Non-enzymatic geometry-selective acylation of tri- and tetrasubstituted α,α'-alkenediols

Article abstract of DOI:10.1002/adsc.201200242

A highly geometry-selective organocatalytic acylation of tri- and tetra-substituted 2-alkylidene-1,3-propanediols has been developed. The highly E-selective acylation of various tetrasubstituted 2-alkylidene-1,3-propanediols was achieved in 96 to >99% selectivity for the first time by a non-enzymatic protocol. Copyright

Full text of DOI:10.1002/adsc.201200242

FULL PAPERS
DOI: 10.1002/adsc.201200242
Non-Enzymatic Geometry-Selective Acylation of Tri- and
Tetrasubstituted a,a’-Alkenediols
Keisuke Yoshida,a Kenji Mishiro,a Yoshihiro Ueda,a Takashi Shigeta,a
Takumi Furuta,a and Takeo Kawabataa,*
a
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
Fax : (+81)-774-38-3197; phone: (+81)-774-38-3190; e-mail: kawabata@scl.kyoto-u.ac.jp
Received: March 22, 2012; Revised: August 8, 2012; Published online: November 13, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200242.
Abstract: A highly geometry-selective organocatalyt- >99% selectivity for the first time by a non-enzy-
ic acylation of tri- and tetra-substituted 2-alkylidene- matic protocol.
1,3-propanediols has been developed. The highly E-
selective acylation of various tetrasubstituted 2-alk- Keywords: acylation; geometry; molecular recogni-
ACHTUNGTRENNUNGylidene-1,3-propanediols was achieved in 96 to tion; organocatalysis; tetrasubstituted olefin
Introduction
was expected to be difficult due to the similar intrin-
sic reactivity of the two primary hydroxy groups.[4] In
The selective manipulation of one of multiple hydroxy accordance with the expectation, non-enzymatic
groups is a fundamental challenge in current organic methods for geometry-selective acylation of unsym-
synthesis.[1] We have developed the organocatalytic metrically trisubstituted 2-alkylidene-1,3-propanediols
regioselective acylation of glycopyranoses[2] and che- has never been reported, while the highly selective
moselective monoacylation of linear diols.[3] Preferen- enzymatic acylation of the diols and deacylation of
tial formation of a hydrogen bond between catalyst the corresponding diesters have been reported.[5] To
1 and the primary OH (circled) of the glycopyranoses the best of our knowledge, however, no methods in-
was proposed to be the origin of the high selectivity cluding enzymatic protocols for the differentiation of
(Figure 1). In this paper, we describe the geometry-se- primary hydroxy groups of tetrasubstituted 2-alkyli-
lective acylation of unsymmetrically substituted alke- dene-1,3-propanediols have been reported. Here we
nediols promoted by organocatalysts (Figure 1, A).
report the highly geometry-selective acylation of tri-
The differentiation of hydroxy groups of unsym- and tetrasubstituted 2-alkylidene-1,3-propanediols
metrically substituted 2-alkylidene-1,3-propanediols based on recognition of the the substrate structure by
artificial organocatalysts.[6,7]
Results and Discussion
We chose trisubstituted alkenediols 2 with a nitrogen
substitutent (Table 1) as the substrate for geometry-
selective acylation because versatile functional group
transformation of the monoacylate is possible as ex-
emplified in the case of a tetrasubstituted alkenediol
(Scheme 1). The NHX group of 2 was expected to
affect the regioselectivity by serving as a hydrogen
bond donor for the recognition by the catalyst
(Figure 1, A). The regiochemical profile for acylation
of 2 was investigated. Treatment of 2a (X=Boc) with
1.1 equiv. of isobutyric anhydride in the presence of
Figure 1. Regioselective acylation catalyzed by 1 and related
organocatalysts.
10 mol% of DMAP in CHCl3 at À408C for 24 h gave
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Table 1. Effects of catalysts and of nitrogen protecting groups on geometry selectivity of acylation of trisubstituted alkene-
diol 2.[a]
Entry
2
X
Cat.
