Asymmetric dihydroxylation-haloetherification strategy for the synthesis of tetrahydrofuran-containing acetogenins

Full text of DOI:10.1021/jo961367i

J . Org. Chem. 1998, 63, 2049-2052
2049
Asym m etr ic
Dih yd r oxyla tion -Ha loeth er ifica tion
Str a tegy for th e Syn th esis of
Tetr a h yd r ofu r a n -Con ta in in g Acetogen in s†
Huiping Zhang, Mohindra Seepersaud,
Sheila Seepersaud, and David R. Mootoo*
Department of Chemistry, Hunter College, 695 Park Avenue,
New York, New York 10021
Received J uly 19, 1996
The tetrahydrofuran (THF)-containing acetogenins are
a relatively new group of natural products which are
known for their potent antitumor and pesticidal activi-
ties.1,2 Over 200 members have been isolated. They are
C35-C39 compounds which generally contain one or two
2,5-disubstituted THF’s, although structures containing
a higher number of THF rings have been found. The 2
and 5 positions of the THF subunits are usually flanked
by a secondary carbinol center. In the mono-THF struc-
tures these positions are attached to hydrocarbon chains,
one of which terminates in a butenolide. The THF resi-
dues in the bis-THF derivatives may be adjacently or
nonadjacently linked. In addition to the number and con-
nectivity of THF rings, structures vary with respect to
the length and degree of oxygenation of the hydrocarbon
chains and the relative and absolute stereochemistry of
the four stereogenic centers in the 2,5-bis(hydroxyalkyl)-
THF subunits. 2,5-trans THF’s are much more predomi-
nant than the cis derivatives (Figure 1).
F igu r e 1. Representative trans-2,5-disubstituted THF aceto-
genins.
There has been considerable interest in the synthesis
of analogues for bioactivity studies3 and in the determi-
The epoxide residue permits entry to derivatives with
different chain length, and the differentiation of the
secondary alcohol positions facilitates the preparation of
analogues in which the configurations at the flanking
carbinol centers can be varied. Furthermore, 1 could be
elaborated into both adjacently and nonadjacently linked
structures.
nation of relative and absolute stereochemistry.4
A
number of different synthetic approaches have been
reported, with the majority centering on the cyclization
of hydroxy olefin and hydroxy epoxide precursors.5-8 We
envisaged the mono-THF 1 as a versatile building block.
† This paper is dedicated to Dr. Erwin Fleissner on his retirement
as Dean of Science and Mathematics at Hunter College.
(1) (a) Rupprecht, J . K.; Hui, Y.-H.; McLaughlin, J . L. J . Nat. Prod.
1990, 53, 237-278. (b) Fang, X.; Rieser, M. J .; Gu, Z.; Zhao, G.;
McLaughlin, J . L. Phytochem. Anal. 1993, 4, 27-48.
(2) For examples of recently isolated acetogenins, see: (a) Hopp, D.
C.; Zeng, L.; Gu, Z.-M.; McLaughlin, J . L. J . Nat. Prod. 1996, 59, 97-
99. (b) Rieser, M. J .; Gu, Z.-M.; Fang, X.- P.; Zeng, L.; Wood, K. V.;
McLaughlin, J . L. J . Nat. Prod. 1996, 59, 100-108.
(3) Naito, H.; Kawahara, E.; Maruta, K.; Maeda, M.; Sasaki, S. J .
Org. Chem. 1995, 60, 4419-4427.
(4) (a) Rieser, M. J .; Hui, Y.-H.; Rupprecht, J . K.; Kozlowski, J . F.;
Wood, K. V.; McLaughlin, J . L.; Hanson, P. R.; Zhuang, Z.; Hoye, T.
R. J . Am. Chem. Soc. 1992, 114, 10203-10213. (b) Fujimoto, Y.;
Murasaki, C.; Shimada, H.; Nishioka, S.; Kakinuma, K.; Singh, S.;
Singh, M.; Gupta, Y. K.; Sahai, M. Chem. Pharm. Bull. 1994, 42, 1175-
1184.
