Effect of β-Substituents on the Regioselectivity of the Diazomethane Ring Expansion of α-Methyl-α-methoxycyclobutanones to Cyclopentanones

Article abstract of DOI:10.1021/jo990226o

The ring expansion of 22 differently β-substituted α-methyl-α-methoxycyclobutanones by diazomethane was studied. Migration of the less-substituted α-carbon was favored with the single exception of a very sterically hindered β-benzyloxy β-substituent.

Full text of DOI:10.1021/jo990226o

3
306
J . Org. Chem. 1999, 64, 3306-3311
Effect of â-Su bstitu en ts on th e Regioselectivity of th e
Dia zom eth a n e Rin g Exp a n sion of
r-Meth yl-r-m eth oxycyclobu ta n on es to Cyclop en ta n on es
Lisa M. Reeder and Louis S. Hegedus*
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523
Received February 8, 1999
The ring expansion of 22 differently â-substituted R-methyl-R-methoxycyclobutanones by diaz-
omethane was studied. Migration of the less-substituted R-carbon was favored with the single
exception of a very sterically hindered â-benzyloxy â-substituent.
In tr od u ction
Cyclobutanones are useful synthetic intermediates,
electronegative halogen groups. However, other factors
including steric effects, ring strain, steric hindrance to
the approach of the diazomethane, and conformation in
the intermediate betaine all can influence the regiose-
lectivity of migration, making predictions difficult.
In the course of studies directed toward the synthesis
of five-membered carbocyclic nucleoside analogues via
diazomethane ring expansion of 2,2,3-trisubstituted cy-
clobutanones, an unexpected influence of the â-substitu-
ent on the regioselectivity of expansion was noted. Below
are detailed the results of studies addressing this ques-
tion.
undergoing a variety of functionalization and ring-
1
expansion processes. They are usually synthesized by
the 2 + 2 cycloaddition reaction of ketenes (generated
2
from acid chlorides) with alkenes. We have developed a
route to functionalized, optically active cyclobutanones
3
(
eq 1) and have utilized them as key intermediates in
the synthesis of the carbocyclic nucleoside analogues (-)-
4
cyclobut-A and (()-3′-epi-cyclobut-A and, via a Baeyer-
Villiger ring expansion, the butenolides (+)-tetrahydro-
5
6
cerulenin and (+)-cerulenin as well as a template for
the synthesis of optically active 4′,4′-disubstituted nu-
cleoside analogues.7
Resu lts a n d Discu ssion
The requisite cyclobutanones were synthesized in fair
to good yield by the photolysis of alkoxycarbene complex
1
with a range of alkenes (eq 2, Table 1). As expected,
the reaction was quite stereoselective, giving almost
exclusively the cyclobutanone having the R-methyl group
syn to the â-substituent. Because electron-deficient alk-
enes undergo reaction with ketenes poorly, electron-
withdrawing â-substituted cyclobutanones 2g, 2h , and
2k were generated by acetylation or triflation of 2f and
by oxidation of 2j. With this broad range of substituted
cyclobutanones in hand, ring expansion studies were
initiated (eq 3).
Cyclobutanones also undergo a variety of carbocyclic
8
ring expansions to give cyclopentanones. Among these,
diazomethane methodology is the most extensively used.9
With unsymmetrical cyclobutanones, diazomethane ring
expansions tend to favor migration of the less-substituted
R-carbon and disfavor migration of R-positions bearing
(1) For reviews, see: (a) Bellus, D.; Ernst, B. Angew. Chem., Int.
Ed. Engl. 1987, 27, 797. (b) Lee-Ruff, E. New Synthetic Pathways from
Cyclobutanones. In Advances in Strain in Organic Chemistry; Halton,
B., Ed.; J AI Press: Greenwich, CT, 1991; Vol. 1.
(2) Tidwell, T. T. Ketenes; J ohn Wiley and Sons: New York, 1995;
and references therein.
(
(
(
(
3) For a review, see: Hegedus, L. S. Tetrahedron 1997, 53, 4105.