R
Solvent
3 [%]
E-3:Z-3
4 [%]
Recovery [%]
[c]
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2a
2b
2c
2c
2c
2c
2d
Boc
COCF3
Ts
DMAP
DMAP
DMAP
DMAP
1
1
1
1
1
1
1
i-Pr
i-Pr
i-Pr
CH3
i-Pr
i-Pr
i-Pr
CH3
CH3
CH3
CH3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
DMF
37
20
47
56
52
51
52
80
71
50
85
18:82
14:86
20:80
48:52
71:29
42:58
63:37
84:16
76:24
50:50
88:12
26
40
29
14
14
26
18
12
12
15
8
–
–
[c]
20
30
13
23
30
8
17
35
7
Ns[d]
Boc
COCF3
Ts
Ts
Ts
9[b]
10[c]
11[d]
Ts
Ns[d]
CHCl3
[a]
Reactions were run at the substrate concentration of 0.01M.
Geometry was determined by NOE experiments (see the Supporting Information).
Not determined.
2-Nitrobenzenesulfonyl.
[b]
[c]
[d]
Scheme 1. Geometry-controlled synthesis of tetrasubstituted alkenes.
an 18:82 mixture of E-3a and Z-3a in 37% yield with [X=2-nitrobenzensulfonyl (Ns)[8]] (entry 11). The
concomitant formation of the diacylate 4a in 26% higher ratio of E-acylation was associated with the
yield (entry 1). Similarly, alkenediols 2b (X=COCF3) higher yield of monoacylation in the reactions cata-
and 2c (X=Ts) gave Z-3b and Z-3c as the major lyzed by 1 (entries 6–11), while Z-selective acylation
monoacylates in DMAP-catalyzed acylations (en- by DMAP catalysis gave only poor yields of the
tries 2 and 3). These results indicate that the Z-hy- mono
droxy group of 2a–2c has a higher intrinsic reactivity cant amounts of the diacylates (entries 1–3). These re-
than the E-hydroxy group. sults may indicate that E-acylation catalyzed by 1 pro-
On the other hand, the E-acylates were the major ceeds in an accelerative manner (see Table 4).[9]
monoacylates in the reactions of 2a and 2c with isobu- We then examined various catalysts 5–8 for regiose-
ACHTUNGTRENaNUNG cylates with concomitant formation of signifi-
tyric anhydride in the presence of catalyst 1 (entries 5 lective acylation of 2d (Table 2). Among the catalysts
and 7). Use of acetic anhydride instead of isobutyric examined, catalyst 7 gave the highest E-selectivity
anhydride resulted in the higher E-selectivity (E- (94:6) in the acetylation at À408C (entry 5). Further
3c:Z-3c=84:16) (entries 7 vs. 8). The highest E-selec- improved E-selectivity (95:5) as well as high yield for
tivity (88:12) was obtained in the acetylation of 2d monoacylation (95%) were obtained in the acylation
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Non-Enzymatic Geometry-Selective Acylation of Tri- and Tetrasubstituted a,a’-Alkenediols
Table 2. Screening of catalysts for geometry-selective acylation of trisubstituted alkenediol 2d.[a]
Entry
Cat.
Temp. [8C]
3d [%]
E-3d:Z-3d
4d [%]/Recovery [%]
1
2
3
4
5
6
7
8
DMAP
À40
À40
À40
À40
À40
À40
25
À60
À60
À60
À60
55
85
80
82
90
88
72
95
82
95
71
48:52
88:12
92:8
81:19
94:6
81:19
86:14
95:5
90:10
93:7
14/30
8/7
4/16
11/8
2/8
6/6
6/15
3/2
1
5
6
7
8
7
7
7
7
7
9[b]
10[c]
11[d]
5/10
8/~0
17/12
88:12
[a]
Reactions were run at the substrate concentration of 0.01M.
Isobutyric anhydride was used as an anhydride.
2c (X=Ts) was used as a substrate.