As part of our studies on the use of conformationally
restricted acetals in stereoselective THF synthesis, we
recently showed that 5,6-O-isopropylidene acetal-alkenes
2 on treatment with iodonium ion gave exclusively the
trans-2,5-disubstituted THF 3.9 Notable aspects of this
methodology are the use of experimentally straightfor-
ward procedures, high THF stereoselectivity, and the
dual role of the cyclic acetal as a stereocontrolling
element as well as a protecting group. Application to the
acetogenin synthon 1 calls for a threo-O-isopropylidene-
E-alkene precursor 4, the synthesis of which could benefit
from recent advances in Sharpless asymmetric hydroxy-
lation technology (Scheme 1).10
The first stage in the synthesis was the design of a
suitable diene compound on which an enantioselective
mono-dihydroxylation could be performed. Toward this
end the diene ester 5-E,E was prepared from 4-(benzyl-
oxy)butanal11 in 67% overall yield over three straight-
forward steps: addition of vinylmagnesium bromide to
(5) For
a recent review on the cyclofunctionalization of double
bonds: Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321-3408.
(6) (a) Sinha, S. C.; Sinha, A.; Yazbak, A.; Keinan, E. J . Org. Chem.
1996, 61, 7640-7641 and references to earlier work cited therein. (b)
Sinha, S. C.; Keinan, E. J . Am. Chem. Soc. 1993, 115, 4891-4892.
(7) Hoye, T. R.; Ye, Z. J . Am. Chem. Soc., 1996, 118, 1801-1802
and references to earlier work cited therein.
(8) For alternative synthetic strategies, see: (a) Koert, U. Tetrahe-
dron Lett. 1994, 35, 2517-2520. (b) Trost, B. M.; Shi, Z. J . Am. Chem.
Soc. 1994, 116, 7459-7460. (c) Yao, Z.-J .; Wu, Y. L. J . Org. Chem.
1995, 60, 1170-1176. (d) Figade`re, B.; Peyrat, J .-F.; Cave´, A. J . Org.
Chem. 1997, 62, 3428-3429. (e) Marshall, J . A.; Hinkle, K. W. J . Org.
Chem. 1997, 62, 5989-5995. (f) Marshall, J . A.; Chen, M. J . Org. Chem.
1997, 62, 5996-6000.
(9) Zhang, H.; Mootoo, D. R. J . Org. Chem. 1995, 60, 8134-8135.
(10) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483-2547.
(11) Dawson, M. I.; Vasser, M. J . Org. Chem. 1977, 42, 2783-2785.
S0022-3263(96)01367-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/27/1998

2050 J . Org. Chem., Vol. 63, No. 6, 1998
Notes
Sch em e 1
Sch em e 3
Sch em e 4
Sch em e 2
of 1 with undecylmagnesium bromide in the presence of
copper(I) iodide14 afforded the diol 8. Hydrogenolysis of
8 followed by TEMPO oxidation15 of the resulting triol
led to 9, which was essentially identical (nmr, RD, mp),
to the known compound6b (Scheme 4). Since 9 is a
precursor to solamin and reticulatacin, this sequence
constitutes a formal synthesis of these natural products.
In summary, a concise, straightforward, and high-
yielding synthesis of a relay compound 1, whose structure
is primed for elaboration into a variety of naturally
occurring mono- and bis-THF acetogenins, has been
developed. The strategy capitalizes on the enantioselec-
tivity and regioselectivity of the Sharpless asymmetric
dihydroxylation and the high trans-THF bias in the
iodoetherification of 5,6-O-isopropylidene alkenes. The
synthon 1 was obtained in 44% yield over eight steps
from 4-(benzyloxy)butanal.