4) Brown, B.; Hegedus, L. S. J . Org. Chem. 1998, 63, 8012.
5) Miller, M. W.; Hegedus, L. S. J . Org. Chem. 1993, 58, 6779.
6) Kedar, T. E.; Miller, M. W.; Hegedus, L. S. J . Org. Chem. 1996,
6
1, 6121.
(
(
7) Reed, A. D.; Hegedus, L. S. Organometallics 1997, 16, 2313.
8) For reviews, see: (a) Wovkulich, P. M. Skeletal Reorganiza-
Freshly prepared diazomethane10 was bubbled through
a solution of the cyclobutanone in THF at 0 °C. After
tions: Chain Extension and Ring Expansion. In Comprehensive
Organic Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, U.K., 1991;
Vol. 1, pp 843-861. (b) Reference 9.
0
.5-1 h at 0 °C, the reaction mixture was warmed to
(
9) Wong, H. C. N. Houben-Weyl Methods of Organic Chemistry; de
Meijere, A., Ed.; Georg Thieme Verlag: Stuttgart, Germany, 1997; Vol.
E17e, pp 495-515.
(10) Diazomethane was prepared from Diazald according to Aldrich
Technical Information Bulletin No. AL-180.
1
0.1021/jo990226o CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/07/1999

Diazomethane Ring Expansion
J . Org. Chem., Vol. 64, No. 9, 1999 3307
Ta ble 1. P r ep a r a tion of Cyclobu ta n on es 2a -t
Ta ble 2. Rin g Exp a n sion of Cyclobu ta n on es 2a -t
a
b
a
b
Yields are for isolated, purified material. The bicyclic ketone
Yields are for isolated pure mixtures of regioisomers. Ratios
c
1
from cyclopentene. The bicyclic ketone from cyclopentadiene.
Prepared by treating 2f with acetic anhydride. Prepared by
treating 2f with triflic anhydride. Prepared by oxidation of 2j with
oxone. Obtained as an 85:15 mixture of syn/anti isomers. The
bicyclic ketone from dihydropyran. Obtained as an inseparable
:1 mixture of diastereoisomers with the relative stereochemistry
of the cyclobutanone as shown. Obtained as an 86:14 mixture of
diastereoisomers.
are for crude reaction mixtures, determined by H NMR spectros-
copy and GLC analysis. c Obtained as a mixture of four diastere-
oisomers.
d
e
f
g
h
i
is unclear from the experimental evidence, since no clear
correlation to either steric or electronic factors is evident.
Of the range of substituents examined, alkyl groups in
the â-position (2a ,b) result in the least regioselectivity,
∼3:2 in favor of regioisomer 3. Since, with the exception
of 2t, regioisomer 3 is strongly favored, this implies that
â-alkyl substitution results in an increased preference for
migration of the more substituted R-carbon, which also
bears an electronegative methoxy group. Fused bicyclic
systems, from cyclic olefins (2c,d ,o), strongly favor (∼10:
1) formation of regioisomer 3.
Electronic factors seem to be of little importance in
directing the insertion process. Both electron-rich (2e,f,i)
and electron-poor substituents (2g,h ) favor regioisomer
3, although the range is fairly broad (∼2:1 to ∼12:1).
Amide (2l) and oxazolidinone substituents (2m ) give
almost exclusively regioisomer 3, while alkoxy groups
(2n -s) also favor formation of 3 but to a lesser degree.
Steric factors play little role in the regioselectivity of
the ring expansion. Ethoxy (2n ), tert-butoxy (2p ), ben-
zyloxy (2q), R-phenethyloxy (2r ), and even the very bulky
2,4,6-triisopropylbenzyloxy (2s) all give roughly the same
regioselectivity in the ring expansion, favoring 3 over 4
by a factor of ∼2. The striking exception to this is the
last entry, 2t, which bears an alkoxy group having
R-branching (as in the case with 2p and 2r ) as well as
the very hindered aryl group found in 2s. In this unique
case, the regioselectivity is reversed, favoring regioisomer
1
j
room temperature then concentrated under vacuum once
the yellow color had dissipated. The product distribution
of the crude reaction mixture was determined by H NMR
spectroscopy (300 MHz), comparing the peak intensities
for the R-methyl group, the R-methoxy group, or both.