[b]
[c]
[d]
2e (X=Tf) was used as a substrate.
of 2d catalyzed by 7 at À608C (entry 8). Use of isobu- use of catalyst 7 (entries 2–6). Slightly lower, yet high
tyric anhydride resulted in a slight decrease in the re- E-selectivity (96:4) and acceptable yields of monoacy-
gioselectivity (E:Z=90:10, entry 9). Substrates 2c lation (73%) were obtained in the acetylation of 9g
(X=Ts) and 2e (X=Tf) were also examined under (R=Br) (entry 7). The high selectivity associated
the optimized conditions employed in entry 8. Acyla- with the high yield for monoacylation (entries 2–6)
tion of 2c and 2e in the presence of 7 gave the corrr- again indicates accelerative acylation.[3,9] On the other
sponding monoacylates in 93% and 88% E-selectivity, hand, regiorandom acylation (50:50) proceeded with
respectively (entries 10 and 11). Accordingly, Ns-sub- low yield (31–41%) of monoacylation in DMF (en-
stituted substrate, catalyst 7, and acetic anhydride tries 9 and 11). High E-selectivity (98:2) was main-
were found to be the proper choices for the E-selec- tained in the acylation of 9c in CHCl3:DMF=4:1
tive acylation.
with a relatively high mono/diacylation ratio (82/6)
The optimum conditions for E-selective acylation (entry 8). Similarly, highly E-selective acylation (98:2)
of trisubstituted alkenediols catalyzed by 7 were ap- took place in CHCl3:DMSO=4:1 with a moderate
plied to the acylation of tetrasubstituted alkenediols mono/diacylation ratio (69/8) (entry 10).
(Table 3).[10] A perfect E-selectivity (>99%) was ob-
Tetrasubstituted alkenemonool E-10d thus obtained
tained in acetylation of 9a (R=Me), albeit with only was readily transformed to highly functionalized al-
À
À
a moderate yield for monoacylation (52%) due to the kenes 12, 13, 14, and 15 via Mitsunobu C C, C O,
À
À
poor solubility of 9a in CHCl3 (entry 1). Uniformly C N bond formation, and oxidative C N bond for-
high E-selectivity (~98:2) and high yields of monoacy- mation, respectively (Scheme 1). Thus, an example of
lation products (93–98%) were observed in the acyla- the geometry-controlled synthesis of tetrasubstituted
tion of various tetrasubstituted alkenediols 9b–9f by
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Table 3. Geometry-selective acylation of tetrasubstituted alkenediols 9.[a]
Entry
R
9
10 [%]
E-10:Z-10[b]
11 [%]/Recovery [%]
1
2
3
4
5
6
Me
Et
Pr
C7H15
CH2CH2CH=CH2
CH2Ph
Br
Pr
Pr
9a
9b
9c
9d
9e
9f
9g
9c
9c
9d
9d
52
93
96
98
97
98
73
82
31
69
41
>99:<1
98:2
98:2
98:2
98:2
24/24
1/2
~0/3
~0/1
~0/3
~0/
15/12
6/~0
4/40
8/6
98:2
7[c]
8[e]
9[f]
10[g]
11[f]
96:4[d]
98:2
50:50
98:2
50:50
C7H15
C7H15
14/36
[a]
Reactions were run at the substrate concentration of 0.01M.
Geometry was determined by NOE experiments (see the Supporting Information).
CHCl3/THF (10:1) was used as a solvent.
[b]
[c]
[d]
E-10g and Z-10g (R=Br) indicate here that NHNs and OAc are at E- and Z-geometry to each other, respectively, al-
though this does not follow the nomenclature.
Run in CHCl3:DMF=4:1
Run in DMF.
[e]
[f]
[g]
Run in CHCl3:DMSO=4:1.
alkenes with four different substituents was demon- ing Z-methoxy derivative of 9d), and 9d/19 (the corre-
strated. sponding E-methoxy derivative of 9d) were per-
We then investigated the mechanistic aspects formed in the presence of the catalyst 7. A 1:1 mix-
toward the understanding the origins of the extremely ture of 9d and 16 was treated under the reaction
high E-selectivity of the acylation of tetrasubstituted conditions identical to those in Table 3 except for the
alkenediols catalyzed by 7. In order to estimate the amount of the anhydride (0.70 equiv. for the total
effects of NHNs of 9d on the regioselectivity of the amount of the alcohols=1.4 equiv. for each of the al-
acylation, the corresponding NMeNs derivative, 16, cohols) (entry 1). A mixture of monoacylates of 9d (E-
was treated under the conditions identical to those for 10d in 91% and Z-10d in 1%), a diacylate of 9d (11d
the acylation in Table 3 (Scheme 2).
