfonylimidate was also achieved. Several transformations of sulfonylimidates to other functional groups were also demonstrated. Finally, direct-type catalytic formation of cβ-amino acid ester from aldehyde and sulfonylimidate was achieved via in situ formation of sulfonylimine and DBU-assisted hydrolysis of sulfonylimidate.

Full text of DOI:10.1246/bcsj.82.1083

© 2009 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 82, No. 9, 1083–1102 (2009) 1083
BCSJ Award Article
Catalytic Mannich-Type Reactions of Sulfonylimidates
Ryosuke Matsubara, Florian Berthiol, Huy V. Nguyen, and Shū Kobayashi*
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033
The HFRE Division, ERATO, Japan Science Technology Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033
Received April 1, 2009; E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
A novel nucleophile, sulfonylimidate, has been successfully employed in Mannich-type reactions. Due to electron-
withdrawing property of sulfonyl group of sulfonylimidate, the acidity of ¡-proton is enhanced so that sulfonylimidate
bearing no activating functional group at ¡-position is deprotonated by relatively weak base. DBU-catalyzed reactions of
sulfonylimidates with protected imines in DMF provided the adducts in high yields with high anti selectivity. This
reaction represents a wide substrate scope and a high catalytic turnover. A thorough kinetic study revealed that rate-
determining step is most likely deprotonation step in case of Ts-imidate. Alkali earth metal alkoxide and its HMDS salt
also catalyze Mannich-type reactions of sulfonylimidates. The reactions catalyzed by Mg(OtBu)2 in DMF provided the
adducts with high anti selectivity, while those catalyzed by [Sr(HMDS)2]2 gave syn selectivity. The asymmetric variant of
Mannich-type reaction of sulfonylimidate was also achieved. Several transformations of sulfonylimidates to other
functional groups were also demonstrated. Finally, direct-type catalytic formation of ¢-amino acid ester from aldehyde
and sulfonylimidate was achieved via in situ formation of sulfonylimine and DBU-assisted hydrolysis of sulfonylimidate.
Recently much attention has been paid to direct-type
reactions, in which no pre-activation of carbonyl compound
is necessary.1 Because the desired adduct through direct-type
reaction is formed formally only via CC bond formation and
proton transfer, no co-product is formed, which makes these
types of reactions attractive. While there have been so many
reports on direct reactions so far, the use of ester or ester
equivalents bearing no activating functional group at ¡ position
such as NO2, N=CR2, COR, OH, CN, and aryl, is still a
challenging topic.2-4 Here we focus on the reactions of
sulfonylimidate, which has been recently found to be an
effective nucleophile in direct-type reactions by our group.5
pure imidate salts in a range of 40-80% yield.7 Subsequent
sulfonylation under the standard conditions (sulfonyl chloride,
Et3N, DMAP, and DCM) led to sulfonylimidate. Most of all the
sulfonylimidates used so far are stable in the air, tolerant to SiO2
chromatography purification, and can be kept for at least several
months in the refrigerator without change in purity.
DBU-Catalyzed Direct Mannich-Type Reaction of Sulfo-
nylimidate. The difficulty in direct-type reactions of ester or
ester derivatives bearing no activating functional groups at
¡-position lies in relatively high pKa value.8 Two strategies to
address this issue have been taken; one is the use of appropriate
2
Lewis acids to lower the ¡-proton pKa , and the other is an
introduction of electron-withdrawing groups into the substitu-
ents located across the carbonyl from the ¡-carbon.4 Our
strategy to be demonstrated in this report is the employment of
C=N double bond compounds instead of carbonyl compounds.
That the nitrogen of C=N double bond accommodates another
bonding enables us to put an electron-withdrawing group on
this nitrogen, leading to the increase of acidity at ¡-position.
Results and Discussion
Synthesis of Sulfonylimidates. All the sulfonylimidates
used in this report were synthesized according to the reported
method (Scheme 1).6 To a mixture of alcohol and nitrile was
bubbled HCl gas at room temperature, and exothermic forma-
tion of imidate salt took place. Evaporation of volatiles afforded
Ar
ArSO2Cl
Et3N, DMAP
O2S
R1
HCl (g)
R2
HCl
NH
N
+
CN
OH
R2 = Me, Et, iPr
R1 OR2
rt
DCM, rt
OiPr
Et
1
2
Scheme 1. Synthetic method of sulfonylimidate.
Published on the web September 9, 2009; doi:10.1246/bcsj.82.1083

1084 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
O
Et3N
(10 mol%)
EtO2C
Ph
EtO2C
Ts
NTs
Ph
NH
X
NH HN
N
OEt
+
+
Me
Ph
Ph
Ph
Ph
DCM, 20 °C
5: X = NTs
7: X = O
6
HBr
HBr
18 h
3a
4
Scheme 2. Direct-type reaction of sulfonylimine 4 with imine 3a.
Table 1. Base-Catalyzed Direct-Type Reactions of Sulfonylimidates (R1 = Ph)
R5
O2S
NH
R5
R2
Ph
base (10 mol%)
R2
O2S
N
N
N
+
rt
OR3
Me
R1
OR3
Me
9
3
8
(1.0 equiv)
(1.1 equiv)
Entry
R2
R3
R5
Base
Solvent
Yield/%
anti/syna)
Product
1
2
3
4
5
6
7
8b)
9b),c)
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
Boc
Boc
Boc
Boc
Me
Me
Me
Me
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Ph
Ph
Ph
Ph
Ph
Ph
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
®
DCM
DCM
DCM
DMF
DMF
DMF
DMF
DMF
DMF
0
0
®
®
®
®
Et3N
DBU
DBU
DBU
DBU
DBU
DBU
DBU
90
Quant
80
72
65
75
95
69/31
62/38
79/21
93/7
95/5
96/4
96/4
9aa
9aa
9ab
9bb
9bc
9bc
9bc
1
a) Determined by H NMR spectroscopy of crude products. b) 0 °C. c) 1.5 equiv of 3 and 1.0 equiv of 8 were
used. Catalyst loading was 5 mol %.
We chose arenesulfonyl group as an electron-withdrawing
group on the nitrogen of C=N double bond, because the
Fine Tuning of the Electronic and Steric Property
commercial availability of a range of arenesulfonyl chloride
makes it easy to fine-tune the electronic as well as steric
property of the molecule. Although the initial object of this
X
Electron-Withdrawing
research was the use of the C=N compound bearing ester
oxidation stage, the acetophenone-derived sulfonylimine was
first employed. As shown in Scheme 2, the sulfonylimine 4
reacted with imine 3a in the presence of a catalytic amount of
Et3N; however, the product was a mixture of sulfonylimine 5
and its tautomerized compound, enesulfonamide 6. For the
purpose of transforming both products to identical product 7,
hydrolysis of a mixture of both products was conducted.
However, a significant amount (ca. 20%) of by-product,
chalcone, was observed.
Since tautomerization is problematic in case of sulfonyl-
imine, we turned our attention to the use of sulfonylimidate
with the expectation that imine-form is more favored than its
tautomerized one due to the stabilization by alkoxy group
(Figure 1). Sulfonylimidate was examined as a nucleophile in
the reaction of Boc imine in the presence of a catalytic amount
of base (Table 1). Although no reaction occurred when no base
or triethylamine was employed (Entries 1 and 2), DBU turned
out to be basic enough to promote the reaction (Entry 3).
Gratifyingly, the adduct, sulfonylimidate, proved to be stable,
no corresponding enamine-form was detected. Optimization of
the protecting group of the electrophile, the sulfonyl group of
the nucleophile, solvent, and temperature revealed that the
conditions shown in Entry 9 were the best, providing the
O2S
N
OR
Stabilization of Imine-Form
alkyl
Figure 1. Sulfonylimidate as a nucleophile.
desired product in high yield with high anti selectivity (The
origin of high anti selectivity will be discussed later with the
results using metal alkoxide catalysts).
The scope of DBU-catalyzed (5 mol %) direct Mannich-type
reactions of sulfonylimidates are shown in Table 2. Substitu-
ents at ¡-position of sulfonylimidates accommodates methyl as
well as ethyl groups (Entry 2). The reaction of sulfonylimidate
8e (R3 = Et, R4 = H, R5 = Ph) was problematic because the
mono-adduct further reacted with another molecule of imine,
leading to the bis-adduct. Surprisingly, the mono-adduct was
not detected under the identical conditions as those of Entry 1,
only a complex diastereomer mixture of bis-adducts were
obtained (not shown). The use of an excess amount (5 equiv) of
sulfonylimidate 8e was essential to obtain a good yield of
the mono-adduct (Entry 3), and the leftover sulfonylimidate

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1085
Table 2. DBU-Catalyzed Direct-Type Reactions of Sulfonylimidates
R5
O2S
R5
R2
R2
DBU (5 mol%)
O2S
N
N
NH
N
+
R4
R1
DMF, 0 °C, 24 h
OR3
R1
OR3
3 (1.5 equiv)
8 (1.0 equiv)
9
R4
Entry
R1
R2
R3
R4
R5
Yield/%
anti/syna)
9
1
2
Ph
Ph
Ph
Ph
Boc
Boc
EtO2C
Ts
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Ts
i-Pr
i-Pr
Et
Me
Et
H
2,5-Xylyl
2,5-Xylyl
Ph
95
94
79
91
91
87
Quant
64
97
92
90
91
80
84
Quant
51
59
56
96/4
97/3
®
9bc
9bd
9ae
9cc
9dc
9ec
9fc
9gc
9hc
9ic
3b),c),d)
4c)
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Me
i-Pr
Me
i-Pr
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
2,5-Xylyl
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
Ph
96/4
95/5
97/3
97/3
93/7
97/3
95/5
98/2
98/2
98/2
87/13
88/12
83/17
84/16
69/31
87/13
14/86
55/45i)
5e)
p-MeOC6H4
p-FC6H4
m-MeC6H4
o-MeC6H4
m-VinylC6H4
2-Furyl
2-Thienyl
2-Pyridyl
PhCH=CH
Cyclopropyl
Cyclopropyl
c-C6H11
c-C6H11
i-Pr
6
7
8e)
9
10
11
12
13c)
14c)
15c),d)
16c),d),g)
17c),d),g)
18c),d),g)
19c),d),g)
20c),f)
21c),d)
9jc
9kc
9lc
Ts
9mc
9nc
9of
9og
9pf
9pg
9qf
9rc
Boch)
Tsh)
Tsh)
Tsh)
i-Pr
t-Bu
EtO2C
Tsh)
54
51
80
Ts
p-MeOC6H4
1
a) Determined by H NMR spectroscopy of the crude product or isolated product. b) 5 equiv of 8e and 1 equiv of 3
were used. c) MS 4A (167 g mol¹1) were added. d) 10 mol % of DBU was used. e) 38 h. f) 40 °C, 36 h. g) rt. h) 3 equiv
of 3 were used. i) Major/minor.
Ar
Ar
O2S
ArO2S
Ph
DBU (10 mol%)
O2S
NH
N
PhCHO
(1.5 equiv)
+
ArSO2NH2
(1.5 equiv)
+
N
OiPr
DMF, 0 °C
MS 4A, 24 h
(Ar = 2,5-xylyl)
Et
OiPr
Me
9sc
8c
(1.0 equiv)
70% yield
anti/syn = 95/5
Scheme 3. 3-component reaction.
8e could be recovered after the reaction (403%). Tosylimine
(Ts imine) as well as Boc imine were useful in this Mannich-
type reaction of sulfonylimidates (Entry 4). Boc imines derived
from aromatic aldehydes bearing electron-donating and
-withdrawing substituents, ortho-, meta-, and para-substituted
benzaldehydes as well as heteroaromatic aldehydes, provided
the desired products in high yields with high anti selectivity
(Entries 5-12). It is noted that aliphatic aldehyde-derived Boc
and Ts imines were also good substrates in the Mannich-type
reaction of sulfonylimidates (Entries 13-20). Ethyl glyoxylate-
derived N-methoxyphenylimine (Entry 21) gave the desired
product in good yield albeit the diastereoselectivity was low.
Although Boc and Ts imine can be readily synthesized from
the corresponding aldehyde and amide in one or two steps, in
situ formation of those imines are desirable. Thus, 3-compo-
nent reaction using benzaldehyde, sulfonylamide, and sulfo-
nylimidate was conducted with a double amount of MS 4A
(Scheme 3). As a result, the desired adduct 9sc was obtained in
good yield with high selectivity.
It is noteworthy that the optimized condition was applicable
to a large scale reaction (Scheme 4).5c Starting from 10 mmol
of sulfonylimidate (2.84 g), 76.4 mg of DBU (5 mol %)
catalyzed Mannich-type reaction under the same conditions
as small scale reaction, affording 4.86 g of the desired adduct
with high anti selectivity (96/4).
We then investigated the decrease of catalyst loading in
DBU-catalyzed anti selective Mannich-type reaction of sulfo-
nylimidate with Boc imine (Table 3). With 1 mol % of DBU,
the reaction proceeded well, giving the desired product in 87%
yield in 6 h (Entry 1). The reaction with 0.3 mol % of DBU
required longer reaction time (52 h) at higher concentration
(1 M) to obtain high yield of the desired product (Entry 2). It is

1086 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
Ar
Ar
O2S
Boc
DBU (76.4 mg, 5 mol%)
O2S
N
Boc
Ph
N
+
NH
N
Me
DMF, 0 °C, 24 h
(Ar = 2,5-xylyl)
Ph
OiPr
OiPr
3b (1.5 equiv)
8c (1.0 equiv)
2.84 g
(10 mmol)
Me
9bc
3.09 g
4.86 g (99% yield)
anti/syn = 96/4
Scheme 4. Large scale synthesis.
Ts
NH
Table 3. Decrease of the Catalyst Loading
Boc
Ph
DBU
durene
Boc
Ts
Et
N
N
+
N
Ts
Boc
N
OiPr
OiPr
N
Ph
DMF-d7, rt
Me
9bg
+
Me
OiPr
8g
3b
Ph
8g
3b
(a)
Ts
NH
Boc
Ph
DBU (x mol%)
DMF (y M), rt
N
OiPr
Me
9bg
Entry
x
y
Time/h
Yield/%
anti/syn
1
2
3
4
5
6
1
0.5
1
®
6
87
95
42
89
97
66
95/5
95/5
77/23
95/5
95/5
95/5
0.3
0.3
0.1
0.1
0.05
52
52
66
166
166
1
1
1
(b)
noted that neat conditions gave lower yield and diastereo-
selectivity (Entry 3), which suggests that DMF is involved in
the stabilization of the transition state (vide infra). The reaction
with 0.1 mol % of DBU proceeded smoothly at 1 M concen-
tration, providing the desired adduct in 89% yield in 66 h
(Entry 4), and in 97% yield in 166 h (Entry 5). Entry 6
represents that as little as 0.05 mol % of DBU still has catalytic
activity to afford moderate yield of the desired product
(TON = 1320).
(c)
To get insight into the mechanism of the present catalysis,
initial rate kinetics on the Boc imine, sulfonylimidate, and DBU
was carried out using benzaldehyde-derived Boc imine and Ts
imidate as model substrates. The product yield was determined
at each specified period by 1H NMR spectroscopy using durene
as an internal standard (Figure 2). A series of investigation
varying concentration of each component revealed the rate
dependency on the Boc imine, the sulfonylimidate, and DBU to
be 0.23, 0.79, and 1.43, respectively (Figure 3).
Assumed catalytic cycle is depicted in Figure 4. The
reaction is initiated by deprotonation of sulfonylimidate ¡-
proton by DBU, leading to the formation of DBUH+ and
enamide anion 10 (step a). DBUH+ is presumably stabilized
by solvation, and accordingly 10 behaves as an independent
naked anion. Anion 10 reacts with Boc imine 3b to form N-
anion species 11 (step b), which is subsequently protonated
(step c) by DBUH+ generated in the preceding deprotona-
tion step a, leading to the desired product 9bg along with
regeneration of DBU for the next catalytic cycle.
Figure 2. Initial reaction profile varying the concentration
of (a) sulfonylimidate 8g, (b) DBU, and (c) Boc imine 3b.
On the basis of the obtained kinetic parameters, deprotona-
tion of ¡-proton of sulfonylimidate (step a) appears to be one
of the rate-determining step. Considering low rate dependency
on Boc imine (0.23 order), C-C bond-forming reaction
between Boc imine and sulfonylimidate anion 10 (step b)
takes place relatively fast, and is little involved in rate-

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1087
(a)
Table 4. Screening of Metal Bases for Anti Selective
Addition Reactions
Ar
Boc
O2S
N
N
+
OiPr
Ph
Et
3b (1.5 equiv) 8c (1.0 equiv)
Ar
O2S
Catalyst (10 mol%)
Boc
Ph
NH
N
MS 4A, DMF
rt, 17 h
(Ar = 2,5-xylyl)
OiPr
log([sulfonylimidate]/mM)
Me
9bc
(b)
Entry
Catalyst
Yield/%
anti/syna)
1
2
3
4
5
6
7
8b)
Ca(OiPr)2
72
75
68
94
78
61
80
>99
93/7
93/7
Sr(OiPr)2
Ba(OiPr)2
Mg(OtBu)2
Ca(OtBu)2
Sr(OtBu)2
Ba(OtBu)2
Mg(OtBu)2
90/10
96/4
87/13
80/20
90/10
94/6
a) Determined by 1H NMR of the crude product. b) Ar =
p-NO2-C6H4.
log([DBU]/mM)
(c)
determination. Regeneration of DBU (step c) might be another
rate-determining step since the involvement of more than 1
molecule of DBU catalyst in the rate-determining step is
suggested by the value of 1.43 observed as the rate dependency
on DBU, although more precise mathematic calculation is
required for thorough interpretation of the obtained results. It is
most likely that the reaction kinetics varies depending on
reaction conditions and substrates employed.
Alkali Earth Metal-Catalyzed Reaction.
The role of
alkali earth metals as catalysts in organic chemistry has
received relatively little interest from the academic community
in recent years. Despite the attractive features of these metals
which are vastly abundant, inexpensive, commercially avail-
able, and have no obvious toxicity associated with them, only
sporadic reports have appeared in the literature.9 Alkali earth
metal alkoxides display dual properties with both Lewis acidic
and Brønsted basic characters, which makes them very
attractive in the direct-type addition reactions of enolates to
electrophiles. Ongoing research within our group seeks to
utilize these properties for the promotion of efficient organic
transformations. We have demonstrated the abilities of calcium
and strontium alkoxides in the catalytic asymmetric Michael
reactions10 and 1,4-additions of glycine derivatives.11
We set out alkali earth metal-catalyzed reaction of sulfonyl-
imidate 8c with screening of catalysts, and the results are
shown in Table 4. Alkali earth metal alkoxides catalyzed the
Mannich-type reactions to afford the desired adducts were
obtained in good yields with high anti selectivity. The best
result was obtained when Mg(OtBu)2 was employed (Entry 4).
Further optimization revealed that syn selectivity was
obtained when the reaction was conducted in THF using
p-nitrobenzenesulfonylimidate (p-Ns-imidate) 8h (Table 5).
The reaction did not proceed when 2,5-dimethylbenzene-
log([imine]/mM)
Figure 3. Determination of reaction depencence on (a)
sulfonylimidate 8g, (b) DBU, and (c) Boc imine 3b.
Ts
Ts
NH
N
Boc
Ph
N
OiPr
DBU
OiPr
8g
9bg
a
c
Ts
N
Ts
Boc
DBUH+
N
N
OiPr
Ph
OiPr
10
11
Boc
b
N
R
3b
Figure 4. Catalytic cycle.

