Preparation of Medium-Ring Lactones and Lactams by Electrophilic Cyclizations

Full text of DOI:10.1021/jo980195h

J . Org. Chem. 1998, 63, 5255-5258
5255
Ta ble 1. In flu en ce of On e-Ca r bon Con for m a tion a l
P r ep a r a tion of Med iu m -Rin g La cton es a n d
La cta m s by Electr op h ilic Cycliza tion s
Con str a in t on th e F or m a tion of Med iolid es
Fadi Homsi and Ge´rard Rousseau*
Laboratoire des Carbocycles (Associe´ au CNRS), Institut de
Chimie Mole´culaire d'Orsay Baˆt. 420, Universite´ de
Paris-Sud, 91405 Orsay, France
Received February 4, 1998
Preparation of medium-ring compounds is still a chal-
lenge in organic synthesis even if some interesting results
have been reported in recent years.1 Our interest in this
research field led us to examine the preparation of
medium-ring lactones2 and ethers3 by electrophilic het-
eroatom cyclizations of linear precursors. The difficulty
of closure inherent in these ring sizes4 led us to study
the structural parameters and the reagents that should
favor it. In our previous work, we have shown that bis-
(collidine)iodine(I) hexafluorophostate (1) is an interest-
ing reagent to carry out such reactions, even though, in
some cases, yields were modest. The search for a more
efficient reagent is probably not the unique answer to
the problems raised by these medium-ring closures.
Substrate modifications should also bring beneficial
results. For example, we found that substitution of one
of the carbons of the chain by an oxygen atom2a or the
introduction of a gem-dimethyl group2b on one of these
carbon atom favored these cyclizations.
Ch a r t 1
Sch em e 1
(sp3 and sp2 carbons). The acids used were prepared by
standard methods and required no special comments,
except for acids 9a -c. The latter were obtained in three
steps from the corresponding 1-bromoalkenes 2b-d by
reaction with the lithium acetylide-ethylenediamine
complex, followed by carboxylation and subsequent cis
hydrogenation (Scheme 1). We found that the cis hydro-
genation could be achieved in the presence of the Lindlar
catalyst desactivated by quinoleine. However, it was
difficult to avoid a partial reduction (e10% from VPC and
1H NMR) of the terminal carbon-carbon double bond.
Reaction of these acids in methylene chloride in the
presence of 1.3 equiv of bis(collidine)iodine(I) hexafluo-
rophosphate 1 led to the formation of iodo lactones. Our
results are reported in Table 2. These lactones were
We report here our results concerning the influence of
the introduction of a geometrical constraint imposed to
one or two carbon atoms of the chain. At first, we decided
to carry out a study on the influence of a conformational
constraint brought by a dioxolane or dithiolane in the â
position, or an exo-carbon-carbon double bond in R
position, of the acid function. The desired acids 2-4 were
prepared by standard procedures. Their iodolactoniza-
tions were carried out at room temperature in methylene
chloride in the presence of 1.3 equiv of bis(collidine)-
iodine(I) hexafluorophosphate (1).2 Our results are re-
ported in Table 1. No reaction was observed with the
7-octanoic acids 2a and 3. Only acids 2b and 4 led in
low yields to the desired iodo lactones 5 and 6, whose
1
mainly characterized from their H and 13C NMR spectra.
Comparison of the results reported in Table 2 with those
reported in Table 1 shows that introduction of a two-
carbon conformational restriction in the chain has a
positive effect. Eight-membered-ring lactones 10a , 16a ,
19a , and 21a were obtained in exceptionally high yields.
The only exception was the cyclization of acid 7, which
led to two diastereoisomeric lactones 8 in moderate
yields. Comparison of this latter result with that ob-
served in the cyclization of acid 20a shows that the
rigidity introduced by a cyclohexane is apparently not
enough to give a satisfactory reaction. Conformationally
more rigid cyclopentane or cyclobutane rings should give
better results. The relative stereochemistry at the C7
in the two diastereoisomers 8 was not determined.
