Highly regio- And stereoselective oxidative hydroacetoxylation of 1,2-allenylic sulfoxides via a different mechanism

Full text of DOI:10.1021/jo802755k

phosphine oxides,7 and butenolide-substituted allenes.8 In all
these reactions, the nature of the heteroatom or substituent in
the allenes determines the stereoselectivity of the reaction: the
reaction of sulfides or selenides affords Z-products while that
of sulfoxides, sulfones, or phosphine oxides affords E-products.
However, the reaction of heteroatom-substituted allenes with
HX has not been studied yet. In this paper we wish to disclose
our recent observation on the oxidative electrophilic hydroac-
etoxylation reaction of 1,2-allenyl sulfoxides with acetic acid
affording 1-sulfonyl-1-alken-3-yl acetates highly regio- and
stereoselectively.
Highly Regio- and Stereoselective Oxidative
Hydroacetoxylation of 1,2-Allenylic Sulfoxides via
a Different Mechanism
Chao Zhou, Zhao Fang, Chunling Fu,* and Shengming Ma*
Laboratory of Molecular Recognition and Synthesis,
Department of Chemistry, Zhejiang UniVersity, Hangzhou
310027, Zhejiang, People’s Republic of China
masm@mail.sioc.ac.cn
ReceiVed December 18, 2008
FIGURE 1. ORTEP representation of Z-3a.
A highly regio- and stereoselective oxidative hydroacetoxy-
lation of 1,2-allenylic sulfoxides affording 1-sulfonyl-1-
alken-3-yl acetates in moderate to good yields was developed.
Through the X-ray diffraction study, it was observed that
the reaction may proceed via a 5-membered cyclic interme-
diate and the -OAc attacks the chiral carbon atom, which is
different from what was observed in our previous study.
In the previous work of our group, we synthesized 1,2-allenyl
sulfones by the oxidation of 1,2-allenyl sulfides in HOAc with
H2O2 (eq 1).6c In one case, the oxidation of 1,2-butadienyl
sulfoxide 1a with H2O2 in HOAc afforded the expected 1,2-
butadienyl phenyl sulfone 2a in 50% yield. In addition,
3-acetoxy-1(Z)-butenyl phenyl sulfone Z-3a was also isolated
in 3% yield, unexpectedly. The structure of the product Z-3a
was confirmed by the X-ray diffraction study (Figure 1).9 By
analyzing the structure of Z-3a, it is obvious that it is the
oxidative hydroacetoxylation of the starting 1,2-allenyl sulfoxide
1a and the E-stereoselectivity observed is similar to what was
observed in the halohydroxylation of sulfoxides and
sulfones.4c,5i,6b Thus, we started to study this type of transforma-
tion with H+ as the electrophile and acetate anion as the
nucleophile.
Electrophilic additions of allenes1,2 are synthetically useful
in organic synthesis since two functionalities may be introduced
within one operation. The most extensively studied one is the
reaction of allenes with X2 (X ) Cl,3,4a Br,3b,4 I,4c,d,5 or IBr4a).
Recently, we have developed highly regio- and stereoselective
halohydroxylations of heteroatom substituted allenes, i.e., 1,2-
allenyl sulfides,5c,e,f selenides,5e,f sulfoxides,4c,5h,i sulfones,6a,b
* Corresponding author. Fax: (+86) 021-62609305.
(1) For reviews on the chemistry of allenes, see: (a) Zimmer, R.; Dinesh,
C. U.; Nandanan, E.; Khan, F. A. Chem. ReV. 2000, 100, 3067. (b) Marshall,
J. A. Chem. ReV. 2000, 100, 3163. (c) Hashmi, A. S. K. Angew. Chem., Int. Ed.
2000, 39, 3590. (d) Bates, R. W.; Satcharoen, V. Chem. Soc. ReV. 2002, 31, 12.
(e) Sydnes, L. K. Chem. ReV. 2003, 103, 1133. (f) Ma, S. Acc. Chem. Res. 2003,
36, 701. (g) Brandsma, L.; Nedolya, N. A. Synthesis 2004, 735. (h) Tius, M. A.
Acc. Chem. Res. 2003, 36, 284. (i) Wei, L.-L.; Xiong, H.; Hsung, R. P. Acc.