1088 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
Table 5. Optimization for Syn Selective Addition Reactions
suflonylimidate 8c was used in THF instead of p-Ns-imidate 8h
(not shown), due to the lower acidity of ¡-proton of 8c. While
moderate syn selectivities were observed when alkali earth
alkoxide was solely used (Entries 1-4), the combination of
alkali earth metal alkoxide with ligand 12 led to high syn
Ar
Boc
O2S
N
N
+
Ph
Et
OiPr
12
selectivity (Entries 5-10). The use of [Sr(HMDS)2]2 and
3b (1.5 equiv) 8h (1.0 equiv)
ligand 12 gave the best result as shown in Entry 8 (92% yield,
syn/anti = 93/7). Interestingly, the Mg(OtBu)2-catalyzed re-
action of p-Ns-imidate in DMF (Table 4, Entry 8) and the
DBU-catalyzed reaction of p-Ns-imidate in THF gave anti
selectivity, which indicates the use of both alkali earth metal
alkoxide as a catalyst and THF as a solvent is essential for high
syn selectivity.
Ar
O2S
Catalyst (10 mol%)
Boc
Ph
NH
N
MS 4A, THF
rt
(Ar = p-NO2-C6H4)
OiPr
Me
9bh
Entry
Catalyst
Time/h Yield/% anti/syna)
The scope of the present reaction conditions was then
surveyed (Table 6). In general, condition A (Mg(OtBu)2 as a
catalyst, 2,5-xylylsulfonylimidate as a substrate in DMF)
gave high anti selectivity, while condition B ([Sr(HMDS)2]2
and ligand 12 as a catalyst, p-Ns-imidate as a substrate
in THF) afforded the desired adduct with high syn selec-
tivity. Aromatic aldehyde-derived Boc imines (Entries 1-9)
including ones with electron-withdrawing or -donating aro-
matic rings, sterically demanding aromatic ring, and hetero-
aromatic rings, afforded the desired adducts in good yields
under both conditions A and B. It is noteworthy that the
reaction of Ts imine instead of Boc imine gave anti adduct as a
major product regardless of reaction conditions (this result
will be discussed later in the discussion about diastereoselec-
tivity). Imines derived from cyclopropanecarboxaldehyde
and cyclohexanecarboxaldehyde were also good substrates
(Entries 11 and 13), and ¡-Et-substituted sulfonylimidate gave
the same level of yield and selectivity as ¡-Me-substituted one
(Entry 12).
1
2
3
4
5b)
6b)
7b)
8b)
9b),c)
Ca(OiPr)2
48
48
48
18
48
48
48
24
48
72
24
56
34
55
>99
68
45
65
92
76
65
77
11/89
32/68
15/85
14/86
11/89
7/93
9/91
7/93
6/94
6/94
Sr(OiPr)2
Ba(OiPr)2
1/2[Sr(HMDS)2]2
Ca(OiPr)2
Sr(OiPr)2
Ba(OiPr)2
1/2[Sr(HMDS)2]2
1/2[Sr(HMDS)2]2
10b),d) 1/2[Sr(HMDS)2]2
11
DBU
74/26
1
a) Determined by H NMR of the crude product. b) Ligand 12
was used. c) At 0 °C. d) At ¹20 °C.
O
O
N
N
12
Table 6. Substrate Scope of Addition Reactions of Sulfonylimidates (R = Me)
Ar
Ar
O2S
NH
O2S
Boc
[Mg] or [Sr] (10 mol%)
N
Boc
N
N
+
OiPr
conditions A or B
R1
OiPr
R1
R
R
3 (1.5 equiv) 5 (1.0 equiv)
9
Mg(OtBu)2 Condition Aa)
[Sr(HMDS)2]2 Condition Ba)
Entry
R1
Yield/%
anti/synb)
Yield/%
anti/synb)
1
2
3
4
5
6
7
8
Ph
94 (9bc)
92 (9dc)
>99 (9ec)
>99 (9fc)
93 (9gc)
>99 (9hc)
90 (9ic)
96/4
95/5
98/2
96/4
93/7
96/4
96/4
98/2
97/3
67/33
85/15
95/5
80/20c)
98 (9bh)
99 (9dh)
87 (9eh)
99 (9fh)
99 (9gh)
90 (9hh)
95 (9ih)
99 (9jh)
70 (9kh)
94 (9ch)
99 (9nh)
85 (9bi)
82 (9th)
7/93
5/95
8/92
6/94
11/89
7/93
6/94
7/93
6/94
93/7
15/85
5/95
16/84
p-MeOC6H4
p-FC6H4
m-MeC6H4
o-MeC6H4
m-Vinyl C6H4
2-Furyl
2-Thienyl
2-Pyridyl
Ph
96 (9jc)
9
95 (9kc)
98 (9cc)
94 (9nc)
80 (9bd)
99c) (9oc)
10c)
11
12d)
13e)
Cyclopropyl
Ph
Cyclohexyl
a) Condition A: DMF, rt, 17 h, Ar = 2,5-xylyl. Condition B: Ligand 12 (11 mol %), THF, rt, 24 h, Ar =
1
p-NO2-C6H4. b) Determined by H NMR spectroscopy of the crude product. c) Ts imine instead of Boc
imine was used. d) R = Et. e) 2 equiv of imine were used.

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1089
Ph
Ph
NO2
NO2
O2S NH HN SO2
13
Sr(OiPr)2 (10 mol%)
Ligand 13 (12 mol%)
Et3N (10 mol%)
Boc
O2S
Boc
N
O2S
NH
N
N
+
OiPr
Et
8h
OiPr
THF, MS 4A, 20 °C
Me
9gh
48 h
85% yield
syn/anti = 83/17
57% ee (syn)
3g
Scheme 5. Catalytic asymmetric addition reaction of sulfonylimidate with N-Boc imine.
Preliminary investigation for the asymmetric variant of the
present Mannich-type reaction revealed moderate enantio-
selectivity to be induced with a combination of Sr(OiPr)2 and
bis(sulfonamide) chiral ligand 139c bearing diphenylethane-
diamine backbone (Scheme 5).12b The addition of a catalytic
amount of triethylamine dramatically accelerated the reaction,
this is presumably because the complex of Sr(OiPr)2 and ligand
13 is less basic than [Sr(HMDS)2]2 and additional Et3N helps
the deprotonation of the ¡-proton of sulfonylimidate. Et3N
is not basic enough to deprotonate the ¡-proton of sulfonyl-
imidate, which leads to the assumption that Sr-ligand complex
works as a Lewis acid coordinating nitrogen of sulfonylimidate
to augment the acidity of the sulfonylimidate ¡-proton.
Rationalization for High Diastereoselectivity. Single-
crystal X-ray diffraction analysis of sulfonylimidate 8a
(R3 = Me, R5 = Ph, in Table 1) and the obtained Mannich
adducts provided not only information about the relative
configuration of the products, but also the general distinctive
structure of sulfonylimidate (Figure 5). Without exception, the
imine adopts an E configuration. The oxygen at the carbon
of the C=N bond is sp2 hybridized, and displays an s-cis
geometry about the N-C-O-C bonds. This phenomena can be
rationalized by considering n-·* interaction between oxygen
lone pair and ·* anti-bonding orbital of C=N group. Predom-
inant E configuration of the imine stems from the steric
repulsion of the alkyl group on oxygen and the sulfonyl group.
It is notable that C1-C2 and C2-C3 bonds rotate so that bulkiest
groups are located in anti-periplanar conformation. As a result,
only in the anti product, the proton of BocN-H and the oxygen
of the sulfonyl group are placed so close to each other that an
intramolecular hydrogen-bonding interaction between them is
suggested. This observation does not contradict the fact that
1H NMR chemical shifts of N-H of anti products are more
deshielded than those of syn products by a range of 0.2-
0.5 ppm without exception.
selectivity in DBU-catalyzed Mannich-type reaction of sulfo-
nylimidate in DMF is demonstrated in Figure 6. Considering
the steric repulsion between the methyl substituent and the Boc
group (repulsion c), and one between the SO2Ar group and the
R group (repulsion b) in TS-2 led us to the conclusion that TS-1
giving anti product is favored. The syn selectivity observed
when pivalaldehyde-derived Ts imine was used (Table 2,
Entry 20) may be rationalized by considering that the repulsion
between the t-Bu group and the Me substituent (repulsion a in
TS-1) is large in TS-1. The formation of s-trans configuration
about the S-N-C-C bonds of the sulfonylimidate anion as
shown in 14 is assumed to be suppressed by steric repulsion
between the i-Pr group and the methyl substituent (repulsion d).
On the contrary to sulfonylimidates bearing i-Pr group, ones
bearing Me group (Table 1, Entries 3 and 4) may take the
s-trans formation as well as s-cis formation, which is the reason
for the observed low anti selectivity.
Figure 7 shows plausible transition state models for alkali
earth metal-catalyzed Mannich-type reactions in DMF and
THF, respectively. In the DMF solvent system, due to the
stabilization of counter cation metal by the aprotic polar
solvent, DMF, enamide anion is thought to be dissociated
from the metal. The naked anion thus formed reacts with imine
in TS-3 rather than TS-4 with minimum steric repulsion in
analogy to DBU-catalyzed reaction, giving anti adduct as a
major product. On the other hand, the use of less polar solvent
enables the formation of metal enamide in which metal and
nitrogen of sulfonylimidate are covalently bonded. Considering
the fact that Ts imine instead of Boc imine showed high anti
selectivity even in THF (Entry 10 in Table 6, Condition B),
syn selectivity can be ascribed to coordination of Boc group
to electron positive metal (TS-6). DBU-catalysis provides
anti selectivity regardless of the choice of solvents (Entry 11
in Table 5), probably because DBUH+ is dissociated from
sulfonylimidate by solvent molecules via hydrogen bonding.
Kinetic Acidity of the ¡-Proton of Sulfonylimidate.
Recently, Barbas, III and co-workers have evaluated kinetic
acidity of the ¡-proton of several active methylene compounds
using proton/deuterium NMR exchange technique, and found
that ¡-phenyl tosylimidate represents a very rapid exchange
rate comparable to that of ¡-nitrophenyl trifluoroethyl thio-
ester.13 To get information about the effect of N-protecting
group of imidate compounds, proton/deuterium exchange
It was confirmed that epimerization of the product sulfonyl-
imidate does not take place under the reaction conditions,
which suggests the observed high diastereoselectivity is
determined kinetically at the stage of C-C bond formation.
On the basis of the experimental information that the imine
adopts an E configuration, the geometry of the generated aza-
enolate is expected to be Z (Scheme 6) under kinetically
controlled conditions. The proposed mechanism for anti

1090 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
8a
syn-9aa
anti-9bc
anti-9cc
syn-9cc
anti-9ch
syn-9th
syn-9bh
Figure 5. X-ray crystal structures of the products.
ArO2S
SO2Ar
OR
ArO2S
N
B:
H
H
SO2Ar
N
N
N
H
Me
B:
Me
OR
OR
OR
H
Me
Me
E
Z
Scheme 6. Proposed geometry of aza-enolate derived from sulfonylimidate.
experiments were carried out for various ¡-methyl imidates
bearing different protecting groups, and diethyl malonate was
also used as a standard substrate. The results (Figure 8)
revealed that an exchange rate determined for p-Ns-imidate 8h
is much higher with a t1/2 of less than 25 min, than Ts-imidate
8g (3 h), p-methoxybenzenesulfonylimidate 8j (4 h), and o-Ns-
imidate 8k (1.3 h), although diethyl malonate showed much
faster exchange rate (<10 min). N-Ethoxycarbonylimidate 15
and N-phosphonylimidate 16 showed no detectable exchange.
Lower exchange rate determined for o-Ns-imidate 8k than that

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1091
tBu
tBu
O
O
O
N
Me
O
d
c
N
O
N
iPr
Me
Me
b
a
N
R
N
ArO2S
R
SO2Ar
SO2Ar
O
iPr
O
14
iPr
TS-1
TS-2
Figure 6. Proposed transition state model.
In DMF
tBu
tBu
O
O
N
O
N
O
Me
[M]L(DMF)n
SO2Ar
Me
R
vs
R
N
ArO2S
O
iPr
[M]L(DMF)n
O
N
iPr
TS-4
TS-3
anti
syn
In THF
tBu
tBu
O
O
O
iPr
N
O
N
O
N
Me
[M]L
Me
R
vs
R
SO2Ar
SO2Ar
O
N
iPr
[M]L
TS-6
TS-5
anti
syn
Figure 7. Proposed transition state models (L = ligand).
of p-Ns-imidate 8h is noteworthy, and this results suggest that
kinetic acidity of ¡-protons of sulfonylimidates is subject to
not only electronic but also steric factors of sulfonyl groups.
Conversion of the Products. While sulfonylimidate is
practically used as a prodrug candidate,14 the usefulness of
sulfonylimidate resides also on its versatility for further
transformation into various functional groups by taking
advantage of its ester oxidation stage. A trial for the conversion
of sulfonylimidate into the corresponding ester was first carried
out under acidic conditions. It was revealed that sulfonyl-
imidate was relatively tolerant to acidic conditions, and harsh
acidic conditions (100 °C, H2SO4) was necessary to hydrolyze
sulfonylimidate 9cc. Under these conditions, N-sulfonylamide
17 was obtained instead of the expected corresponding ester
(Scheme 7). Conversion of sulfonylimidate 9ba into the
corresponding ester 18 was achieved in 90% yield under
basic conditions at room temperature without epimerization
(Scheme 8).15 Treatments of sulfonylimidate 9bc (R = Boc)
and 9cc (R = Ts) with an excess amount of Red-Al provided
the corresponding aldehyde, 19a and 19b, respectively
(Scheme 9). No corresponding aldimine-type product 20 was
observed in contrast to N-sulfinylamidate reported by Ellman
and co-workers.16
Direct Formation of Amino Acid Ester. The experimental
results that 3-componet reaction using aldehyde, sulfonamide,
and sulfonylimidate provided the desired product through in
situ formation of electrophilic sulfonylimine, and that DBU can
catalyze hydrolysis of sulfonylimidate into the corresponding
ester in the presence of water, prompted us to design a novel
catalytic system for facile formation of biologically important
compounds, ¢-amino acid derivatives.17 Sulfonylimidate 8l
was treated with benzaldehyde in the presence of catalytic
amounts of 2,5-dimethylbenzenesulfonamide and DBU, afford-
ing ¢-sulfonylamino acid ester 21 in high yield (Scheme 10).
The structure of 21 was unambiguously determined by single-
crystal X-ray diffraction analysis. A plausible mechanism on
the formation of ¢-amino acid ester is displayed in Figure 9.
Sulfonamide 22 and benzaldehyde first react to form an
electrophile, sulfonylimine 23, and H2O. The sulfonylimine 23
thus formed readily reacts with sulfonylimidate 8l in the
presence of DBU, providing the adduct, sulfonylimidate 24,
which is subsequently hydrolyzed by H2O with the assist of

1092 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
R
O
P
O
NO2
OiPr
EtO
EtO
O2S
O2S
N
N
EtO
N
N
O
O
OiPr
OiPr
OiPr
EtO
OEt
Me
Me
Me
Me
8k
8g: R = Me
8h: R = NO2
8j: R = OMe
diethyl malonate
15
16
Figure 8. Deuterium exchange experiment of active methylene compounds.
Ar
O2S
Ph
H2SO4 (7.0 equiv)
DBU (10 mol%)
Ts
O2S
NH
Boc
Ph
Ts
Boc
Ph
NH NHSO2Ar
NH
O
NH
N
N
iPrOH-H2O (95/5)
100 °C, 3 h
quant
DMF-H2O (95/5)
rt, 33 h
OMe
Ph
OiPr
Ph
O
Me
OMe
Me
18
Me
9cc
Me
9ba
Scheme 8. Conversion of the products (2).
90% yield
17
(Ar = 2,5-xylyl)
Scheme 7. Conversion of the products (1).
Ar
R
R
SO2Ar
H
O2S
NH
O
Red-Al (7.0 equiv)
R
NH
N
NH
N
Ph
H
Ph
Ph
OiPr
THF, -70 °C, 18h
(Ar = 2,5-xylyl)
Me
Me
20
Me
9bc: R = Boc
9cc: R = Ts
From 9bc; 19a (R = Boc): 87% yield
From 9cc; 19b (R = Ts): 83% yield
Scheme 9. Conversion of the products (3).
PhCHO
H2NSO2Ar (10 mol%)
(1.0 equiv)
ArO2S
DBU (20 mol%)
NH
O
+
DMF, rt, 78 h
Slow addition of 8l over 32 h
(Ar = 2,5-xylyl)
Ph
OMe
ArO2S
N
Me
21 (X-ray)
90% yield
Et
OMe
8l
anti/syn = 87/13
(1.2 equiv)
Scheme 10. Direct formation of ¢-amino acid ester from aldehyde and sulfonylimidate.

