Deprotection of Allyl Groups with Sulfinic Acids and Palladium Catalyst

Full text of DOI:10.1021/jo971194c

8932
J . Org. Chem. 1997, 62, 8932-8936
Ch a r t 1
Dep r otection of Allyl Gr ou p s w ith Su lfin ic
Acid s a n d P a lla d iu m Ca ta lyst
Masanori Honda, Hiromasa Morita, and Isao Nagakura*
Chemical Process Development Laboratory, Drug Substance
Manufacturing Plant, Pfizer Pharmaceuticals Inc. 5-gochi,
Taketoyo-Cho, Chita-gun, Aichi, 470-23, J apan
Received J uly 1, 1997X
Allyl or alloxycarbonyl groups have been frequently
used as suitable protecting groups for acids, alcohols, and
amines in the synthesis of carbohydrates,1 peptides,2
nucleotides,3 and other natural products.4 It is known
that the cleavage of the allyl groups is accomplished by
palladium-catalyzed reaction with a carboxylic acid as
an allyl scavenger that attacks the allyl group, forming
the π allylpalladium complex.5 Although several meth-
ods have hitherto been developed for deprotection of the
allyl group,6 in the context of our studies dealing with
the mild deprotection of allyl esters of unstable penems,
we have found that sulfinic acid or its salt in the presence
of a catalytic amount of tetrakis(triphenylphosphine)-
palladium [Pd(PPh3)4] was highly effective for facilitating
the carbon-oxygen bond cleavage.7 Furthermore, under
these mild reaction conditions, cleavage of O-allyl ethers
and N-allyl amines was also facilitated. Herein we
describe the deprotection of a wide range of allyl deriva-
tives, such as allyl esters, allyl carbonates, and allyl
carbamates as well as O-allyl ethers and N-allyl amines
to afford the corresponding carboxylic acid, alcohol, or
amine in excellent yield.
In 1979, Tsuji and Yamakawa found that the pal-
ladium-catalyzed hydrogenolysis of allyl groups with
ammonium formate was highly effective for the depro-
tection of a 2-propenyl ester to give the carboxylic acid
and propene.8 The more promising results for industrial
synthesis were obtained by J effrey and McCombie, who
reported that allyl esters, carbonates, and carbamates
are deprotected by treatment with a carboxylic acid in
the presence of Pd(PPh3)4 and additional triphenylphos-
phine (PPh3).9 According to the J effrey-McCombie
method by using sodium 2-ethylhexanoate (SEH) and a
catalytic amount of Pd(PPh3)4 with PPh3 in dichlo-
romethane, the deprotection of the 2-chloroallyl ester 1
proceeded to give a carboxylic acid 6 in a 76% yield (entry
3 in Table 1).10 Although the methallyl ester 2 was
subjected to the same procedures, the deprotection
resulted in a 52% yield of the carboxylic acid 6 due to
the slow reaction and instability of the compounds under
the reaction conditions (entry 5).
X Abstract published in Advance ACS Abstracts, October 15, 1997.
(1) (a) Spijker, N. M.; Keuning, C. A.; Hooglugt, M.; Veeneman, G.
H.; Vanboeckel, C. A. A. Tetrahedron 1996, 52, 5945. (b) Hayashi, M.;
Tanaka, M.; Itoh, M.; Miyauchi, H. J . Org. Chem. 1996, 61, 2938. (c)
Alzeer, J .; Cai, C.; Vasella, A. Helv. Chim. Acta 1995, 78, 242. (d)
Mayer, T. G.; Kratzer, B.; Schmidt, R. R. Angew. Chem., Int. Ed. Engl.
1994, 33, 2177. (e) Paulson, H.; Wilkens, R.; Folker, R.; Brockhausen,
I. Liebigs Ann. Chem. 1992, 1303. (f) Nakayama, K.; Uoto, K.; Higashi,
K.; Soga, T.; Kusama, T. Chem. Pharm. Bull. 1992, 40, 1718. (g)
Boeckel, C. A. A.; Basten, J . E. M.; Lucas, H.; Aelst, S. F. Angew. Chem.,
Int. Ed. Engl. 1988, 27, 1177. (h) Dziewiszek, K.; Banaszek, A.;
Zamojski, A. Tetrahedron Lett. 1987, 28, 1569.
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Waldmann, H.; Nagele, E. Angew. Chem., Int. Ed. Engl. 1995, 34, 2259.
(c) Ueno, Y.; Suda, F.; Taya, Y.; Noyori, R.; Hayakawa, Y.; Hata, T.
Bioorg. Med. Chem. Lett. 1995, 5, 823. (d) Beugelmans, R.; Neuville,
L.; Bois-Choussy, M.; Chastanet, J .; Zhu, J . Tetrahedron Lett. 1995,
36, 3129. (e) Baldwin, J . E.; Moloney, M. G.; North, M. Tetrahedron
1989, 45, 6319.
(3) (a) Bergmann, F.; Kueng, E.; Iaiza, P.; Bannwarth, W. Tetrahe-
dron 1995, 51, 6971. (b) Nishiyama, S.; Yamamura, S.; Kato, K.; Takita,
T. Tetrahedron Lett. 1988, 29, 4739. (c) Hayakawa, Y.; Kato, H.;
Uchiyama, M.; Kajino, H.; Noyori, R. J . Org. Chem. 1986, 51, 2402.
(4) (a) Roush, W. R.; Lin, X. J . Am. Chem. Soc. 1995, 117, 2236. (b)
Raymond, J . C.; Kelly, D. H.; DiMichele, L. M.; Shuman, R. F.;
Grabowski, E. J . J . J . Org. Chem. 1994, 59, 7704. (c) J ones, R. J .;
Rapoport, H. J . Org. Chem. 1990, 55, 1144. (d) Paquette, L. A.;
Macdonald, D.; Anderson, L. G.; Wright, J . J . Am. Chem. Soc. 1989,
111, 8037. (e) Hanessian, S.; Alpegiani, M. Tetrahedron 1989, 45, 941.
(f) Boeckmann, R. K.; Perni, R. B. J . Org. Chem. 1986, 51, 5486.
(5) (a) Tsuji, J .; Mandai, T. Synthesis 1996, 1. (b) Tsuji, J . Palladium
Reagents and Catalysts: Innovations in Organic Synthesis; J ohn Wiley
& Sons: Chichester, 1995.