However, it was possible to measure by NMR the
coupling constants between the two hydrogens fixed at
the cycle junction (J ) 6.5, 7.5 Hz). These values means
that we probably have a cis cycle junction, since higher
values would be expected for a trans cycle junction (this
determination was not possible on the starting acid 7).
1
structures were easily established from their H and 13C
NMR spectra. We suggest that the low reactivity of the
acids 2a ,b and 3 is due in part to the presence of a
hydrogen bond that induces an unfavorable conformation
of the chain during the cyclization (Chart 1). The
influence of a one-carbon conformational constraint is
thus insufficient to allow the formation of medium-ring
lactones in our reaction conditions.
These results led us to examine the influence of a
conformational constraint brought by two carbon atoms
(1) For reviews see: (a) Petasis, N. A.; Patane, M. A. Tetrahedron
1992, 48, 5757. (b) Roxburgh, C. J . Tetrahedron 1993, 49, 10749. (c)
Evans, P. A.; Holmes, A. B. Tetrahedron 1991, 47, 9131. (d) Rousseau,
G. Tetrahedron 1995, 51, 2777. (e) Moody, C. J .; Davies, M. J . In
Studies in Natural Products Chemistry; Attar-ur-Rahman, Ed.; Elsevi-
er Science Publishers: New York, 1992; Vol. 10, p 201. (f) Rousseau,
G.; Homsi, F. Chem. Soc. Rev. 1997, 26, 453.
(2) (a) Simonot, B.; Rousseau, G. J . Org. Chem. 1994, 59, 5912. (b)
Simonot, B.; Rousseau, G. Tetrahedron Lett. 1993, 34, 4527.
(3) Brunel, Y.; Rousseau, G. J . Org. Chem. 1996, 61, 5793.
(4) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95.
S0022-3263(98)00195-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/08/1998

5256 J . Org. Chem., Vol. 63, No. 15, 1998
Notes
Ta ble 2. P r ep a r a tion of Iod o La cton es
Sch em e 2
appeared to be due to the competitive addition of the
iodonium salt 1 on the furan ring, which led to noniden-
tified polar products. It is interesting to not that the
Z-acid 9c and E-acid 12 led to iodo lactones with the same
global yields, though the Z-lactones were reported to be
thermodynamically less stable than the E-lactones.7
Such a result means, as we previously reported,2 that
these electrophilic cyclizations occur under kinetic con-
trol. In both cases, the decrease in entropy appeared to
be enough to allow the ring closure. For lactones with
nine-membered ring size and higher, we observed in
general8 a competition between the exo- and endo-mode
cyclizations. Apparently, as the ring size of lactone
increases, the endo-exo ratio increases.
We tested the reduction of the iodine atom. Unsatis-
factory results were observed using the standard tribu-
tyltin hydride procedure. However, reduction of lactone
10a was efficently carried out using sodium borohydride
in the presence of a catalytic amount of trimethyltin
chloride.9 However, this method was unsuccessful with
the benzo lactone 16a for which only tar material was
obtained. In this latter case, we found that the reduction
could be carried out with sodium borohydride in DMSO
or HMPA10 (Scheme 2).
Nothing seems to be known concerning the obtention
of medium-ring lactams1c,f by electrophilic cyclizations.
We decided to investigate this possibility using sulfona-
mides. The desired amide 23 was obtained by reaction
of the acid chloride prepared from the acid 15a with the
lithium salt of toluenesulfonamide (25% yield). When the
reaction was carried out in the presence of bis(collidine)-
iodine(I) hexafluorophosphate (1), we isolated the corre-
sponding lactam 24a in 44% yield. This cyclization was
also observed with the corresponding bromo reagent, with
lower yields (Scheme 3). These results open the possibil-
ity to obtain medium-ring lactams by electrophilic cy-
clizations.