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1093
PhCHO
SO2Ar
N
Ph
H
H2O
23
H2NSO2Ar (22)
Ar
O2S
N
Ar
Ar
O2S
NH
ArO2S
Ph
Et
OMe
O2S
NH
O
cat. DBU
N
8l
OMe
Ph
OMe
Me
21
Me
24
Figure 9. Formation of ¢-amino acid ester.
(Ar = 2,5-xylyl)
DBU to generate the ester product 21 and sulfonamide 22. The
hydrolysis of sulfonylimidate 24 competes with that of starting
material sulfonylimidate 8l, leading to decrease of the yield. To
address this issue, sulfonylimidate 8l was slowly added over
32 h to delay the hydrolysis of 8l.
in situ formation of sulfonylimine and DBU-assisted hydrolysis
of sulfonylimidate. Further elaboration of sulfonylimidate
would lead to catalysis which otherwise cannot be achieved,
and is currently underway in our laboratory.
Experimental
General. Melting points are uncorrected. 1H and 13C NMR
spectra were recorded on a JEOL JNM-ECX-400, JNM-ECX-
500, and JNM-ECX-600 spectrometer in CDCl3 or C6D6 unless
otherwise noted. Tetramethylsilane (TMS) served as internal
standard (¤ 0) for 1H NMR, and CDCl3 (¤ 77.0) and C6D6 (¤
128.0) were used as internal standard for 13C NMR. IR spectra
were measured on a JASCO FT/IR-610 spectrometer. Column
chromatography was conducted on Silica gel 60 (Merck) and
preparative thin-layer chromatography was carried out using
Wakogel B-5F. X-ray diffraction analysis was performed on a
Rigaku-RAXIS-RAPID diffractometer. All reactions were carried
out under argon atmosphere in dried glassware. All solvents
were dried and distilled by standard procedures. All N-protected
imines employed in this report were synthesized according
Conclusion
A novel nucleophile, sulfonylimidate, has been successfully
employed in Mannich-type reactions. Due to electron-with-
drawing property of sulfonyl group of sulfonylimidate, the
acidity of ¡-proton is enhanced so that sulfonylimidates bearing
no activating functional group at ¡-position are deprotonated by
relatively weaker base. DBU-catalyzed reactions of sulfonyl-
imidates with protected imines in DMF provided the adducts in
high yield with high anti selectivity. This reaction represents a
wide substrate scope and a high catalytic turnover. A thorough
kinetic study for this reaction revealed the rate dependency of
this reaction on Boc imine, sulfonylimidate, and DBU to be
0.23, 0.79, and 1.43, respectively. This result suggests that
deprotonation of sulfonylimidate by DBU is a rate-determining
step and that C-C bond forming step is not involved in rate-
determining step, although which step is a rate-determining step
may depend on the substrate.
Alkali earth metal alkoxide and its HMDS salt also catalyzed
Mannich-type reactions of sulfonylimidates. The reactions of
2,5-dimethylbenzenesulfonylimidate catalyzed by Mg(OtBu)2
in DMF provided the adducts with high anti selectivity, while
those of p-Ns-imidate catalyzed by [Sr(HMDS)2]2 gave syn
selectivity. The application of syn selective Mannich-type
reaction of sulfonylimidate to asymmetric variant was realized
by the use of chiral ligand 13. High diastereoselectivities in
each condition are rationalized on the basis of the experimental
results including X-ray diffraction analyses of various sulfo-
nylimidates. Conversions of sulfonylimidates into the corre-
sponding N-sulfonylamide, ester, and aldehyde derivatives
were performed in acidic, basic, and reductive conditions,
respectively, displaying a versatility of sulfonylimidate func-
tional group. Finally a direct catalytic formation of ¢-amino
acid ester from aldehyde and sulfonylimidate was achieved via
to the reported method.5a All the metal salts used in this work
12a
except [Sr(HMDS)2]2
were purchased and used without any
purification.
Preparation of Sulfonylimidates. Sulfonylimidates 6a-6h
were synthesized by using the similar method to the reported one.6a
General procedure is as follows.
Imidate HCl Salt Formation. HCl gas was bubbled into a
mixture of nitrile (400 mmol) and alcohol (400 mmol) for 10-
20 min (exothermic). In some cases (especially when i-PrOH was
used as an alcohol), temperature higher than room temperature was
necessary for the reaction, that is why the reaction was not cooled
during the exothermic reaction. After completion of bubbling
of HCl, the mixture was left for 3-10 h under Ar atmosphere.
Removal of all the volatiles by evaporation gave us almost
pure imidate HCl salt in 40-80% yield (moderate yield may be
caused by evaporation of the volatile starting materials during
the course of the exothermic reactions), which can be used in the
next reaction without further purification. Further purification is
possible by washing the solid with dry Et2O. Imidate HCl salts are
hygroscopic, but can be kept under inert gas atmosphere in the
refrigerator for at least 1 year.

1094 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
Representative Procedure for the Syntheses of Sulfonylimi-
dates. To a solution of imidate HCl salt 1 (R1 = Et, R2 = i-Pr,
3.01 g, 19.85 mmol) in dichloromethane (DCM, 50 mL) was added
Et3N (8.3 mL, 59.55 mmol) dropwise at rt. To the resultant
suspension was added TsCl (3.785 g, 19.85 mmol) and DMAP
(242.5 mg, 1.985 mmol). The reaction mixture was stirred until
TsCl was consumed (40 h). The mixture was poured into water,
and extracted with DCM. The organics were dried over
anhydrous Na2SO4. Filtration and evaporation of the solvents
afforded the crude product, which was purified by column
chromatography on SiO2 to give us a pure sulfonylimidate 8g
(4.565 g, 85% yield).
1030, 1018, 945, 815, 709, 687, 593, 555 cm¹1; HRMS (FAB):
Exact mass calcd for C11H16NO3S [M + H]+, 242.0851. Found
242.0856.
Isopropyl N-( p-Toluenesulfonyl)propionimidate (8g): Mp
1
38-39 °C; H NMR (CDCl3): ¤ 7.82 (d, 2H, J = 8.5 Hz), 7.29 (d,
2H, J = 7.9 Hz), 5.10-4.97 (m, 1H), 2.88 (q, 2H, J = 7.6 Hz),
2.42 (s, 3H), 1.23 (d, 6H, J = 6.2 Hz), 1.21 (t, 3H, J = 6.2 Hz);
13C NMR (CDCl3): ¤ 176.3, 142.9, 139.4, 129.3, 126.4, 71.9, 27.8,
21.5, 21.1, 10.1; IR (neat): 2983, 2942, 1597, 1496, 1465, 1383,
1356, 1312, 1235, 1183, 1157, 1093, 1032, 1017, 955, 909, 838,
814, 799, 692, 600, 555, 529 cm¹1; HRMS (FAB): Exact mass
calcd for C13H20NO3S [M + H]+, 270.1164. Found 270.1167.
Isopropyl N-(4-Nitrobenzenesulfonyl)propionimidate (8h):
Methyl N-Benzenesulfonylpropionimidate (8a):
1H NMR
1
(CDCl3): ¤ 7.98-7.94 (m, 2H), 7.60-7.48 (m, 3H), 3.75 (s, 3H),
2.95 (q, 2H, J = 7.6 Hz), 1.24 (t, 3H, J = 7.7 Hz); 13C NMR
(CDCl3): ¤ 177.6, 142.0, 132.4, 128.7, 126.5, 55.4, 27.5, 10.0; IR
(neat): 3063, 2985, 2950, 2887, 1602, 1541, 1507, 1446, 1377,
1305, 1235, 1155, 1091, 1023, 945, 798, 758, 733, 690, 621, 585,
536 cm¹1; HRMS (FAB): Exact mass calcd for C10H14NO3S
[M + H]+, 228.0694. Found 228.0697.
Mp 70-71 °C; H NMR (CDCl3): ¤ 8.35 (br d, 2H, J = 9.2 Hz),
8.12 (br d, 2H, J = 9.2 Hz), 5.00 (septet, 1H, J = 6.3 Hz), 2.98
(q, 2H, J = 8.0 Hz), 1.27 (t, 3H, J = 8.0 Hz), 1.26 (d, 6H, J = 6.3
Hz); 13C NMR (CDCl3): ¤ 177.5, 149.8, 147.6, 127.8, 124.1, 72.9,
28.6, 21.1, 10.2; IR (neat): 3021, 2987, 1579, 1532, 1350, 1308,
1216, 1158, 1094 cm¹1; HRMS (APCI): Exact mass calcd for
C12H17N2O5S [M + H]+, 301.0858. Found 301.0871.
Isopropyl N-Benzenesulfonylpropionimidate (8b): 1H NMR
(CDCl3): ¤ 8.09-8.06 (m, 2H), 7.64-7.60 (m, 3H), 4.70 (sept, 1H,
J = 6.3 Hz), 2.88 (qd, 2H, J = 7.3, 1.7 Hz), 1.05 (td, 3H, J = 7.3,
1.2 Hz), 0.83 (d, 6H, J = 6.3 Hz); 13C NMR (CDCl3): ¤ 176.0,
143.6, 132.0, 128.8, 126.9, 71.6, 28.2, 20.9, 10.4; IR (neat):
3055, 2988, 1506, 1448, 1308, 1265, 1157, 1093, 896, 740, 705,
634, 459, 445, 413 cm¹1; HRMS (FAB): Exact mass calcd for
C12H18NO3S [M + H]+, 256.1007. Found 256.1010.
Isopropyl N-(4-Nitrobenzenesulfonyl)butyrimidate (8i): Mp
49-50 °C; H NMR (CDCl3): ¤ 8.35 (br d, 2H, J = 8.6 Hz), 8.12
1
(br d, 2H, J = 8.6 Hz), 5.00 (septet, 1H, J = 6.3 Hz), 2.88 (t, 2H,
J = 7.5 Hz), 1.77 (tq, 2H, J = 8.0, 8.0 Hz), 1.26 (d, 6H, J = 6.3
Hz), 1.02 (t, 3H, J = 8.0 Hz); 13C NMR (CDCl3): ¤ 176.7, 149.8,
147.7, 127.8, 124.0, 72.8, 36.6, 21.2, 19.6, 13.7; IR (neat): 2972,
2938, 1582, 1530, 1349, 1311, 1160, 1093 cm¹1; HRMS (APCI):
Exact mass calcd for C13H19N2O5S [M + H]+, 315.1015. Found
315.1028.
Isopropyl N-(2,5-Xylylsulfonyl)propionimidate (8c):
Mp
32-33 °C; 1H NMR (CDCl3): ¤ 8.20 (s, 1H), 6.90 (d, 1H, J =
7.4 Hz), 6.84 (dd, 1H, J = 7.4, 1.4 Hz), 4.74 (sept, 1H, J = 6.3 Hz),
2.91 (q, 2H, J = 7.4 Hz), 2.77 (s, 3H), 1.94 (s, 3H), 1.07 (t, 3H,
J = 7.4 Hz), 0.83 (d, 6H, J = 6.3 Hz); 13C NMR (CDCl3): ¤ 176.2,
141.2, 135.9, 134.4, 133.0, 132.2, 128.9, 71.2, 28.4, 21.1, 20.6,
20.2, 10.4; IR (neat): 3055, 2988, 1590, 1458, 1308, 1265, 1154,
1092, 1066, 896, 740, 705, 642, 459, 413 cm¹1; HRMS (ESI):
Exact mass calcd for C14H22NO3S [M + H]+, 284.1320. Found
284.1323.
Methyl N-(2,5-Xylylsulfonyl)propionimidate (8l): Mp 71-
72 °C; H NMR (C6D6): ¤ 8.17-8.15 (m, 1H), 6.94-6.85 (m, 2H),
1
3.10 (s, 3H), 2.87 (q, 2H, J = 7.6 Hz), 2.72 (s, 3H), 1.95 (s, 3H),
1.02 (t, 3H, J = 7.4 Hz); 13C NMR (C6D6): ¤ 177.1, 140.9, 135.9,
134.5, 133.1, 132.3, 128.9, 54.6, 27.9, 20.5, 20.2, 10.0; IR (neat):
2982, 2949, 2884, 1602, 1491, 1461, 1442, 1378, 1307, 1234,
1191, 1154, 1142, 1094, 1065, 1028, 944, 884, 821, 798, 747, 705,
630, 579, 548, 503 cm¹1; HRMS (FAB): Exact mass calcd for
C12H18NO3S [M + H]+, 256.1007. Found 256.1000.
Isopropyl N-(2,5-Xylylsulfonyl)butyrimidate (8d): Mp 35-
36 °C; 1H NMR (CDCl3): ¤ 8.18 (s, 1H), 6.92 (d, 1H, J = 8.0 Hz),
6.84 (d, 1H, J = 8.0 Hz), 4.77 (sept, 1H, J = 6.2 Hz), 2.93-2.87
(m, 2H), 2.77 (s, 3H), 1.95 (s, 3H), 1.65 (sext, 2H, J = 7.4 Hz),
0.87 (d, 6H, J = 6.2 Hz), 0.82 (t, 3H, J = 7.4 Hz); 13C NMR
(CDCl3): ¤ 175.3, 141.2, 135.9, 134.4, 133.0, 132.2, 128.3, 71.2,
36.5, 21.1, 20.6, 20.2, 20.0, 13.8; IR (neat): 3055, 2987, 2933,
2878, 1590, 1457, 1373, 1303, 1219, 1154, 1102, 1067, 918, 896,
739, 706, 641, 459, 412 cm¹1; HRMS (FAB): Exact mass calcd for
C15H24NO3S [M + H]+, 298.1477. Found 298.1465.
Ethyl N-Benzenesulfonylacetimidate (8e): 1H NMR (CDCl3):
¤ 7.94 (d, 2H, J = 7.9 Hz), 7.60-7.46 (m, 3H), 4.16 (q, 2H, J =
7.2 Hz), 2.49 (s, 3H), 1.27 (t, 3H, J = 7.1 Hz); 13C NMR (CDCl3):
¤ 173.7, 141.7, 132.3, 128.6, 126.5, 64.6, 20.5, 13.5; IR (neat):
3066, 2986, 2940, 2904, 1748, 1606, 1474, 1447, 1396, 1376,
1306, 1158, 1118, 1093, 1046, 1121, 998, 869, 803, 735, 689,
633, 588, 567, 525 cm¹1; HRMS (FAB): Exact mass calcd for
C10H14NO3S [M + H]+, 228.0694. Found 228.0695.
General Procedure of DBU-Catalyzed Addition Reactions of
Sulfonylimidates to Imines. To MS 4A (50 mg) was added a
solution of imine (0.45 mmol) in DMF (0.5 mL) and sulfonyl-
imidate (0.3 mmol). The mixture was cooled to 0 °C and a solution
of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene, 5 mol %) in DMF
(100 ¯L) was added. The mixture was stirred for 24 h and then
diluted by addition of Et2O. The mixture obtained after filtration
(for removal of MS 4A) was washed with water 3 times, then dried
over anhydrous Na2SO4. Filtration and removal of solvents
afforded the crude product. Diastereo ratio was determined by
1H NMR spectroscopy analysis of the crude product. Purification
of the crude product was conducted by chromatography on SiO2, to
afford the desired product 9. When it was difficult to determine
the diastereomer ratio at the crude product stage, the ratio was
determined by the weight of the separated diastereomers after
purification.
Procedure of Addition Reaction of Sulfonylimidate 8e to N-
Boc Imine 3a (Table 2, Entry 3). To MS 4A (50 mg) was added
a solution of imine 3a (53.2 mg, 0.3 mmol) in DMF (0.5 mL). The
mixture was cooled to 0 °C, then sulfonylimidate 8e (340.9 mg,
1.5 mmol) and a solution of DBU in DMF (10 mol %, 100 ¯L)
were added successively. The mixture was stirred for 30 min at
0 °C, and then diluted by addition of Et2O. The mixture obtained
after filtration (for removal of MS 4A) was washed with water 3
Methyl N-( p-Toluenesulfonyl)propionimidate (8f): Mp 46-
46.5 °C; 1H NMR (CDCl3): ¤ 7.82 (d, 2H, J = 8.2 Hz), 7.28 (d, 2H,
J = 8.2 Hz), 3.72 (s, 3H), 2.92 (q, 2H, J = 7.6 Hz), 2.40 (s, 3H),
1.22 (t, 3H, J = 7.6 Hz); 13C NMR (CDCl3): ¤ 177.4, 143.1, 139.1,
129.3, 126.6, 55.4, 27.4, 21.5, 10.0; IR (neat): 2983, 2949,
1605, 1496, 1464, 1442, 1378, 1314, 1235, 1190, 1155, 1092,

