Reactivity of α-(benzoyloxy)crotylstannane with aldehydes in liquid phase and on solid support. Synthesis of substituted lactones

Full text of DOI:10.1021/jo010152s

J . Org. Chem. 2001, 66, 7195-7198
7195
Ta ble 1. Syn th esis of En ol Ben zoa te Ad d u cts
Rea ctivity of r-(Ben zoyloxy)cr otylsta n n a n e
3:4:5a
w ith Ald eh yd es in Liqu id P h a se a n d on
Solid Su p p or t. Syn th esis of Su bstitu ted
La cton es
series
R
yield (%)
a
b
c
d
e
Ph
70
58
62
48
52
74:9:17
84:8:8
67:20:13
63:<1:37
36:<1:64
p-ClC6H4
p-NO2C6H4
n-C6H13
J anine Cossy,* Chrystelle Rasamison, and
Domingo Gomez Pardo
c-C6H11
Ratios determined by 1H NMR spectra on the crude.
a
Laboratoire de Chimie Organique associe´ au CNRS, ESPCI,
10 rue Vauquelin, 75231 Paris Cedex 05, France
rification of these adducts can be difficult because of tin
byproducts, which are often not easily removed. Thus,
by developing a solid-support application of these reac-
tions we could expect to solve this purification problem.
Our initial plan was to prepare the R-oxygenated
crotylstannane reagent of type A through addition of the
hydroxy stannane 15 (from crotonaldehyde and Bu3SnLi)6
to a polystyrene-supported chloropyran7 (Scheme 1, eq
1). However, the tetrahydropyranyl ethers A could not
be prepared.
It is possible that polymeric resins incorporating a
ROCH2Cl grouping would permit the preparation of
supported R-oxygenated crotylstannanes, but instead of
exploring this option, we elected to examine supported
benzoate derivatives of type B. These could be readily
prepared through esterification of the R-hydroxy stan-
nane 1 with a readily available polystyrene carboxylic
acid (Scheme 1, eq 2).
However, as Lewis acid-promoted additions of R-acyl-
oxyallylic stannanes to aldehydes had not previously been
examined, we felt it was necessary to first carry out
preliminary solution-phase studies to establish the scope
and feasibility of such additions. Accordingly, the ben-
zoate reagent 28 was prepared by benzoylation of the
hydroxycrotylstannane 1 (Scheme 2). This stannane was
treated with a series of aldehydes in the presence of
excess BF3‚OEt2 at -78 °C in CH2Cl2 to afford various
enol benzoate adducts (Table 1).
The stereochemistry of the double bond in adducts 3-5
was deduced from the 1H NMR spectrum of each mixture.
These spectra also provided the isomer ratios. The
relative stereochemistry was initially assigned by analogy
with the previously reported reactions of the OMOM or
OBOM analogues.3,4 The assignments were confirmed by
conversion to the known lactones 7 and 8 after cleavage
of the enol benzoates with NaOMe and oxidation of the
resulting lactols 6 with PCC as summarized in Scheme
3 and Table 2. These findings show that the reactivity of
R-(benzoyloxy)crotylstannanes in Lewis acid promoted
additions to aldehydes is similar to that of R-(alkoxy)-
crotylstannanes, except for p-nitrobenzaldehyde, which
gave more of the anti-Z isomer 4c (Table 1) than that
obtained with the R-(alkoxy)crotylstannanes.4c
janine.cossy@espci.fr
Received February 7, 2001
Solid-phase synthesis1 has gained in popularity as a
result of its relative ease of automation and the emer-
gence of high-throughput screening. Combinatorial chem-
istry had its beginnings with the sequential synthesis of
peptide libraries on solid supports and is now being
applied to the synthesis of catalysts, polymers, pharma-
ceutical lead compounds, and more recently, complex
natural products such as epothilone.2 The application of
combinatorial synthesis methods to various classes of
chiral organic backbone structures such as polypropi-
onates, which are present in a great number of biologi-
cally interesting natural products, represents a challenge
for modern organic chemistry. Although these compounds
can be synthesized in solution, the workup and removal
of byproducts can be tedious.
Recent studies by Marshall3 and Gung4 have shown
that in the presence of a Lewis acid R-(alkoxy)crotylstan-
nanes add to aldehydes to produce polypropionate inter-
mediates with high stereoselectivity. However, the pu-
(1) For reviews, see: (a) Brown, R. C. D. J . Chem. Soc., Perkin Trans.