We extensively investigated an alternative method for
deprotection of the allyl ester 1 and found that sulfinic
acids or their salts are the most effective allyl scavengers
in the presence of a palladium catalyst. Use of carboxylic
acids,8 morpholine,11 dimedone,12 and N,N’-dimethylbar-
bituric acid13 as allyl scavengers led to poor results. As
(8) Tsuji, J .; Yamakawa, T. Tetrahedron Lett. 1979, 63.
(9) J effrey, P. D.; McCombie, S. W. J . Org. Chem. 1982, 47, 587.
(10) (a) Volkmann, R. A.; Kelbaugh, P. R.; Nason, D. M.; J asys, V.
J . J . Org. Chem. 1992, 57, 4352. (b) Phillips, D.; O´ıNeill, B. T.
Tetrahedron Lett. 1990, 31, 3291. (c) Volkmann, R. A.; Lindner, D. L.
US Patent 4,794,179, 1988.
(6) (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; J ohn Wiley & Sons: New York, 1991. (b) Kocienski, P. J .
Protecting Groups; Georg Thieme Verlag: Stuttgart, 1994.
(7) (a) Tamura, R.; Kai, Y.; Kakihara, M.; Hayashi, K.; Tsuji, M.;
Nakamura, T.; Oda, D. J . Org. Chem. 1986, 51, 4375. (b) Inomata, K.;
Yamamoyo, T.; Kotake, H. Chem. Lett. 1981, 1357.
(11) Kuntz, H.; Waldmann, H. Angew. Chem., Int. Ed. Engl. 1984,
23, 71.
(12) (a) Kuntz, H.; Unverzagt, C. Angew. Chem., Int. Ed. Engl. 1984,
23, 436. (b) Zhang, H. X.; Guibe´, F.; Balavoine, G. Tetrahedron Lett.
1988, 29, 623.
(13) Kuntz, H.; Ma˜rz, J . Angew. Chem., Int. Ed. Engl. 1988, 27, 1375.
S0022-3263(97)01194-8 CCC: $14.00 © 1997 American Chemical Society

Notes
entry
J . Org. Chem., Vol. 62, No. 25, 1997 8933
Ta ble 1. Dea llyla tion w ith Su lfin ic Acid s in th e P r esen ce of P a lla d iu m Ca ta lysta
catalyst
palladium
additive
(equiv)
time
(min)
yield
(%)b
substrate
mol %
nucleophile
solvent
CH2Cl2
THF/MeOH
CH2Cl2
THF/MeOH
CH2Cl2
THF/MeOH
THF/MeOH
THF/MeOH
THF/MeOH
THF/MeOH
THF/MeOH
THF/MeOH
CH2Cl2
product
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1
1
1
2
2
1
1
1
1
1
1
1
1
3
4
5
8
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(OAc)2
5.0
5.9
5.4
7.0
7.7
21.2
20.5
13.7
7.3
5.9
6.0
6.3
6.0
4.3
5.0
4.6
5.6
6.0
7.0
7.0
7.0
7.0
10.6
PhSO2H
TolSO2Na
SEH
TolSO2Na
SEH
PPh3 (0.15)
none
PPh3 (0.14)
none
PPh3 (0.15)
TEP (0.74)
TEP (0.70)
TEP (0.42)
none
60
105
120
130
120
80
6
6
6
6
6
96
97
76
94
52
80
45
85
96
72
90
86
70
91
94
87
99
80
98
99
79
93
89
TolSO2Na
SEH
6
Pd(OAc)2
360
6
Pd(ACN)2Cl2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
TolSO2Na
17.5 (h)
6
6
6
6
6
6
6
6
STSc
150
130
315
80
25
35
30
25
60
60
SCNBSd
i-BuSO2Na
Rongalite
TolSO2TBAf
TolSO2Na
TolSO2Na
TolSO2Na
TolSO2Na
TolSO2Na
TolSO2H
TolSO2H
TolSO2H
TolSO2H
TolSO2H
none
none
none
none
none
none
none
none
none
none
none
none
none
none
THF/MeOH
THF/MeOH
THF/MeOH
THF/MeOH
THF/MeOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
6
9
10
12
13
15
17
19
11
14
14
16
18
20
30
25
40
60
60
a
b
d
All reaction were carried out at rt. Isolated yield. c STS: sodium 2-thiophenesulfinate. SCNBS: sodium 4-chloro-3-nitrobenzene-
sulfinate. e Rongalit: sodium formaldehyde sulfoxylate. f TBA: tetrabutylammonium.
shown in Table 1, the deallylation employing com-
mercially available benzenesulfinic acid (PhSO2H) or
sodium toluenesulfinate (TolSO2Na) provided the acid 6
in high yield (entries 1, 2, and 4). The reaction of 1 using
TolSO2Na also proceeds in the presence of other pal-
ladium catalysts such as palladium acetate or dichlorobis-
(acetonitrile)palladium and triethyl phosphite14 (TEP) to
give 6 in good yield (entries 6 and 8), while with SEH
the yield is still low (entry 7).
respectively, in excellent yield (entries 17 and 18). In
the case of the allyl carbonate 1220 and the allyl carbam-
ate 15,21 the palladium-catalyzed deallylation using
TolSO2H is comparable to those of the allyl ester (entries
19 and 21). As shown in the Table 1, sulfinic acids are
highly effective allyl scavengers as compared with SEH,
and the zerovalent catalyst Pd(PPh3)4 is clearly far
superior to all the other palladium compounds in terms
of the reaction speed and yield.
Deallylation of 1 with monosodium p-sulfinobenzoate15
bearing two possible nucleophilic sites proceeded smoothly
to afford the acid 6 and 2-chloro-2-propenyl p-carboxy-
phenyl sulfone 716 resulting from attack by sulfur. 1H
NMR analysis of the products suggested the absence of
2-chloro-2-propenyl sulfinobenzoate resulting from oxy-
gen attack of the carboxylate. Other aromatic sulfinic
compounds bearing either a heterocycle (entry 9) or
electron-donating and -withdrawing substituents (entry
10) and aliphatic sulfinic compounds17 (entries 11 and
12) can alternatively be used for the deallylation of allyl
esters irrespective of acid salt forms such as sodium,
lithium, or tetrabutylammonium (entry 13).