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1095
times, then dried over anhydrous Na2SO4. Filtration and removal
of solvents afforded the crude product. Purification of the crude
product was conducted by chromatography on SiO2, to afford the
desired product 9ae (95.8 mg, 79%) and the recovered sulfonyl-
imidate 8e (275 mg, 1.21 mmol).
Na2SO4. Filtration and removal of solvents afforded the crude
product. Diastereomeric ratio was determined by H NMR spec-
1
troscopy analysis of the crude product. Purification of the
crude product was conducted by chromatography on SiO2, to
afford the desired product 9gh (85% yield, syn/anti = 83/17). The
enantiomeric excess of the syn product was determined by HPLC
(57% ee).
Methyl anti-N-(Benzenesulfonyl)-3-(ethoxycarbonylamino)-
2-methyl-3-phenylpropionimidate (anti-9aa): 1H NMR (C6D6):
¤ 8.10-8.07 (m, 2H), 7.38 (d, 2H, J = 7.6 Hz), 7.08-7.04 (m, 2H),
7.03-6.95 (m, 4H), 6.74 (d, 1H, J = 9.6 Hz), 5.08 (t, 1H, J = 10.3
Hz), 4.45-4.38 (m, 1H), 3.98-3.88 (m, 2H), 3.20 (s, 3H), 0.92 (t,
3H, J = 6.9 Hz), 0.88 (t, 3H, J = 7.2 Hz); 13C NMR (C6D6): ¤
177.9, 155.8, 142.6, 140.9, 132.4, 129.1, 128.8, 127.6, 127.0, 60.8,
59.4, 55.2, 45.6, 14.9, 14.6; IR (neat): 3375, 3064, 3030, 2982,
2951, 1722, 1602, 1518, 1447, 1369, 1303, 1245, 1222, 1152,
1090, 1059, 1025, 999, 950, 907, 842, 772, 758, 734, 701, 689,
623, 525, 426 cm¹1; HRMS (FAB): Exact mass calcd for
C20H25N2O5S [M + H]+, 405.1484. Found 405.1494.
Methyl syn-N-(Benzenesulfonyl)-3-(ethoxycarbonylamino)-
2-methyl-3-phenylpropionimidate (syn-9aa): Mp 130-131 °C;
1H NMR (C6D6): ¤ 7.96-7.93 (m, 2H), 7.48 (d, 2H, J = 6.9 Hz),
7.18-7.13 (m, 3H), 7.02 (t, 1H, J = 7.2 Hz), 6.95-6.90 (m, 2H),
5.38 (t, 1H, J = 10 Hz), 4.76 (d, 1H, J = 9.6 Hz), 4.39-4.30 (m,
1H), 4.06-3.88 (m, 2H), 2.88 (s, 3H), 1.47 (d, 3H, J = 6.9 Hz),
0.94 (t, 3H, J = 6.9 Hz); 13C NMR (C6D6): ¤ 176.4, 156.3, 143.0,
141.2, 132.1, 128.8, 128.7, 126.9, 60.8, 60.1, 57.3, 54.6, 44.5,
20.5, 15.5, 14.6, 14.2; IR (neat): 3343, 3063, 2924, 2853, 1715,
1697, 1607, 1532, 1448, 1375, 1305, 1287, 1261, 1237, 1155,
1084, 1035, 951, 927, 905, 733, 701, 689, 622, 586 cm¹1; HRMS
(FAB): Exact mass calcd for C20H25N2O5S [M + H]+, 405.1484.
Found 405.1502.
Procedure of 3-Component Reaction between Benzaldehyde,
Sulfonamide, and Sulfonylimidate 8c. To a suspension of MS
4A (100 mg) in DMF (0.5 mL) were added benzaldehyde (45.7 ¯L,
0.45 mmol) and 2,5-xylylsulfonylamide (83.4 mg, 0.45 mmol). The
mixture was stirred at rt for 20 min, and then cooled to 0 °C. To
the suspension were added sulfonylimidate 8c (85.0 mg, 0.3 mmol)
and a solution of DBU in DMF (10 mol %, 100 ¯L) successively.
The mixture was stirred for 23 h at 0 °C, and then diluted by
addition of Et2O. The mixture obtained after filtration (for removal
of MS 4A) was washed with water 3 times, then dried over
anhydrous Na2SO4. Filtration and removal of solvents afforded
the crude product. Diastereo ratio was determined by 1H NMR
spectroscopy analysis of the crude product (anti/syn = 95/5).
Purification of the crude product was conducted by chromatog-
raphy on SiO2, to afford the desired product 9sc (116.8 mg, 70%
yield).
General Procedure of Alkali Earth Metal-Catalyzed Addi-
tion Reactions of Sulfonylimidates to N-Protected Imines.
Condition A:
To a flask containing MS 4A (50 mg) and
Mg(OtBu)2 (10 mol %) was added DMF (0.3 mL), followed
by sulfonylimidate (0.3 mmol) and finally a solution of imine
(0.45 mmol) in DMF (0.3 mL). The mixture was stirred for 17 h
at rt and then diluted by addition of Et2O. The mixture obtained
after filtration (for removal of MS 4A) was washed with water 3
times, then dried over anhydrous Na2SO4. Filtration and removal
of solvents afforded the crude product. Diastereomeric ratio
was determined by 1H NMR spectroscopy analysis of the crude
product. Purification of the crude product was conducted by
chromatography on SiO2, to afford the desired product 9. When it
was difficult to determine the diastereomeric ratio at the crude
product stage, the ratio was determined by the weight of the
separated diastereomers after purification.
Isopropyl
anti-N-(Benzenesulfonyl)-3-(ethoxycarbonyl-
Mp
amino)-2-methyl-3-phenylpropionimidate (anti-9ab):
78 °C; 1H NMR (CDCl3): ¤ 8.13-8.07 (m, 2H), 7.40 (d, 2H,
J = 6.9 Hz), 7.07 (t, 2H, J = 6.9 Hz), 7.04-6.98 (m, 4H), 6.77 (d,
1H, J = 9.6 Hz), 5.09 (t, 1H, J = 11.0 Hz), 4.83 (quint, 1H, J =
6.2 Hz), 4.41 (qd, 1H, J = 11.0, 6.9 Hz), 4.02-3.85 (m, 2H), 1.08
(d, 3H, J = 6.2 Hz), 0.98 (d, 3H, J = 6.2 Hz), 0.94-0.88 (m, 6H);
13C NMR (CDCl3): ¤ 176.8, 155.7, 143.0, 141.1, 132.4, 129.0,
128.9, 128.2, 127.7, 126.9, 72.5, 60.7, 59.2, 45.7, 20.8, 20.4, 14.9,
14.6; IR (neat): 3063, 3033, 2983, 2938, 2880, 1724, 1593, 1520,
1481, 1456, 1448, 1385, 1374, 1361, 1302, 1245, 1222, 1154,
1091, 1056, 1026, 1000, 974, 929, 909, 852, 829, 769, 758, 738,
702, 689, 671, 636, 597, 566, 537, 504, 470, 418 cm¹1; HRMS
(FAB): Exact mass calcd for C22H29N2O5S [M + H]+, 433.1797.
Found 433.1803.
Condition B:
To a flask containing MS 4A (50 mg),
[Sr(HMDS)2]2 (10 mol % of Sr), and ligand 12 (11 mol %) was
added THF (0.3 mL), the mixture was stirred at rt for 1 h.
Afterwhich sulfonylimidate (0.3 mmol) and finally a solution of
imine (0.45 mmol) in THF (0.3 mL) was added. The mixture was
stirred for 24 h at rt, then diluted with EtOAc and quenched with aq
NH4Cl. The mixture obtained were separated and then dried over
anhydrous Na2SO4. Filtration and removal of solvents afforded the
1
crude product. Diastereomeric ratio was determined by H NMR
spectroscopy analysis of the crude product. Purification of the
crude product was conducted by chromatography on SiO2, to
afford the desired product 9. When it was difficult to determine the
diastereomeric ratio at the crude product stage, the ratio was
determined by the weight of the separated diastereomers after
purification.
Isopropyl
syn-N-(Benzenesulfonyl)-3-(ethoxycarbonyl-
Mp
amino)-2-methyl-3-phenylpropionimidate (syn-9ab):
145-147 °C; 1H NMR (CDCl3): ¤ 8.02-7.97 (m, 2H), 7.54 (d,
2H, J = 6.9 Hz), 7.18-7.13 (m, 3H), 7.01 (t, 1H, J = 7.5 Hz),
6.98-6.93 (m, 2H), 5.29 (t, 1H, J = 9.7 Hz), 4.52 (d, 1H, J = 9.7
Hz), 4.46 (quint, 1H, J = 6.2 Hz), 4.34 (dq, 1H, J = 9.7, 7.7 Hz),
4.04-3.86 (m, 2H), 1.54 (d, 3H, J = 6.9 Hz), 0.95 (t, 3H, J = 6.9
Hz), 0.71 (d, 3H, J = 6.2 Hz), 0.45 (d, 3H, J = 5.5 Hz); 13C NMR
(CDCl3): ¤ 175.2, 156.3, 143.4, 141.4, 132.0, 128.8, 128.7, 128.3,
126.8, 71.8, 60.8, 57.5, 44.2, 20.6, 20.0, 16.0, 14.5; IR (neat):
3063, 3033, 2982, 2936, 2876, 1698, 1596, 1532, 1481, 1447,
1382, 1355, 1305, 1286, 1262, 1236, 1157, 1093, 1082, 1034,
1001, 980, 929, 908, 844, 766, 737, 702, 689, 638, 587, 540,
418 cm¹1; HRMS (FAB): Exact mass calcd for C22H29N2O5S
[M + H]+, 433.1797. Found 433.1779.
Experimental Procedure for the Catalytic Asymmetric
Reaction.
To a flask containing MS 4A (50 mg), Sr(OiPr)2
(6.2 mg, 10 mol %), and ligand 13 (19.8 mg, 12 mol %) was added
THF (0.8 mL), the mixture was stirred at rt for 1 h. Afterwhich
p-nitrobenzenesulfonylimidate 8h (90.1 mg, 0.3 mmol), o-tolalde-
hyde-derived Boc imine 3g (98.7 mg, 0.45 mmol), THF (0.2 mmol)
and a solution of Et3N (3.03 mg, 10 mol %) in THF (0.05 mL) were
successively added in this order. The mixture was stirred for 48 h at
20 °C, then diluted with EtOAc and quenched with aq NH4Cl. The
mixture obtained were separated and then dried over anhydrous

1096 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
Isopropyl anti-N-(Benzenesulfonyl)-3-(tert-butoxycarbonyl-
amino)-2-methyl-3-phenylpropionimidate (anti-9bb): 1H NMR
(C6D6): ¤ 8.14 (d, 2H, J = 6.8 Hz), 7.38 (d, 2H, J = 7.4 Hz), 7.07-
6.95 (m, 6H), 6.66 (d, 1H, J = 9.6 Hz), 5.06 (t, 1H, J = 10.5 Hz),
4.86-4.80 (m, 1H), 4.43-4.32 (m, 1H), 1.34 (s, 9H), 1.12 (d, 3H,
J = 6.2 Hz), 0.95 (d, 3H, J = 6.8 Hz), 0.91 (d, 3H, J = 6.2 Hz);
13C NMR (C6D6): ¤ 176.7, 154.9, 143.2, 132.3, 129.0, 128.8,
127.6, 126.9, 78.7, 72.5, 58.8, 45.8, 28.4, 20.8, 20.6, 14.9; IR
(neat): 3387, 2979, 2938, 1717, 1592, 1508, 1455, 1386, 1364,
1302, 1247, 1155, 1090, 1054, 1002, 973, 909, 851, 757, 737, 700,
688, 635, 590, 538 cm¹1; HRMS (FAB): Exact mass calcd for
C24H33N2O5S [M + H]+, 461.2110. Found 461.2099.
132.6, 128.9, 128.8, 128.6, 127.6, 127.0, 73.0, 62.1, 46.7, 21.4,
21.1, 20.9, 20.6, 20.5, 14.6; IR (neat): 3056, 2986, 2938, 2880,
1589, 1494, 1457, 1438, 1423, 1386, 1355, 1333, 1305, 1291,
1266, 1162, 1101, 1092, 1063, 975, 910, 896, 856, 822, 814, 738,
706, 668, 645, 581, 565, 549, 500, 463, 418 cm¹1; HRMS (FAB):
Exact mass calcd for C28H35N2O5S2 [M + H]+, 543.1987. Found
543.1990.
Isopropyl
syn-2-Methyl-3-phenyl-3-( p-toluenesulfonyl-
Mp
amino)-N-(2,5-xylylsulfonyl)propionimidate (syn-9cc):
1
160-161 °C; H NMR (CDCl3): ¤ 7.80 (s, 1H), 7.46 (d, 2H, J =
8.5 Hz), 7.21 (d, 1H, J = 7.4 Hz), 7.11 (d, 1H, J = 7.9 Hz), 7.07-
7.00 (m, 7H), 5.17 (d, 1H, J = 9.6 Hz), 4.77-4.68 (m, 1H), 4.52 (t,
1H, J = 9.4 Hz), 4.17-4.10 (m, 1H), 2.39 (s, 3H), 2.35 (s, 3H),
2.31 (s, 3H), 1.44 (d, 3H, J = 6.8 Hz), 1.14 (d, 3H, J = 6.2 Hz),
0.78 (d, 3H, J = 6.2 Hz); 13C NMR (CDCl3): ¤ 174.6, 142.9,
139.5, 138.5, 137.8, 135.6, 134.2, 133.1, 132.0, 129.2, 128.1,
128.0, 127.6, 127.4, 127.0, 72.1, 60.3, 44.6, 21.4, 21.1, 20.8, 20.5,
19.6, 15.6; IR (neat): 3276, 3032, 2983, 2877, 1592, 1492, 1455,
1381, 1331, 1303, 1184, 1159, 1096, 1062, 981, 909, 813, 764,
733, 704, 669, 646, 607, 562, 511 cm¹1; HRMS (FAB): Exact mass
calcd for C28H35N2O5S2 [M + H]+, 543.1987. Found 543.1971.
Isopropyl anti-3-(tert-Butoxycarbonylamino)-3-( p-methoxy-
Isopropyl
anti-3-(tert-Butoxycarbonylamino)-2-methyl-3-
Mp
phenyl-N-(2,5-xylylsulfonyl)propionimidate (anti-9bc):
122-123 °C; 1H NMR (CDCl3): ¤ 8.19 (s, 1H), 7.36 (d, 2H,
J = 6.8 Hz), 7.05-6.93 (m, 4H), 6.89 (d, 1H, J = 7.3 Hz), 6.62
(d, 1H, J = 9.6 Hz), 5.03 (t, 1H, J = 10.5 Hz), 4.87 (quint, 1H,
J = 6.2 Hz), 4.48 (sext, 1H, J = 5.9 Hz), 2.86 (s, 3H), 1.96 (s, 3H),
1.34 (s, 9H), 1.15 (d, 3H, J = 5.7 Hz), 0.98 (d, 3H, J = 6.2 Hz),
0.91 (d, 3H, J = 6.2 Hz); 13C NMR (CDCl3): ¤ 177.5, 154.7,
141.4, 140.5, 136.1, 134.5, 133.4, 132.4, 128.9, 128.3, 127.9,
127.7, 78.6, 72.1, 58.9, 46.0, 28.4, 21.0, 21.0, 20.6, 20.6, 14.9; IR
(neat): 3060, 3032, 2941, 2936, 2881, 1715, 1588, 1513, 1495,
1456, 1389, 1365, 1299, 1267, 1248, 1225, 1155, 1102, 1066,
1053, 1004, 973, 930, 910, 884, 851, 824, 738, 707, 644, 599, 553,
499, 465 cm¹1; HRMS (ESI): Exact mass calcd for C26H37N2O5S
[M + H]+, 489.2423. Found 489.2417.
phenyl)-2-methyl-N-(2,5-xylylsulfonyl)propionimidate
(anti-
1
9dc): Mp 142-145 °C; H NMR (CDCl3): ¤ 8.20 (s, 1H), 7.29
(d, 2H, J = 9.1 Hz), 6.98 (d, 1H, J = 7.4 Hz), 6.89 (d, 1H, J =
7.4 Hz), 6.65-6.55 (m, 3H), 5.02 (t, 1H, J = 9.5 Hz), 4.91 (quint,
1H, J = 6.2 Hz), 4.38 (qd, 1H, J = 11.3, 6.2 Hz), 3.27 (s, 3H), 2.87
(s, 3H), 1.97 (s, 3H), 1.36 (s, 9H), 1.16 (d, 3H, J = 6.2 Hz), 1.04
(d, 3H, J = 6.8 Hz), 0.93 (d, 3H, J = 6.2 Hz); 13C NMR (CDCl3):
¤ 177.7, 159.6, 154.7, 140.6, 136.1, 134.6, 133.4, 132.4, 131.8,
128.9, 128.7, 114.5, 78.6, 72.1, 58.4, 54.7, 46.2, 28.4, 21.0, 21.0,
20.6, 20.6, 15.0; IR (neat): 3055, 2984, 2937, 1713, 1586, 1513,
1457, 1422, 1386, 1365, 1299, 1265, 1155, 1101, 1054, 1036, 910,
832, 740, 706, 644, 609, 419 cm¹1; HRMS (FAB): Exact mass
calcd for C27H39N2O6S [M + H]+, 519.2529. Found 519.2512.
Isopropyl
anti-3-(tert-Butoxycarbonylamino)-2-ethyl-3-
Mp
phenyl-N-(2,5-xylylsulfonyl)propionimidate (anti-9bd):
1
95-96 °C; H NMR (CDCl3): ¤ 8.18 (s, 1H), 7.44 (d, 2H, J = 7.4
Hz), 7.08-6.93 (m, 4H), 6.92-6.80 (m, 2H), 5.08 (t, 1H, J = 10.5
Hz), 4.93 (quint, 1H, J = 6.2 Hz), 4.32 (td, 1H, J = 11.4, 4.0 Hz),
2.87 (s, 3H), 1.95 (s, 3H), 1.65-1.59 (m, 1H), 1.34 (s, 9H), 1.40-
1.20 (m, 1H), 1.16 (d, 3H, J = 6.2 Hz), 0.95-0.88 (m, 6H);
13C NMR (CDCl3): ¤ 176.9, 153.8, 141.9, 140.6, 136.1, 134.5,
133.4, 132.4, 129.0, 128.9, 128.3, 127.7, 78.6, 72.0, 58.4, 53.7,
28.4, 23.9, 21.1, 21.0, 20.7, 20.6, 11.8; IR (neat): 3062, 3031,
2978, 2934, 2878, 2717, 1717, 1586, 1509, 1496, 1458, 1390,
1365, 1297, 1251, 1202, 1154, 1100, 1065, 1011, 991, 915, 885,
865, 837, 822, 774, 747, 707, 642, 599, 553, 532, 499, 464, 437,
419 cm¹1; HRMS (FAB): Exact mass calcd for C27H39N2O5S
[M + H]+, 503.2580. Found 503.2554.
Isopropyl
anti-3-(tert-Butoxycarbonylamino)-3-( p-fluoro-
(anti-
phenyl)-2-methyl-N-(2,5-xylylsulfonyl)propionimidate
1
9ec): Mp 131-133 °C; H NMR (CDCl3): ¤ 8.19 (s, 1H), 7.21-
7.12 (m, 2H), 6.96 (d, 1H, J = 7.4 Hz), 6.88 (d, 1H, J = 7.4 Hz),
6.69-6.59 (m, 3H), 4.95 (t, 1H, J = 10.2 Hz), 4.87 (quint, 1H,
J = 6.0 Hz), 4.29 (sext, 1H, J = 6.4 Hz), 2.85 (s, 3H), 1.95 (s, 3H),
1.35 (s, 9H), 1.14 (d, 3H, J = 5.6 Hz), 0.95 (d, 3H, J = 6.2 Hz),
0.91 (d, 3H, J = 6.2 Hz); 13C NMR (CDCl3): ¤ 177.2, 160.6 (d,
Ethyl
N-(Benzenesulfonyl)-3-(ethoxycarbonylamino)-3-
1
phenylpropionimidate (9ae): Mp 80-81 °C; H NMR (C6D6):
¤ 8.10-8.05 (m, 2H), 7.30-7.26 (m, 2H), 7.10-7.00 (m, 6H), 6.26
(d, 1H, J = 9.1 Hz), 5.57-5.47 (m, 1H), 4.03-3.92 (m, 2H), 3.81-
3.59 (m, 3H), 2.95 (dd, 1H, J = 5.1, 14.2 Hz), 0.95 (t, 3H, J =
7.1 Hz), 0.82 (t, 3H, J = 7.1 Hz); 13C NMR (C6D6): ¤ 172.8, 155.9,
142.7, 142.0, 132.4, 129.0, 128.8, 127.0, 126.6, 64.8, 60.8, 53.3,
41.1, 14.6, 13.2; IR (neat): 3360, 3065, 2982, 1719, 1599, 1523,
1473, 1446, 1397, 1374, 1305, 1243, 1155, 1091, 1041, 888, 755,
734, 700, 689, 631 cm¹1; HRMS (FAB): Exact mass calcd for
C20H25N2O5S [M + H]+, 405.1484. Found 405.1487.
JC-F = 244.3 Hz), 154.7, 140.4, 137.1, 136.2, 134.5, 133.5, 132.4,
3
2
129.3 (d, JC-F = 8.4 Hz), 128.9, 115.7 (d, JC-F = 21.5 Hz), 78.8,
72.1, 58.2, 46.0, 28.4, 21.0, 21.0, 20.6, 14.8; IR (neat): 3056, 2984,
2933, 1714, 1588, 1542, 1457, 1366, 1298, 1266, 1226, 1156,
1096, 1055, 837, 741, 706, 644, 507, 527, 499 cm¹1; HRMS
(FAB): Exact mass calcd for C26H36N2O5SF [M + H]+, 507.2329.
Found 507.2326.
Isopropyl anti-3-(tert-Butoxycarbonylamino)-2-methyl-m-
tolyl-N-(2,5-xylylsulfonyl)propionimidate (anti-9fc): Mp 110-
112 °C; 1H NMR (CDCl3): ¤ 8.18 (s, 1H), 7.27-7.20 (m, 2H), 6.98
(dd, 2H, J = 16.1, 8.2 Hz), 6.90 (d, 1H, J = 6.8 Hz), 6.85 (d, 1H,
J = 7.4 Hz), 6.62 (d, 1H, J = 9.6 Hz), 5.04 (t, 1H, J = 10.5 Hz),
4.90 (quint, 1H, J = 6.2 Hz), 4.40 (qd, 1H, J = 11.1, 6.2 Hz), 2.86
(s, 3H), 2.02 (s, 3H), 1.98 (s, 3H), 1.34 (s, 9H), 1.17 (d, 3H,
J = 6.2 Hz), 1.02 (d, 3H, J = 6.2 Hz), 0.93 (d, 3H, J = 6.2 Hz);
13C NMR (CDCl3): ¤ 177.6, 154.7, 141.4, 138.6, 136.1, 133.4,
132.4, 129.0, 128.4, 128.3, 124.7, 78.6, 72.1, 58.9, 46.1, 28.4,
28.3, 21.3, 21.1, 21.0, 20.6, 15.0; IR (neat): 3056, 2982, 2936,
2880, 1714, 1588, 1508, 1495, 1457, 1386, 1366, 1298, 1266,
Isopropyl
anti-2-Methyl-3-phenyl-3-( p-toluenesulfonyl-
Mp
amino)-N-(2,5-xylylsulfonyl)propionimidate (anti-9cc):
140-142 °C; 1H NMR (CDCl3): ¤ 8.21 (s, 1H), 7.34 (d, 2H,
J = 7.9 Hz), 6.98 (d, 1H, J = 7.9 Hz), 6.95-6.86 (m, 3H), 6.86-
6.70 (m, 4H), 6.48 (d, 2H, J = 8.5 Hz), 5.02 (quint, 1H, J = 6.2
Hz), 4.69 (t, 1H, J = 10.2 Hz), 4.30 (qd, 1H, J = 10.7, 6.8 Hz),
3.11 (s, 3H), 1.97 (s, 3H), 1.81 (s, 3H), 1.40 (d, 3H, J = 5.2 Hz),
1.00 (d, 3H, J = 6.2 Hz), 0.93 (d, 3H, J = 6.8 Hz); 13C NMR
(CDCl3): ¤ 176.9, 141.8, 140.2, 139.3, 138.6, 136.1, 135.0, 133.6,