1 1998, 3293. (b) Booth, S.; Hermkens, P. H. H.; Ottenheijm, H. C. J .;
Rees, D. C. Tetrahedron 1998, 54, 15385. (c) Blackburn, C.; Albericio,
F.; Kates, S. A. Drugs Future 1997, 22, 1007. (d) Hermkens, P. H. H.;
Ottenheijm, H. C. J .; Rees, D. C. Tetrahedron 1997, 53, 5643. (e)
Balkenhohl, F.; Von dem Bussche-Hu¨nnefeld, C.; Lansky, A.; Zechel,
C. Angew. Chem., Int. Ed. Engl. 1996, 35, 2288. (f) Hermkens, P. H.
H.; Ottenheijm, H. C. J .; Rees, D. C. Tetrahedron 1996, 52, 4527. (g)
Thompson, L. A.; Ellman, J . A. Chem. Rev. 1996, 96, 555. (h) Fru¨chtel,
J . S.; J ung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17. (i) Terrett,
N. K.; Gardner, M.; Gordon, D. W.; Kobylecki, R. J .; Steele, J .
Tetrahedron 1995, 51, 8135. (j) Gordon, E. M.; Barrett, R. W.; Dower,
W. J .; Fodor, S. P. A.; Gallop, M. A. J . Med. Chem. 1994, 37, 1385. (k)
Gallop, M. A.; Barrett, R. W.; Dower, W. J .; Fodor, S. P. A.; Gordon, E.
M. J . Med. Chem. 1994, 37, 1233.
(2) (a) Cargill, J . F.; Lebl, M. Curr. Opin. Chem. Biol. 1997, 1, 67.
(b) Spaller, M. R.; Burger, M. T.; Fardis, M.; Bartlett, P. A. Curr. Opin.
Chem. Biol. 1997, 1, 47. (c) Gravert, D. J .; J anda, K. D. Chem. Rev.
1997, 97, 489. (d) Pirrung, M. C. Chem. Rev. 1997, 97, 473. (e) Nefzi,
A.; Ostresh, J . M.; Houghten, R. A. Chem. Rev. 1997, 97, 449. (f)
Nicolaou, K. C.; Vourloumis, D.; Li, T.; Pastor, J .; Winssinger, N.; He,
Y.; Ninkovic, S.; Sarabia, F.; Vallberg, H.; Roschangar, F.; King, N.
P.; Finlay, M. R. V.; Giannakakou, P.; Verdier-Pinard, P.; Hamel, E.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2097.
Since R-(benzoyloxy)crotylstannanes and R-(alkoxy)-
crotylstanannes behave similarly in Lewis acid promoted
additions to aldehydes, we decided to examine the solid-
phase reactions. The commercially available carboxylic
polystyrene resin13 was treated with stannane 1, 1-(3-
(3) (a) Marshall, J . A. Chem. Rev. 1996, 96, 31. (b) Marshall, J . A.;
J ablonowski, J . A.; Welmaker, G. J . J . Org. Chem. 1996, 61, 2904. (c)
Marshall, J . A.; Yashunsky, D. V. J . Org. Chem. 1991, 56, 5493. (d)
Marshall, J . A.; Welmaker, G. J . Tetrahedron Lett. 1991, 32, 2101. (e)
Marshall, J . A.; Gung, W. Y. Tetrahedron 1989, 45, 1043. (f) Marshall,
J . A.; Gung, W. Y. Tetrahedron Lett. 1988, 29, 1657. (g) Marshall, J .
A.; Crooks, S. L.; DeHoff, B. S. J . Org. Chem. 1988, 53, 1616. (h)
Marshall, J . A.; DeHoff, B. S.; Crooks, S. L. Tetrahedron Lett. 1987,
28, 527.
(4) (a) Gung, B. W.; Wolf, M. A. J . Org. Chem. 1992, 57, 1370. (b)
Gung, B. W.; Smith, D. T.; Wolf, M. A. Tetrahedron 1992, 48, 5455. (c)
Gung, B. W.; Smith, D. T.; Wolf, M. A. Tetrahedron Lett. 1991, 32, 13.
(d) Gung, B. W.; Peat, A. J .; Snook, B. M.; Smith, D. T. Tetrahedron
Lett. 1991, 32, 453.
(5) Pratt, A. J .; Thomas, E. J . J . Chem. Soc., Chem. Commun. 1982,
1115.
(6) Still, W. C. J . Am. Chem. Soc. 1978, 100, 1481.
(7) Cossy, J .; Rasamison, C.; Gomez Pardo, D. Unpublished results.
(8) Pratt, A. J .; Thomas, E. J . J . Chem. Soc., Perkin Trans. 1 1989,
1521.
10.1021/jo010152s CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/18/2001

7196 J . Org. Chem., Vol. 66, No. 21, 2001
Notes
Sch em e 1
Sch em e 2
Sch em e 4
Sch em e 3
Ta ble 3. Syn th esis of La cton es on Solid Su p p or t
series
R
yielda (%)
7:8b
Ta ble 2. Syn th esis of La cton es 7a -e a n d 8a -e
a
b
c
d
e
Ph
70
82
72
63
61
93:7
89:11
75:25
100:0
100:0
series
R
yielda (%)
7:8b
p-ClC6H4
p-NO2C6H4
n-C6H13
a
b
c
d
e
Ph8,9
p-ClC6H4
66
47
70
40
60
93:7
90:10
72:28
100:0
100:0
8,10
8
c-C6H11
p-NO2C6H4
8,11
a
b
n-C6H13
c-C6H11
The yields are reported for the four-step process. Ratios
12
determined by 1H NMR spectra on the crude.
a
b
The yields are reported for the two-step process. Ratios
determined by 1H NMR spectra on the crude.