The same reaction conditions when applied to butenyl,
cinnamyl, and propenyl esters proceeded smoothly to give
the acid 6 in high yields (entries 14-16). As the present
deallylation can be performed under very mild reaction
conditions, the penem 8 and the cephem 1018 were readily
deprotected to afford the corresponding acids 919 and 11,
The excellent results described above prompted us to
investigate the possibility of applying the same cleavage
conditions to the oxygen-carbon bonds of an ether and
the nitrogen-carbon bond of an amine. Several methods
have been developed for deprotection of O-allyl ethers6a,22
or N-allyl compounds.6a,23 However, these deprotections
are quite limited by the low chemoselectivity or the
severe reaction conditions which affect the rest of the
functional groups in the substrate. Our method for the
deprotection of allyl groups with a sulfinic acid and Pd-
(PPh3)4 is applicable to O-allyl ethers or N-allyl com-
pounds due to the very mild reaction conditions and high
chemoselectivity. Not only did the deprotection of the
allyl ether of the sugar 1324 proceed readily at room
temperature without affecting the acid-sensitive O-iso-
propylidene group, the N-allyl amine 17 was deprotected
easily as well (entries 20 and 22). The O-allyl oxime of
the avermectin macrolide 19 was deprotected to 2025 in
high yield without affecting the olefin moieties and
(20) Genet, J . P.; Blart, E.; Savignac, M.; Lemeune, S.; Audoire, S.
L.; Paris, J . M.; Bernard, J . M. Tetrahedron 1994, 50, 497.
(21) Brunner, W. Monatch. Chem. 1933, 63, 374, 380.
(14) Stern, E. W. J . Chem. Soc., Chem. Commun. 1970, 736.
(15) Preparation: Smiles, S.; Harrison, D. C. J . Chem. Soc. 1922,
121, 2022. The pKa value (1.29) of benezenesulfinic acid: Veltwisch,
D.; J anata, E.; Asmus, K. D. J . Chem. Soc. Perkin Trans. 2 1980, 146.
(16) Tornetta, B.; Guerrera, F.; Mazzario, C. Boll. Chim. Farm. 1973,
112, 832, 836. (b) Chem. Abstr. 1967, 67, 82952 g.
(17) Preparation of aliphatic sulfinic acids: Blanco, J . M.; Caamano,
O.; Eirin, A.; Fernandez, F.; Medina, L. Synthesis 1990, 584. Other
sulfinic acids were prepared according to the conventional method:
Organic Synthesis; J ohn Wiley & Sons: New York, 1941; Coll. Vol. I,
pp 7 or 492.
(22) Allyl ethers: (a) Yadav, J . S.; Chandrasekhar, S.; Sumithra,
G.; Kache, R. Tetrahedron Lett. 1996, 37, 6603. (b) Lee, J .; Cha, J . K.
Tetrahedron Lett. 1996, 37, 3663. (c) Diaz, R. R.; Melgarejo, C. R.;
Lopez-Espinosa, M. T. P.; Cubero, I. I. J . Org. Chem. 1994, 59, 7928.
(d) Beugelmans, R.; Bourdet, S.; Bigot, A.; Zhu, J . Tetrahedron Lett.
1994, 35, 4349. (e) Ito, H.; Taguchi, T.; Hanzawa, Y. J . Org. Chem.
1993, 58, 774. (f) Kadam, S. M.; Nayak, S. K.; Banaeji, A. Tetrahedron
Lett. 1992, 33, 5129.
(23) Allyl amines: (a) Lamaire-Audoire, S.; Savignac, M.; Genet, J .
P.; Bernard, J . M. Tetrahedron Lett. 1995, 36, 1267. (b) Garro-Helion,
F.; Merzouk, A.; Guibe, F. J . Org. Chem. 1993, 58, 6109. (c) Mori, M.;
Ban, Y. Chem. Pharm. Bull. 1976, 24, 1992.
(18) Buckwell, S.; Stephen, C.; Page, M. I.; Waley, S. G.; Longridge,
J . L. J . Chem. Soc., Perkin Trans. 2 1988, 1815.
(19) Volkmann, R. A.; Carrol, R. D.; Drolet, R. B.; Elliott, M. L.;
Moore, B. S. J . Org. Chem. 1982, 47, 3344.
(24) Bessodes, M.; Shamsazar, J .; Antonakis, K. Synthesis 1988, 560.

8934 J . Org. Chem., Vol. 62, No. 25, 1997
Notes
the precipitates were dissolved in water (3 mL + 1.5 mL × 3).
The aqueous solution was acidified with an ion-exchange resin
(Manufactured by Mitsubishi Chem. under the trade name of
DIAION PK216H), and acetone (7.5 mL) was added. The resin
was filtered off and washed with acetone-water (2:1, 1.5 mL ×
3). The combined filtrates were concentrated at 24 °C by an
evaporator to strip acetone and freeze-dried to give light yellow
powders (209 mg) in 97% yield.
Sch em e 1
P r ep a r a tion of 2-Meth yl-2-p r op en yl (5R,6S)-6-(1(R)-Hy-
d r oxyeth yl)-2-(1(R)-oxo-3(S)-th iola n ylth io)-2-p en em -3-ca r -
boxyla te (2). The sodium salt of the carboxylic acid 6 (0.670
g, 1.34 mmol) was dissolved in N,N-dimethylformamide (2 mL),
and 1-bromo-2-methyl-2-propene (0.540 mL, 4.04 mmol) was
added dropwise at 0 °C. The reaction mixture was stirred at rt
for 23 h and poured into water (50 mL) and extracted with CH2-
Cl2. The extract was washed with water and concentrated in
vacuo. The resulting residue was chromatographed on silica gel
(EtOAc:MeOH 20:1-10:1) to give the 2-methyl-2-propenyl ester
glycosidic linkages (entry 23). The aminopenem 2126
which is unstable in basic or acidic conditions could be
converted into the inseparable enamine-imine mixture
(22 and 23) in a 1:1 ratio27 using our reaction conditions
at room temperature for 60 min (Scheme 1).
In conclusion, sulfinic acids or the corresponding salts
in the presence of a catalytic amount of Pd(PPh3)4 are
highly effective for facilitating the carbon-oxygen bond
cleavage of allyl esters and ethers as well as the carbon-
nitrogen bond of N-allyl amines. Considering the syn-
thetic availability and chemostability of the allyl pro-
tecting group, our allyl deprotection method offers a new
synthetic option toward complicated natural products
such as polyether ionophores, macrolides, nucleotides,
oligosaccharides, and alkaloids.