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1097
1155, 1102, 1054, 1007, 974, 942, 908, 885, 846, 822, 791,
740, 708, 644, 606, 554, 499, 445, 419 cm¹1; HRMS (FAB):
Exact mass calcd for C27H39N2O5S [M + H]+, 503.2580. Found
503.2554.
1714, 1588, 1507, 1494, 1456, 1420, 1387, 1366, 1299, 1265,
1233, 1155, 1101, 1054, 1003, 973, 909, 850, 822, 739, 707, 644,
607, 553, 503, 412 cm¹1; HRMS (FAB): Exact mass calcd for
C24H35N2O5S2 [M + H]+, 495.1987. Found 495.1980.
Isopropyl anti-3-(tert-Butoxycarbonylamino)-3-(o-methyl-
Isopropyl anti-3-(tert-Butoxycarbonylamino)-2-methyl-3-(2-
pyridyl)-N-(2,5-xylylsulfonyl)propionimidate (anti-9kc): Mp
113-115 °C; 1H NMR (CDCl3): ¤ 8.79 (s, 1H), 8.45-8.35 (m, 1H),
8.17 (s, 1H), 7.46 (d, 1H, J = 7.9 Hz), 6.96 (d, 1H, J = 7.4 Hz),
6.87 (d, 1H, J = 7.4 Hz), 6.73-6.60 (m, 2H), 5.00 (t, 1H, J =
9.9 Hz), 4.84 (quint, 1H, J = 6.2 Hz), 4.27 (qd, 1H, J = 11.3,
6.8 Hz), 2.83 (s, 3H), 1.96 (s, 3H), 1.33 (s, 9H), 1.11 (d, 3H,
J = 6.2 Hz), 0.88 (d, 3H, J = 6.2 Hz), 0.87 (d, 3H, J = 6.2 Hz);
13C NMR (CDCl3): ¤ 176.9, 154.7, 150.0, 149.7, 140.3, 136.4,
136.2, 134.5, 133.8, 133.6, 132.4, 128.9, 123.9, 79.0, 72.3, 56.6,
45.6, 28.4, 21.0, 20.9, 20.6, 14.7; IR (neat): 3059, 2980, 2934,
2880, 1715, 1591, 1507, 1495, 1456, 1429, 1390, 1366, 1298,
1255, 1154, 1101, 1054, 1027, 1005, 973, 910, 883, 852, 820, 779,
735, 708, 643, 602, 554, 499, 460, 412 cm¹1; HRMS (FAB):
Exact mass calcd for C25H36N3O5S [M + H]+, 490.2376. Found
490.2356.
phenyl)-2-methyl-N-(2,5-xylylsulfonyl)propionimidate
(anti-
9gc): 1H NMR (CDCl3): ¤ 8.20 (s, 1H), 7.58 (d, 1H, J = 7.3
Hz), 7.07-6.82 (m, 5H), 6.64 (d, 1H, J = 9.1 Hz), 5.44 (t, 1H,
J = 10.5 Hz), 4.90 (quint, 1H, J = 6.2 Hz), 4.46 (qd, 1H, J = 11.3,
6.8 Hz), 2.87 (s, 3H), 2.52 (s, 3H), 1.97 (s, 3H), 1.32 (s, 9H), 1.15
(d, 3H, J = 6.2 Hz), 1.00 (d, 3H, J = 6.8 Hz), 0.90 (d, 3H, J =
6.2 Hz); 13C NMR (CDCl3): ¤ 177.5, 154.9, 140.6, 140.3, 136.5,
136.1, 134.5, 133.4, 132.4, 130.6, 128.9, 127.6, 127.4, 126.5, 78.6,
72.1, 46.9, 26.4, 21.1, 21.0, 20.6, 20.6, 19.9, 14.1; IR (neat): 3063,
2980, 2933, 2880, 1715, 1591, 1509, 1494, 1458, 1385, 1364,
1299, 1248, 1233, 1155, 1102, 1056, 1003, 971, 955, 910, 884,
850, 822, 793, 760, 748, 734, 708, 643, 601, 583, 556, 518, 500,
459, 412 cm¹1; HRMS (FAB): Exact mass calcd for C27H39N2O5S
[M + H]+, 503.2580. Found 503.2554.
Isopropyl
anti-3-(tert-Butoxycarbonylamino)-3-(m-vinyl-
(anti-
phenyl)-2-methyl-N-(2,5-xylylsulfonyl)propionimidate
Isopropyl
anti-2-Methyl-5-phenyl-3-( p-toluenesulfonyl-
1
9hc): Mp 87-91 °C; H NMR (CDCl3): ¤ 8.19 (s, 1H), 7.52 (s,
1H), 7.28 (d, 1H, J = 7.9 Hz), 7.10 (d, 1H, J = 7.4 Hz), 6.98 (t,
1H, J = 7.9 Hz), 6.96 (d, 1H, J = 7.4 Hz), 6.88 (d, 1H, J = 7.9
Hz), 6.67 (d, 1H, J = 9.6 Hz), 6.46 (dd, 1H, J = 17.6, 10.7 Hz),
5.57 (d, 1H, J = 17.6 Hz), 5.07 (t, 1H, J = 10.2 Hz), 5.00 (d, 1H,
J = 10.7 Hz), 4.88 (quint, 1H, J = 6.2 Hz), 4.41 (qd, 1H, J = 11.3,
6.8 Hz), 2.86 (s, 3H), 1.96 (s, 3H), 1.34 (s, 9H), 1.16 (d, 3H,
J = 6.2 Hz), 0.98 (d, 3H, J = 6.8 Hz), 0.92 (d, 3H, J = 6.2 Hz);
13C NMR (CDCl3): ¤ 177.4, 154.7, 141.8, 140.5, 138.4, 136.9,
136.2, 134.5, 133.4, 132.4, 129.4, 128.9, 126.8, 126.1, 125.7,
114.1, 78.7, 72.1, 58.9, 46.1, 28.4, 21.0, 20.6, 20.6, 14.9; IR (neat):
3087, 3048, 2981, 2933, 2879, 1718, 1602, 1507, 1457, 1389,
amino)-N-(2,5-xylylsulfonyl)pent-4-enimidate (anti-9lc): Mp
125-128 °C; 1H NMR (CDCl3): ¤ 8.22 (s, 1H), 7.67 (d, 2H,
J = 7.9 Hz), 7.04-6.98 (m, 3H), 6.95 (d, 1H, J = 7.9 Hz), 6.88 (dd,
1H, J = 7.4, 1.1 Hz), 6.73 (dd, 2H, J = 7.6, 2.0 Hz), 6.58 (d, 2H,
J = 7.9 Hz), 6.37 (d, 1H, J = 9.1 Hz), 5.84 (d, 1H, J = 15.9 Hz),
5.24 (dd, 1H, J = 15.9, 9.1 Hz), 5.00 (quint, 1H, J = 6.2 Hz), 4.32
(q, 1H, J = 9.8 Hz), 4.10 (qd, 1H, J = 10.8, 6.8 Hz), 2.97 (s, 3H),
1.97 (s, 3H), 1.70 (s, 3H), 1.37 (d, 3H, J = 6.2 Hz), 1.12 (d, 3H,
J = 6.2 Hz), 0.98 (d, 3H, J = 6.2 Hz); 13C NMR (CDCl3): ¤ 176.7,
142.4, 140.3, 139.8, 136.2, 136.0, 134.9, 134.3, 133.5, 132.5,
129.6, 129.3, 128.8, 128.3, 127.6, 126.8, 126.2, 72.9, 60.7, 44.7,
21.4, 21.1, 20.9, 20.6, 20.6, 14.8; IR (neat): 3060, 3029, 2982,
2935, 2877, 1595, 1493, 1457, 1385, 1338, 1303, 1212, 1183,
1153, 1104, 1050, 971, 909, 887, 815, 752, 708, 668, 646, 625,
599, 573, 545, 517, 501, 465, 437, 419 cm¹1; HRMS (FAB):
Exact mass calcd for C30H37N2O5S2 [M + H]+, 569.2144. Found
569.2150.
1363, 1309, 1250, 1140, 1092, 1055, 1004, 973, 908, 857, 844,
¹1
804, 784, 748, 708, 682, 643, 600, 552, 503, 460, 412 cm
;
HRMS (FAB): Exact mass calcd for C28H39N2O5S [M + H]+,
515.2580. Found 515.2570.
Isopropyl anti-3-(tert-Butoxycarbonylamino)-3-(2-furyl)-2-
methyl-N-(2,5-xylylsulfonyl)propionimidate (anti-9ic):
Mp
Isopropyl anti-3-Cyclopropyl-2-methyl-3-( p-toluenesulfo-
1
84 °C; H NMR (CDCl3): ¤ 8.17 (s, 1H), 6.97-6.90 (m, 2H), 6.87
(d, 1H, J = 7.4 Hz), 6.18 (d, 1H, J = 9.6 Hz), 6.09 (d, 1H, J =
2.7 Hz), 5.94-5.90 (m, 1H), 5.21 (t, 1H, J = 10.2 Hz), 4.87 (quint,
1H, J = 6.2 Hz), 4.59 (qd, 1H, J = 11.3, 6.8 Hz), 2.82 (s, 3H), 1.95
(s, 3H), 1.34 (s, 9H), 1.13 (d, 3H, J = 6.2 Hz), 1.06 (d, 3H, J =
6.7 Hz), 0.89 (d, 3H, J = 6.2 Hz); 13C NMR (CDCl3): ¤ 176.6,
154.6, 153.1, 140.6, 136.1, 134.6, 133.3, 132.4, 128.9, 110.3,
108.1, 78.8, 72.1, 52.1, 43.7, 28.3, 21.0, 21.0, 20.6, 20.5, 14.8; IR
(neat): 3139, 3121, 3056, 2980, 2936, 2879, 1715, 1583, 1509,
1456, 1390, 1367, 1299, 1256, 1200, 1155, 1137, 1103, 1064,
1051, 1010, 971, 910, 884, 860, 848, 822, 798, 754, 731, 709, 680,
644, 592, 556, 498, 424 cm¹1; HRMS (FAB): Exact mass calcd for
C24H35N2O6S [M + H]+, 479.2216. Found 479.2225.
nylamino)-N-(2,5-xylylsulfonyl)propionimidate
(anti-9mc):
Mp 97-100 °C; 1H NMR (CDCl3): ¤ 8.14 (s, 1H), 7.76 (d, 2H,
J = 8.5 Hz), 6.85 (d, 1H, J = 8.0 Hz), 6.79 (d, 1H, J = 7.4 Hz),
6.73 (d, 2H, J = 8.5 Hz), 6.18 (d, 1H, J = 8.5 Hz), 4.84 (quint, 1H,
J = 6.2 Hz), 4.16 (qd, 1H, J = 9.6, 6.8 Hz), 3.25 (q, 1H, J = 9.0
Hz), 2.84 (s, 3H), 1.97 (s, 3H), 1.89 (s, 3H), 1.18 (d, 3H, J =
6.2 Hz), 1.16 (d, 3H, J = 6.2 Hz), 0.88 (d, 3H, J = 6.2 Hz), 0.37-
0.27 (m, 1H), 0.10- ¹0.10 (m, 3H), ¹0.13- ¹0.25 (m, 1H);
13C NMR (CDCl3): ¤ 176.8, 142.1, 141.4, 140.4, 136.0, 134.9,
133.4, 132.4, 129.3, 128.9, 127.1, 72.8, 61.4, 46.7, 21.4, 21.1,
21.0, 20.6, 15.9, 15.5, 4.8, 2.7; IR (neat): 3063, 2982, 2936, 2881,
1594, 1493, 1456, 1385, 1357, 1332, 1302, 1239, 1158, 1101,
1052, 1027, 981, 962, 909, 887, 816, 748, 709, 665, 645, 627, 601,
569, 548, 501, 464, 442, 419 cm¹1; HRMS (FAB): Exact mass
calcd for C25H35N2O5S2 [M + H]+, 507.1987. Found 507.2003.
Isopropyl anti-3-(tert-Butoxycarbonylamino)-2-methyl-3-(2-
thienyl)-N-(2,5-xylylsulfonyl)propionimidate (anti-9jc):
Mp
104-107 °C; 1H NMR (CDCl3): ¤ 8.17 (s, 1H), 7.00-6.85 (m, 3H),
6.76 (d, 1H, J = 4.6 Hz), 6.61 (dd, 1H, J = 5.1, 3.4 Hz), 6.32 (d,
1H, J = 9.1 Hz), 5.35 (t, 1H, J = 10.5 Hz), 4.87 (quint, 1H, J =
6.2 Hz), 4.59 (qd, 1H, J = 10.8, 6.8 Hz), 2.81 (s, 3H), 1.96 (s, 3H),
1.33 (s, 9H), 1.10 (d, 6H, J = 6.8 Hz), 0.88 (d, 3H, J = 6.2 Hz);
13C NMR (CDCl3): ¤ 176.7, 154.6, 144.7, 140.5, 136.1, 134.5,
133.4, 132.4, 128.9, 127.1, 125.6, 124.8, 78.9, 72.1, 54.0, 46.3,
26.4, 21.0, 20.6, 20.5, 15.2; IR (neat): 3056, 2983, 2934, 2880,
Isopropyl
anti-3-(tert-Butoxycarbonylamino)-3-cyclopro-
pyl-2-methyl-N-(2,5-xylylsulfonyl)propionimidate (anti-9nc):
1H NMR (CDCl3): ¤ 7.86 (s, 1H), 7.27 (d, 1H, J = 9.2 Hz), 7.20
(d, 1H, J = 7.8 Hz), 5.28 (d, 1H, J = 10.1 Hz), 5.09-4.93 (m, 1H),
3.74 (dq, 1H, J = 6.9, 10.6 Hz), 3.44 (dt, 1H, J = 10.1, 10.1 Hz),
2.64 (s, 3H), 2.38 (s, 3H), 1.38 (s, 9H), 1.34 (d, 3H, J = 6.9 Hz),
1.22 (d, 3H, J = 6.0 Hz), 1.19 (d, 3H, J = 6.4 Hz), 0.90-0.76 (m,
1H), 0.66-0.52 (m, 1H), 0.45-0.30 (m, 3H); 13C NMR (CDCl3): ¤