Exp er im en ta l Section
TLC was performed on aluminum sheets precoated with silica
gel 60 (HF-254, E. Merck) to a thickness of 0.25 mm. Flash
column chromatography was performed using Kieselgel 60 (230-
400 mesh, E. Merck) and usually employed a stepwise solvent
polarity gradient, correlated with TLC mobility. Unless other-
give the allylic alcohol, followed by a “one-pot” vinyl ether
exchange-Claisen rearrangement protocol,12 and reac-
tion of the resulting aldehyde with (carbomethoxymeth-
ylene)triphenylphosphorane. Treatment of 5-E,E with
AD-mix â for 3 d at 0 °C gave the diol 6 in 90% yield in
greater than 95% ee.13 Isopropylidenation of the diol
residue in 6, thence reduction of the ester, led to the key
isopropylidene E-alkene substrate 4 (Scheme 2).
Treatment of 4 with iodonium dicollidine perchlorate
(IDCP) in 1% aqueous acetonitrile led to formation of a
single trans THF-iodide product 7 in 91% yield. As
expected from our previous work the iodocyclization of
the triol derivative of 4 was less selective, giving a 1:3
mixture of cis:trans THF’s. Accordingly, the trans ster-
eochemistry was tentatively assigned to 7.9 Treatment
of the THF-iodohydrin 7 with K2CO3/MeOH gave the
desired epoxy-THF 1 in 94% yield (Scheme 3).
1
wise stated, H and 13C NMR spectra were recorded at 300 and
75.5 MHz, respectively, in C6D6 or CDCl3 solutions, with CHCl3
or C6H6, respectively, as internal standard.
Meth yl (2E,6E)-10-(Ben zyloxy)-2,6-d eca d ien oa te (5-E,E)
a n d Meth yl (2Z,6E)-(Ben zyloxy)-2,6-d eca d ien oa te (5-Z,E).
Vinylmagnesium bromide (12.5 mL of a 1 M solution in THF,
12.5 mmol) was added dropwise, over a period of 20 min, at 0
°C to a solution of 4-(benzyloxy)butanal11 (1.70 g, 9.60 mmol) in
dry THF (30 mL), under an atmosphere of argon. After stirring
for an additional 30 min, the reaction mixture was diluted with
saturated NH4Cl (30 mL) and extracted with diethyl ether. The
organic phase was dried (Na2SO4), filtered, and concentrated in
vacuo. The residue was purified by flash column chromatogra-
phy to give 6-(benzyloxy)-1-hexen-3-ol (1.78 g, 90%): Rf ) 0.20
(20% EtOAc:petroleum ether); 1H NMR (C6D6) δ 1.53-1.69 (m,
4H), 2.60 (bs, 1H), 3.26 (t, 2H, J ) 6.0 Hz), 3.97 (q, 1 H, J ) 4.5
Hz), 4.29 (s, 2H), 4.95 (bd, 1H, J ) 10.4 Hz), 5.21 (bd, 1H, J )
17.2 Hz), 5.76 (m, 1H), 7.19 (m, 5H); 13C NMR (C6D6) δ 26.2,
34.5, 70.5, 72.6, 72.9, 113.7, 127.6, 127.7, 128.5, 139.2 142.1; MS
(NH3/DCI) m/z 207 (M + H)+.
To confirm the stereochemical assignment, and also to
illustrate its synthetic utility, 1 was converted to the
known THF-lactone 9. Butyrolactones such as 9 have
been used as precursors to mono-THF acetogenins and
adjacently connected oligo-THF’s.6b,8d Thus, treatment
A mixture of the allylic alcohol from the previous step (1.68
g, 8.16 mmol), n-butyl vinyl ether (20 mL), and Hg(OAc)2 (2.54
(12) Nagaoka, H.; Iwashima, M.; Abe, H.; Yamada, Y. Tetrahedron
Lett. 1989, 30, 5911-5914.
(14) Naito, H.; Kawahara, E.; Maruta, K.; Maeda, M.; Sasaki, S. J .
Org. Chem. 1995, 60, 4419-4427.
(15) Siedlecka, R.; Skarzewski, J .; Młochowski, J . Tetrahedron Lett.
1990, 31, 2177-2180.
(13) Enantiomeric excess determined by 1HNMR analysis of the bis-
Mosher ester of 6 (ref 4a). The absolute configuration of 6 was
confirmed by conversion of 6 to 9 (vide infra).