2 as a white solid (455 mg) in 63% yield: mp 82-83 °C; [R]23
D
1
+61.6° (c 0.32, CHCl3); H NMR (270 MHz, CDCl3) δ 5.70 (d, J
) 1.5 Hz, 1H), 5.08 (s, 1H), 4.95 (s, 1H), 4.75 (d, J ) 13.2 Hz,
1H), 4.52 (d, J ) 13.2 Hz, 1H), 4.24 (m, 1H), 3.94 (dd, J ) 14.3,
8.4 Hz, 1H), 3.74 (dd, J ) 7.0, 1.5 Hz, 1H), 3.66 (t, J ) 8.4 Hz,
1H), 3.20-3.10 (m, 1H), 2.90-2.64 (m, 4H), 2.18 (s, 1H), 1.80
(s, 3H), 1.36 (d, J ) 6.2 Hz, 3H); 13C NMR (67.5 MHz, CDCl3) δ
171.7, 159.4, 151.3, 139.4, 118.4, 113.5, 71.4, 68.5, 65.5, 64.7,
61.2, 52.7, 46.6, 33.2, 21.9, 19.5; IR (KBr) 3264, 1779, 1673, 1492,
1323, 1213, 1125, 1017 cm-1. Anal. Calcd for C16H21O5NS3: C,
47.62;H, 5.25; N, 3.47; S, 23.84. Found: C, 47.69; H, 5.01; N,
3.51; S, 24.09.
Rem ova l of th e 2-Meth yl-2-p r op en yl Gr ou p fr om 2. The
carboxylic acid 6, a light yellow powder (198 mg, 0.567 mmol),
was obtained in 94% yield from 2 (244 mg, 0.604 mmol) by the
same procedure as described in method B.
P r ep a r a tion of 2-Bu ten yl (5R,6S)-6-(1(R)-Hyd r oxyeth yl)-
2-(1(R)-oxo-3(S)-th iola n ylth io)-2-p en em -3-ca r boxyla te (3).
The sodium salt of the carboxylic acid 6 (1.75 g, 4.71 mmol) was
dissolved in N,N-dimethylformamide (5.2 mL), and 1-bromo-2-
butene (1.91 g, 14.1 mmol) was added. The reaction mixture
was stirred at rt for 20 h and poured into water (50 mL). After
stirring for 30 min, the light yellow solids were filtered off. The
filtrate was extracted with CH2Cl2 (30 mL). The extract was
dried over MgSO4, concentrated, and washed with EtOAc (5 mL)
and n-hexane (5 mL) to give light yellow solids. The solids (2.0
g) were combined, recrystallized from EtOH (20 mL), filtered
off, and dried in vacuo to give the 2-butenyl ester 3 as a white
solid (1.04 g) in 55% yield. The mother liquor was concentrated,
washed with EtOAc (2 mL), and dried in vacuo to give the
butenyl ester (0.24 g) as the second crop in 13% yield. The first
and second crops were combined: mp 161-162 °C; [R]23D +96.2°
(c 0.30, CHCl3); 1H NMR (270 MHz, CDCl3) δ 5.95-5.57 (m, 3H),
4.85-4.62 (m, 2H), 4.31-4.18 (m, 1H), 3.93 (dd, J ) 14.3, 8.4
Hz, 1H), 3.72 (dd, J ) 7.0, 1.5 Hz, 1H), 3.64 (t, J ) 8.4 Hz, 1H),
3.21-3.10 (m, 1H), 2.90-2.62 (m, 4H), 2.27 (s, 1H), 1.72 (d, J )
6.6 Hz, 3H), 1.36 (d, J ) 6.2 Hz, 3H); 13C NMR (67.5 MHz,
CDCl3) δ 171.8, 159.6, 150.9, 130.0, 123.9, 118.6, 71.4, 66.0, 65.5,
64.7, 61.2, 52.6, 46.6, 33.2, 21.9, 17.8; IR (KBr) 3280, 1778, 1768,
. Anal. Calcd for C16H21O5-
NS3: C, 47.62; H, 5.25; N, 3.47; S, 23.84. Found: C, 47.58; H,
5.35; N, 3.49; S, 24.12.
Rem ova l of th e 2-Bu ten yl Gr ou p fr om 3. The carboxylic
acid 6, a light yellow powder (178 mg, 0.509 mmol), was obtained
in 91% yield from the 2-butenyl ester 3 (227 mg, 0.562 mmol)
by the same procedure as described in method B.
P r ep a r a tion of Cin n a m yl (5R,6S)-6-(1(R)-Hyd r oxyeth yl)-
2-(1(R)-oxo-3(S)-th iola n ylth io)-2-p en em -3-ca r boxyla te (4).
The sodium salt of the carboxylic acid 6 (6.88 g, 18.5 mmol) was
dissolved in N,N-dimethylformamide (25 mL), and cinnamyl
bromide (3.65 g, 18.5 mmol) was added at rt. The reaction
mixture was stirred at rt for 20 h, poured into water (500 mL),
and then extracted with CH2Cl2 (250 mL). The extract was
washed with water (50 mL) and concentrated in vacuo. Isopro-
pyl ether (200 mL) was added to the resulting residue, and the
resulting precipitates were collected by filtration. The collected
solids were recrystallized from 2-propanol (50 mL), filtered off,
and then dried in vacuo to give the cinnamyl ester 4 as a light
yellow solid (2.32 g) in 31% yield: mp 173-174 °C; [R]25D +42.2°
(c 0.24, CHCl3); 1H NMR (270 MHz, CDCl3) δ 7.42-7.22 (m, 5H),
Exp er im en ta l Section
Gen er a l P r oced u r es. Melting points are uncorrected. 1H
NMR spectra were recorded at 270 MHz. 13C NMR spectra were
recorded at 67.5 MHz. Chemical shifts are expressed in parts
per million (δ) relative to tetramethylsilane for 1H NMR and
DMSO-d6 (δ) for 13C NMR. IR spectra of samples were recorded
in KBr pressed disks for crystalline samples. Optical rotations
were measured at ambient temperature at the sodium line.
Column chromatography was performed on 230-400 mesh silica
gel. Alkyl sulfinates were prepared from the corresponding
phthalimidomethyl sulfone.17 Other sulfinates were prepared
in the usual way by the reaction of sulfonyl chloride and sodium
28
sulfite or zinc powder. Pd(PPh3)4 was purchased from Kanto
Chemical Co. Inc. (Tokyo, J apan).