1098 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
177.6, 155.2, 139.5, 135.6, 134.1, 133.2, 132.1, 128.1, 76.8, 71.9,
56.3, 45.5, 28.2, 21.1, 20.8, 20.8, 20.0, 15.1, 15.0, 4.4, 0.0; IR
(neat): 3386, 3082, 2979, 2935, 2882, 1715, 1590, 1513, 1457,
1390, 1365, 1299, 1252, 1229, 1156, 1103, 1057, 1023, 1001, 957,
747, 723, 707, 644, 600, 559, 533, 499 cm¹1; HRMS (FAB):
Exact mass calcd for C23H37N2O5S [M + H]+, 453.2423. Found
453.2434.
1H NMR (CDCl3): ¤ 7.81 (d, 2H, J = 8.2 Hz), 7.75 (d, 2H, J =
8.2 Hz), 7.33-7.25 (m, 4H), 5.08-4.97 (m, 1H), 4.39 (d, 1H,
J = 8.7 Hz), 3.71 (dq, 1H, J = 6.4, 9.2 Hz), 3.62 (dt, 1H, J = 3.2,
9.2 Hz), 2.42 (s, 6H), 1.71-0.65 (m, 11H), 1.25 (d, 3H, J = 6.4
Hz), 1.22 (d, 3H, J = 6.4 Hz), 1.06 (d, 3H, J = 6.9 Hz); 13C NMR
(CDCl3): ¤ 175.5, 143.1, 143.0, 139.3, 138.9, 129.4, 129.3, 127.0,
126.5, 72.3, 60.8, 41.6, 41.4, 31.0, 26.6, 26.4, 26.1, 26.0, 21.5,
21.5, 21.0, 20.9, 15.1; IR (neat): 3295, 2981, 2928, 2854, 1596,
1496, 1449, 1381, 1300, 1184, 1159, 1093, 1053, 1019, 982, 960,
909, 839, 814, 718, 693, 609, 569, 547 cm¹1; HRMS (FAB):
Exact mass calcd for C27H39N2O5S2 [M + H]+, 535.2300. Found
535.2297.
Isopropyl syn-3-(tert-Butoxycarbonylamino)-3-cyclopropyl-
2-methyl-N-(2,5-xylylsulfonyl)propionimidate
(syn-9nc):
1H NMR (CDCl3): ¤ 7.85 (s, 1H), 7.24 (d, 1H, J = 7.8 Hz), 7.18
(d, 1H, J = 7.8 Hz), 5.10-4.98 (m, 1H), 4.54 (d, 1H, J = 9.6 Hz),
3.80-3.66 (m, 1H), 3.29 (q, 1H, J = 9.5 Hz), 2.62 (s, 3H), 2.37 (s,
3H), 1.45 (s, 9H), 1.26 (d, 3H, J = 6.0 Hz), 1.25 (d, 3H, J = 6.8
Hz), 1.21 (d, 3H, J = 6.4 Hz), 1.02-0.91 (m, 1H), 0.56-0.26 (m,
4H); 13C NMR (CDCl3): ¤ 176.4, 155.9, 139.8, 135.6, 134.1,
133.1, 132.0, 128.1, 79.3, 71.9, 56.8, 45.8, 28.3, 21.3, 21.2, 20.8,
19.8, 15.6, 15.3, 5.7, 2.2; IR (neat): 3366, 2979, 2933, 1698, 1591,
1519, 1455, 1365, 1286, 1155, 1103, 1060, 1018, 956, 910, 824,
748, 706, 644, 500 cm¹1; HRMS (FAB): Exact mass calcd for
C23H37N2O5S [M + H]+, 453.2423. Found 453.2400.
Methyl
anti-3-Isopropyl-2-methyl-N-( p-toluenesulfonyl)-
Mp
3-( p-toluenesulfonylamino)propionimidate (anti-9pf):
1
147-148 °C; H NMR (CDCl3): ¤ 7.88 (d, 2H, J = 8.5 Hz), 7.71
(d, 2H, J = 8.5 Hz), 7.32 (d, 2H, J = 7.9 Hz), 7.19 (d, 2H, J =
7.9 Hz), 5.63 (d, 1H, J = 9.6 Hz), 3.82 (dq, 1H, J = 6.8, 10.2 Hz),
3.62 (dt, 1H, J = 2.8, 10.2 Hz), 3.57 (s, 3H), 2.44 (s, 3H), 2.37 (s,
3H), 1.93-1.83 (m, 1H), 1.21 (d, 3H, J = 6.2 Hz), 0.83 (d, 3H,
J = 6.8 Hz), 0.71 (d, 3H, J = 6.8 Hz); 13C NMR (CDCl3): ¤ 177.4,
143.3, 142.6, 139.6, 138.7, 129.3, 129.2, 126.7, 126.6, 62.2, 55.6,
42.5, 28.9, 21.5, 21.4, 20.6, 15.3, 14.8; IR (neat): 3307, 2965,
1601, 1540, 1496, 1455, 1329, 1304, 1287, 1157, 1090, 1044,
950, 814, 734, 688, 666, 596, 584, 547 cm¹1; HRMS (FAB):
Exact mass calcd for C22H31N2O5S2 [M + H]+, 467.1674. Found
467.1673.
Methyl anti-3-Cyclohexyl-2-methyl-N-( p-toluenesulfonyl)-
3-( p-toluenesulfonylamino)propionimidate
(anti-9of):
1H NMR (CDCl3): ¤ 7.86 (apparent d, 2H, J = 8.5 Hz), 7.70 (d,
2H, J = 7.9 Hz), 7.32 (d, 2H, J = 7.9 Hz), 7.19 (d, 2H, J = 7.9
Hz), 5.60 (d, 1H, J = 9.6 Hz), 3.87 (dq, 1H, J = 6.2, 10.2 Hz), 3.56
(dt, 1H, J = 2.3, 9.6 Hz), 3.50 (s, 3H), 2.44 (s, 3H), 2.37 (s, 3H),
1.80-1.72 (m, 1H), 1.68-1.54 (m, 3H), 1.52-1.36 (m, 2H), 1.20 (d,
3H, J = 6.8 Hz), 1.18-1.08 (m, 2H), 0.84 (m, 3H); 13C NMR
(CDCl3): ¤ 177.5, 143.3, 142.6, 139.6, 129.3, 129.2, 126.6, 61.9,
55.5, 41.7, 39.8, 30.9, 26.3, 26.1, 25.4, 21.5, 21.4, 15.5; IR (neat):
3306, 2928, 2854, 1600, 1495, 1447, 1380, 1329, 1303, 1289,
1182, 1158, 1091, 1039, 1011, 951, 913, 887, 862, 814, 735, 706,
689, 596, 567, 547 cm¹1; HRMS (FAB): Exact mass calcd for
C25H35N2O5S2 [M + H]+, 507.1987. Found 507.1970.
Methyl
syn-3-Isopropyl-2-methyl-N-( p-toluenesulfonyl)-
(syn-9pf):
3-( p-toluenesulfonylamino)propionimidate
1H NMR (CDCl3): ¤ 7.83 (d, 2H, J = 8.2 Hz), 7.73 (d, 2H, J =
8.2 Hz), 7.29 (d, 2H, J = 8.2 Hz), 7.25 (d, 2H, J = 8.2 Hz), 4.51 (d,
1H, J = 10.1 Hz), 3.80-3.66 (m, 2H), 3.71 (s, 3H), 2.41 (s, 3H),
2.39 (s, 3H), 1.63-1.49 (m, 1H), 1.13 (d, 3H, J = 6.9 Hz), 0.76 (d,
3H, J = 6.9 Hz), 0.71 (d, 3H, J = 6.9 Hz); 13C NMR (CDCl3): ¤
176.6, 143.2, 143.1, 139.1, 138.8, 129.5, 129.4, 126.9, 126.5, 60.9,
55.6, 41.8, 31.2, 21.5, 21.5, 20.4, 16.7, 14.2; IR (neat): 3295,
2965, 2882, 1599, 1495, 1455, 1436, 1325, 1290, 1157, 1092,
1039, 952, 909, 814, 688, 666, 603, 573, 548 cm¹1; HRMS (FAB):
Exact mass calcd for C22H31N2O5S2 [M + H]+, 467.1674. Found
467.1682.
Methyl syn-3-Cyclohexyl-2-methyl-N-( p-toluenesulfonyl)-
3-( p-toluenesulfonylamino)propionimidate
(syn-9of):
1H NMR (CDCl3): ¤ 7.85 (d, 2H, J = 8.2 Hz), 7.73 (d, 2H,
J = 8.2 Hz), 7.30 (d, 2H, J = 8.2 Hz), 7.27 (d, 2H, J = 8.2 Hz),
4.43 (d, 1H, J = 9.6 Hz), 3.85-3.79 (m, 1H), 3.73-3.67 (m, 4H),
2.43 (s, 3H), 2.41 (s, 3H), 1.70-1.46 (m, 5H), 1.20-0.93 (m, 8H),
0.65-0.55 (m, 1H); 13C NMR (CDCl3): ¤ 176.6, 143.1, 143.1,
139.2, 138.7, 129.4, 129.3, 127.0, 126.6, 60.3, 55.7, 41.2, 40.9,
30.3, 27.6, 26.2, 26.0, 25.9, 21.5, 21.5, 14.2, 13.5; IR (neat): 3293,
2928, 2854, 1599, 1496, 1448, 1319, 1300, 1185, 1157, 862, 814,
737, 687, 606, 570, 553 cm¹1; HRMS (FAB): Exact mass calcd for
C25H35N2O5S2 [M + H]+, 507.1987. Found 507.1970.
Isopropyl
anti-3-Isopropyl-2-methyl-N-( p-toluenesulfo-
(anti-9pg):
nyl)-3-( p-toluenesulfonylamino)propionimidate
1H NMR (CDCl3): ¤ 7.87 (d, 2H, J = 8.2 Hz), 7.72 (d, 2H,
J = 8.2 Hz), 7.31 (d, 2H, J = 7.7 Hz), 7.20 (d, 2H, J = 8.2 Hz),
5.74 (d, 1H, J = 9.1 Hz), 4.91-4.83 (m, 1H), 3.79 (dq, 1H, J = 6.3,
10.0 Hz), 3.67 (dt, 1H, J = 2.3, 9.0 Hz), 2.43 (s, 3H), 2.38 (s, 3H),
1.90-1.80 (m, 1H), 1.33 (d, 3H, J = 6.3 Hz), 1.23 (d, 3H, J = 6.3
Hz), 1.19 (d, 3H, J = 6.8 Hz), 0.80 (d, 3H, J = 6.8 Hz), 0.69 (d,
3H, J = 6.8 Hz); 13C NMR (CDCl3): ¤ 176.4, 143.1, 142.5, 139.9,
139.0, 129.3, 129.2, 126.5, 126.5, 73.2, 62.3, 42.6, 29.2, 21.5,
21.4, 21.2, 20.9, 20.6, 15.6, 14.9; IR (neat): 3647, 3273, 2968,
2936, 2877, 1918, 1736, 1592, 1496, 1455, 1387, 1373, 1331,
1286, 1241, 1184, 1155, 1089, 1042, 968, 909, 883, 849, 814, 727,
694, 666, 609, 579, 547 cm¹1; HRMS (FAB): Exact mass calcd for
C24H35N2O5S2 [M + H]+, 495.1987. Found 495.1969.
Isopropyl
anti-3-Cyclohexyl-2-methyl-N-( p-toluenesulfo-
(anti-9og):
nyl)-3-( p-toluenesulfonylamino)propionimidate
1H NMR (CDCl3): ¤ 7.85 (d, 2H, J = 8.2 Hz), 7.71 (d, 2H,
J = 8.2 Hz), 7.30 (d, 2H, J = 8.2 Hz), 7.20 (d, 2H, J = 7.8 Hz),
5.68 (d, 1H, J = 9.6 Hz), 4.88-4.76 (m, 1H), 3.84 (dq, 1H, J = 6.9,
10.0 Hz), 3.59 (dt, 1H, J = 2.7, 9.2 Hz), 2.43 (s, 3H), 2.37 (s, 3H),
1.75-0.75 (m, 11H), 1.30 (d, 3H, J = 6.4 Hz), 1.22 (d, 3H, J =
6.0 Hz), 1.17 (d, 3H, J = 6.4 Hz); 13C NMR (CDCl3): ¤ 176.4,
143.1, 142.5, 139.8, 129.3, 129.1, 126.5, 126.5, 73.1, 61.9, 41.8,
39.8, 30.8, 26.3, 26.1, 25.8, 21.5, 21.4, 21.2, 20.8, 15.7; IR (neat):
3277, 2982, 2929, 2854, 2308, 1593, 1495, 1449, 1385, 1374,
1331, 1302, 1182, 1158, 1091, 1020, 968, 909, 887, 862, 840, 814,
735, 694, 671, 605, 582, 547 cm¹1; HRMS (FAB): Exact mass
calcd for C27H39N2O5S2 [M + H]+, 535.2300. Found 535.2297.
Isopropyl
syn-3-Isopropyl-2-methyl-N-( p-toluenesulfo-
(syn-9pg):
nyl)-3-( p-toluenesulfonylamino)propionimidate
1H NMR (CDCl3): ¤ 7.80 (d, 2H, J = 8.5 Hz), 7.75 (d, 2H,
J = 7.9 Hz), 7.31-7.26 (m, 4H), 5.06-4.96 (m, 1H), 4.42-4.35 (m,
1H), 3.71-3.62 (m, 2H), 2.42 (s, 3H), 2.41 (s, 3H), 1.65-1.55 (m,
1H), 1.25 (d, 3H, J = 6.2 Hz), 1.22 (d, 3H, J = 6.2 Hz), 1.11 (d,
3H, J = 6.2 Hz), 0.79 (d, 3H, J = 6.8 Hz), 0.73 (d, 3H, J = 6.8
Hz); 13C NMR (CDCl3): ¤ 175.4, 143.1, 143.1, 139.3, 139.0,
Isopropyl
syn-3-Cyclohexyl-2-methyl-N-( p-toluenesulfo-
(syn-9og):
nyl)-3-( p-toluenesulfonylamino)propionimidate