NaOMe in MeOH-THF (1/4) at 40 °C15 to yield the lactol
products 6, which were directly oxidized to the corre-
sponding lactones 7 and 8 in 60%-80% overall yield over
four steps (Scheme 4). The results are summarized in
Table 3.
The lactones were obtained with a diastereoselectivity
similar to that of the liquid-phase synthesis. Yields were
high (60-80%), and the products were not contaminated
by tin byproducts. Thus, it is clear that this solid-phase
strategy could be useful for the preparation of lactone
libraries.
dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
(EDCI), and 4-(dimethylamino)pyridine (DMAP) in CH2-
Cl2 to give the supported ester derivative B.14 The
aldehyde was introduced at room temperature, and BF3‚
OEt2 was added dropwise at -78 °C. After 5 h, the resin
was washed, and then the enol ester C was cleaved with
(9) (a) Frenette, R.; Kakushima, M.; Zamboni, R.; Young, R. N.;
Verhoeven, T. R. J . Org. Chem. 1987, 52, 304. (b) Tokuda, M.;
Yokoyama, Y.; Taguchi, T.; Suzuki, A.; Itoh, M. J . Org. Chem. 1972,
37, 1859.
(10) Satoh, M.; Washida, S.; Takeuchi, S.; Asaoka, M. Heterocycles
2000, 52, 227.
(11) Fukuzawa, S.-I.; Seki, K.; Tatsuzawa, M.; Mutoh, K. J . Am.
Chem. Soc. 1997, 119, 1482.
(12) (a) Frenette, R.; Monette, M.; Bernstein, M. A.; Young, R. N.;
Verhoeven, T. B. J . Org. Chem. 1991, 56, 3083. (b) Otsubo, K.; Inanaga,
J .; Yamaguchi, M. Tetrahedron Lett. 1986, 27, 5763.
(13) The carboxylic polystyrene resin (1% DVB cross-linked) with a
loading of 2 mmol/g was purchased from Advanced Chemtech.
(14) Cossy, J .; Rasamison, C.; Gomez Pardo, D.; Marshall, J . A.
Synlett 2001, 629.
Exp er im en ta l Section
Gen er a l Meth od s. Unless otherwise specified, materials
were purchased from commercial suppliers and used without
further purification. THF was distilled from Na/benzophenone-
ketyl immediately prior to use. CH2Cl2, i-Pr2NH, and i-Pr2NEt
(15) Dilley, G. J .; Durgin, T. L.; Powers, T. S.; Winssinger, N. A.;
Zhu, H.; Pavia, M. R. Mol. Div. 1995, 1, 13.

Notes
J . Org. Chem., Vol. 66, No. 21, 2001 7197
were distilled from calcium hydride under argon. Moisture-
sensitive reactions were conducted in oven-dried glassware
under an argon atmosphere. Analytical thin-layer chromatog-
7.53-7.40 (m, 2 H), 7.35-7.15 (m, 5 H), 5.52 (dd, J ) 12.5, 8.5
Hz, 0.08 H), 4.97 (dd, J ) 9.6, 6.2 Hz, 0.08 H), 4.84 (dd, J ) 9.9,
6.6 Hz, 0.84 H), 4.65-4.50 (m, 1 H), 3.29-3.09 (m, 1 H), 2.85
(bs, 1 H), 1.17 (d, J ) 6.6 Hz, 2.52 H), 1.05 (d, J ) 6.6 Hz, 0.24
H), 1.01 (d, J ) 7.0 Hz, 0.24 H).13C NMR for the major
diastereomer (75 MHz, CDCl3): δ 163.2 (s), 141.1 (s), 134.4 (d),
133.5 (d), 133.1 (s),129.8 (d), 128.9 (s), 128.4 (d), 128.2 (d), 127.8
(d), 115.9 (d), 76.8 (d), 37.4 (d), 16.0 (q).
raphy was performed on Merck precoated silica gel (60 F254
)
plates, and flash column chromatography was accomplished on
Merck Kieselgel 60 (230-400 mesh). HRMS were obtained from
Centre de Spectrochimie Organique de l’Ecole Normale Su-
pe´rieure de Paris. NMR spectra were recorded at 300 MHz (1H)
or 75 MHz (13C) in CDCl3 as solvent. Chemical shifts (δ) are
expressed in ppm relative to residual CHCl3 at δ ) 7.27 for 1H
and to CDCl3 at δ ) 77.1 for 13C. MS: Mass spectra were
obtained by GC/MS with electron-impact ionization at 70 eV.
Only selected ions are reported.