in 3%), monoacylates of 16 (E-17 in 6% and Z-17 in
E-Acylation took place predominantly with much 4%), and a diacylate of 16 (1%) were obtained (yield
less selectivity (E-17:Z-17=64:36) compared to that based on each of the alcohols). Total yield of the acyla-
of 9d. This result indicates that NHNs of 9d plays an tion of 9d was 95% and that of 16 was 11%. The rela-
important role for achieving high geometry-selectivity tive rate of acylation between 9d and 16 was deter-
in the acylation catalyzed by 7.
mined to be 26 according to the equation shown in the
The kinetic aspects of the geometry-selective acyla- footnote [d] in Table 4.[11] Thus, the acidic hydrogen of
tion were investigated (Table 4). Competitive acyla- NHNs in 9d is expected to be responsible for the E-se-
tion reactions between 9d/16, 9d/18 (the correspond- lective acylation as well as accelerative monoacylation.
Scheme 2. Regiochemical profile of acylation of NMeNs derivative 16 catalyzed by 7.
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Non-Enzymatic Geometry-Selective Acylation of Tri- and Tetrasubstituted a,a’-Alkenediols
Table 4. Competitive acylation between 9d and 16, 18, or 19 in the presence of 7.[a]
Entry Competing Products
Acylates of 9d [%][b]/
Acylate(s) of the competing alcohol
[%][c]
Fast-
Relative
alcohol
[%]
reacting rate[d]
alcohol
1
16
E-10d (91), Z-10d (1), 11d (3)
E-17 (6), Z-17 (4), diacylate of 16
(1)
95/11
9d
26
2
3
18
19
E-10d (93), Z-10d (1), 11d (5)
acylate of 18 (5)
E-10d (92), Z-10d (1), 11d (3)
99/5
96/8
9d
9d
89
40
acylate of 19 (8)
[a]
[b]
[c]
Reactions were run at the substrate concentration of 0.01M.
Sum of the yields of the acylates of 9d (%).
Sum of the yields of the acylates of 16 for entry 1, and the yield (%) of the acylate of 18 and 19 for entries 2 and 3, re-
spectively.
k(fast-reacting
[d]
alcohol)/k(slow-reacting
alcohol)=ln{1Àconversion[1+
(AÀB)/
E
U
(AÀB)/
the yield (%) of the acylate of 18 and 19 for entries 2 and 3, respectively. Conversion was calculated based on the total
amount of two alcohols.
Formation of a hydrogen bond between the NHNs and of 7 on treatment of a 1:1 mixture of 9d and 18
the reactive intermediate (acylpyridinium) generated (entry 2). This suggests that the Z-OH of 9d affects
from catalyst 7 may be the possible origin of the ob- the accelerative acylation of the E-OH. On the other
served phenomena (Figure 2). Alkenediol 9d under- hand, the E-OH of 9d does not significantly affect the
went acylation 89 times faster than 18 in the presence acylation of the Z-OH, since net acylation of Z-OH
of 9d {4%=1% (Z-10d)+3% (11d)} was comparable
with acylation of Z-OH of 19 (8%) (entry 3). The rel-
ative rate of acylation between 18 and 19 was deter-
mined to be 4.8 (fast-reacting alcohol: 18) by an inde-
pendent experiment on the kinetic studies under
pseudo-first-order conditions using an excess amount
(10 equiv.) of acetic anhydride in the presence of 7 at
À608C. This suggests that the NHNs group is a direct-
ing group for E-acylation. In addition to the NHNs
directing group, another directing group (Z-OH) ap-
pears be necessary for almost exclusive E-selective
acylation. All of these results suggest that NHNs and
the Z-OH of 9 are critically involved in the E-acyla-
tion probably as hydrogen bond donors. The impor-
tance of the hydrogen-bonding interaction between
the catalyst and the substrate for selective acylation
was also suggested by the solvent effects (Table 3, en-
tries 3, 4 vs. 9, 11). Geometry selectivity was ham-
Figure 2. A hypothetical model for the geometry-selective
acylation catalyzed by 7.