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1099
129.5, 129.3, 126.9, 126.5, 72.3, 61.1, 42.4, 31.0, 21.5, 21.5, 21.0,
20.9, 20.8, 15.9, 15.5; IR (neat): 3295, 2977, 2933, 2878, 1594,
1456, 1374, 1317, 1290, 1159, 1092, 1040, 909, 839, 814, 718,
693, 666, 608, 572, 548, 458 cm¹1; HRMS (FAB): Exact mass
calcd for C24H35N2O5S2 [M + H]+, 495.1987. Found 495.1969.
128.8, 128.3, 127.3, 73.1, 62.5, 46.4, 21.4, 21.1, 20.8, 20.5,
20.4, 20.0, 14.5; IR (neat): 3060, 3029, 2982, 2936, 2878, 1592,
1578, 1493, 1458, 1386, 1359, 1331, 1292, 1226, 1208, 1162,
1102, 1065, 1030, 973, 910, 855, 824, 768, 747, 725, 707,
645, 607, 580, 548, 516, 501, 464, 436, 419 cm¹1; HRMS (FAB):
Exact mass calcd for C29H37N2O5S2 [M + H]+, 557.2144. Found
557.2151.
Methyl
anti-N-( p-Toluenesulfonyl)-3-( p-toluenesulfonyl-
1H NMR
amino)-2,4,4-trimethylpentanimidate (anti-9qf):
(CDCl3): ¤ 7.83 (d, 2H, J = 8.2 Hz), 7.73 (d, 2H, J = 8.2 Hz),
7.31 (d, 2H, J = 8.2 Hz), 7.25 (d, 2H, J = 8.2 Hz), 5.47 (d, 1H,
J = 9.6 Hz), 4.03 (dq, 1H, J = 6.8, 6.9 Hz), 3.68 (s, 3H), 3.43 (dd,
1H, J = 5.5, 10.4 Hz), 2.43 (s, 3H), 2.40 (s, 3H), 1.25 (d, 3H,
J = 6.9 Hz), 0.87 (s, 9H); 13C NMR (CDCl3): ¤ 177.4, 143.4,
142.8, 139.6, 138.8, 129.4, 126.6, 66.6, 55.5, 39.4, 36.4, 27.5,
Isopropyl 3-Cyclohexyl-2-methyl-3-( p-toluenesulfonylami-
no)-N-(2,5-xylylsulfonyl)propionimidate (anti-9oc): 1H NMR
(C6D6): ¤ 8.25-8.22 (s, 1H), 7.83 (d, 2H, J = 7.9 Hz), 6.93 (d, 1H,
J = 7.4 Hz), 6.87 (d, 1H, J = 7.9 Hz), 6.78 (d, 2H, J = 7.9 Hz),
6.15 (d, 1H, J = 9.1 Hz), 4.98 (quintet, 1H, J = 6.2 Hz), 4.32-4.22
(m, 1H), 3.90-3.84 (m, 1H), 2.94 (s, 3H), 1.99-1.96 (m, 1H), 1.97
(s, 3H), 1.88 (s, 3H), 1.64 (d, 1H, J = 11.9 Hz), 1.54 (d, 1H,
J = 11.9 Hz), 1.47 (d, 1H, J = 13.0 Hz), 1.42 (d, 2H, J = 12.5 Hz),
1.33 (d, 3H, J = 6.2 Hz), 1.33-1.30 (m, 1H), 1.13 (d, 3H, J =
6.8 Hz), 0.98 (d, 3H, J = 6.2 Hz), 1.11-0.70 (m, 4H); 13C NMR
(C6D6): ¤ 177.3, 142.3, 141.1, 140.4, 136.0, 134.9, 133.4, 132.4,
129.3, 129.0, 127.0, 73.0, 62.1, 42.7, 40.2, 31.2, 26.7, 26.5, 26.1,
21.4, 21.0, 21.0, 20.6, 20.5, 15.7; IR (neat): 3273, 2977, 2926,
2847, 1589, 1449, 1334, 1303, 1159, 1092, 1066, 909, 814, 708,
643, 547, 508 cm¹1; HRMS (DART): Exact mass calcd for
C28H41N2O5S2 [M + H]+, 549.2457. Found 549.2438.
21.5, 21.5, 18.4; IR (neat): 3325, 2954, 1601, 1540, 1455, 1315,
¹1
1259, 1185, 1157, 1091, 1025, 927, 814, 675, 594, 572, 547 cm
;
HRMS (FAB); Exact mass calcd for C23H33N2O5S2 [M + H]+,
481.1831. Found 481.1832.
Methyl
syn-N-( p-Toluenesulfonyl)-3-( p-toluenesulfonyl-
Mp 189-
amino)-2,4,4-trimethylpentanimidate (syn-9qf):
190 °C; 1H NMR (CDCl3): ¤ 7.84 (d, 2H, J = 8.2 Hz), 7.74 (d,
2H, J = 8.2 Hz), 7.30 (d, 2H, J = 8.2 Hz), 7.26 (d, 2H, J = 8.2
Hz), 4.72-4.65 (m, 1H), 3.88-3.80 (m, 2H), 3.71 (s, 3H), 2.42 (s,
3H), 2.40 (s, 3H), 1.18 (d, 3H, J = 6.2 Hz), 0.82 (s, 9H); 13C NMR
(CDCl3): ¤ 177.7, 143.1, 142.9, 139.2, 139.1, 129.4, 129.3, 126.8,
126.5, 63.1, 55.4, 40.0, 36.4, 26.8, 21.5, 21.4, 16.4; IR (neat):
3303, 2952, 1600, 1540, 1456, 1436, 1315, 1301, 1286, 1155,
1093, 1071, 953, 916, 814, 688, 605, 574 cm¹1; HRMS (FAB):
Exact mass calcd for C23H33N2O5S2 [M + H]+, 481.1831. Found
481.1832.
Isopropyl
3-(tert-Butoxycarbonylamino)-2-methyl-N-(4-
nitrophenylsulfonyl)-3-phenylpropionimidate (syn-9bh): Mp
156-157 °C; 1H NMR (C6D6): ¤ 7.65-7.63 (d, 2H, J = 9.2 Hz),
7.55-7.53 (d, 2H, J = 9.2 Hz), 7.42-7.41 (d, 2H, J = 7.2 Hz),
7.15-7.11 (m, 2H), 7.00-6.98 (t, 1H, J = 7.2 Hz), 5.27-5.22 (t, 1H,
J = 10.3 Hz), 4.46-4.42 (m, 1H), 4.22-4.17 (d, 1H, J = 10.3 Hz),
4.16-4.11 (m, 1H), 1.51-1.50 (d, 3H, J = 6.3 Hz), 1.39 (s, 9H),
0.73-0.72 (d, 3H, J = 6.3 Hz), 0.49-0.47 (d, 3H, J = 6.3 Hz);
13C NMR (C6D6): ¤ 176.5, 155.3, 149.8, 147.7, 141.4, 128.9,
128.5, 128.3, 127.6, 123.9, 79.3, 72.6, 56.9, 45.1, 28.4, 20.6, 20.0,
Methyl
N-(Benzenesulfonyl)-3-(ethoxycarbonyl)-3-( p-
methoxyphenylamino)-2-methylpropionimidate (Major-9rc):
Mp 99-100 °C; 1H NMR (CDCl3): ¤ 8.09-8.04 (m, 2H), 7.02-
6.95 (m, 3H), 6.74-6.67 (m, 4H), 4.90 (d, 1H, J = 11.9 Hz), 4.56
(qd, 1H, J = 10.2, 6.8 Hz), 4.37 (t, 1H, J = 10.8 Hz), 3.93-3.78 (m,
2H), 3.29 (s, 3H), 3.08 (s, 3H), 1.29 (d, 3H, J = 6.2 Hz), 0.82 (t, 3H,
J = 7.1 Hz); 13C NMR (CDCl3): ¤ 176.5, 171.8, 153.9, 142.8,
141.0, 132.4, 128.8, 127.0, 116.2, 115.1, 62.1, 61.1, 55.1, 42.6,
14.4, 14.1; IR (neat): 3055, 2986, 2953, 2836, 1735, 1607, 1514,
16.2; IR (neat): 3367, 2982, 2942, 1715, 1698, 1582, 1531, 1455,
¹1
1349, 1305, 1160, 1081, 1010, 907, 855, 746, 701, 657, 607 cm
;
HRMS (DART): Exact mass calcd for C24H32N3O7S [M + H]+,
506.1960. Found 506.1959.
Isopropyl 3-(tert-Butoxycarbonylamino)-3-(4-methoxyphen-
1457, 1447, 1421, 1305, 1265, 1242, 1191, 1156, 1092, 1034, 953,
yl)-2-methyl-N-(4-nitrophenylsulfonyl)propionimidate
(syn-
¹1
896, 825, 737, 705, 624, 603, 527, 451, 419 cm
Methyl
.
9dh): Mp 164-165 °C; 1H NMR (C6D6): ¤ 7.68-7.66 (d, 2H,
J = 9.2 Hz), 7.57-7.56 (d, 2H, J = 9.2 Hz), 7.37-7.35 (d, 2H,
J = 8.9 Hz), 6.76-6.74 (d, 2H, J = 8.9 Hz), 5.23-5.18 (t, 1H,
J = 10.3 Hz), 4.50-4.45 (m, 1H), 4.30-4.28 (d, 1H, J = 10.3 Hz),
4.18-4.12 (m, 1H), 3.23 (s, 3H), 1.55-1.53 (d, 3H, J = 6.9 Hz),
1.41 (s, 9H), 0.76-0.75 (d, 3H, J = 6.3 Hz), 0.56-0.55 (d, 3H,
J = 6.3 Hz); 13C NMR (C6D6): ¤ 176.8, 159.9, 155.6, 150.0, 148.0,
133.6, 129.3, 128.5, 128.4, 128.2, 127.9, 124.1, 114.4, 79.3, 72.6,
56.5, 54.9, 45.4, 28.6, 20.8, 20.4, 16.3; IR (neat): 3370, 3104,
2980, 2936, 2837, 1712, 1698, 1583, 1531, 1513, 1456, 1349,
1304, 1246, 1160, 1092, 1036, 1010, 983, 907, 879, 855, 833,
746 cm¹1; HRMS (DART): Exact mass calcd for C25H34N3O8S
[M + H]+, 536.2066. Found 536.2042.
N-(Benzenesulfonyl)-3-(ethoxycarbonyl)-3-( p-
methoxyphenylamino)-2-methylpropionimidate (Minor-9rc):
1H NMR (CDCl3): ¤ 8.14-8.05 (m, 2H), 7.05-6.95 (m, 3H), 6.74
(d, 2H, J = 9.1 Hz), 6.62 (d, 2H, J = 9.1 Hz), 4.50 (t, 1H, J =
9.4 Hz), 4.40 (qd, 1H, J = 9.0, 6.8 Hz), 4.07-3.92 (m, 2H), 3.84 (d,
1H, J = 10.2 Hz), 3.35 (s, 3H), 3.21 (s, 3H), 1.35 (d, 3H, J = 8.0
Hz), 0.94 (t, 3H, J = 7.1 Hz); 13C NMR (CDCl3): ¤ 176.3, 171.7,
143.1, 141.6, 132.3, 128.8, 127.2, 115.9, 115.1, 61.5, 60.7, 55.2,
55.0, 42.9, 14.8, 14.1; IR (neat): 3063, 3033, 2984, 2951, 2907,
2834, 1735, 1608, 1511, 1446, 1369, 1306, 1241, 1198, 1156,
1092, 1077, 1060, 1027, 953, 852, 824, 758, 734, 690, 624,
¹1
587, 519, 446, 418 cm
.
Isopropyl anti-2-Methyl-3-phenyl-N-(2,5-xylylsulfonyl)-3-
(2,5-xylylsulfonylamino)propionimidate (anti-9sc): Mp 99-
Isopropyl 3-(tert-Butoxycarbonylamino)-3-(4-fluorophenyl)-
2-methyl-N-(4-nitrophenylsulfonyl)propionimidate (syn-9eh):
Mp 189-190 °C; 1H NMR (C6D6): ¤ 7.65-7.63 (d, 2H, J = 8.9
Hz), 7.56-7.53 (d, 2H, J = 8.9 Hz), 7.27-7.24 (m, 2H), 6.81-6.78
(t, 2H, J = 8.6 Hz), 5.17-5.13 (t, 1H, J = 9.8 Hz), 4.43-4.39 (m,
1H), 4.15-4.13 (d, 1H, J = 9.8 Hz), 4.05-3.99 (m, 1H), 1.47-1.46
(d, 3H, J = 6.3 Hz), 1.40 (s, 9H), 0.72-0.71 (d, 3H, J = 6.3 Hz),
0.47-0.45 (d, 3H, J = 6.3 Hz); 13C NMR (C6D6): ¤ 176.7, 164.3,
162.3, 155.9, 150.5, 148.2, 137.6, 130.3, 129.1, 128.7, 128.5,
128.2, 124.5, 116.3, 116.1, 80.0, 73.2, 56.7, 45.7, 29.0, 21.1,
100 °C; 1H NMR (CDCl3): ¤ 8.23 (s, 1H), 7.39 (s, 1H), 7.12
(d, 1H, J = 9.1 Hz), 6.97-6.90 (m, 3H), 6.87 (dd, 1H, J = 7.6,
1.4 Hz), 6.73-6.65 (m, 3H), 6.53 (qd, 2H, J = 7.6, 1.4 Hz), 5.03
(quint, 1H, J = 6.2 Hz), 4.68 (dd, 1H, J = 11.0, 9.3 Hz), 4.48 (qd,
1H, J = 11.0, 6.5 Hz), 3.00 (s, 3H), 2.62 (s, 3H), 1.95 (s, 3H), 1.78
(s, 3H), 1.40 (d, 3H, J = 6.2 Hz), 0.96 (d, 3H, J = 6.2 Hz), 0.91 (d,
3H, J = 6.2 Hz); 13C NMR (CDCl3): ¤ 177.0, 140.1, 140.0, 138.0,
136.1, 135.2, 135.0, 133.6, 133.2, 132.6, 132.2, 131.9, 129.7,

1100 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
20.7, 16.4; IR (neat): 3366, 2981, 2834, 1698, 1599, 1583, 1532,
1510, 1456, 1349, 1302, 1225, 1159, 1091, 1011, 907, 838,
746 cm¹1; HRMS (DART): Exact mass calcd for C24H31N3O7SF
[M + H]+, 524.1867. Found 524.1867.
44.4, 28.6, 20.7, 20.5, 15.7; IR (neat): 3368, 3107, 2981, 1716,
1597, 1583, 1532, 1455, 1350, 1306, 1238, 1160, 1093, 1011, 945,
908, 884, 856, 746, 685 cm¹1; HRMS (DART): Exact mass calcd
for C22H30N3O8S [M + H]+, 496.1754. Found 496.1776.
Isopropyl
3-(tert-Butoxycarbonylamino)-2-methyl-N-(4-
Isopropyl
3-(tert-Butoxycarbonylamino)-2-methyl-N-(4-
(syn-9jh):
nitrophenylsulfonyl)-3-m-tolylpropionimidate (syn-9fh): Mp
143-144 °C; 1H NMR (C6D6): ¤ 7.66-7.63 (d, 2H, J = 8.9 Hz),
7.57-7.55 (d, 2H, J = 8.9 Hz), 7.27-7.23 (m, 2H), 7.09-7.06 (t,
1H, J = 7.6 Hz), 6.86-6.85 (d, 1H, J = 7.6 Hz), 5.24-5.20 (t, 1H,
J = 10.3 Hz), 4.47-4.42 (m, 1H), 4.31-4.24 (m, 1H), 4.16-4.12
(m, 1H), 2.16 (s, 3H), 1.54-1.53 (d, 3H, J = 6.3 Hz), 1.40 (s, 9H),
0.74-0.73 (d, 3H, J = 6.3 Hz), 0.52-0.51 (d, 3H, J = 6.3 Hz);
13C NMR (C6D6): ¤ 176.8, 155.7, 150.1, 148.2, 141.4, 138.7,
129.1, 128.7, 125.0, 125.5, 124.2, 79.5, 72.8, 52.2, 45.6, 28.8,
21.7, 20.9, 20.4, 16.4; IR (neat): 3367, 2980, 2935, 1698, 1594,
1583, 1531, 1455, 1349, 1305, 1242, 1159, 1090, 1010, 938, 907,
855, 745, 705, 685 cm¹1; HRMS (DART): Exact mass calcd for
C25H34N3O7S [M + H]+, 520.2117. Found 520.2093.
nitrophenylsulfonyl)-3-(2-thienyl)propionimidate
Mp 126-128 °C; 1H NMR (C6D6): ¤ 7.71-7.69 (d, 2H, J = 8.6
Hz), 7.58-7.55 (d, 2H, J = 8.6 Hz), 7.32-7.31 (d, 1H, J = 2.3 Hz),
6.73-6.70 (m, 2H), 5.53-5.49 (t, 1H, J = 10.3 Hz), 4.54-4.49 (m,
1H), 4.17-4.08 (m, 2H), 1.50-1.49 (d, 3H, J = 6.9 Hz), 1.39 (s,
9H), 0.74-0.73 (d, 3H, J = 6.3 Hz), 0.58-0.57 (d, 3H, J = 6.3 Hz);
13C NMR (C6D6): ¤ 176.5, 155.4, 150.1, 147.9, 144.7, 127.9,
127.3, 125.1, 124.1, 79.6, 72.9, 51.6, 45.9, 28.6, 20.7, 20.2, 16.3;
IR (neat): 3373, 2981, 1714, 1697, 1594, 1582, 1531, 1349, 1306,
1159, 1092, 1010, 908, 855, 745, 657 cm¹1; HRMS (DART):
Exact mass calcd for C22H30N3O7S2 [M + H]+, 512.1525. Found
512.1509.
Isopropyl
3-(tert-Butoxycarbonylamino)-2-methyl-N-(4-
Isopropyl
3-(tert-Butoxycarbonylamino)-2-methyl-N-(4-
(syn-9gh):
nitrophenylsulfonyl)-3-(3-pyridyl)propionimidate (syn-9kh):
Mp 175-177 °C; H NMR (C6D6): ¤ 8.91 (s, 1H), 8.42-8.41 (d,
1
nitrophenylsulfonyl)-3-o-tolylpropionimidate
23
1
½¡ꢀD +72.6 (57% ee, c 0.975, CHCl3); Mp 120-121 °C; H NMR
(C6D6): ¤ 7.69-7.68 (d, 2H, J = 8.6 Hz), 7.61-7.60 (d, 1H, J =
7.8 Hz), 7.56-7.55 (d, 2H, J = 8.6 Hz), 7.23-7.20 (m, 1H), 6.98-
6.95 (t, 1H, J = 7.8 Hz), 6.91-6.90 (d, 1H, J = 7.8 Hz), 5.45-5.41
(t, 1H, J = 10.3 Hz), 4.40-4.35 (m, 1H), 4.25-4.19 (m, 1H), 4.04-
4.01 (d, 1H, J = 10.3 Hz), 2.47 (s, 3H), 1.67-1.66 (d, 3H, J =
6.9 Hz), 1.40 (s, 9H), 0.69-0.68 (d, 3H, J = 6.3 Hz), 0.33-0.31 (d,
3H, J = 6.3 Hz); 13C NMR (C6D6): ¤ 176.8, 155.7, 150.0, 148.0,
140.0, 137.1, 131.0, 127.8, 127.1, 126.5, 124.1, 79.3, 72.5, 52.4,
45.3, 28.5, 20.8, 20.1, 19.8, 16.9; IR (neat): 3369, 2979, 2933,
1714, 1699, 1594, 1583, 1531, 1456, 1349, 1304, 1159, 1089,
1011, 907, 855, 745, 657 cm¹1; HRMS (DART): Exact mass
calcd for C25H34N3O7S [M + H]+, 520.2117. Found 520.2099.
Chiral HPLC; Daicel Chiralcel OD-H; hexane/iPrOH = 9/1, flow
rate = 0.3 mL min¹1: tR = 24.6 min (Minor enantiomer obtained
from R,R ligand), tR = 33.9 min (Major enantiomer obtained from
R,R ligand). The absolute configuration of the major product has
not been determined.
1H, J = 4.0 Hz), 7.64-7.54 (m, 5H), 6.80 (brs, 1H), 5.19-5.15 (t,
1H, J = 10.3 Hz), 4.41-4.36 (m, 2H), 4.12-4.08 (m, 1H), 1.46-
1.44 (d, 3H, J = 6.9 Hz), 1.37 (s, 9H), 0.70-0.68 (d, 3H, J = 6.3
Hz), 0.49-0.48 (d, 3H, J = 6.3 Hz); 13C NMR (CDCl3): ¤ 175.5,
155.0, 149.8, 149.2, 147.1, 135.8, 134.5, 127.9, 127.7, 127.5,
124.0, 123.5, 80.2, 73.3, 54.4, 44.6, 28.2, 20.8, 15.4; IR (neat):
3364, 3213, 2981, 2928, 1712, 1597, 1583, 1531, 1349, 1305,
1160, 1091, 1010, 906, 855, 746, 715, 684 cm¹1; HRMS (DART):
Exact mass calcd for C23H31N4O7S [M + H]+, 507.1913. Found
507.1932.
Isopropyl 2-Methyl-N-(4-nitrophenylsulfonyl)-3-phenyl-3-
( p-toluenesulfonylamino)propionimidate (syn-9ch): Mp 159-
1
160 °C; H NMR (C6D6): ¤ 7.99-7.97 (d, 2H, J = 9.2 Hz), 7.63-
7.61 (d, 2H, J = 9.2 Hz), 7.38-7.36 (d, 2H, J = 8.0 Hz), 6.88-6.86
(d, 2H, J = 8.6 Hz), 6.79-6.71 (m, 4H), 6.44-6.42 (d, 2H, J =
8.6 Hz), 5.02-4.96 (m, 1H), 4.71-4.67 (t, 1H, J = 10.6 Hz), 4.21-
4.15 (m, 1H), 1.74 (s, 3H), 1.46-1.45 (d, 3H, J = 6.3 Hz), 1.02-
1.01 (d, 3H, J = 6.3 Hz), 0.89-0.86 (d, 3H, J = 6.3 Hz); 13C NMR
(CDCl3): ¤ 177.1, 150.0, 147.0, 142.5, 137.7, 137.4, 128.9, 128.5,
128.0, 127.8, 127.1, 126.6, 124.2, 74.3, 61.7, 46.6, 29.7, 21.3, 21.1,
21.0, 14.7; IR (neat): 3289, 2983, 2922, 2853, 1594, 1583, 1531,
1456, 1349, 1301, 1160, 1090, 1057, 977, 909, 855, 812, 747,
701 cm¹1; HRMS (DART): Exact mass calcd for C26H30N3O7S2
[M + H]+, 560.1525. Found 560.1550.
Isopropyl
3-(tert-Butoxycarbonylamino)-2-methyl-N-(4-
(syn-
nitrophenylsulfonyl)-3-(3-vinylphenyl)propionimidate
1
9hh): Mp 117-118 °C; H NMR (C6D6): ¤ 7.66-7.60 (m, 3H),
7.57-7.52 (m, 2H), 7.32-7.27 (m, 1H), 7.10-7.05 (m, 2H), 6.65
(dd, 1H, J = 10.8, 17.6 Hz), 5.84 (d, 1H, J = 17.6 Hz), 5.23 (t, 1H,
J = 10.2 Hz), 5.16 (d, 1H, J = 10.2 Hz), 4.40 (quintet, 1H, J =
6.2 Hz), 4.25-4.10 (m, 2H), 1.55 (d, 3H, J = 6.2 Hz), 1.39 (s, 9H),
0.71 (d, 3H, J = 6.2 Hz), 0.50-0.42 (m, 3H); 13C NMR (C6D6): ¤
176.6, 155.6, 150.0, 147.9, 141.8, 138.6, 137.2, 129.3, 128.7,
128.5, 127.8, 126.4, 125.8, 124.1, 114.7, 79.4, 72.7, 57.1, 28.6,
20.8, 20.2, 16.4; IR (neat): 3734, 3367, 2980, 2938, 1717, 1698,
1594, 1582, 1531, 1455, 1349, 1304, 1159, 1090, 1010, 907,
855, 745, 684 cm¹1; HRMS (DART): Exact mass calcd for
C26H34N3O7S [M + H]+, 532.2117. Found 532.2093.
Isopropyl
3-(tert-Butoxycarbonylamino)-3-cyclopropyl-2-
(syn-9nh):
methyl-N-(4-nitrophenylsulfonyl)propionimidate
Mp 112-113 °C; 1H NMR (C6D6): ¤ 7.82-7.80 (d, 2H, J = 8.6
Hz), 7.65-7.62 (d, 2H, J = 8.6 Hz), 4.74-4.66 (m, 1H), 4.05-4.03
(d, 1H, J = 9.8 Hz), 3.84-3.80 (m, 1H), 3.62-3.57 (m, 1H), 1.43 (s,
9H), 1.25-1.24 (d, 3H, J = 6.9 Hz), 1.00-0.90 (m, 1H), 0.90-0.89
(d, 3H, J = 6.3 Hz), 0.84-0.82 (d, 3H, J = 6.3 Hz), 0.51-0.44 (m,
1H), 0.44-0.37 (m, 2H), 0.36-0.32 (m, 1H); 13C NMR (C6D6): ¤
177.7, 156.3, 150.2, 148.4, 128.8, 128.1, 124.3, 79.1, 73.0, 57.2,
46.6, 28.8, 21.1, 16.5, 15.1, 6.1, 3.2; IR (neat): 3382, 2981, 2933,
1715, 1698, 1582, 1531, 1456, 1349, 1302, 1251, 1159, 1093,
1013, 908, 855, 746, 685 cm¹1; HRMS (DART): Exact mass calcd
for C21H32N3O7S [M + H]+, 470.1961. Found 470.1960.
Isopropyl 3-(tert-Butoxycarbonylamino)-3-(2-furyl)-2-meth-
yl-N-(4-nitrophenylsulfonyl)propionimidate (syn-9ih):
Mp
110-111 °C; 1H NMR (C6D6): ¤ 7.75-7.72 (d, 2H, J = 9.2 Hz),
7.62-7.60 (d, 1H, J = 9.2 Hz), 6.99-6.98 (d, 1H, J = 2.9 Hz),
6.53-6.52 (d, 1H, J = 2.9 Hz), 6.02-6.01 (d, 1H, J = 2.9 Hz),
5.48-5.44 (t, 1H, J = 10.3 Hz), 4.61-4.56 (m, 1H), 4.23-4.21 (d,
2H, J = 10.3 Hz), 4.11-4.05 (m, 1H), 1.49-1.47 (d, 3H, J = 6.9
Hz), 1.40 (s, 9H), 0.76-0.74 (d, 3H, J = 6.3 Hz), 0.65-0.64 (d, 3H,
J = 6.3 Hz); 13C NMR (C6D6): ¤ 176.6, 155.6, 154.3, 150.1, 148.0,
142.3, 128.5, 127.9, 124.2, 110.7, 107.3, 100.5, 79.6, 72.9, 50.5,
Isopropyl 2-[(tert-Butoxycarbonylamino)phenylmethyl]-N-
(4-nitrophenylsulfonyl)butanimidate (syn-9bi):
Mp 156-
1
157 °C; H NMR (C6D6): ¤ 7.60-7.54 (m, 4H), 7.40-7.38 (d, 2H,
J = 7.7 Hz), 7.11-7.08 (t, 2H, J = 7.7 Hz), 6.99-6.96 (t, 1H, J =
7.7 Hz), 5.34-5.30 (t, 1H, J = 9.7 Hz), 4.52-4.48 (m, 2H), 4.20-