3-Meth yl-4-(4-n itr op h en yl)-1-bu ten e-1,4-d iol Mon oben -
zoa te (3c, 4c, 5c). Following the procedure outlined above for
benzaldehyde, p-nitrobenzaldehyde (0.19 g, 1.3 mmol) afforded
an oil that was purified by flash column chromatography on
silica gel (EtOAc/cyclohexane 20/80) to give an inseparable
mixture (ratio 67/20/13 according to 1H NMR) of diastereomers
syn-(Z) 3c, anti-(Z) 4c, and syn-(E) 5c (0.18 g, 0.54 mmol, 62%
yield) as an oil. IR (neat): 3522, 1729, 1522, 1347, 1265, 1110
(E)-1-Ben zoyloxy-2-bu ten yl(tr ibu tyl)stan n an e (2). Tribut-
yltin hydride (6.7 mL, 24.9 mmol, 1 equiv) was added to a
solution of LDA (24.9 mmol, 1 equiv) in THF (50 mL) at 0 °C.
After 15 min, the solution was cooled to -78 °C, and crotonal-
dehyde (2.06 mL, 24.9 mmol, 1 equiv) was added dropwise. After
30 min, the reaction was quenched by addition of an aqueous
NH4Cl solution (0.9 M, 60 mL) and warmed to 20 °C. The
aqueous layer was extracted with Et2O, and the combined
organic phases were dried over MgSO4 and filtered. The solvent
was removed in vacuo, and (E)-1-(tributylstannyl)-2-buten-1-ol
1 was obtained as an unstable yellow oil used immediately
without purification. Crude 1 was added to a solution of DMAP
(1.5 g, 12.48 mmol, 0.5 equiv), i-Pr2NEt (8.9 mL, 50 mmol, 2
equiv), and benzoyl chloride (4.4 mL, 37.4 mmol, 1.5 equiv) in
anhydrous CH2Cl2 (20 mL) at 0 °C. The reaction mixture was
allowed to warm slowly to room temperature. After 16 h at room
temperature, the organic layer was washed with an aqueous HCl
solution (0.5 M). After drying over MgSO4, the solvent was
removed in vacuo to afford an oil that was purified by flash
column chromatography on silica gel (eluting with a gradient of
0-0.5% of EtOAc in cyclohexane) to give 2 (10.4 g, 22.4 mmol,
90% yield) as a yellow oil. IR (neat): 1702, 1450, 1335, 1271,
1
cm-1. H NMR (300 MHz, CDCl3): δ 8.20-7.90 (m, 4 H), 7.67-
7.40 (m, 5 H), 7.19-7.14 (m, 0.33 H), 7.18 (dd, J ) 6.6, 1.1 Hz,
0.67 H), 5.54 (dd, J ) 12.5, 8.1 Hz, 0.13 H), 4.97 (dd, J ) 9.6,
6.2 Hz, 0.2 H), 4.87 (dd, J ) 9.9, 6.6 Hz, 0.67 H), 4.78 (d, J )
5.2 Hz, 0.13 H), 4.72 (d, J ) 6.2 Hz, 0.87 H), 3.20 (m, 1 H), 2.85
(bs, 1 H), 1.15 (d, J ) 7.0 Hz, 2.01 H), 1.12-1.02 (m, 0.99 H).13
C
NMR for the major diastereomer (75 MHz, CDCl3): δ 163.1 (s),
150.2 (s), 147.0 (s), 134.7 (d), 133.6 (d), 129.6 (d), 128.6 (d), 127.2
(d), 123.0 (d),115.4 (d), 76.7 (d), 37.5 (d), 15.7 (q).
3-Meth yl-1-d ecen e-1,4-d iol Mon oben zoa te (3d , 5d ). Fol-
lowing the procedure outlined above for benzaldehyde, heptanal
(0.18 mL, 1.3 mmol) afforded an oil that was purified by flash
column chromatography on silica gel (EtOAc/cyclohexane 8/92)
to give an inseparable mixture (ratio 63/37 according to 1H NMR)
of diastereomers syn-(Z) 3d and syn-(E) 5d (0.12 g, 0.41 mmol,
48% yield) as an oil. IR (neat): 3445, 1729, 1452, 1265, 1113,
1027 cm-1 1H NMR (300 MHz, CDCl3): δ 8.13-8.05 (m, 2 H),
.
7.65-7.55 (m, 1 H), 7.52-7.42 (m, 2 H), 7.38 (dd, J ) 12.5, 1.1
Hz, 0.37 H), 7.32 (dd, J ) 6.6, 1.1 Hz, 0.63 H), 5.61 (dd, J )
12.5, 8.8 Hz, 0.37 H), 4.93 (dd, J ) 9.7, 6.4 Hz, 0.63 H), 3.58-
3.45 (m, 1 H), 3.04-2.87 (m, 0.63 H), 2.60 (bs, 1 H), 2.40-2.30
(m, 0.37 H), 1.13 (d, J ) 6.6 Hz, 1.89 H), 1.11 (d, J ) 7.0 Hz,
1.11 H), 1.75-0.80 (m, 13 H). 13C NMR (75 MHz, CDCl3): δ 163.7
(s), 163.3 (s), 136.0 (d), 134.1 (d), 133.4 (d), 133.3 (d), 129.8 (d),
129.0 (s), 128.4 (d), 128.3 (d), 117.7 (d), 117.0 (d), 75.3 (d), 75.1
(d), 38.5 (d), 36.0 (d), 34.4 (t), 33.9 (t), 31.7 (t), 30.0 (t), 29.5 (t),
29.1 (t), 27.7 (t), 26.7 (t), 25.7 (t), 22.4 (t), 15.9 (q), 15.2 (q), 13.9
(q), 13.4 (q).