Notes
J . Org. Chem., Vol. 63, No. 6, 1998 2051
g, 7.96 mmol) was heated at reflux for 18 h over an argon
atmosphere. The mixture was then cooled to room temperature,
diluted with saturated aqueous Na2CO3 (20 mL), and extracted
with CH2Cl2. The organic phase was dried (Na2SO4), filtered,
and concentrated in vacuo. Flash column chromatography of
the residual oil afforded 4(E)-8-(benzyloxy)-4-octenal (1.60 g,
85%): Rf ) 0.65 (20% EtOAc:petroleum ether); 1H NMR (C6D6)
δ 1.58 (m, 2H), 1.83 (m, 2H), 2.04 (m, 4H), 3.27 (t, 2H, J ) 6.3
Hz), 4.32 (s, 2H), 5.23 (m, 2H), 7.18 (m, 5H), 9.28 (s, 1H). 13C
NMR (C6D6) δ 25.3, 29.4, 29.9, 43.4, 69.7, 72.9, 127.5, 127.6,
127.7, 128.4, 131.1, 139.0, 200.2; MS (NH3/DCI) m/z 250 (M +
NH4)+, 233 (M + H)+.
CH2Cl2. The organic phase was washed with water, saturated
aqueous NaHCO3, and brine and then dried (Na2SO4), filtered,
and concentrated in vacuo. Purification of the residue by flash
column chromatography gave the isopropylidene alkene 4 (380
mg, 92%): [R]25D ) +20.4° (c 1.0, CHCl3); Rf ) 0.20 (30% EtOAc:
petroleum ether); 1H NMR (C6D6) δ 1.30-2.27 (m, 8H), 1.39 (s,
6H), 3.35 (m, 2H), 3.55 (m, 2H), 3.86 (bs, 2H), 4.31 (s, 2H), 5.53
(m, 2H), 7.20 (m, 5H); 13C NMR (C6D6) δ 26.9, 27.6, 29.2, 29.9,
32.8, 63.3, 70.2, 73.0, 80.7, 81.0, 108.1, 127.7, 127.8, 128.3, 128.4,
130.5, 131.1, 138.0. Anal. Calcd for C20H30O4: C:71.81, H: 9.05.
Found: C: 71.93, H: 9.05.
(4R,5R,8R,9S)-1-(Ben zyloxy)-4,10-d ih yd r oxy-5,8-ep oxy-
9-iod od eca n e (7). IDCP (420 mg, 0.89 mmol) was added to a
solution of isopropylidene alkene 4 (120 mg, 0.36 mmol) in 1%
aqueous CH3CN (10 mL). The solution was stirred for 5 min at
room temperature and then diluted with 10% aqueous Na2S2O3,
(5 mL) and extracted with diethyl ether. The combined organic
phase was dried (Na2SO4), filtered, and concentrated in vacuo.
Purification of the residue by flash column chromatography gave
To a solution of the aforementioned aldehyde (1.2 g, 5.2 mmol)
in CH3CN (80 mL) was added (carbomethoxymethylene)tri-
phenylphosphorane (3.91 g, 11.7 mmol). The mixture was
heated at 60 °C for 40 min and then cooled to room temperature
and filtered. The filtrate was concentrated in vacuo and the
residue purified by flash column chromatography to afford the
2E,6E-methyl ester 5-E,E (1.29 g, 87%) and the 2Z,6E isomer
5-Z,E (0.11 g, 8%). For 5-E,E: Rf ) 0.55 (10% EtOAc: petroleum
ether); 1H NMR (C6D6) δ 1.55 (m, 2H), 1.87 (m, 4H), 2.05 (m,
2H), 3.29 (t, 2H, J ) 6.4 Hz), 3.42 (s, 3H), 4.34 (s, 2H), 5.23 (m,
2H), 5.82 (d, 1H, J ) 15.6 Hz), 7.00 (m, 1H), 7.18 (m, 5H); 13C
NMR (C6D6) δ 29.5, 30.0, 31.2, 32.2, 50.9, 69.7, 72.9, 121.7, 127.5,
127.7, 128.0, 131.2, 139.3, 148.5, 166.4; MS (NH3/DCI) m/z 306
(M + NH4)+; 289 (M + H)+. Anal. Calcd for C18H24O3: C:74.96,
H: 8.38. Found: C: 74.83, H: 8.90. For 5-Z,E: Rf ) 0.50 (10%
EtOAc/petroleum ether); 1H NMR (C6D6) δ 1.60 (m, 2H), 2.04
(m, 4H), 2.78 (q, 2H, J ) 7.2 Hz), 3.28 (t, J ) 6.4 Hz), 3.36 (s,
3H), 4.32 (s, 2H) 5.34 (m, 2H), 5.78 (d, 1H, J ) 11.5 Hz), 5.87
(m, 1H), 7.18 (m, 5H); 13C NMR (C6D6) δ 29.8, 30.2, 30.8, 32.9,
51.2, 70.5, 73.6, 120.6, 127.5, 128.0, 128.7, 130.4, 131.7, 140.3,
150.5, 167.0. MS (NH3/DCI) m/z 306 (M + NH4)+, 289 (M + H)+.