Chem. Res. 2003, 36, 773. (j) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001,
34, 535. (k) Wang, K. K. Chem. ReV. 1996, 96, 207. (l) Ma, S. Chem. ReV.
2005, 105, 2829. (m) Ma, S. Aldrichim. Acta 2007, 40, 91. (n) Methot, J. L.;
Roush, W. R. AdV. Synth. Catal. 2004, 346, 1035. (o) Ye, L.-W.; Zhou, J.; Tang,
Y. Chem. Soc. ReV. 2008, 37, 1140. (p) Brasholz, M.; Reissig, H.-U.; Zimmer,
R. Acc. Chem. Res. 2009, 42, 45.
No reaction was observed when water was used as the solvent
(entry 1, Table 1). Further study indicated that conducting the
reaction with different amounts of H2O2 (entries 2-5, Table 1)
or at different concentrations (entries 6-9, Table 1) can
obviously improve the yield of the allylic acetate Z-3a. mCPBA
(2) (a) Smadja, W. Chem. ReV. 1983, 83, 263. (b) Waters, W. L.; Linn, W. S.;
(5) (a) Georgoulis, C.; Smadja, W.; Valery, J. M. Synthesis 1981, 572. (b)
Coulomb, F.; Roumestant, M.-L.; Gore, J. Bull. Soc. Chim. Fr. 1973, 3352. (c)
Ma, S.; Hao, X.; Huang, X. Org. Lett. 2003, 5, 1217. (d) Ma, S.; Hao, X.; Huang,
X. Chem. Commun. 2003, 1082. (e) Ma, S.; Hao, X.; Meng, X.; Huang, X. J.
Org. Chem. 2004, 69, 5720. (f) Fu, C.; Chen, G.; Liu, X.; Ma, S. Tetrahedron
2005, 61, 7768. (g) Fu, C.; Ma, S. Eur. J. Org. Chem. 2005, 3942. (h) Fu, C.;
Huang, X.; Ma, S. Tetrahedron Lett. 2004, 45, 6063. (i) Ma, S.; Wei, Q.; Wang,
H. Org. Lett. 2000, 2, 3893. (j) Lu¨, B.; Jiang, X.; Fu, C.; Ma, S. J. Org. Chem.
2008, 74, 438. (k) Jiang, X.; Fu, C.; Ma, S. Chem. Eur. J. 2008, 31, 9656.
(6) (a) Zhou, C.; Fu, C.; Ma, S. Angew. Chem., Int. Ed. 2007, 46, 4379. (b)
Zhou, C.; Fu, C.; Ma, S. Tetrahedron 2007, 63, 7612. (c) Guo, H.; Ma, S.
Synthesis 2007, 17, 2731.
Caserio, M. C. J. Am. Chem. Soc. 1968, 90, 6741.
(3) (a) Mueller, W. H.; Butler, P. E.; Griesbaum, K. J. Org. Chem. 1967,
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W. H.; Berchet, G. J. J. Am. Chem. Soc. 1933, 55, 1628. (d) Poutsma, M. L. J.
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10.1021/jo802755k CCC: $40.75
Published on Web 03/05/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2887–2890 2887

TABLE 1. Oxidative Electrophilic Hydroacetoxylation Reaction of
1,2-Butadienyl Phenyl Sulfoxide 1a with H2O2 in HOAca
NMR yields
entry
[c] (mol/L)
H2O2 (equiv)
2a
Z-3a
1b
2
3
4
5
6
7
8
9
0.25
0.25
0.25
0.25
0.25
0.5
0.25
0.083
0.05
0.083
0.083
11
4.4
1.7
1.3
0.9
1.1
1.1
1.1
1.1
d
0
27
13
4
0
0
0
0
0
4
0
37
38
42
42
30
45
FIGURE 2. ORTEP representation of Z-3h.
ing 1,2-allenylsulfones. It should be noted that 3-phenyl-1,2-
butadienyl phenyl sulfoxide and 3-ethyl-1,2-pentadienyl phenyl
sulfoxide failed to afford the expected products.