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gested to serve as hydrogen bond donor in the selec-
tive acylation (Table 4, entry 2), conformer II was ex-
cluded as the reactive species for the acylation. On
the other hand, a stable conformer I (Figure 3, b)
without the hydrogen bond between SO2 and Z-OH
was assumed to be the species responsible for the se-
lective acylation, although conformer I was estimated
to be 3.7 kcalmolÀ1 less stable than the conformer II.
In conformer I, the distance between the nitrogen
atom of the NHNs group and the oxygen atom of the
reacting E-OH is 5.6 ꢁ, and that between the oxygen
atoms of the Z-OH and the reacting E-OH is 2.8 ꢁ.
The most stable conformer of the N-acetylpyridinium
ion of catalyst 7 was generated with AMBER* force
field using the GB/SA solvation model for chloroform
(Figure 3, a). The distance between the oxygen atom
of the amide carbonyl group and the carbon atom of
the reactive acetyl group is 7.5 ꢁ, and that between
the oxygen atom of the ester carbonyl group and the
carbon atom of the reactive acetyl group is 4.9 ꢁ.
These calculated distances between functional groups
roughly account for the proposed interaction between
Figure 3. Conformers of the N-acetylpyridinium ion of cata-
lyst 7 and the substrate 9a generated by MacroModel (V
9.0). (a) The most stable conformer of the N-acetyl pyridini-
um ion of 7. (b) The most stable conformer of 9a among the
conformers without the hydrogen bond between SO2 and Z-
OH. (c) The global minimum conformation of 9a.
pered (50: 50) in the acylation in DMF (entries 9 and the N-acetylpyridinium ion and the substrate shown
11). Surprisingly, high E-selectivity was still main- in Figure 2, if the typical hydrogen bond distance
tained in the acylation in CHCl3:DMF=4:1 and (2.7–3.0 ꢁ) is considered. This is merely a hypothetical
CHCl3:DMSO=4:1 (entries 8 and 10). These results understanding for the observed selectivity. Efforts for
imply that the hydrogen-bonding interaction between obtaining spectroscopic evidence for the substrate-cat-
the catalyst and the substrate is still working in such alyst interaction are currently underway in our labo-
solvents with relatively high polarity. The kinetic ratory.
study in Table 4 and the regiochemical results in
Scheme 2 suggest that the hydrogen-bonding interac-
tion between NHNs group and the Z-OH of the sub- Conclusions
strates and the catalyst might be responsible for the
selective and accelerative acylation. Based on this as- In conclusion, we have developed an organocatalytic
sumption, a hypothetical transition state model for method for the E-selective acylation of tri- and tetra-
the geometry-selective acylation is shown in Figure 2. substituted 2-alkylidene-1,3-propanediols. The highly
Since the hydrogen of the NHNs group is the most geometry-selective acylation of various tetrasubstitut-
acidic in the substrate, it would preferentially form ed 2-alkylidene-1,3-propanediols was achieved for the
a hydrogen bond with an amide carbonyl of the acyl- first time by a non-enzymatic protocol.
pyridinium ion.[12] As the result of the formation of
this hydrogen bond, the Z-OH of the substrate locates
itself near the ester carbonyl group of the catalyst,
and may form an additional hydrogen bond between
Experimental Section
them. The cooperative effect of the two hydrogen
bonds would fix the conformation of the substrate at
the transition state for acylation, where the E-OH is
General Procedure for Geometry-Selective
Acylations of Table 1, Table 2, and Table 3
in close proximity to the reactive carbonyl group, re- To a solution of diol substrate (20.0 mg, 1.0 equiv.), catalyst
(10 mol%) and 2,4,6-collidine (1.7 equiv.) in solvent (con-
centration of the substrate: 0.01M) was added acid anhy-
dride (1.03 equiv.) at the temperature indicated in Table 1,
Table 2, and Table 3. The resulting mixture was stirred at
the same temperature for 24 h. The reaction was quenched
with MeOH (10 mL), and the solvent was evaporated. The
residue was dissolved in AcOEt, washed with 1N HCl,
brine, dried over Na2SO4, filtered and concentrated under
vacuum. The crude compound was purified by preparative
TLC (SiO2, hexane:AcOEt=1:2) to afford the mono- and
sulting in the selective acylation of the E-OH.