R em ova l of t h e 2-Ch lor o-2-p r op en yl Gr ou p fr om 1.
Meth od A. Benzenesulfinic acid (2.87 g, 20.2 mmol) was added
at rt to a suspension of 1 (7.82 g, 18.4 mmol), PPh3 (723 mg,
2.76 mmol), and Pd(PPh3)4 (1.06 g, 0.92 mmol) in CH2Cl2 (196
mL). After the reaction mixture was stirred for 1 h at rt, the
resulting crystals were collected by filtration, washed three times
with CH2Cl2 (7 mL), and then dried in vacuo to give the
carboxylic acid 6 as an off-white powder (6.19 g) in 96% yield:
1H NMR (270 MHz, DMSO-d6) δ 5.74 (d, J ) 1.5 Hz, 1H), 4.02-
3.72 (m, 4H), 3.05-2.94 (m, 1H), 2.90-2.78 (m, 1H), 2.75-2.59
(m, 2H), 2.47-2.31 (m, 1H), 1.16 (d, J ) 6.2 Hz, 3H). Meth od
B. A solution of sodium p-toluenesulfinate tetrahydrate (155
mg, 0.615 mmol) in MeOH (2.3 mL) was added at rt to a
suspension of 1 (261 mg, 0.615 mmol) and Pd(PPh3)4 (41.7 mg,
36.1 µmol) in THF (3.9 mL). The reaction mixture was stirred
at rt for 105 min, and EtOAc (12 mL) was added dropwise to
precipitate the sodium salt of the target compound. Celite (0.8
g) was added to the mixture. After filtration, the precipitates
and Celite were washed with EtOAc (3 mL + 1.5 mL × 3), and
1675, 1496, 1328, 1126, 957 cm-1
(25) Bishop, B. F.; Pacey, M. S. Perry, D. M. Patent WO9415944-
A1 1994.
(26) Nagakura, I.; Kadoi, H.; Yamasaki, T. Heterocycles 1997, 45,
835.
(27) For inseparable 22-23 (1:1) mixture: Girijavallqabhan, V. M.;
Ganguly, A. K.; Liu, Y.; Pinto, P. A.; Patel, N.; Hare, R. H.; Miller, G.
H. J . Antibiot. 1986, 34, 1187.
(28) The reaction rate is highly dependent on the quality of Pd-
(PPh3)4, and the concomitant addition of PPh3 accelerates the reac-
tion.14

Notes
J . Org. Chem., Vol. 62, No. 25, 1997 8935
6.74 (d, J ) 16.1 Hz, 1H), 6.32 (dt, J ) 15.8, 6.3 Hz, 1H), 5.69
(d, J ) 0.5 Hz, 1H), 4.96-4.83 (m, 2H), 4.28-4.23 (m, 1H), 3.93
(dd, J ) 14.3, 8.4 Hz, 1H), 3.74 (dd, J ) 7.0, 1.5 Hz, 1H), 3.69-
3.63 (m, 1H), 3.15-3.12 (m, 1H), 2.83 (ddd, J ) 14.3, 8.4, 1.8
Hz, 1H), 2.75-2.63 (m, 2H), 1.37 (d, J ) 6.2 Hz, 3H); 13C NMR
(67.5 MHz, CDCl3) δ 171.7, 159.5, 151.4, 134.5, 128.5, 128.4,
128.0, 126.7, 122.7, 71.4, 65.8, 65.5, 64.7, 61.2, 52.7, 46.6, 33.2,
21.9; IR (KBr) 3488, 1750, 1680, 1475, 1344 739, 692 cm-1. Anal.
Calcd for C21H23O5NS3: C, 54.17; H, 4.98; N, 3.01; S, 20.66.
Found: C, 54.09; H, 4.98; N, 2.91; S, 20.74.
mL), and the solution was adjusted to pH 6 with aqueous 5 N
sodium hydroxide solution. This was mixed with sodium 7-benz-
amido-3-(acetoxymethyl)-3-cepham-4-carboxylate (1.00 g, 2.51
mmol), stirred at rt for 2 h while keeping the pH value at 6.6 by
addition of an aqueous 1 N NaOH solution, and then extracted
three times with CHCl3 (4.6 mL + 2.3 mL × 2). The CHCl3
extracts were mixed with allyl bromide (912 mg, 7.53 mmol) and
stirred at 50 °C for 2 h. The reaction solution was poured into
EtOAc (200 mL), washed three times with water (20 mL), dried
over MgSO4, and then concentrated. The resulting residue was
purified by a silica gel column chromatography (CHCl3:acetone
97:3-95:5) to give the 2-propenyl ester 10 as a light yellow
Rem ova l of th e Cin n a m yl Gr ou p fr om 4. The carboxylic
acid 6, a light yellow powder (177 mg, 0.507 mmol), was obtained
in 94% yield from the cinnamyl ester 4 (251 mg, 0.540 mmol)
by the same procedure as described in method B.
viscous liquid (905 mg) in 87% yield; [R]24 +58.7° (c 0.15,
D
CHCl3); 1H NMR (270 MHz, CDCl3) δ 7.84 (dd, J ) 8.2, 1.3 Hz,
2H), 7.58-7.42 (m, 3H), 7.30 (d, J ) 8.8 Hz, 1H), 6.06-5.89 (m,
2H), 5.42-5.15 (m, 3H), 5.08 (d, J ) 4.8 Hz, 1H), 4.85 (d, J )
13.6 Hz, 1H), 4.75 (dd, J ) 6.0, 0.9 Hz, 2H), 3.61 (d, J ) 18.3
Hz, 1H), 3.42 (d, J ) 18.3 Hz, 1H), 2.09 (s, 3H); 13C NMR (67.5
MHz, CDCl3) δ 170.5, 167.3, 164.8, 161.0, 132.7, 131.8, 128.7,
127.3, 125.9, 125.6, 119.5, 76.5, 66.9, 63.0, 59.8, 57.6, 26.5, 20.7;
Rem ova l of th e 2-P r op en yl Gr ou p fr om 5. The carboxylic
acid 6, a light yellow powder (405 mg, 1.16 mmol), was obtained
from the 2-propenyl ester 5 (500 mg, 1.28 mmol) by the same
procedure as described in method B. Meth od C. A solution of
sodium p-toluenesulfinate tetrahydrate (1.06 g, 4.23 mmol) in
water (7 mL) was added at rt to a suspension of the 2-propenyl
ester 5 (1.54 g, 3.95 mmol) and Pd(PPh3)4 (209 mg, 0.180 µmol)
in THF (20 mL). The reaction mixture was stirred at rt for 25
min. After partition of ether (20 mL), the ether layer was
extracted with water (1 mL). The water extracts were treated
with active charcoal (0.28 g) and filtered. The filter cake was
rinsed with water (1.5 mL). The combined aqueous solution was
cooled to 5 °C, acidified to a pH of 2.5 with HCl and stirred at
5 °C for 30 min. The precipitates were filtered off, washed with
water (1 mL), and dried in vacuo to give the carboxylic acid 6 as
a pale pink powder (1.20 g) in 87% yield.