R. Matsubara et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) 1101
anti-N-(Benzenesulfonyl)-3-(tert-butoxycarbonyl-
4.16 (m, 1H), 1.98 (brs, 1H), 1.78 (brs, 1H), 1.39 (s, 9H), 1.10-
1.07 (t, 3H, J = 7.2 Hz), 0.79-0.78 (d, 3H, J = 6.3 Hz), 0.57-
0.55 (d, 3H, J = 6.3 Hz); 13C NMR (C6D6): ¤ 174.9, 155.3, 149.8,
147.8, 141.2, 128.8, 128.3, 127.6, 123.9, 79.4, 72.5, 56.2, 51.0,
28.4, 23.6, 20.9, 20.4, 11.4; IR (neat): 3373, 2977, 2938, 1712,
1698, 1597, 1583, 1531, 1456, 1364, 1349, 1305, 1254, 1160,
1088, 1013, 911, 855, 745, 701 cm¹1; HRMS (DART): Exact mass
calcd for C25H34N3O7S [M + H]+, 520.2117. Found 520.2139.
Methyl
amino)-2-methyl-3-phenylpropionimidate (9ba):
Mp 99-
100 °C; 1H NMR (CDCl3): ¤ 8.01 (d, 2H, J = 7.4 Hz), 7.59 (t,
1H, J = 7.4 Hz), 7.53 (t, 2H, J = 7.7 Hz), 7.35-7.25 (m, 5H), 6.01
(d, 1H, J = 9.6 Hz), 4.75 (t, 1H, J = 10.2 Hz), 4.07-3.96 (m, 1H),
3.75 (s, 3H), 1.35 (s, 9H), 1.03 (d, 3H, J = 6.8 Hz); 13C NMR
(CDCl3): ¤ 177.6, 154.6, 141.8, 140.2, 132.6, 128.7, 128.7, 127.8,
127.1, 126.5, 79.2, 58.2, 55.5, 45.1, 28.2, 14.8; IR (neat): 3381,
2977, 1716, 1602, 1508, 1455, 1392, 1365, 1304, 1246, 1154,
1090, 1057, 1002, 950, 881, 757, 734, 700, 688, 623 cm¹1; HRMS
(FAB): Exact mass calcd for C22H29N2O5S [M + H]+, 433.1797.
Found 433.1811.
Isopropyl
3-(tert-Butoxycarbonylamino)-3-cyclohexyl-2-
(syn-9th):
methyl-N-(4-nitrophenylsulfonyl)propionimidate
Mp 191-192 °C; 1H NMR (C6D6): ¤ 7.78 (d, 2H, J = 8.2 Hz),
7.59 (d, 2H, J = 8.9 Hz), 4.71 (quintet, 1H, J = 6.2 Hz), 4.27-4.20
(m, 1H), 3.94 (d, 1H, J = 11.0 Hz), 3.80-3.75 (m, 1H), 1.95 (d,
1H, J = 12.4 Hz), 1.78 (d, 1H, J = 13.7 Hz), 1.75-1.65 (m, 2H),
1.55 (d, 1H, J = 13.7 Hz), 1.45 (s, 9H), 1.40-1.32 (m, 1H), 1.26 (d,
3H, J = 6.9 Hz), 1.30-1.20 (m, 1H), 1.20-1.10 (m, 1H), 1.05-0.95
(m, 1H), 0.91 (d, 3H, J = 6.2 Hz), 0.90-0.87 (m, 1H), 0.82 (d, 3H,
J = 6.2 Hz), 0.79-0.71 (m, 1H); 13C NMR (C6D6): ¤ 178.2, 156.7,
150.4, 148.4, 129.2, 128.5, 128.3, 124.5, 79.3, 73.0, 59.0, 57.4,
43.2, 42.1, 31.9, 29.1, 27.6, 27.4, 27.2, 27.0, 21.2, 15.1; IR (neat):
3389, 2977, 2928, 2847, 1715, 1698, 1578, 1531, 1455, 1349,
1301, 1159, 1093, 992, 908, 855, 746, 684, 658 cm¹1; HRMS
(DART): Exact mass calcd for C24H38N3O7S [M + H]+, 512.2430.
Found 512.2422.
tert-Butyl anti-2-(Methoxycarbonyl)-1-phenylpropylcarba-
1
mate (18): Mp 89-90 °C; H NMR (CDCl3): ¤ 7.34-7.28 (m,
2H), 7.27-7.20 (m, 3H), 5.78 (s, 1H), 4.83 (s, 1H), 3.58 (s, 3H),
2.92 (s, 1H), 1.42 (s, 9H), 1.23 (d, 3H, J = 6.2 Hz); 13C NMR
(CDCl3): ¤ 175.3, 155.4, 127.3, 126.6, 126.2, 79.4, 51.6, 45.2,
28.3, 15.3; IR (neat): 3428, 3360, 2977, 2356, 1716, 1497, 1455,
1434, 1365, 1289, 1245, 1168, 1085, 1051, 1005, 879, 756, 701,
585 cm¹1; HRMS (FAB): Exact mass calcd for C16H24NO4
[M + H]+, 294.1705. Found 294.1696.
Procedure for Red-Al Reduction of Sulfonylimidates 9bc
and 9cc to Aldehydes 19a and 19b. The procedure for the
conversion of 9bc to 19a is as follows. A solution of 9bc (100 mg,
0.205 mmol) in 2 mL of THF was cooled to ¹70 °C, and then Red-
Al (65% w/w toluene solution, 385 ¯L, 7.0 equiv) was added
slowly lest the temperature should increase. The mixture was
stirred at ¹70 °C for 18 h, and the reaction was quenched by
addition of MeOH (0.1 mL) at ¹70 °C. The mixture was stirred for
5 min at that temperature, and H2O was added. The temperature
was allowed to increase to rt, and AcOEt and a saturated aqueous
solution of NH4Cl were added. After filtration, the obtained
filtrate was extracted with AcOEt three times, and the organics
were dried over anhydrous Na2SO4. Filtration and removal of
solvents afforded the crude product. Purification of the crude
product was conducted by chromatography on neutral SiO2, to
afford the aldehyde 19a (46.9 mg, 87% yield). Aldehyde 19b was
obtained by following the same procedure mentioned above (83%
yield).
Procedure for the Conversion of Sulfonylimidate 9cc to
Compound 17. To sulfonylimidate 9cc (50 mg, 0.092 mmol)
were added a mixture of isopropanol and H2O (95/5, 0.5 mL) and
concentrated H2SO4 (66 mg, ca. 7.0 equiv). The reaction mixture
was stirred at 80 °C for 40 min. TLC analysis revealed that no
reaction had occurred, then the mixture was heated to 100 °C and
stirred for 3 h. After cooling to rt, the mixture was diluted by
addition of CH2Cl2. A saturated aqueous solution of NaHCO3 was
added, and the mixture was extracted with CH2Cl2 three times. The
organics were dried over anhydrous MgSO4. Filtration and
removal of solvents afforded compound 17 (46.1 mg, quant).
The obtained compound 17 was found to be pure by 1H NMR
spectroscopy analysis in DMSO-d6 (17 was very hard to dissolve
in any usual organic solvents except polar solvents such as
DMSO).
anti-2-Methyl-3-phenyl-3-( p-toluenesulfonylamino)-N-(2,5-
xylylsulfonyl)propionamide (17):
tert-Butyl anti-2-Formyl-1-phenylpropylcarbamate (19a):
Mp 82-83 °C; 1H NMR (CDCl3): ¤ 9.66 (d, 1H, J = 2.3 Hz),
7.37-7.22 (m, 5H), 5.28 (s, 1H), 4.78 (s, 1H), 2.81 (s, 1H), 1.39 (s,
9H), 1.02 (d, 3H, J = 6.8 Hz); 13C NMR (CDCl3): ¤ 203.3, 155.2,
139.9, 128.7, 127.7, 126.8, 79.9, 52.1, 28.2, 11.8; IR (neat): 3343,
2978, 2933, 2817, 2723, 1716, 1699, 1519, 1507, 1455, 1392,
1366, 1288, 1249, 1169, 1086, 1002, 755, 701 cm¹1; HRMS
(FAB): Exact mass calcd for C15H22NO3 [M + H]+, 264.1599.
Found 264.1606.
Mp 218-219 °C; 1H NMR
(DMSO-d6): ¤ 12.08 (s, 1H), 8.67 (d, 1H, J = 9.6 Hz), 7.76 (s,
1H), 7.37-7.33 (m, 1H), 7.25-7.20 (m, 3H), 7.03-6.87 (m, 7H),
4.41 (t, 1H, J = 9.9 Hz), 2.72-2.60 (m, 1H), 2.50 (s, 3H), 2.34 (s,
3H), 2.18 (s, 3H), 0.59 (d, 3H, J = 7.4 Hz); 13C NMR (DMSO-d6):
¤ 172.2, 141.5, 138.3, 137.0, 135.4, 134.0, 133.9, 132.2, 130.3,
128.6, 127.8, 126.8, 126.3, 58.9, 46.6, 20.8, 20.3, 19.1, 14.7; IR
(neat): 3251, 3063, 3032, 2979, 2926, 2878, 1693, 1655, 1647,
1638, 1617, 1599, 1560, 1542, 1493, 1457, 1382, 1341, 1288,
1223, 1201, 1163, 1123, 1087, 1062, 898, 849, 815, 766, 702,
667 cm¹1; HRMS (FAB): Exact mass calcd for C25H29N2O5S2
[M + H]+, 501.1518. Found 501.1538.
Procedure for the Conversion of Sulfonylimidate 9ba to
Ester 18. To sulfonylimidate 9ba (82.3 mg, 0190 mmol) were
added a mixture of DMF and H2O (95/5, 0.38 mL), and a solution
of DBU in DMF (10 mol %, 30 ¯L). The mixture was stirred at rt
for 33 h, and then diluted by addition of Et2O. The mixture was
washed with water 3 times, then dried over anhydrous Na2SO4.
Filtration and removal of solvents afforded the crude product.
Purification of the crude product was conducted by chromatog-
raphy on SiO2, to afford the desired ester 18 (50.4 mg, 90%
yield).
anti-2-Methyl-3-phenyl-3-(p-toluenesulfonylamino)propanal
1
(19b): Mp 137-138 °C; H NMR (CDCl3): ¤ 9.64 (d, 1H, J =
2.8 Hz), 7.47 (d, 2H, J = 7.9 Hz), 7.15-6.96 (m, 7H), 5.90 (d, 1H,
J = 8.5 Hz), 4.54 (t, 1H, J = 8.5 Hz), 2.84-2.75 (m, 1H), 2.30 (s,
3H), 0.96 (d, 3H, J = 6.8 Hz); 13C NMR (CDCl3): ¤ 203.2, 143.0,
137.8, 137.2, 129.2, 128.4, 127.6, 127.0, 127.0, 59.1, 51.9, 21.3,
11.8; IR (neat): 3268, 3068, 3030, 2972, 2926, 2872, 2727, 1724,
1598, 1495, 1456, 1325, 1185, 1160, 1090, 1045, 914, 812, 761,
702, 670, 566, 547 cm¹1; HRMS (FAB): Exact mass calcd for
C17H20NSO3 [M + H]+, 318.1184. Found 318.1169.
Procedure for Direct Formation of Ester 21 from Benz-
aldehyde and Sulfonylimidate 8l. To a solution of benzaldehyde
(60.9 ¯L, 0.6 mmol) and DBU (18.3 mg, 0.12 mmol) in 0.2 mL of
DMF was added 2,5-xylylsulfonylamide (11.1 mg, 0.06 mmol). To

1102 Bull. Chem. Soc. Jpn. Vol. 82, No. 9 (2009) BCSJ AWARD ARTICLE
the mixture was slowly added over 32 h a solution of sulfonyl-
imidate 8l (183.8 mg, 0.72 mmol) in 1 mL of DMF. After
completion of slow addition, the mixture was stirred at rt for
further 46 h (total 78 h), and then diluted by addition of Et2O. The
mixture was washed with water 3 times, then dried over anhydrous
Na2SO4. Filtration and removal of solvents afforded the crude
product. Purification of the crude product was conducted by
chromatography on SiO2, to afford the desired ester 21 (dia-
stereomers mixture, 196.2 mg, 90% yield, anti/syn = 87/13).
Methyl anti-2-Methyl-3-phenyl-3-(2,5-xylylsulfonylamino)-
Shibasaki, J. Am. Chem. Soc. 2007, 129, 9588. c) H. Morimoto, T.
Yoshino, T. Yukawa, G. Lu, S. Matsunaga, M. Shibasaki, Angew.
Chem., Int. Ed. 2008, 47, 9125.
4
Kobayashi and co-workers used (N-Boc)acylanilides in
Barium-catalyzed aldol and Mannich-type reactions. a) S. Saito, S.
Kobayashi, J. Am. Chem. Soc. 2006, 128, 8704. b) S. Saito, T.
Tsubogo, S. Kobayashi, Chem. Commun. 2007, 1236.
5
a) R. Matsubara, F. Berthiol, S. Kobayashi, J. Am. Chem.
Soc. 2008, 130, 1804. b) S. B. J. Kan, R. Matsubara, F. Berthiol, S.
Kobayashi, Chem. Commun. 2008, 6354. c) R. Matsubara, S.
Kobayashi, Synthesis 2008, 3009. d) H. V. Nguyen, R. Matsubara,
S. Kobayashi, Angew. Chem., Int. Ed. 2009, 48, 5790.
1
propionate (21): Mp 116-117 °C; H NMR (CDCl3): ¤ 7.49 (s,
1H), 7.13-7.09 (m, 3H), 7.06 (d, 1H, J = 7.4 Hz), 7.02-6.93 (m,
3H), 6.03 (d, 1H, J = 8.5 Hz), 4.44 (t, 1H, J = 7.7 Hz), 3.60 (s,
3H), 2.90-2.80 (m, 1H), 2.47 (s, 3H), 2.20 (s, 3H), 1.09 (d, 3H,
J = 6.8 Hz); 13C NMR (CDCl3): ¤ 175.0, 138.7, 138.3, 135.6,
133.4, 132.8, 132.0, 129.5, 128.2, 127.6, 126.5, 60.4, 51.9, 45.8,
20.5, 19.7, 15.3; IR (neat): 3292, 2983, 2953, 2878, 1734, 1717,
1540, 1507, 1489, 1456, 1436, 1322, 1278, 1206, 1158, 1063, 916,
818, 766, 751, 701, 616, 594 cm¹1; HRMS (FAB): Exact mass
calcd for C19H24NSO4 [M + H]+, 362.1426. Found 362.1419.
Crystallographic data reported in this manuscript have been
deposited with Cambridge Crystallographic Data Centre as sup-
plementary publication no. CCDC-660388 (8a), -660391 (syn-
9aa), -660389 (anti-9bc), -660390 (anti-9cc), -660392 (syn-9cc),
-716446 (anti-9ch), -716444 (syn-9th), -716445 (syn-9bh), and
-660393 (21). Copies of the data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge, CB2
1EZ, U.K.; fax: +44 1223 336033; or deposit@ccdc.cam.ac.uk).
6
Sulfonylimidates are readily prepared. a) R. Kupfer, M.
Nagel, E.-U. Würthwein, R. Allmann, Chem. Ber. 1985, 118, 3089.
b) W. Walter, J. Krohn, Justus Liebigs Ann. Chem. 1973, 443.
c) E. J. Yoo, I. Bae, S. H. Cho, H. Han, S. Chang, Org. Lett. 2006,
8, 1347, and the references cited therein.
7
Low yields can be mainly ascribed to the evaporation of
volatile starting materials during bubbling of HCl gas.
8
9
F. G. Bordwell, Acc. Chem. Res. 1988, 21, 456.
a) G. Doddi, G. Ercolani, P. La Pegna, P. Mencarelli,
J. Chem. Soc., Chem. Commun. 1994, 1239. b) S. V. Bordawekar,
E. J. Doskocil, R. J. Davies, Catal. Lett. 1997, 44, 193. c) D. A.
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Supporting Information
Kinetic study. This material is available free of charge on the
web at http://www.csj.jp/journals/bcsj/.
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