Meth yl (2E,6R,7R)-10-(Ben zyloxy)-6,7-d ih yd r oxy-2-d e-
cen oa te (6). AD-mix-â (4.84 g, 1.4 g/mmol alkene) and meth-
anesulfonamide (329 mg, 3.46 mmol) were added to a solution
of diene 5-E,E (1.0 g, 3.46 mmol) in tert-butyl alcohol (17.3 mL)
and water (17.3 mL). After stirring at 0 °C for 3 d, Na2SO3 (300
mg) was added and the solution extracted with CH2Cl2. The
organic phase was dried (Na2SO4), filtered, and concentrated in
vacuo. Purification of the residue by flash column chromatog-
raphy gave ene diol 6 (1.0 g, 90%): Rf ) 0.15 (30% EtOAc:
petroleum ether); [R]25D ) +15.5° (c 1.0, CHCl3); Rf ) 0.15 (30%
trans-THF 7 (138 mg, 91%): [R]25 ) +11.3° (c 0.8, CHCl3); Rf
D
) 0.20 (30% EtOAc:petroleum ether); 1H NMR (400 MHz, C6D6)
δ 1.20-1.50 (m, 5H), 1.68 (m, 1H), 1.88 (m, 2H), 2.44 (bs, 1H,
D2O exchange), 2.72 (bs, 1H, D2O exchange), 3.17 (m, 1H), 3.31
(m, 2H), 3.65 (m, 2H), 3.79 (m, 2H), 3.90 (m, 1H), 4.31 (s, 2H),
7.18 (m, 5H); 13C NMR (C6D6) δ 27.1, 28.6, 31.5, 34.6, 41.5, 68.0,
71.0, 73.7, 74.2, 82.6, 84.7, 127.7, 128.0, 128.3, 139.2; MS (NH3/
DCI) m/z 438 (M + NH4)+. Anal. Calcd for C17H25O4I: C: 48.56,
H: 6.00. Found: C: 48.57, H: 6.29.
(4R ,5R ,8R ,9R )-1-(B e n zy lo x y )-5,8:9,10-d ie p o x y -4-h y -
d r oxyd eca n e (1). K2CO3 (100 mg) was added to a solution of
compound 7 (50 mg, 0.12 mmol) in MeOH (5 mL). The reaction
mixture was stirred for 5 min at room temperature and then
diluted with water (5 mL) and extracted with CH2Cl2. The
organic phase was dried (Na2SO4), filtered, and concentrated in
vacuo. The residue was purified by flash column chromatogra-
phy to give 1 (33 mg, 94%): [R]25 ) +13.1° (c 0.9, CHCl3); Rf )
D
0.20 (30% EtOAc:petroleum ether); 1H NMR (C6D6) δ 1.21-1.97
(m, 8H), 2.38 (m, 2H), 2.59 (m, 1H), 3.26 (m, 1H), 3.38 (m, 2H),
3.48 (m, 1H), 3.67 (m, 1H), 4.29 (ABq, 2H, ∆δ ) 0.08 ppm, J )
13.0 Hz), 7.21 (m, 5H); 13C NMR (C6D6) δ 26.5, 28.1, 29.3, 30.9,
43.3, 53.9, 70.5, 72.9, 73.7, 78.8, 83.6; 127.7, 128.0, 128.3, 139.4;
HRCIMS calcd for C17H24O4 (M + H)+ 293.1753. Found 293.1758.