IR (KBr) 3280, 1776, 1748, 1720, 1646, 1522, 1390, 1038 cm-1
.
Anal. Calcd for C20H20O6N2S: C, 57.68, H, 4.84, N, 6.73.
Found: C, 57.62, H, 4.81, N, 6.70.
Rem ova l of th e 2-P r op en yl Gr ou p fr om 10. Methanol
solution (3.0 mL) of sodium p-toluenesulfinate tetrahydrate (218
mg, 0.871 mmol) was added at rt to a solution of the 2-propenyl
ester 10 (330 mg, 0.792 mmol) and Pd(PPh3)4 (54.9 mg, 47.5
µmol) in THF (5.0 mL). The reaction mixture was stirred for
60 min at rt. After addition of EtOAc (16 mL), the mixture was
stirred for 30 min. The resulting precipitate was collected by
filtration, washed three times with EtOAc (2 mL), and dried in
vacuo at rt to give the sodium salt of the carboxylic acid 11 as
a white powder (253 mg) in 80% yield.
Rem ova l of th e Allyloxyca r bon yl Gr ou p fr om 12. p-
Toluenesulfinic acid (59.3 mg, 0.380 mmol) was added to a CH2-
Cl2 solution (3.3 mL) of 3-O-(allyloxycarbonyl)-1,2:5,6-di-O-
isopropylidene-R-D-glucofuranose (12) (115 mg, 0.334 mmol) and
Pd(PPh3)4 (27.0 mg, 23.4 µmol). The reaction mixture was
stirred for 30 min at rt, mixed with triethylamine (6.8 mg, 67
µmol), and then subjected to a silica gel chromatography
(hexanes:EtOAc 1:1) to give di-O-isopropylidene-R-D-glucofura-
nose (14) as a white solid (85.6 mg) in 98% yield.
Rem ova l of th e Allyl Gr ou p fr om 13. p-Toluenesulfinic
acid (78.5 mg, 0.503 mmol) was added at rt to a solution of 3-O-
allyl-1,2:5,6-di-O-isopropylidene-R-D-glucofuranose (13) (136 mg,
0.452 mmol) and Pd(PPh3)4 (36.6 mg, 31.7 µmol) in CH2Cl2 (4.5
mL). The reaction mixture was stirred at rt for 25 min, and
triethylamine (9.1 mg, 90 µmol) was added. The mixture was
subjected to a silica gel chromatography (hexanes:EtOAc 1:1)
to give di-O-isopropylidene-R-D-glucofuranose (14) as a white
solid (117 mg) in 99% yield.
Rem ova l of th e 2-Ch lor o-2-p r op en yl Gr ou p fr om 1 w ith
Mon osod iu m p-Su lfin oben zoa te. Tetrahydrofuran (3.37 mL)
and water (1.35 mL) were added at rt to a mixture of monoso-
dium p-sulfinobenzoate (118 mg), the 2-chloro-2-propenyl ester
1 (200 mg, 0.471 mmol), and Pd(PPh3)4 (28.7 mg, 24.8 µmol).
The reaction mixture was stirred at rt for 90 min. After addition
of water (1 mL), the mixture was extracted three times with
ether (9 mL + 4.5 mL × 2). The aqueous layer was cooled to 5
°C, acidified to a pH of 2.5 by adding concd HCl, and stirred at
5 °C for 30 min. The precipitates were filtered off, washed three
times with water (1 mL × 3), and dried in vacuo to give a
mixture (246 mg, an off-white powder) of the carboxylic acid 6
and 2-chloro-2-propenyl p-carboxyphenyl sulfone 7 in a molar
ratio of 4:3.
6: 1H NMR (270 MHz, DMSO-d6) δ 5.71 (d, J ) 1.5 Hz), 4.00-
3.72 (m), 3.04-2.97 (m), 2.90-2.78 (m), 2.75-2.61 (m), 2.46-
2.33 (m), 1.16 (d, J ) 6.2 Hz).
7: 1H NMR (270 MHz, DMSO-d6) δ 8.17 (d, J ) 8.4 Hz), 8.03
(d, J ) 8.4 Hz), 5.54 (d, J ) 1.8 Hz), 5.46 (s), 4.63 (s).
P r ep a r a tion of 2-Ch lor o-2-p r op en yl (2S,5R)-3,3-Dim eth -
yl-4,4,7-tr ioxo-4-th ia (VI)-1-a za bicyclo[3.2.0]h ep ta n e-2-ca r -
boxyla te (8). Sodium 4,4-dioxopenicillanate19 (3.25 g, 12.7
mmol) and 1-bromo-2-chloro-2-propene (3.96 g, 25.5 mmol) in
hexamethylphosphoramide (26 mL) were stirred at 55 °C for 18
h. The mixture was diluted with ether (300 mL), washed three
times with water (50 mL), dried over MgSO4, and then concen-
trated. The resulting residue was dissolved in MeOH (10 mL)
and mixed with n-hexane (100 mL) to effect precipitation of solid
material. After 15 min of stirring, the precipitates were collected
by filtration, washed three times with n-hexane (10 mL), and
then dried in vacuo to give the 2-chloro-2-propenyl ester 8 as a
Rem ova l of th e Allyloxyca r bon yl Gr ou p fr om 15. Pd-
(PPh3)4 (30.3 mg, 26.2 µmol) was added to a CH2Cl2 solution (3.7
mL) of p-toluenesulfinic acid (64.3 mg, 0.411 mmol) and allyl
N-(p-methoxyphenyl)carbamate (15) (77.6 mg, 0.374 mmol). The
reaction mixture was stirred for 40 min at rt. The reaction
solution was subjected to a silica gel chromatography (hexanes:
EtOAc 65:35 to 6:4) to give p-anisidine 16 (36.3 mg) in 79% yield.