1
1115, 1069 cm-1. H NMR (300 MHz, CDCl3): δ 8.10-8.04 (m,
2 H), 7.59-7.51 (m, 1 H), 7.49-7.40 (m, 2 H), 5.82 (ddq, J )
15.1, 6.6, 1.5 Hz, 1 H), 5.60 (dt, J ) 7.0, 1.5 Hz, 1 H), 5.58-5.44
(m, 1 H), 1.75 (dt, J ) 6.6, 1.5 Hz, 3 H), 1.60-1.47 (m, 6 H),
1.38-1.23 (m, 6 H), 1.03-0.82 (m, 15 H). 13C NMR (75 MHz,
CDCl3): δ 166.2 (s), 132.6 (d), 130.5 (d), 130.0 (s), 129.4 (d), 128.1
(d), 119.6 (d), 72.2 (d), 28.7 (t), 27.6 (t), 17.6 (q), 13.5 (q), 7.9 (t).
MS (EI, relative intensity): m/z 409 (M.+ - Bu., 99), 353 (24),
291 (32), 235 (80), 179 (99), 121 (24), 105 (100), 77 (40), 69 (35).
HRMS (EI): calcd for C23H38O2Sn (M.+) 467.1972, found 467.1991.
3-Meth yl-4-p h en yl-1-bu ten e-1,4-d iol Mon oben zoa te (3a ,
4a , 5a ). To a solution of benzaldehyde (0.13 mL, 1.3 mmol, 1.5
equiv) and (E)-1-benzoyloxy-2-butenyl(tributyl)stannane 2 (0.40
g, 0.87 mmol, 1 equiv) in CH2Cl2 (10 mL) at -78 °C was added
4-Cycloh exyl-3-m eth yl-1-bu ten e-1,4-d iol Mon oben zoa te
(3e, 5e). Following the procedure outlined above for benzalde-
hyde, cyclohexanecarboxaldehyde (0.16 mL, 1.3 mmol) afforded
an oil that was purified by flash column chromatography on
silica gel (EtOAc/cyclohexane 8/92) to give an inseparable
mixture (ratio 36/64 according to 1H NMR) of diastereomers syn-
(Z) 3e and syn-(E) 5e (0.13 g, 0.45 mmol, 52% yield) as an oil.
.
BF3 OEt2 (0.16 mL, 1.3 mmol, 1.5 equiv). After 5 h, the reaction
was quenched with a saturated aqueous NaHCO3 (5 mL),
extracted with ether, washed with a saturated aqueous NaCl
solution, dried over MgSO4, and concentrated under reduced
pressure. The crude product was purified by flash column
chromatography on silica gel (EtOAc/cyclohexane 9/91) to give
IR (neat): 3422, 1727, 1451, 1337, 1265, 1120 cm-1 1H NMR
.
(300 MHz, CDCl3): δ 8.10 (d, J ) 8.5 Hz, 2 H), 7.65-7.35 (m,
3.37 H), 7.28 (d, J ) 7.0 Hz, 0.64 H), 5.63 (dd, J ) 12.5, 8.5 Hz,
0.64 H), 4.96 (dd, J ) 9.7, 6.4 Hz, 0.37 H), 3.30-3.20 (m, 0.64
H), 3.12-3.02 (m, 0.37 H), 2.55-2.45 (m, 1 H), 1.98-1.85 (m, 1
H), 1.80-0.90 (m, 13 H). 13C NMR (75 MHz, CDCl3): δ 163.7
(s), 163.4 (s), 135.7 (d), 133.6 (d), 133.4 (d), 133.3 (d), 129.8 (d),
129.7 (d), 129.0 (s), 128.3 (d), 128.1 (d), 118.7 (d), 117.8 (d), 79.5
(d), 79.3 (d), 40.6 (d), 40.3 (d), 34.9 (d), 32.7 (d), 30.0 (t), 29.7 (t),
27.4 (t), 26.8 (t), 26.6 (t), 26.1 (t), 15.6 (q), 14.4 (q).
Gen er a l P r oced u r e. P r ep a r a tion of γ-Bu tyr ola cton es
fr om En ol Ester s. To a solution of enol esters (0.3 mmol, 1
equiv) in MeOH (5 mL) under an argon atmosphere at room
temperature was added MeONa (48 mg, 0.9 mmol, 3 equiv), and
the reaction mixture was warmed to 40 °C. After 1 h at 40 °C,
the solution was cooled to room temperature and neutralized
with aqueous HCl (1.2 M) until pH ∼7. The aqueous layer was
extracted with Et2O, and the combined organic phases were
washed with water, dried over MgSO4, and filtered. The solvent
was removed in vacuo to give the γ-butyrolactol 6 as a mixture
of diastereomers. The oxidation of the crude γ-butyrolactol 6 was
achieved with pyridinium chlorochromate (194 mg, 0.9 mmol, 3
equiv) and anhydrous sodium acetate (12 mg, 0.15 mmol, 0.5
equiv) in the presence of molecular sieves 3 Å (388 mg) in CH2-
Cl2 (2 mL). After 5 h at room temperature, the reaction mixture
was filtered through silica gel and concentrated under reduced
1
an inseparable mixture (ratio 74/9/17 according to H NMR) of
diastereomers syn-(Z) 3a , anti-(Z) 4a , and syn-(E) 5a (0.17 g,
0.61 mmol, 70% yield) as an oil. IR (neat): 3446, 1728, 1451,
1268, 1111, 1026 cm-1 1H NMR (300 MHz, CDCl3): δ 8.11-
.