To estimate the validity of the molecular assembly
shown in Figure 2, conformational analyses of sub-
strate 9a and the N-acetylpyridinium ion of catalyst 7
were performed (Figure 3) by a molecular modelling
search using MacroModel V 9.0. Conformer II
(Figure 3, c) was obtained as the most stable one by
a conformational search of 9a, in which the Z-OH
forms a hydrogen bond with the oxygen of SO2 of the
Ns group. Since the Z-OH of the substrate was sug- diacylates, and the recovered diol substrate. The E/Z ratio
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Non-Enzymatic Geometry-Selective Acylation of Tri- and Tetrasubstituted a,a’-Alkenediols
of the monoacylate was determined by the integration of
1H NMR.
5.9 Hz, 1H), 2.71 (d, J=5.4 Hz, 2H), 1.66 (s, 3H), 1.40–1.09
(m, 18H), 0.90 (t, J=7.2 Hz, 3H); 13C NMR (toluene-d8):
d=169.7, 164.8, 138.8, 134.2, 132.5, 131.5, 130.6, 130.0, 104.2,
62.4, 45.5, 44.2, 31.8, 30.9, 29.6, 29.1, 28.7, 27.8, 26.6, 25.3,
22.7, 13.9; IR (neat): n=3335, 2926, 2855, 1783, 1746,
1542 cmÀ1; MS (FAB): m/z (rel intensity)=591 (M+Na+,
8), 533 (10), 404 (5), 271 (8); HR-MS: m/z=591.1991, calcd.
for C26H36N2O10SNa (M+Na)+: 591.1988.
(E)-2-(Hydroxymethyl)-4-(2-nitrophenylsulfonamido)but-
2-enyl isobutyrate (E-3d): colorless oil. 1H NMR (CDCl3):
d=8.17–8.09 (m, 1H), 7.92–7.84 (m, 1H), 7.81–7.71 (m,
2H), 5.74 (s, 1H), 5.58 (t, J=6.4 Hz, 1H), 4.53 (s, 2H), 4.16
(s, 2H), 3.88 (t, J=6.4 Hz, 2H), 2.39 (s, 1H), 2.06 (s, 3H);
13C NMR (CDCl3): d=171.0, 147.9, 138.2, 133.9, 133.7,
132.9, 131.0, 126.1, 125.4, 65.8, 58.2, 40.5, 20.9; IR (KBr): n=
3525, 3333, 3099, 3023, 2937, 2889, 1731, 1593, 1540, 1366,
1340, 1239 cmÀ1; MS (FAB): m/z (rel intensity)=345 (M+
H+, 10); HR-MS (FAB): m/z=345.0773, calcd. for
C13H17N2O7S (M+H)+: 345.0757. The (E)-stereochemistry
was determined by differential NOE experiments as shown
in the Supporting Information.
(Z)-2-(Hydroxymethyl)-4-(2-nitrophenylsulfonamido)but-
2-enyl isobutyrate (Z-3d): colorless oil. 1H NMR (CDCl3):
d=8.10–8.03 (m, 1H), 7.84–7.77 (m, 1H), 7.73–7.65 (m,
2H), 5.61 (t, J=7.1 Hz, 2H), 4.55 (s, 2H), 3.99 (s, 2H), 3.82
(t, J=6.2 Hz, 2H), 2.05 (s, 1H), 1.99 (s, 3H); 13C NMR
(CDCl3): d=171.2, 147.9, 138.0, 133.8, 133.7, 132.9, 131.0,
125.7, 125.4, 64.4, 59.3, 40.6, 20.8; IR (KBr): n=3526, 3333,
3099, 3023, 2930, 1731, 1593, 1540, 1441, 1365, 1340, 1238,
1165 cmÀ1; MS (FAB): m/z (rel intensity)=345 (M+H+,
10), 327 (5); HR-MS (FAB): m/z=345.0755, calcd. for
C13H17N2O7S (M+H)+: 345.0757. The (Z)-stereochemistry
was determined by differential NOE experiments as shown
in the Supporting Information.