We confirmed this assumption by molecular calculations.5
From our experience with this kind of cyclizations, we
think that the trans acid should give a lower yield of
lactone. For higher ring-size lactones, the results were
less conclusive. Indeed, if satisfactory yields were ob-
served in the cyclization of benzoic acids 15b-d , it was
not the case with unsaturated acids 9b-c, 12, and 18b.
We can explain this difference in yield by the fact that
with the unsubstituted R,â-ethylenic acids 9b-c and 12
we probably had a competitive addition of the iodonium
on the conjugated double bond, which led to nonidentified
polymeric materials. This assumption was confirmed
when 2-octenoic acid reacted with iodonium reagent 1 to
give polymeric materials.6 This competitive polymeri-
zation was not observed with the acid 9a , due probably
to the easier cyclization into eight-membered lactone 10b.
The low yield observed in the formation of lactone 19b
In conclusion, we have reported in this paper that
medium-ring heterocycles (lactones and lactams) could
be obtained by electrophilic cyclizations if two conditions
could be fulfilled:
(6) A hypothesis to explain these polymerizations may be the
intermediate formation of R-lactones (by 3-exo cyclization), which are
known to be only low-temperature stable species. See: Wierlacher, S.;
Sander, W.; Liu, M. T. H. J . Org. Chem. 1992, 57, 1051 and references
cited therein.
(7) Fouque, E.; Rousseau, G.; Seyden-Penne, J . J . Org. Chem. 1990,
55, 4817.
(8) We cannot exclude that the absence of endo-lactone in the
cyclization of the furanoic acid 18b was due to its degradation during
the workup of the reaction mixture.
(9) Corey, E. J .; Suggs, J . W. J . Org. Chem. 1975, 40, 2555.
(10) Hutchins, R. O.; Kandasamy, D.; Dux, F., III; Maryanoff, C.
A.; Rotstein, D.; Goldsmith, B.; Burgogne, W.; Cistone, F.; Dalessandro,
J .; Puglis, J . J . Org. Chem. 1978, 43, 2259.
(5) Molecular calculations were made using MAD (2.3 version)
program.

Notes
J . Org. Chem., Vol. 63, No. 15, 1998 5257
(Z)-8-(Iod om eth yl)-2-octen olid e (10b): oil; 1H NMR
δ
Sch em e 3
1.10-1.90 (m, 6H), 1.90-2.20 (m, 2H), 3.40 (m, 2H), 4.85 (m,
1H), 5.90 (dd, J ) 11, 2 Hz, 1H), 6.50 (dt, J ) 11.0, 6.0 Hz, 1H).
Anal. Calcd for C9H13O2I: C, 38.59; H, 4.68. Found: C, 38.52;
H,4.60.
(Z)-8-Iod o-2-n on en olid e (11b): oil; 1H NMR δ 1.10-2.20 (m,
6H), 2.00-2.50 (m, 2H), 4.20 (m, 2H), 5.15 (m, 1H), 5.90 (d, J )
9 Hz, 1H), 6.35 (dt, J ) 9, 7 Hz, 1H). Anal. Calcd for C9H13O2I:
C, 38.59; H, 4.68. Found: C, 38.74; H,4.92.
(E)-9-(Iod om eth yl)-2-n on en olid e (13): oil; 1H NMR δ 1.10-
1.80 (m, 8H), 2.12-2.38 (m, 2H), 3.22-3.38 (m, 2H), 4.80-4.95
(m, 1H), 5.70-5.90 (m, 1H), 6.82-7.10 (dt, J ) 16, 6 Hz, 1H);
13C NMR δ 7.40, 23.34, 25.28, 25.53, 34.60, 36.46, 72.00, 122.71,
142.63, 170.12. Anal. Calcd for C10H15O2I: C, 40.84; H, 5.14.
Found: C, 41.02; H, 5.08.
(1) A conformational constraint must be introduced in
the chain. From our results it appears that the confor-
mational restriction must be introduced to at least two
vicinal atoms to obtain satisfactory yields.11
(2) The reagent must be highly electrophilic with an
unreactive counteranion.