56 (53c)
53
50
41
10
11
To study the mechanism, DOAc was used as the solvent, and
under the typical reaction conditions (1.1 equiv of H2O2 (30%),
100 °C, 17 h), 95% of D-incorporation was observed for the
olefinic proton in compound d-3m, namely D+ was connected
to the center carbon atom of the allene moiety in the starting
allene 1m (eq 2).
e
0
a The substrate 1a (0.5 mmol) was dissolved in a half-volume of
HOAc and heated to 100 °C, then a solution of H2O2 in the other
half-volume of HOAc was added dropwise with stirring. The resulting
mixture was heated at 100 °C for 17 h. b The reaction was carried out in
water. c Isolated yield. d mCPBA was used as the oxidant. e tBuOOH
was used as the oxidant.
TABLE 2. Oxidative Electrophilic Hydroacetoxylation Reaction of
1,2-Allenyl Sulfoxides 1 with H2O2 in HOAca
Further study indicated that when 1b was stirred for 15 h in
HOAc at 95 °C in the absence of H2O2, sulfinylallyl acetate 4b
was formed in 41% isolated yield (eq 3). However, when 1,2-
allenyl sulfone 2b was stirred in HOAc at 100 °C, no reaction
was observed with 2b being recovered in 46% yield (eq 4). On
the basis of these results, we reasoned that the reaction may
first undergo hydroacetoxylation, which was followed by
oxidation of the sulfoxide functionality.
isolated
yield of Z-3
entry
R1
R2
R3
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
CH3 (1a)
H (1b)
53 (Z-3a)
50 (Z-3b)
55 (Z-3c)
54 (Z-3d)
42 (Z-3e)
40 (Z-3f)
45 (Z-3g)
80 (Z-3h)
67 (Z-3i)
62 (Z-3j)
73 (Z-3k)
46 (Z-3l)
83 (Z-3m)
C2H5 (1c)
n-C4H9 (1d)
n-C5H11 (1e)
n-C6H13 (1f)
n-C7H15 (1g)
CH3 (1h)
H (1i)
H (1j)
Bn (1k)
CH3 (1l)
CH3 (1m)
C2H5
n-C4H9
allyl
n-C4H9
H
9
10
11
12
13
p-BrC6H4
p-BrC6H4
C2H5
To study the influence of the sulfoxide group on the
stereoselectivity of the electrophilic addition process, we
synthesized optically active substrate (R)-1l from (R)-3-butyn-
2-ol. Under the standard conditions, the reaction afforded the
expected product (S)-(Z)-3l in 41% yield. To determine the
a The reaction was conducted by dissolving the substrate 1a (0.5
mmol) in 3.0 mL of HOAc and heating to 100 °C. Then a solution of
H2O2 in 3.0 mL of HOAc was added dropwise with stirring.
and tBuOOH gave inferior results (entries 10 and 11, Table 1).
Finally it is observed that the best result was obtained when
the reaction of 1a (0.083 M in HOAc) with 1.1 equiv of H2O2
was conducted at 100 °C for 17 h affording Z-3a in 56% yield
(entry 8, Table 1).
(9) Crystal data for compound Z-3a: C12H14O4S, MW ) 254.29, monoclinic,
space group C2/c, final R indices [I > 2σ(I)], R1 ) 0.0462, wR2 ) 0.0768, R
indices (all data) R1 ) 0.0811, wR2 ) 0.0847, a ) 20.253(2) Å, b ) 7.9925(8)
Å, c ) 16.7147(18) Å, R ) 90°, ꢀ ) 109.567 (2)°, γ ) 90°, V ) 2525.8(5) Å3,
T ) 296(2) K, Z ) 8, reflections collected/unique 7232/2745 (Rint ) 0.0643),
number of observations [I > 2σ(I)] 1568, parameters 168. Supplementary
crystallographic data have been deposited at the Cambridge Crystallographic
Data Center, CCDC 707622.