P r ep a r a tion of N-Allyl-N-p en tyla n ilin e (17). N-Allyl-
aniline (1.95 g, 14.7 mmol) and bromopentane (2.22 g, 14.7
mmol) were stirred at 80 °C for 16 h. After being cooled to rt,
the mixture was treated with a solution of sodium hydroxide
(714 mg, 17.9 mmol) in water (1.5 mL), stirred for 30 min, and
extracted with ether (80 mL). The extract was dried over
potassium carbonate and concentrated in vacuo. The residue
was chromatographed on silica gel (CHCl3:acetone:water 95:5:
0.1-90:10:0.2) to give N-allyl-N-pentylaniline 17 as a colorless
oil (1.68 g) in 56% yield; 1H NMR (270 MHz, CDCl3) δ 7.21 (dd,
J ) 8.5, 0.8 Hz, 1H), 7.18 (dd, J ) 8.5, 0.8 Hz, 1H), 6.71-6.61
(m, 3H), 5.91-5.77 (m, 1H), 5.21-5.11 (m, 2H), 3.91-3.89 (m,
2H), 3.27 (t, J ) 7.7 Hz, 2H), 1.63-1.54 (m, 2H), 1.37-1.28 (m,
4H), 0.91 (t, J ) 7.0 Hz, 3H); 13C NMR (67.5 MHz, CDCl3) δ
148.4, 134.3, 129.1, 115.7, 115.6, 111.9, 53.1, 50.8, 29.3, 27.0,
white solid (3.36 g) in 86% yield: mp 79.5-80.5 °C; [R]24
D
1
+192.9° (c 0.31, CHCl3); H NMR (270 MHz, CDCl3) δ 5.58 (m,
1H), 5.52 (d, J ) 1.8 Hz, 1H), 4.90 (dd, J ) 13.0, 0.9 Hz, 1H),
4.68 (dd, J ) 12.8, 0.7 Hz, 1H), 4.64-4.62 (m, 1H), 4.44 (s, 1H),
3.48 (m, 2H), 1.66 (s, 3H), 1.46 (s, 3H); 13C NMR (67.5 MHz,
CDCl3) δ 170.7, 166.3, 134.6, 118.0, 68.0, 63.1, 62.8, 61.0, 38.3,
20.2, 18.3; IR (KBr) 1793, 1763, 1644, 1318 cm-1. Anal. Calcd
for C11H14O5NSCl: C, 42.93; H, 4.59; N, 4.55; S, 10.42. Found:
C, 43.03; H, 4.54; N, 4.54; S, 10.69.
Rem ova l of th e 2-Ch lor o-2-p r op en yl Gr ou p fr om 8. The
carboxylic acid 9, a white powder (242 mg, 1.04 mmol), was
obtained in 99% yield from the 2-chloro-2-propenyl ester 8 (323
mg, 1.05 mmol) by the same procedure as described in method
B.
22.6, 14.1; IR (neat) 3072, 2944, 2880, 1600, 1507, 745, 690 cm-1
HRMS (EI) Calcd for C14H21N 203.1674, found 203.1673.
.
P r ep a r a t ion of 2-P r op en yl 7-Ben za m id o-3-(a cet oxy-
m eth yl)-3-cep h a m -4-ca r boxyla te (10). Tetrabutylammonium
hydrogen sulfate (1.08 g, 3.19 mmol) was dissolved in water (4.6
Rem ova l of th e Allyl Gr ou p fr om 17. p-Toluenesulfinic
acid (188 mg, 1.20 mmol) was added at rt to a solution of N-allyl-
N-pentylaniline 17 (221 mg, 1.08 mmol) and Pd(PPh3)4 (87.8 mg,

8936 J . Org. Chem., Vol. 62, No. 25, 1997
Notes
75.9 µmol) in CH2Cl2 (11 mL). The reaction mixture was stirred
at rt for 60 min, and saturated aqueous sodium hydrogen
carbonate (6.8 mL) was added. After stirred for 5 min, the
mixture was extracted with ether (80 mL). The extract was
dried over MgSO4 and concentrated in vacuo. Silica gel chro-
matography (hexanes:EtOAc 9:1) of the residue afforded N-
pentylaniline 18 as a colorless oil (164 mg) in 93% yield.
P r ep a r a tion of (2a E,4E,8E)-(4′R,5′S,6S,6′R,7S,11R,13S,-
15S,17a R,20a R,20bS)-6′-Cycloh exyl-4′,20b-d ih yd r oxy-20-(2-
pr open yloxyim in o)-5′,6,8,19-tetr am eth yl-3′,5′,6,6′,7,10,11,14,-
15,17a,20,20a,20b-tr idecah ydr o-17-oxospir o[11,15-m eth an o-
2H,13H,17H-fu r o[4,3,2-pq][2,6]ben zod ioxa cycloocta d ecin -
13,2′-[2H ]p yr a n ]-7-yl 2,6-Did eoxy-4-O-(2,6-d id eoxy-3-O-
m eth yl-r-L-a r a bin o-h exopyr an osyl)-3-O-m eth yl-r-L-a r a bin o-
h exop yr a n osid e (19). 25-Cyclohexylavermectin B2 (5.00 g,
5.47 mmol) was dissolved in CH2Cl2 (70 mL), and activated
MnO2 (17.5 g, 0.201 mol) was added. After stirring for 15 h, an
additional activated MnO2 (4.0 g, 46 mmol) was added in two
portions. After 23 h, the reaction mixture was filtered, and
MnO2 was washed with CH2Cl2 (100 mL). The filtrate and the
washing liquid were combined and concentrated in vacuo to give
the 20-oxo form (4.14 g) as a light white yellow solid in 83%
yield. The 20-oxo form given above (800 mg, 878 mmol) was
dissolved in a mixture of MeOH (6 mL) and dioxane (6 mL).
O-Allylhydroxyamine hydrochloride (580 mg, 5.25 mmol) in
water (6 mL) was added dropwise to the mixture at rt. After
being stirred for 16 h, the reaction solution was poured into
water (30 mL). The resulting white solids were filtered and
washed with water (15 mL). The solids were chromatographed
on silica gel (hexanes:EtOAc 5:3-5:4) to give the O-allyloxime
1H), 3.82-3.35 (m, 16H), 3.25 (t, J ) 9.1 Hz, 1H), 3.16 (t, J )
9.1 Hz, 1H), 2.60-2.20 (m. 6H), 2.06-1.40 (m, 22H), 1.35-1.12
(m, 12H), 0.92-0.84 (m, 4H).