(E)-10-Iod o-2-d ecen olid e (14): oil; 1H NMR δ 1.10-1.80 (m,
8H); 2.12-2.38 (m, 2H), 4.10-4.40 (m, 2H), 4.50-4.70 (m, 1H),
5.70-5.90 (m, 1H), 6.82-7.10 (dt, J ) 16, 6 Hz, 1H); 13C NMR
δ 7.11, 23.24, 25.22, 25.50, 34.55, 36.33, 72.10, 120.7, 149.80,
165.02. Anal. Calcd for C10H15O2I: C, 40.84; H, 5.14. Found:
C, 41.11; H, 5.23.
Exp er im en ta l Section
7-(Iodom eth yl)-6-oxa-7,8,9,10-tetr ah ydr oben zocycloocten -
5-on e (16a ): white crystals; mp 86-88 °C; 1H NMR δ 1.90-
2.20 (m, 4H), 2.70-2.95 (m, 2H), 3.15-3.40 (m, 2H), 4.25-4.40
(m, 1H), 7.15-7.55 (m, 4H); 13C NMR δ 9.04, 26.16, 32.43, 34.39,
79.72, 126.96, 128.47, 129.79, 130.90, 131.85, 139.22, 170.75.
Anal. Calcd for C12H13O2I: C, 45.59; H, 4.14. Found: C, 45.51;
H, 4.09.
Gen er a l Rem a r k s. All NMR spectra were measured in
CDCl3, and chemical shifts are expressed in ppm relation to
internal CHCl3. All solvents were purified by known standard
procedures; in particular, methylene chloride was distilled from
CaH2. The iodolactonizations were conducted in the dark. After
the reactions, the iodo lactones could be handled for a short time
wihout special care and stored at -20 °C in the dark. 1H NMR
spectra were measured in CDCl3 at 200 or 250 MHz. Bis-
(collidine)iodine(I) hexafluorophosphate (1) and bis(collidine)-
bromine(I) hexafluorophosphate (25) were prepared using the
same procedure as previously reported.2a,12
Gen er a l P r oced u r e for th e Iod ola cton iza tion . To a
solution of bis(collidine)iodine(I) hexafluorophosphate (0.36 g,
0.7 mmol) in dry methylene chloride (70 mL) was added by a
push syringe over 10 h 0.54 mmol of the desired acid in
methylene chloride (10 mL). Subsequently, 1 g of silica gel was
added to the reaction mixture, and the solvent was removed.
The solid was put on the top of a flash silica gel column and a
mixture pentane-ethyl acetate or pentane-ether used for the
elution.
7-(Iod om eth yl)-6-oxa -8,9,10,11-tetr a h yd r o-(7H)-ben zocy-
clon on en -5-on e (16b): oil; 1H NMR δ 1.40-2.10 (m, 6H), 2.65
(ddd, J ) 4, 7.5, 12 Hz, 1H), 3.50 (d, J ) 5, 2H), 3.30 (m, 1H),
4.10-4.40 (m, 2H), 5.05 (m, 1H), 7.20-7.50 (m, 3H), 7.90 (dd, J
) 6, 1 Hz, 1H); 13C NMR δ 7.57, 23.03, 31.18, 32.12, 33.33, 67.94,
126.34, 130.42, 130.83, 131.39, 132.30, 144.81, 169.98. Anal.
Calcd for C13H15O2I: C, 47.29; H, 4.58. Found: C, 47.22; H, 4.28.