(4R,5R,8R,9R)-1-(Ben zyloxy)-5,8-ep oxy-4,9-d ih yd r oxy-
h en icosa n e (8). A solution of undecylmagnesium bromide (5.0
mL of a ca. 0.4 M solution in THF, 6.0 mmol) was added dropwise
to a suspension of CuBr (30 mg, 0.21 mmol) in anhydrous THF
(2 mL) at 0 °C. A solution of 1 (98 mg, 0.34 mmol) in anhydrous
THF (1 mL) was then introduced at 0 °C, and the reaction
mixture was stirred for 2 h at this temperature. At this time
saturated aqueous NH4Cl/aqueous ammonia (9/1, 10 mL) was
added and the mixture extracted with diethyl ether. The organic
phase was dried (Na2SO4), filtered, and concentrated in vacuo.
The residue was purified by flash column chromatography to
give 8 (101 mg, 67%): Rf ) 0.75 (50% EtOAc:petroleum ether);
1H NMR (C6D6) δ 0.92 (t, 3H, J ) 7.5 Hz), 1.18-1.90 (m, 29H),
1.99 (m, 1H), 3.36 (m, 4H), 3.62 (m, 2H), 4.34 (m, 2H), 7.20 (m,
5H). 13C NMR (C6D6) 14.6, 23.8, 26.9, 27.3, 29.8, 30.7, 31.1, 31.4,
33.3, 34.8, 71.4, 73.8, 75.0, 75.2, 83.9, 84.2, 127.7, 128.0, 128.2,
139.5. HRCIMS calcd for C28H49O4 (M + H)+ 449.3622. Found
449.3631.
1
EtOAc:petroleum ether); H NMR (C6D6) δ 1.29-1.80 (m, 6H),
2.05-2.23 (m, 2H), 3.15-3.40 (m, 4H), 3.42 (s, 3H), 4.29 (s, 2H),
5.88 (d, 1H, J ) 15.6 Hz), 7.03-7.31 (m, 5H); 13C NMR (C6D6) δ
26.2, 28.4, 30.8, 31.9, 50.6, 70.3, 72.8, 73.5, 74.0, 121.2, 127.4,
128.5, 127.7, 127.8, 138.2, 149.1, 166.5. Anal. Calcd for
C18H26O5: C: 67.05, H: 8.12. Found: C: 66.73, H: 8.38.
The %ee of 6 was determined by preparation of the bis-(R)-
MTPA ester of 6 and comparison of its 1HNMR spectrum with
the bis-(R)-MTPA ester mixture of racemic 6 obtained from the
OsO4 reaction on 5-E,E. The ee was determined to be greater
than 95%.4a
(2E,6R,7R)-10-(Ben zyloxy)-6,7-(isop r op ylid en ed ioxy)-2-
d ecen e (4). 2,2-Dimethoxypropane (0.30 mL, 2.48 mmol) and
(()-10-camphorsulfonic acid (22 mg, 0.09 mmol) were added to
a solution of diol 6 (400 mg, 1.24 mmol) in anhydrous CH2Cl2
(20 mL). The reaction mixture was stirred for 30 min and then
neutralized by addition of 1 M NaOMe/MeOH. The solvent was
removed in vacuo and the residue purified by flash column
chromatography to yield the isopropylidene ester (419 mg,
THF -la cton e (9). Formic acid (0.05 mL) was added under
argon to a mixture of 8 (74 mg, 0.17 mmol) and 10% palladium
on carbon (25 mg) in methanol (5 mL). The reaction mixture
was stirred over an atmosphere of hydrogen for 18 h and then
purged with argon and filtered through a pad of Celite. The
filtrate was evaporated and the residue subjected to flash
chromatography to give the debenzylated triol product (42 mg,
71%). Rf ) 0.20 (50% EtOAc:petroleum ether); 1H NMR (C6D6)
δ 0.92 (t, J ) 7.5 Hz, 3H), 1.20-1.86 (m, 30H), 3.42 (m, 1H),
3.50-3.80 (m, 3H), 4.30-4.54 (m, 2H); 13C NMR (C6D6) δ 14.7,
23.5, 26.5, 29.4, 29.5, 29.9, 30.2, 30.6, 31.1, 32.7, 34.1, 63.1, 74.9,
83.2, 83.6.