8.03 (m, 2 H), 7.65-7.46 (m, 1 H), 7.40-7.20 (m, 2 H), 7.30-
7.00 (m, 7 H), 5.46 (dd, J ) 12.5, 8.5 Hz, 0.17 H), 4.92 (dd, J )
9.6, 6.3 Hz, 0.09 H), 4.79 (dd, J ) 9.6, 6.3 Hz, 0.74 H), 4.54 (m,
0.91 H), 4.44 (dd, J ) 7.0, 2.6 Hz, 0.09 H), 3.20 (m, 1 H), 1.10 (d,
J ) 6.6 Hz, 2.22 H), 1.05 (d, J ) 6.6 Hz, 0.51 H), 0.95 (d, J ) 7.0
Hz, 0.27 H).13C NMR for the major diastereomer (75 MHz,
CDCl3) δ: 163.2 (s), 142.5 (s), 134.2 (d), 133.4 (d), 129.8 (d), 129.0
(s), 128.4 (d), 128.1 (d), 128.0 (d), 126.4 (d), 116.1 (d), 78.2 (d),
37.4 (d), 17.1 (q).
4-(4-Ch lor oph en yl)-3-m eth yl-1-bu ten e-1,4-diol Mon oben -
zoa te (3b, 4b, 5b). Following the procedure outlined above for
benzaldehyde, p-chlorobenzaldehyde (0.18 g, 1.3 mmol) afforded
an oil that was purified by flash column chromatography on
silica gel (EtOAc/cyclohexane 8/92) to give an inseparable
mixture (ratio 84/8/8 according to 1H NMR) of diastereomers syn-
(Z) 3b, anti-(Z) 4b, and syn-(E) 5b (0.16 g, 0.50 mmol, 58% yield)
as an oil. IR (neat): 3456, 1732, 1266, 1113, 1070 cm-1. 1H NMR
(300 MHz, CDCl3): δ 8.12-7.97 (m, 2 H), 7.66-7.56 (m, 1 H),

7198 J . Org. Chem., Vol. 66, No. 21, 2001
Notes
pressure. The crude γ-butyrolactone was purified by flash
chromatography.
was processed as described in the general procedure described
above. The crude γ-butyrolactone was purified by flash column
chromatography on silica gel (EtOAc/cyclohexane 13/87) to give
7d (22 mg, 0.12 mmol, 40% yield). IR (neat): 1772, 1421, 1265,
4-Meth yl-5-p h en yld ih yd r ofu r a n -2(3H)-on e (7a , 8a ). An
inseparable mixture of enol esters 3a , 4a , and 5a (85 mg, 0.3
mmol) was processed as described in the general procedure
above. The crude γ-butyrolactone was purified by flash column
chromatography on silica gel (EtOAc/cyclohexane 10/90) to give
a mixture (ratio 93/7 according to 1H NMR) of diastereomers
cis-7a and trans-8a (35 mg, 0.2 mmol, 66% yield). IR (neat):
1
1169, 896 cm-1. H NMR (300 MHz, CDCl3): δ 4.49-4.39 (m, 1
H), 2.70 (dd, J ) 16.9, 7.7 Hz, 1 H), 2.66-2.51 (m, 1 H), 2.20
(dd, J ) 16.5, 3.7 Hz, 1 H), 1.77-1.59 (m, 1 H), 1.57-1.45 (m, 1
H), 1.40-1.23 (m, 8 H), 1.02 (d, J ) 7.0 Hz, 3 H), 0.94-0.84 (m,
3 H). 13C NMR (75 MHz, CDCl3): δ 176.8 (s), 83.5 (d), 37.4 (t),
32.9 (d), 31.5 (t), 29.7 (t), 29.0 (t), 25.7 (t), 22.4 (t), 13.9 (q), 13.7
(q). MS (EI, relative intensity): m/z 184(M.+, 0,1), 142 (19), 99
(100), 97 (19), 71 (21).
1780, 1456, 1306, 1217, 1159, 988 cm-1 1H NMR (300 MHz,
.