8-Iod o-6-oxa -7,8,9,10,11,12-h exa h yd r oben zocyclod ecen -
1
5-on e (17b): oil; H NMR δ 1.15-1.70 (m, 4H), 1.78-1.95 (m,
1H), 2.30-2.60 (m, 2H), 3.25 (m, 1H), 4.15-4.35 (m, 2H), 5.05
(dd, J ) 9, 3.5 Hz, 1H), 7.20-7.50 (m, 3H), 7.80 (dd, J ) 6, 1
Hz, 1H); 13C NMR δ 23.18,27.60, 29.08, 32.15,36.62, 70.50,
126.31, 130.57, 130.98, 132.05, 143.46, 169.53. Anal. Calcd for
C13H15O2I: C, 47.29; H, 4.58. Found: C, 47.10; H, 4.49.
6-(Iodom eth yl)-5-oxa-6,7,8,9-tetr ah ydr ofu r an cycloocten -
9-(Iod om eth yl)-1,4,8-tr ioxa sp ir o[4.3]tr id eca n -7-on e (5):
1
1
oil; H NMR δ 1.40-2.00 (m, 8H), 2.52 (d, J ) 20 Hz) and 2.75
4-on e (19a ): white solid; H NMR δ 1.85-2.20 (m, 4H), 2.65-
(d, J ) 20 Hz) (AB system), 3.30 (d, J ) 7.5 Hz, 2H), 3.90-4.05
(m, 4H), 4.83-5.00 (m, 1H); 13C NMR δ 16.86, 23.77, 25.56,
30.38,36.65, 43.82, 49.65, 61.17, 67.12, 71.07, 166.70. Anal.
Calcd for C11H17O4I: C, 38.84; H, 5.04. Found: C, 39.03; H, 5.23.
9-(Iod om eth yl)-3-m eth ylen eoxoca n e-2-on e (6): oil; 1H
NMR δ 1.30-1.60 (m, 4H), 1.70-2.00 (m, 4H), 2.40-2.50 (m,
2H), 3.20-3.35 (m, 2H), 4.65-4.80 (m, 1H), 5.30 (m, 2H). Anal.
Calcd for C9H13O2I: C, 38.59; H, 4.68. Found: C, 38.47; H, 4.81.
(2R,3S)-7-(Iodom eth yl)-6-oxa-decah ydr oben zocycloocten -
5-on e (8). The two diastereoisomers were separated by liquid
chromatography over silica gel (ether-pentane 5:95). Less polar
isomer (34%): oil; 1H NMR δ 1.25-2.05 (m, 14H), 2.25-2.40 (m,
1H), 2.60-2.70 (m, 1H), 3.30 (d, J ) 6 Hz, 2H), 4.85-5.00 (m,
1H); 13C NMR δ 6.74, 21.06, 23.17, 24.41, 32.21, 35.88, 35.96,
40.08, 43.62, 76.71, 178.55. Anal. Calcd for C12H19O2I: C, 44.74;
H, 5.94. Found: C, 44.95; H, 6.06. More polar isomer (76%):
2.80 (m, 1H), 3.05-3.20 (m, 1H), 3.23-3.45 (m, 2H), 4.58-4.80
(m, 1H), 6.63 (d, J ) 2 Hz, 1H), 7.33 (d, J ) 2 Hz, 1H); 13C NMR
δ 19.75, 27.89, 34.94, 78.50, 111.78, 112.85, 141.40, 157.50,
165.15. Anal. Calcd for C10H11O3I: C, 39.24; H, 3.62; I, 41.46.
Found: C, 38.63; H, 3.77; I, 40.14.
6-(Iod om eth yl)-5-oxa -7,8,9,10-tetr a h yd r o-(6H)-fu r a n cy-
clon on en -4-on e (19b): oil; 1H NMR δ 1.55-1.90 (m, 6H), 2.02-
2.20 (m, 1H), 2.78-2.95 (m, 1H), 3.30-3.50 (m, 2H), 4.65-4.80
(m, 1H), 6.70 (d, J ) 2 Hz, 1H), 7.28 (d, J ) 2 Hz, 1H). Anal.
Calcd for C11H13O3I: C, 41.27; H, 4.09. Found: C, 41.63; H, 3.85.