The ratios were confirmed by GLC analysis. The crude
material was then purified (for chemical yield) by flash
chromatography or evaporative distillation. When pos-
sible, the regioisomers were separated and fully charac-
terized. The results are reported in Table 2.
1
Since the R-substitution pattern in cyclobutanones
2
a -t is identical, any differences in regioselectivity in
the ring expansion must be due to the influence of the
9
â-substituent. Published studies indicate that migration
of the less-substituted R-position is favored and that
electronegative groups suppress migration. Both of these
factors should strongly favor formation of regioisomer 3.
Although this is indeed the major regioisomer observed
in the diazomethane ring expansion of cyclobutanones
, the observed ratios of 3 to 4 vary from 100/0 to 1/2
depending on the â-substituent, an effect not previously
addressed systematically.
2
Although â-substitution clearly influences the regiose-
lectivity of ring expansion, the root cause of this influence

3
4
308 J . Org. Chem., Vol. 64, No. 9, 1999
Reeder and Hegedus
by a factor of 2. The enol ether of this same sterically
precipitated chromium hexacarbonyl was removed by filtration
through Celite and then the filtrate concentrated in vacuo.
Syn/anti ratios were obtained by 1H NMR (300 MHz) and
confirmed by GLC analysis. The product was purified by either
silica gel chromatography or vacuum distillation (Kugelrohr).
-Meth oxy-2-m eth yl-3-bu tylcyclobu tan -1-on e (2a). From
15 mg (1.25 mmol) of [(methoxy)(methyl)carbene]pentacar-
bonylchromium (0) (1) and 1.6 mL (12.59 mmol) of 1-hexene
in 12 mL of CH Cl was obtained after vacuum distillation
hindered alcohol [1-(triisopropylphenyl)ethanol] under-
goes highly diastereoselective 2 + 2 cycloaddition with
dichloroketenes,11 a fact rationalized by the lowest energy
conformation of the enol ether. How it reverses the
regioselectivity of the ring expansion of 2t to 3t and 4t
is less obvious.
That the R-alkoxy group in cyclobutanones 2a -t is the
major determinant of the regioselective outcome of the
diazomethane ring expansion is seen from the results
shown in eq 4. Cyclobutanones 5a and 5b, lacking the
2
3
2
2
(Kugelrohr, 110 °C/0.7 mmHg), 118 mg (55%) of 2a as an oil:
1
H NMR δ 3.35 (s, 3H), 2.84 (dd, J ) 13.3, 20.4 Hz, 1H), 2.50
(
0
1
m, 2H), 1.75-1.61 (m, 1H), 1.48-1.25 (m, 5H), 1.29 (s, 3H),
.91 (br s, 3H); 13C NMR δ 209, 93, 52, 45, 34, 31, 30, 22, 15,
R-methoxy group present in cyclobutanones 2 (SmI
2
-1
4; IR (neat) ν 1779 cm ; MS (FAB) 171 (M + H); HRMS
4
reduction), undergo diazomethane ring expansion favor-
ing migration of the more substituted R-carbon. â-Sub-
stituents play a subsidiary but sometimes significant role
in directing diazomethane ring expansions of cyclobu-
tanones.
(
18 2
FAB) calcd for C10H O 171.1385, found 171.1382.
2
-Me t h oxy-2-m e t h yl-3-t r im e t h ylsilylm e t h yle n e cy-
clobu ta n -1-on e (2b). From 330 mg (1.31 mmol) of 1 and 2.1
mL (13.19 mmol) of allyl trimethylsilane in 12 mL of CH Cl
2
2
was obtained after vacuum distillation (Kugelrohr, 65 °C/0.7
mmHg), 205 mg (78%, 91/9 syn/anti) of 2b as an oil. syn-2b:
1
H NMR δ 3.33 (s, 3H), 2.83 (dd, J ) 9.2, 16.4 Hz), 2.58-2.32
(
m, 2H), 1.25 (s, 3H), 0.93 (dd, J ) 3.6, 14.4 Hz, 1H), 0.61 (dd,
13
J ) 11.7, 14.8 Hz, 1H), 0.00 (s, 9H); C NMR δ 209, 94, 52,
-
1
4
7, 30, 17, 15, -1; IR (neat) ν 1769 cm . Anal. Calcd for
Si: C, 59.95; H, 10.06. Found: C, 59.80; H, 9.99.