CDCl3): δ 7.44-7.22 (m, 5 H), 5.61 (d, J ) 6.3 Hz, 0.93 H), 4.95
(d, J ) 8.5 Hz, 0.07 H), 2.97-2.75 (m, 1.93 H), 2.55-2.30 (m,
1.07 H), 1.20 (d, J ) 6.6 Hz, 0.21 H), 0.70 (d, J ) 7.0 Hz, 2.79
H). 13C NMR for the major diastereomer (75 MHz, CDCl3): δ
176.6 (s), 136.0 (s), 128.3 (d), 127.9 (d), 125.3 (d), 83.9 (d), 36.6
(t), 34.8 (d), 15.0 (q). 13C NMR for the minor diastereomer (75
MHz, CDCl3): δ 175.9 (s), 137.8 (s), 128.6 (d), 128.6 (d), 125.8
(d), 88.0 (d), 39.7 (d), 37.1 (t), 16.3 (q). MS for the major
diastereomer (EI, relative intensity): m/z 177 (M.+ + 1, 8), 176
(M.+, 70), 107 (100), 106 (21), 105 (97), 77 (26). MS for the minor
diastereomer (EI, relative intensity): m/z 177 (M.+ + 1, 10), 176
(M.+, 77), 107 (100), 106 (21), 105 (95), 77 (26).
5-Cycloh exyl-4-m eth yld ih yd r ofu r a n -2(3H)-on e (7e). An
inseparable mixture of enol esters 3e and 5e (86 mg, 0.3 mmol)
was processed as described in the general procedure described
above. The crude γ-butyrolactone was purified by flash column
chromatography on silica gel (EtOAc/cyclohexane 15/85) to give
7e (33 mg, 0.18 mmol, 60% yield). IR (neat): 1774, 1458, 1174,
1
1148, 984, 936 cm-1. H NMR (300 MHz, CDCl3): δ 4.02 (dd, J
) 9.6, 4.4 Hz, 1 H), 2.72 (dd, J ) 16.9, 7.3 Hz, 1 H), 2.62-2.49
(m, 1 H), 2.20 (dd, J ) 16.5, 1.1 Hz, 1 H), 2.10-0.80 (m, 8 H),
1.00 (d, J ) 7.0 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ 176.8
(s), 87.7 (d), 38.6 (t), 37.3 (d), 31.8 (d), 27.9 (t), 27.7 (t), 26.1 (t),
25.3 (t), 17.4 (t), 13.3 (q). MS (EI, relative intensity): m/z 182
(M.+, 1), 154 (22), 111 (19), 99 (100), 83 (24), 71 (24), 55 (22).
P r ep a r a tion of Su p p or t-Bou n d r-(Ben zoyloxy)cr otyl-
sta n n a n e (B). To a suspension of carboxypolystyrene (1.0 g, 2
mmol/g, 2 mmol) in CH2Cl2 (20 mL) at room temperature were
added successively EDCI (1.9 g, 10 mmol, 5 equiv), DMAP (0.74
g, 6 mmol, 3 equiv), and 1 (3.6 g, 10 mmol, 5 equiv). After 16 h,
the resin was filtered, alternately thoroughly washed with CH2-
Cl2 and Et2O, and dried in vacuo to give the crotylstannane-
supported reagent B. IR (KBr): 3022, 2922, 2844, 1728, 1700,
5-(4-Ch lor oph en yl)-4-m eth yldih ydr ofu r an -2(3H)-on e (7b,
8b). An inseparable mixture of enol esters 3b, 4b, and 5b (95
mg, 0.3 mmol) was processed as described in the general
procedure described above. The crude γ-butyrolactone was
purified by flash column chromatography on silica gel (EtOAc/
cyclohexane 8/92) to give a mixture (ratio 90/10 according to 1H
NMR) of diastereomers cis-7b and trans-8b (30 mg, 0.14 mmol,
47% yield). IR (neat): 1786, 1493, 1458, 1214, 1157, 1091, 990
cm-1 1H NMR (300 MHz, CDCl3): δ 7.41-7.34 (m, 2 H), 7.27
.
(d, J ) 8.1 Hz, 0.2 H), 7.19 (d, J ) 8.4 Hz, 1.8 H), 5.58 (d, J )
5.9 Hz, 0.9 H), 4.91 (d, J ) 8.1 Hz, 0.1 H), 2.95-2.79 (m, 2 H),
2.43-2.28 (m, 1 H), 1.20 (d, J ) 6.6 Hz, 0.3 H), 0.70 (d, J ) 7.3
Hz, 2.7 H). 13C NMR for the major diastereomer (75 MHz,
CDCl3): δ 176.2 (s), 134.5 (s), 133.8 (s), 128.6 (d), 126.7 (d), 83.2
(d), 37.0 (t), 34.7 (d), 14.0 (q). 13C NMR for the minor diastere-
omer (75 MHz, CDCl3): δ 175.6 (s), 136.3(s), 134.5 (s), 128.8 (d),
127.1 (d), 87.2 (d), 39.8 (d), 37.0 (t), 16.2 (q). MS for the major
diastereomer (EI, relative intensity): m/z 212 (M.+ + 2, 17), 210
(M.+, 49), 143 (24), 142 (24), 141 (100), 140 (57), 139 (95), 70
(22). MS for the minor diastereomer (EI, relative intensity): m/z
212 (M.+ + 2, 18), 210 (M.+, 56), 143 (23), 142 (24), 141 (100),
1350 cm-1 13C NMR (75 MHz, CDCl3) δ: 130.6 (d), 127.8 (m,
.
polystyrene), 119.4 (d), 71.9 (d), 40.3 (m, polystyrene), 28.8 (t),
27.2 (t), 17.7 (q), 13.6 (q), 9.5 (t).