A flask was charged with a solution of the triol from the
previous step (20.0 mg, 0.056 mmol) in CH2Cl2 (1 mL), TEMPO
(0.1 mg, 0.001 mmol), saturated aqueous NaHCO3 (0.8 mL), KBr
(6.6 mg 0.06 mmol) and nBu4NCl (0.8 mg, 0.003 mmol). To this
cooled (0 °C) and well-stirred mixture was added a solution made
93%): [R]25 ) +23.3° (c 1.9, CHCl3); Rf ) 0.80 (10% EtOAc:
D
petroleum ether); 1H NMR (C6D6) δ 1.26-2.11 (m, 8H), 1.33, 1.34
(both s, 6H), 3.42 (s, 3H), 3.22-3.52 (m, 4H), 4.32 (s, 2H), 5.84
(d, 1H, J ) 15.6 Hz), 6.97 (dt, 1H, J ) 3.5, 15.7 Hz), 7.18 (m,
5H); 1H NMR (C6D6) δ 26.6, 27.2, 28.7, 29.5, 31.1, 50.6, 69.8,
72.7, 80.1, 80.6, 107.8, 121.4, 127.4, 127.5, 127.7, 128.2, 138.0,
148.2, 166.2; MS (NH3/DCI) m/z 380 (M + NH4)+, 363 (M + H)+.
DIBALH (2.58 mL, 1 M in heptane, 2.58 mmol) was added to
a solution of the isopropylidene ester obtained from the previous
step (450 mg, 1.29 mmol), in anhydrous CH2Cl2 (20 mL) at -40
°C, under an atmosphere of argon. The reaction was stirred at
this temperature for 30 min and then quenched by the addition
of MeOH and warmed to room temperature. Saturated aqueous
potassium sodium tartrate (20 mL) was added, and the mixture
stirred for an additional 1 h and then extracted with with

2052 J . Org. Chem., Vol. 63, No. 6, 1998
Additions and Corrections
of NaClO (0.11 mL of a 2.0 M aqueous solution, 0.22 mmol),
saturated aqueous NaHCO3 (0.8 mL), and brine (1.5 mL)
dropwise over 45 min. The mixture was stirred for 1 h at 0 °C
and then for 20 min at 20 °C. The progress of the reaction was
carefully monitored by TLC. The aqueous phase was extracted
with CH2Cl2, and the combined extracts were washed with
saturated aqueous NaHCO3 and brine, dried (Na2SO4), and
filtered. Evaporation of the solvent and flash chromatography
of the crude residue gave 9 (12.0 mg, 61%); Rf ) 0.50 (50%
Ack n ow led gm en t . This investigation was sup-
ported in part by a “Research Centers in Minority
Institutions” award, RR-03037, from the Division of
Research Resources, National Institutes of Health.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of (4E)-8-(benzyloxy)-4-octenal, 1, 4, 5-E,E, 5-Z,E, 6,
6-bis-MTPA ester, (()-6-bis-MTPA ester, 7, 8, and 9 (28 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
EtOAc:petroleum ether); mp 94-96 °C; [R]25 ) -7.16° (c
D
0.72, CHCl3). Literature: 95-96 °C; [R]25 ) -7.36° (c 1.44,
D
CHCl3). 1H NMR (CDCl3) was identical to previously prepared
9.6b HRCIMS calcd for C21H39O4 (M + H)+ 355.2848. Found
355.2848.