7-(Iod om eth yl)-6-oxa -1,2,3,4,7,8,9,10-octa h yd r oben zocy-
cloocten -5-on e (21a ): white solid; mp 81 °C; 1H NMR δ 1.35-
2.65 (m, 12H), 3.15-3.40 (m, 2H), 4.60-4.75 (m, 1H); 13C NMR
δ 9.00, 21.14, 21.49, 22.12, 26.34, 29.77, 33.28, 34.64, 79.11,
123.46, 141.40, 172.05. Anal. Calcd for C12H17O2I: C, 45.02;
H, 5.35. Found: C, 45.28; H, 5.48.
7-(Iod om eth yl)-6-oxa -1,2,3,4,7,8,9,10-octa h yd r o-(7H)-ben -
zocyclon on en -5-on e (21b): oil; 1H NMR δ 1.35-1.85 (m, 10H),
1.95-2.23 (m, 5H), 2.36-2.55 (m, 1H), 3.18-3.33 (m, 1H), 3.35
(dd, J ) 6, 1 Hz, 2H), 4.87-4.90 (m, 1H); 13C NMR δ 8.52, 21.96,
22.65 (2C), 25.92, 29.76, 33.10, 33.52, 34.20, 75.52, 125.63,
152.33, 171.12. Anal. Calcd for C13H19O2I: C, 46.72; H, 5.73.
Found: C, 46.98; H, 5.91.
1
solid; mp 88-89 °C; H NMR δ 1.10-1.85 (m, 11H), 1.85-2.10
(m, 4H), 2.62-2.75 (m, 1H), 3.30 (dd, J ) 7, 2 Hz, 2H), 4.75-
4.85 (m, 1H); 13C NMR δ 7.87, 22.30, 23.68 (2C), 25.26, 31.08,
33.28 (2C), 37.35, 43.24, 78.15, 177.13. Anal. Calcd for
C12H19O2I: C, 44.74; H, 5.94. Found: C, 44.81; H, 6.01.
(Z)-7-(Iod om eth yl)-2-h ep ten olid e (10a ): white crystals; mp
86-88 °C; 1H NMR δ 1.65-2.00 (m, 4H), 2.10-2.30 (m, 1H),
2.30-2.65 (m, 1H), 3.10-3.30 (m, 2H), 4.75 (m, 1H), 5.8 (m, 1H),
6.25 (m, 1H); 13C NMR δ 6.37, 19.77, 31.02, 35.38, 78.11, 117.46,
141.90, 168.56. Anal. Calcd for C8H11O2I: C, 36.11; H, 4.17.
Found: C, 35.91; H,4.07.
8-Iod o-6-oxa -1,2,3,4,7,8,9,10,11,12-d eca h yd r oben zocyclo-
1
d ecen -5-on e (22b): oil; H NMR δ 1.30-2.40 (m, 15H), 2.60-
2.80 (m, 1H), 4.15-4.28 (m, 1H), 4.85 (t, J ) 10 Hz, 1H), 4.85
(dd, J ) 5, 10 Hz, 1H); 13C NMR δ 21.88, 22.47, 24.80, 25.91,
26.58, 27.18, 31.75, 31.93, 36.57, 70.07, 126.02, 147.09, 169.31.
Anal. Calcd for C13H19O2I: C, 46.72; H, 5.73. Found: C, 47.11;
H, 5.82.
(11) We recently found that oxocanes could be also formed in
excellent yields if a conformational constraint was introduced in the
chain. Renard, S. Unpublished results.
(12) Homsi, F.; Robin, S.; Rousseau, G. Organic Syntheses, submitted
for publication.
(Z)-9-Meth yl-2-h ep ten olid e (25). To the iodo lactone 10a
(0.5 g, 1.88 mmol) and trimethyltin chloride (0.15 g, 0.75 mmol)
in air-free ethanol (40 mL) cooled to 15 °C, was rapidly added

5258 J . Org. Chem., Vol. 63, No. 15, 1998
Notes
with a syringe sodium borohydride (0.09 g) dissolved in ethanol
(10 mL). The reaction mixture was irradiated with a 200-W
mercury lamp for 30 min. Then oxalic acid dihydrate (0.015 g)
was added followed 5 min later by methylene chloride (200 mL).