Gen er a l Con d ition s for P r ep a r a tion of γ-Bu tyr ola c-
ton es 7 a n d 8 fr om Resin B. The resin B (0.10 g, 0.12 mmol,
1 equiv) was washed with anhydrous CH2Cl2 to remove water
under an argon atmosphere at room temperature. To a suspen-
sion of resin B and RCHO (1.2 mmol, 10 equiv) in CH2Cl2 (3
mL) at -78 °C was added dropwise BF3‚OEt2 (0.02 mL, 0.18
mmol, 1.5 equiv) with stirring. After 5 h at -78 °C, the mixture
was allowed to reach room temperature, and the resin was
filtered, washed with saturated aqueous NaHCO3, then alter-
nately thoroughly washed with CH2Cl2 and Et2O, and dried in
vacuo. Resin C was then suspended in MeOH/THF (1/4) (5 mL)
at room temperature. After addition of NaOMe (0.13 g, 2.4 mmol,
20 equiv), the resulting slurry was stirred at 40 °C for 1 h, before
neutralization by an aqueous solution of HCl (1.2 M). The
mixture was filtered, and the filtrate was dried over MgSO4. The
solvent was removed in vacuo to give the γ-butyrolactol 6 as a
mixture of diastereomers. The crude γ-butyrolactol 6 was
oxidized by using pyridinium chlorochromate (78 mg, 0.36 mmol,
3 equiv) in the presence of anhydrous sodium acetate (5 mg, 0.06
mmol, 0.5 equiv) and molecular sieves 3 Å (156 mg) in CH2Cl2
(2 mL). After 6 h at room temperature, the reaction mixture was
filtered through silica gel and concentrated under reduced
pressure to produce γ-butyrolactones 7 and 8.
140 (57), 139 (94), 70(21). HRMS (EI) calcd for C11H11O2Cl (M.+
210.0448, found 210.0444.
)
4-Meth yl-5-(4-n itr op h en yl)d ih yd r ofu r a n -2(3H)-on e (7c,
8c). An inseparable mixture of enol esters 3c, 4c, and 5c (98
mg, 0.3 mmol) was processed as described in the general
procedure described above. The crude γ-butyrolactone was
purified by flash column chromatography on silica gel (EtOAc/
cyclohexane 20/80) to give a mixture (ratio 72/28 according to
1H NMR) of diastereomers cis-7c and trans-8c (47 mg, 0.21
mmol, 70% yield). IR (neat): 1788, 1524, 1350, 1265, 1158, 994
cm-1 1H NMR for the major diastereomer (300 MHz, CDCl3):
.
δ 8.30-8.24 (m, 2 H), 7.50-7.45 (m, 2 H), 5.68 (d, J ) 5.9 Hz, 1
H), 3.02-2.88 (m, 1 H), 2.38 (dd, J ) 16.2, 2.2 Hz, 1 H), 0.70 (d,
J ) 7.4 Hz, 3 H). 1H NMR for the minor diastereomer (300 MHz,
CDCl3): δ 8.27 (d, J ) 8.8 Hz, 2 H), 7.55 (d, J ) 8.5 Hz, 2 H),
5.04 (d, J ) 8.1 Hz, 1 H), 2.83 (dd, J ) 15.4, 5.9 Hz, 1 H), 2.53-
2.34 (m, 2 H), 1.26 (d, J ) 6.2 Hz, 3 H).13C NMR for the major
diastereomer (75 MHz, CDCl3): δ 175.6 (s), 147.5 (s) 143.4 (s),
126.2 (d), 123.9 (d), 82.6 (d), 37.1 (t), 34.6 (d), 15.0 (q).13C NMR
for the minor diastereomer (75 MHz, CDCl3): δ 175.1 (s), 148.0
(s), 145.1 (s), 126.4 (d), 123.9 (d), 86.3 (d), 39.9 (d), 36.7 (t), 16.3
(q). MS for the major diastereomer (EI, relative intensity): m/z
221 (M.+, 4), 152 (100), 115 (19), 107 (33), 70 (45). MS for the
minor diastereomer (EI, relative intensity): m/z 221 (M.+, 3),
152 (100), 115 (17), 107 (31), 70 (36). HRMS (CI): calcd for
C11H11O4N (M+ + H) 222.0766, found 222.0770.
Ack n ow led gm en t. We acknowledge the advice and
encouragement of Professor J . A. Marshall throughout
the course of this investigation.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
7b,c and 8c and GC/MS spectra of 7b, 8b, 7c, and 8c. This
material is available free of charge via the Internet at
http://pubs.acs.org.
5-Hexyl-4-m eth yld ih yd r ofu r a n -2(3H)-on e (7d ). An in-
separable mixture of enol esters 3d and 5d (87 mg, 0.3 mmol)
J O010152S