Rem ova l of th e Allyl Gr ou p fr om 21. Pd(PPh3)4 (45.9 mg,
39.7 µmol) was added at rt to a solution of 21 (269 mg, 0.521
mmol) and p-toluenesulfinic acid (90.9 mg, 0.582 mmol) in CH2-
Cl2 (5.2 mL). The reaction mixture was stirred at rt for 20 min.
After addition of saturated aqueous sodium hydrogen carbonate
(3 mL), the mixture was extracted with ether (50 mL). The
extract was washed with brine, dried over MgSO4 and concen-
trated in vacuo. Silica gel chromatography (hexanes:EtOAc 85:
15) of the residue afforded a mixture of 22 and 23 (198 mg) as
a slightly yellow oil in 80% yield; IR (neat) 3296, 2960, 2936,
2864, 1788, 1744, 1656, 1571, 1421, 1253, 837, 779 cm-1; HRMS
(FAB) Calcd for C24H35O4N2SSi + H 475.2008, found 475.2075.
Rem ova l of th e 2-Ch lor o-2-p r op en yl Gr ou p fr om
1
Usin g P a lla d iu m Dia ceta te. The carboxylic acid 6, a light
yellow powder (121 mg, 0.346 mmol), was obtained in 80% yield
from the 2-chloro-2-propenyl ester 1 (182 mg, 0.430 mmol) by
the same procedure as described in method B except that
palladium diacetate (20.5 mg, 91.3 µmol) and triethyl phosphite
(52.6 mg, 0.317 mmol) were used.
Rem ova l of th e 2-Ch lor o-2-p r op en yl Gr ou p fr om
1
Usin g Dich lor obis(a ceton itr ile)p a lla d iu m . The carboxylic
acid 6, a light yellow powder (166 mg, 0.475 mmol), was obtained
in 85% yield from the 2-chloro-2-propenyl ester 1 (237 mg, 0.558
mmol) by the same procedure as described in method B except
that dichlorobis(acetonitrile)palladium (19.9 mg, 13.7 µmol) and
triethyl phosphite (38.3 mg, 0.230 mmol) were used.
Rem ova l of th e 2-Ch lor o-2-p r op en yl Gr ou p fr om
1
19 as a white solid (520 mg) in 61% yield: mp 169-171 °C; [R]25
Usin g Sod iu m Hyd r oxym eth a n esu lfin a te. The carboxylic
acid 6, a light yellow powder (94.5 mg, 0.270 mmol), was
obtained in 86% yield from the 2-chloro-2-propenyl ester 1 (142
mg, 0.335 mmol) by the same procedure as described in method
B except that sodium hydroxymethanesulfinate (61.9 mg, 0.402
mmol) was used.
D
+28.0° (c 0.55, CHCl3); 1H NMR (270 MHz, CDCl3) δ 6.10-5.70
(m, 5H), 5.45-5.20 (m, 4H), 5.04-4.95 (m, 1H), 4.80-4.65 (m,
4H), 4.60 (s, 1H), 3.95 (s, 1H), 3.90-3.37 (m, 17H), 3.25 (t, J )
9.1 Hz, 1H), 3.15 (t, J ) 9.1 Hz, 1H), 2.60-2.20 (m, 6H), 2.03-
1.40 (m, 22H), 1.34-1.15 (m, 12H), 0.96-0.80 (m, 4H); 13C NMR
(67.5 MHz, CDCl3) δ 173.1, 150.1, 138.3, 138.2, 135.6, 133.9,
132.4, 124.8, 124.3, 121.2, 117.7, 117.5, 99.6, 98.4, 94.8, 81.7,
80.3, 79.3, 78.6, 78.1, 76.0, 75.9, 73.2, 72.5, 69.9, 68.6, 68.2, 68.1,
67.6, 67.2, 56.4, 56.3, 46.3, 41.1, 40.6, 39.8, 38.1, 35.1, 34.1, 31.1,
26.9, 26.4, 24.4, 20.1, 18.4, 17.6, 17.4, 15.1, 13.7; IR (KBr) 3528,
2944, 1734, 1720, 1452, 1381, 1342, 986 cm-1. Anal. Calcd for
Rem ova l of th e 2-Ch lor o-2-p r op en yl Gr ou p fr om
1
Usin g Tetr a bu tyla m m on iu m Ben zen esu lfin a te. CH2Cl2
(7.0 mL) was added at rt to a mixture of tetrabutylammonium
benzenesulfinate (300 mg, 0.81 mmol), 1 (300 mg, 0.707 mmol)
and Pd(PPh3)4 (49 mg, 42.4 µmol). The reaction mixture was
stirred for 25 min at rt and extracted with water (1.5 mL and 1
mL × 2). The water layers were combined, cooled to 5 °C,
acidified to pH 2.5 by adding aqueous 1 N HCl, and then stirred
at 5 °C for 30 min. The precipitate thus formed was collected
by filtration, washed with cold water (2 mL), and dried in vacuo
to give acid 6 as a white powder (173 mg) in 70% yield.
C
53H79O15N: C, 65.61, H, 8.21, N, 1.44. Found: C, 65.27, H,
8.08, N, 1.53.
Rem ova l of th e Allyl Gr ou p fr om 19. The O-allyloxime
19 (53.0 mg, 54.0 µmol) and p-toluenesulfinic acid (14.9 mg, 95.4
µmol) were dissolved in CHCl3 (550 µL). Pd(PPh3)4 (6.6 mg, 5.7
µmol) was added. The reaction mixture was stirred for 1 h at
rt. Silica gel chromatography (hexanes:EtOAc 2:3 to 1:4) of the
mixture afforded the oxime 2025 as a light brown powder (44.7
mg) in 89% yield: mp 197-199 °C; 1H NMR (270 MHz, CDCl3)
δ 7.94 (s, 1H), 5.92-5.74 (m, 4H), 5.50-5.30 (m, 2H), 5.03-4.92
(m, 1H), 4.80-4.70 (m, 2 H), 4.67 (s, 1H), 3.95 (s, 1H), 3.85 (s,
Ack n ow led gm en t. We thank Ms. Y. Matsuoka and
Ms. A. Ando of Pfizer Central Research for combustion
analysis and HRMS.
J O971194C