(10) Crystal data for compound Z-3h: C14H18O4S, MW ) 282.34, monoclinic,
space group P2(1)/c, final R indices [I > 2σ(I)], R1 ) 0.0664, wR2 ) 0.1588, R
indices (all data) R1 ) 0.1147, wR2 ) 0.1824, a ) 8.3591(13) Å, b ) 23.949(4)
Å, c ) 8.0712(13) Å, R ) 90°, ꢀ ) 111.071(3)°, γ ) 90°, V ) 1507.7(4) Å3,
T ) 296(2) K, Z ) 4, reflections collected/unique 8774/3276 (Rint ) 0.1402),
number of observations [I > 2σ(I)] 1695, parameters 184. Supplementary
crystallographic data have been deposited at the Cambridge Crystallographic
Data Center, CCDC 707621.
It was found that the reaction is quite general. Different R1,
R2, and R3 can be introduced to the starting 1,2-allenyl sulfoxides
to afford differently substituted 3-acetoxy-1-alkenyl sulfones Z-3
in moderate to good yields (Table 2). The structure of these
products was further confirmed by the X-ray diffraction study
of Z-3h (Figure 2).10 The major byproducts are the correspond-
(7) Guo, H.; Qian, R.; Guo, Y.; Ma, S. J. Org. Chem. 2008, 73, 7934.
(8) Gu, Z.; Deng, Y.; Shu, W.; Ma, S. AdV. Synth. Catal. 2007, 349, 1653.
2888 J. Org. Chem. Vol. 74, No. 7, 2009

SCHEME 1. Synthesis of Optically Active Derivatives
(S)-(Z)-5l for the Determination of the Absolute
Configuration of (S)-(Z)-3la
SCHEME 2. Mechanism of the Oxidative
Hydroacetoxylation of 1,2-Allenyl Sulfoxidesa
a Reagents and conditions: (a) Et3N, CH2Cl2, -78 °C, 10 min then CH3I,
rt, 65%, 98.2% ee (referred to the axial chirality); (b) H2O2, HOAc, 95 °C,
17 h, 41%, 94.8% ee; (c) K2CO3, MeOH, -30 °C, 4 h, 61%, 93.3% ee; (d)
Et3N, DMAP, 4-nitrobenzoyl chloride, CH2Cl2, rt, 12 h, 82%, 92.4% ee.
a Referred to axial chirality.
SCHEME 3. Preparation of Optically Active
1-Sulfonyl-1-alken-3-yl Acetatesa
a Referred to axial chirality.
3-sulfonylallylic acetates highly regio- and stereoselectively. The
axial chirality can be transferred into the center chirality in the
final products highly efficiently. Due to the highly loaded
functionalities and the Z CdC bonds in the products, this
reaction may be useful in organic synthesis.
FIGURE 3. ORTEP representation of (S)-(Z)-5l.
absolute configuration of this product, it was hydrolyzed and
subsequently converted to its p-nitrobenzoate during which the
absolute configuration should remain unchanged (Scheme 1).11
The (S)-absolute configuration of this benzoate was then
established by the X-ray diffraction study (Figure 3).12 This
result is very different from what was observed in the halohy-
droxylation of 1,2-allenyl sulfoxides and sulfones.4c,5i,7
On the basis of these results, we proposed a mechanism that
is shown as follows: First, electrophilic addition of the proton
with the relatively electron-rich carbon-carbon double bond
in (R)-1l followed by intramolecular attack of the sulfinyl oxygen
would afford the five-membered cyclic intermediate 6 determin-
ing the Z-selectivity in this addition reaction. SN2 attack of
CH3COO- at the allylic carbon atom instead of the sulfinyl
group we observed before4c,5i,7 results in the inversion of the
chiral center (Scheme 2). Oxidation of the sulfoxide functionality
by H2O2 forms the final product (S)-(Z)-3l.
General Experimental Methods
Proton nuclear magnetic resonance spectra (1H NMR) were
recorded on instruments operating at 300 or 400 MHz. 13C NMR
were recorded at 75 or 100 MHz. Deuteriochloroform (CDCl3) was
used as solvent in all NMR experiments. Chemical shifts (δ) are
given in parts per million (ppm). Infrared spectra were recorded
on a FT-IR spectrometer. Mass spectra were carried out in EI mode.
HRMS spectra were carried out in EI and MALDI mode. The
enantiomeric excesse values (ee) were determined by HPLC analysis
with chiral columns. Thin layer chromatography was performed
on precoated glass back plates and visualized with UV light at 254
nm. Flash column chromatography was performed on silica gel
(10-40 µm).