(E)-2-(Hydroxymethyl)-3-methyl-4-(2-nitro-phenylsulfon-
amido)but-2-enyl acetate (E-10a): colorless powder; mp 72–
758C. 1H NMR (CDCl3): d=8.15–8.08 (m, 1H), 7.90–7.84
(m, 1H), 7.79–7.73 (m, 2H), 5.82 (s, 1H), 4.64 (s, 2H), 4.17
(s, 2H), 3.82 (d, J=6.0 Hz, 2H), 2.47 (s, 1H), 2.07 (s, 3H),
1.79 (s, 3H); 13C NMR (CDCl3): d=171.5, 147.9, 135.8,
133.7, 133.7, 133.1, 132.8, 130.9, 125.4, 63.1 60.3, 45.9, 20.9,
17.1; IR (KBr): n=3488, 3220, 2927, 1737, 1543, 1440, 1429,
1381, 1362, 1334, 1295, 1237, 1157, 1031 cmÀ1; MS (FAB):
m/z (rel intensity)=381 (M+Na+, 10), 359 (M+H+, 5);
HRMS (FAB): m/z=359.0912, calcd. for C13H17N2O7S (M+
H)+: 345.0757. The (E)-stereochemistry was determined by
differential NOE experiments as shown in the Supporting
Information.
(E)-2-[(4-Bromo-2-chlorophenoxy)methyl]-3-[(2-nitrophe-
nylsulfonamido)methyl]dec-2-enyl acetate (13): colorless oil.
1H NMR (CDCl3): d=8.12–8.06 (m, 1H), 7.84–7.78 (m,
1H), 7.73–7.67 (m, 2H), 7.47 (d, J=1.8 Hz, 1H), 7.31 (dd,
J=8.7, 1.8 Hz, 1H), 6.79 (d, J=8.7 Hz, 1H), 5.47 (t, J=
6.0 Hz, 1H), 4.71 (s, 2H), 4.58 (s, 2H), 3.84 (d, J=6.4 Hz,
2H), 2.17 (t, J=6.9 Hz, 2H), 2.03 (s, 3H), 1.36–1.24 (m,
10H), 0.88 (t, J=6.9 Hz, 3H); 13C NMR (CDCl3): d=170.8,
153.3, 148.0, 142.2, 133.7, 133.4, 132.8, 132.7, 131.1, 130.6,
129.2, 125.3, 124.5, 115.7, 113.6, 67.0, 62.0, 44.0, 31.7, 31.0,
29.5, 29.1, 28.8, 22.6, 20.9, 14.1; IR (KBr): n=3335, 2927,
2856, 1733, 1717, 1541, 1473, 1362, 1241, 1167, 1125,
1025 cmÀ1; MS (FAB): m/z (rel intensity)=633 (M+H+, 2).
186 (5); HR-MS (FAB): m/z=633.0856, calcd. for
C26H3381Br35ClN2O7S (M+H)+: 633.0860.
(E)-2-{[N-(tert-Butoxycarbonyl)-2-nitrophenylsulfonami-
do]methyl}-3-[(2-nitrophenylsulfonamido]methyl)dec-2-enyl
acetate (14): colorless oil. 1H NMR (CDCl3): d=8.32–8.26
(m, 1H), 8.21–8.16 (m, 1H), 7.93–7.87 (m, 1H), 7.81–7.71
(m, 5H), 6.04 (t, J=6.2 Hz, 1H), 4.67 (s, 2H), 4.51 (s, 2H),
3.85 (d, J=6.0 Hz, 2H), 2.26 (t, J=7.8 Hz, 2H), 2.08 (s,
3H), 1.43–1.26 (m, 19H), 0.89 (t, J=7.2 Hz, 3H); 13C NMR
(CDCl3): d=171.1, 150.0, 148.0, 147.3, 141.3, 134.4, 133.9,
133.7, 133.5, 133.4, 132.8, 131.9, 130.9, 128.0, 125.5, 124.6,
86.1, 77.2, 61.0, 46.7, 43.4, 31.8, 31.0, 29.6, 29.1, 27.8, 22.6,
21.0, 14.1; IR (KBr): n=3336, 3100, 2931, 2858, 1748, 1733,
1716, 1557, 1541, 1472, 1457, 1362, 1223, 1123, 1046 cmÀ1
;
MS (FAB): m/z (rel intensity)=727 (M+H+, 5); HR-MS
(FAB): m/z=727.2300, calcd. for C31H43N4O12S2 (M+H)+:
727.2319.