J O961367I
Additions and Corrections
Vol. 61, 1996
Na ok i Asa o, Ta k a sh i Sh im a d a , Tom ok o Su d o, Na ofu m i
Tsu k a d a , Ka zu h ik o Ya za w a , You n g Soo Gyou n g, Ta d a o
F e´lix Bu squ e´, P ed r o d e Ma r ch ,* Ma r ta F igu er ed o,
J osep F on t,* Mon tser r a t Mon sa lva tje, Alber t Vir gili,
AÄ n gel AÄ lva r ez-La r en a , a n d J u a n F . P in iella . Diastereofacial
Selectivity in the Cycloaddition of Nitrones to (E)-γ-Oxygenated
R,â-Unsaturated Esters.
Uyeh a r a , a n d Yosh in or i Ya m a m oto*. Highly Diastereose-
lective Conjugate Addition of Lithium Dialkylamides to R,â-
Unsaturated Esters Having a Chiral Center at the γ-Position.
Page 6282. The following acknowledgment should be
added.
Page 8578. Charts 1 and 3. Formula 6 in Chart 1 and
formulae 11a ,b and 17a -d in Chart 3 should have the
opposite absolute configuration at the chiral center.
Corrected structures are as follows:
Ack n ow led gm en t. Prof. Y. S. Gyoung acknowledges
financial support from the Korean Science and Engineer-
ing Foundation (956-0300-001-2).
J O9740352
S0022-3263(97)04035-8
Published on Web 02/24/1998
La´szlo´ P osza´va´cz a n d Gyu la Sim ig*. Synthesis of 4-Amino-
5H-1,2-oxathiole 2,2-Dioxides by Cyclization of Cyanohydrin
Mesylates. New Routes to â-Amino and â-Keto Sulfonic Acids.
J O9740305
Page 7021, column 2, 15th line. With respect to the
sentence “To the best of our knowledge, compounds 3 are
the first 4-amino substituted 1,2-oxathioles, which may
find interesting applications in organic synthesis.”, we
regret our failure to mention the pioneering studies
reported by Dr. Mar´ıa-J ose´ Camarasa and his co-workers
on the cyclization of cyanohydrin mesylates to 4-amino
substituted 1,2-oxathioles. References are given below:
S0022-3263(97)04030-9
Published on Web 02/24/1998
Vol. 62, 1997
Nobu ya Ka ta gir i,* Ma sa h ir o Ta k eba ya sh i, Hid ea k i
Kok u fu d a , Ch ik a r a Ka n ek o, Kou ich i Ka n eh ir a , a n d
Ma sa h ir o Tor ih a r a . Efficient Synthesis of Carbovir and Its
Congener via π-Allylpalladium Complex Fomation by Ring
Strain-Assisted C-N Bond Cleavage.
(1) Calvo-Mateo, A.; Camarasa, M. J .; D´ıaz-Ort´ız, A.;
de las Heras, F. G. J . Chem. Soc., Chem. Commun. 1988,
1114.
Page 1580. Reference 3a should read as follows:
Daluge, S. M.; Good, S. S.; Martin, M. T.; Tibbels, S. R.;
Miller, W. H.; Averett, D. R.; Clair, M. S. St.; Ayers, K.
M. In Abstracts of the 34th interscience Conference on
Antimicrobial Agents and Chemotherapy; American So-
ciety for Microbiology: Washington, DC, 1994; Abstr. I6,
p 7.
(2) Pe´rez-Pe´rez, M. J .; Balzarini, J .; Hosoya, M.; De
Clercq, E.; Camarasa, M. J . BioMed. Chem. Lett. 1992,
2, 647.
(3) Camarasa, M. J .; Pe´rez-Pe´rez, M. J .; San-Fe´lix, A.;
Balzarini, J .; De Clercq, E. J . Med. Chem. 1992, 35, 2721.
J O974034+
J O974033H
S0022-3263(97)04034-6
S0022-3263(97)04033-4
Published on Web 02/24/1998
Published on Web 03/03/1998