Synthesis of 4-(Phenylsulfonyl)but-3(Z)-en-2-yl acetate
(Z-3a): Typical Procedure. To a solution of 1a (88.7 mg, 0.5
mmol) in HOAc (3.0 mL) at 100 °C was added a solution of
freshly ordered H2O2 (30%, 57 µL, d ) 1.11 g/mL, 0.063 g,
0.56 mmol) in HOAc (3.0 mL) dropwise within 20 min. After
being stirred at 100 °C for 17 h as monitored by TLC, the
resulting mixture was quenched with 10 mL of an aqueous
saturated solution of NaHCO3, extracted with diethyl ether (15
mL × 3), washed with an aqueous saturated solution of NaHCO3,
and dried over anhydrous Na2SO4. After filtration and evapora-
tion, column chromatography on silica gel (petroleum ether/ethyl
acetate ) 5/1) afforded Z-3a (66.9 mg, 53%) as a solid, mp
88-89 °C (n-hexane/diethyl ether). 1H NMR (400 MHz, CDCl3)
δ 8.02-7.97 (m, 2 H), 7.65-7.59 (m, 1 H), 7.57-7.51 (m, 2
H), 6.44-6.36 (m, 1 H), 6.20-6.10 (m, 2 H), 2.01 (s, 3 H),
1.46 (d, J ) 6.4 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 170.2,
145.2, 140.2, 133.7, 129.2, 129.1, 127.6, 66.7, 20.9, 20.4; IR
(KBr) ν (cm-1) 3048, 3024, 2992, 2940, 1729, 1632, 1578, 1450,
1364, 1310, 1294, 1248, 1148, 1092, 1044; MS (70 eV, EI) m/z
(%) 254 (M+, 3.07), 43 (100). Anal. Calcd for C12H14O4S: C,
56.68; H, 5.55. Found: C, 56.68; H, 5.52.
On the basis of this observation, this reaction was used further
for the preparation of optically active 3-acetoxy-1-butenyl
sulfones 3f and 3m from the easily available optically active
1,2-allenyl sulfoxides5b 1f and 1m without obvious loss of the
enantiopurity (Scheme 3).
In conclusion, we have demonstrated that the reaction of 1,2-
allenyl sulfoxides with HOAc in the presence of H2O2 afforded
(11) Marino, J. P.; Anna, L. J.; Ferna´ndez de la Pradilla, R.; Mart´ınez, M. V.;
Montero, C.; Viso, A. J. Org. Chem. 2000, 65, 6462.
(12) Crystal data for compound Z-5l: C34H28Br2N2O12S2, MW ) 880.52,
orthorhombic, space group P2(1)2(1)2(1), final R indices [I > 2σ(I)], R1 ) 0.0379,
wR2 ) 0.0886, R indices (all data) R1 ) 0.0569, wR2 ) 0.0988, a ) 6.7518(3)
Å, b ) 17.3942(7) Å, c ) 31.4299(13) Å, R ) 90°, ꢀ ) 90°, γ ) 90°, V )
3691.2(3) Å3, T ) 296(2) K, Z ) 4, reflections collected/unique 42884/6492
(Rint ) 0.0479), number of observations [I > 2σ(I)] 5154, parameters 469.
Supplementary crystallographic data have been deposited at the Cambridge
Crystallographic Data Center, CCDC 707623.
J. Org. Chem. Vol. 74, No. 7, 2009 2889

Acknowledgement. We gratefully acknowledge the National
Natural Science Foundation of China (No. 20572093) and the
National Basic Research Porgram of China (No. 2009CB825300)
for financial support. Shengming Ma is a Qiushi Adjunct
Professor at Zhejiang University. We thank Youqian Deng in
our group for reproducing the results presented in entries 6 and
8 in Table 2 and the two reactions in Scheme 3.
Supporting Information Available: Detailed experimental
procedures and analytical data for all new products not listed
1
in the text, H and 13C NMR spectra of all new compounds,
and cif files for Z-3a, Z-3h, and (S)-Z-5l. This material is
available free of charge via the Internet at http://pubs.acs.
org.
JO802755K
2890 J. Org. Chem. Vol. 74, No. 7, 2009