The resulting solution was washed once with saturated NaHCO3
and dried over MgSO4 and the solvent removed under reduced
pressure. The product was purified by chromatography over
silica gel (elution: 70% hexane-30% ethyl acetate) to give 0.20
g (86%) of lactone 25: 1H NMR δ 1.30 (d, J ) 5.5 Hz, 3H), 1.50-
2.20 (m, 4H), 2.45 (m, 2H), 4.80 (m, 1H), 5.70 (dt, J ) 12, 0.5
Hz, 1H), 6.20 (dt, J ) 4, 12 Hz, 1H); 13C NMR δ 19.53, 21.41,
31.13, 37.47, 74.62, 117.48, 141.40, 169.89. Anal. Calcd for
C8H12O2: C, 68.55; H, 8.63. Found: C, 58.71; H, 8.90.
3-(Iod om eth yl)-2-(tolu en e-4-su lfon yl)-3,4,5,6-tetr a h yd r o-
(2H)-ben zo[c]a zocin -1-on e (24a ). The iodolactamization was
conducted following the general procedure used for the iodola-
ctonization. A white solid that decomposed at 163-165 °C was
isolated by chromatography over silica gel: 1H NMR δ 1.45-
2.20 (m, 4H), 2.37-2.50 (s, 3H), 2.50-2.65 (m, 1H), 2.80-2.93
(m, 1H), 3.18-3.28 (m, 1H), 3.28-3.40 (m, 1H), 4.20-4.40 (m,
1H), 7.13-7.42 (m, 4H), 7.42-7.55 (m, 2H), 7.78-8.00 (m, 2H);
13C NMR δ 6.90, 21.47, 25.90, 32.16, 33.48, 66.94, 83.50, 126.89,
127.39 (2C), 129.11 (2C), 130.03, 132.64, 138.76, 141.34, 143.22,
168.43. Anal. Calcd for C19H20INO3S: C, 48.62; H, 4.30.
Found: C, 48.81; H, 4.22.
iodo lactone 16a (0.52 g, 1.6 mmol), dry HMPA (80 mL), and
NaBH4 (0.12 g, 3.2 mmol). The reaction mixture was stirred
for 6 min at room temperature. Subsequently, water (200 mL)
was added and the aqueous solution extracted with ether (3 ×
40 mL). The organic layers were combined, washed ounce with
water, and dried over MgSO4, and the solvent was removed on
a rotary evaporator. The residue was purified by chromatog-
raphy over silica gel (80% hexane-20% ethyl acetate) to give
0.24 g (82%) of lactone 26: 1H NMR δ 1.25-1.35 (d, J ) 7.5 Hz,
3H), 1.50-2.20 (m, 4H), 2.70-2.90 (m, 2H), 4.35-4.45 (m, 1H),
7.15-7.35 (m, 3H), 7.35-7.50 (m, 1H); 13C NMR δ 23.40, 26.52,
32.85, 36.35, 77.16, 126.72, 128.30, 129.71, 131.48, 131.63,
140.30, 171.84. Anal. Calcd for C12H14O2: C, 75.76; H, 7.42.
Found: C, 75.93; H, 7.66.
Su p p or tin g In for m a tion Ava ila ble: Preparations and
spectral data for the acids 2-4, 7, 9, 12, 15, 18, and 20 and
the amide 23. 1H and 13C spectral data for the lactones 11c,
16c,d , 17c,d , and the amide 24b (9 pages). This material is
contained in libraries on microfiche, immediately 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.
7-Met h yl-6-oxa -7,8,9,10-t et r a h yd r ob en zocyclooct en -5-
on e (26). To a 500 mL round-bottomed flask were added the
J O980195H