Procedure for the Competitive Acylation of Table 4
A solution of diol 9d, the competing alcohol 16 or 18 or 19
(1.0 equiv.), catalyst 7 (10 mol% for the total amount of the
alcohols) and 2,4,6-collidine (1.7 equiv. for the total amount
of the alcohols) in CHCl3 (concentration of the substrate:
0.01M) was stirred at room temperature for 15 min. After
being cooled to À608C, acetic anhydride (0.70 equiv. of total
amount of the alcohols=1.4 equiv. for each of the alcohols)
was added and stirred at À608C for 24 h. The reaction was
quenched with MeOH (10 mL), and the solvent was evapo-
rated. The residue was dissolved in AcOEt, washed with 1N
HCl, brine, dried over Na2SO4, filtered and concentrated
under vacuum. The crude compound was purified by prepa-
rative TLC (SiO2, hexane:AcOEt=1:2) to afford the mono-
and diacylates of 9d and the competing alcohol. E/Z ratios
of 10d (monoacylate of 9d) and 17 (monoacylate of 16)
were determined by the integration of the 1H NMR spec-
trum.
Procedure for Mitsunobu Reactions in Scheme 1
To a solution of E-10d (20 mg, 0.05 mmol) in THF were
added the nucleophile (0.50 mmol), DIAD (0.15 mmol) and
PPh3 (0.15 mmol) at room temperature. After being stirred
for 1 h at room temperature, the solvent was evaporated
under vacuum to give a residue. The residue was purified by
preparative TLC on silica gel to give the corresponding Mit-
sunobu products. For the synthesis of 12, 13 and 14, Mel-
drumꢂs acid, 4-bromo-2-chlorophenol and NsNHBoc were
employed as nucleophiles to give 12 (yield: 19 mg, 66%), 13
(yield: 28 mg, 87%) and 14 (yield: 36 mg, quant.), respec-
tively.
(E)-2-[(2,2-Dimethyl-4,6-dioxo-1,3-dioxan-5-yl)methyl]-3-
[(2-nitrophenylsulfonamido)methyl]dec-2-enyl acetate (12):
colorless oil. 1H NMR (toluene-d8): d=7.82 (dd, J=7.8,
1.4 Hz, 1H), 6.91 (dd, J=7.8, 1.4 Hz, 1H), 6.73 (dt, J=7.8,
1.4 Hz, 1H), 6.58 (dt, J=7.8, 1.4 Hz, 1H), 5.99 (t, J=6.2 Hz,
1H), 4.59 (s, 2H), 3.77 (d, J=5.9 Hz, 2H), 3.73 (t, J=
Adv. Synth. Catal. 2012, 354, 3291 – 3298
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3297

Keisuke Yoshida et al.
FULL PAPERS
Y. Kawashima, N. Koyata, Y. Murakami, N. Imai, Tetra-
hedron 2008, 64, 9305–9308.
Acknowledgements
[6] For excellent recent reviews on (a) organocatalytic acyl
transfer reactions and (b) chiral DMAP-type catalysts,
see: a) C. E. Mꢃllen, P. R. Schreiner, Angew. Chem.
2011, 123, 6136–6167; Angew. Chem. Int. Ed. 2011, 50,
6012–6042; b) R. P. Wurtz, Chem. Rev. 2007, 107, 5570–
5595.
This work was supported by Grant-in-Aid for Scientific Re-
search (A) from Ministry of Education, Culture, Sports, Sci-
ence and Technology, Japan, and by Grant-in-Aid for JSPS
Fellows to K. M. and Y. U.
[7] Regioselective acylation of polyol derivatives via a mo-
lecular recognition process by peptite-based catalysts
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Adv. Synth. Catal. 2012, 354, 3291 – 3298