-Met h oxy-7-m et h ylb icyclo[3.2.0]h ep t a n -6-on e (2c).
From 310 mg (1.23 mmol) of 1 and 1.1 mL (12.39 mmol) of
cyclopentene in 12 mL of CH Cl was obtained after vacuum
10 20 2
C H O
7
2
2
distillation (Kugelrohr, 100 °C/0.7 mmHg), 160 mg (84%) of
2
2
c as an oil: 1H NMR δ 3.80 (t, J ) 8.2 Hz, 1H), 3.32 (s, 3H),
.72 (t, J ) 8.5 Hz, 1H), 2.11-2.01 (m, 1H), 1.93-1.62 (m, 3H),
1
3
Exp er im en ta l Section
1.59-1.31 (m, 2H), 1.14 (s, 3H); C NMR δ 214, 97, 62, 52,
-
1
4
3, 29, 28, 26, 11; IR (neat) ν 1779 cm ; MS (FAB) 155 (M +
H); HRMS (FAB) calcd for C 155.1072, found 155.1069.
-Meth oxy-2-m eth yl-3-p-h yd r oxyp h en ylcyclobu ta n -1-
on e (2f). From 830 mg (3.31 mmol) of 1 and 600 mg (4.97
mmol) of p-hydroxy styrene in 25 mL of CH Cl was obtained
Ma ter ia ls. The following compounds were prepared accord-
9
14 2
H O
ing to literature methods: [(methoxy)(methyl)carbene]pentac-
2
1
2
arbonylchromium (0) (1), 2-methoxy-2-methyl-3-phenylcy-
1
3
clobutan-1-one (2e), 7-methoxy-7-methylbicyclo[3.2.0]hept-
2
2
1
3
2
-en-6-one (2d ), 3-ethoxy-2-methoxy-2-methylcyclobutan-1-
after chromatography (20% EtOAc/Hex), 346 mg (51%) of 2f
1
3
one (2n ), 8-methoxy-8-methyl-2-oxabicyclo[4.2.0]octan-7-one
2o), diazomethane, and 2-methoxy-2-methyl-3-(2-oxo-1-
pyrrolidinyl)cyclobutan-1-one (2l).
Gen er a l P r oced u r es. The 300 MHz H NMR and 75 MHz
C NMR spectra were recorded in CDCl
are given in ppm relative to CHCl . Purification of compounds
was achieved by column chromatographic techniques using
Merck silica gel (230-400 mesh) as the stationary phase or
vacuum distillation (Kugelrohr).
GLC analyses were conducted on an HP5 25 M × 0.125 mm
i.d. column. GLC conditions: initial temperature 100 °C (8 psi
head pressure), ramp at 10 °C/min, final temperature 250 °C
for 10 min.
as a solid: 1H NMR δ 7.10 (d, J ) 8.6 Hz, 2H), 6.85 (d, J ) 8.6
1
3
10
(
Hz, 2H), 4.87 (br s, 1H), 3.84 (t, J ) 10.4 Hz, 1H), 3.50 (s, 3H,
1
3
OCH
3
), 3.14 (dd, J ) 10.2, 17.4 Hz, 1H), 3.00 (dd, J ) 10.2,
1
13
1
1
7.3 Hz, 1H), 1.03 (s, 3H); C NMR δ 209, 154, 129.2, 129.0,
15, 95 (C
1
3
3
, and chemical shifts
), 53, 42, 38, 16; IR (film) ν 3357, 1774 cm ; MS
207.1021,
-1
2
3
(
FAB) 207 (M + H); HRMS (FAB) calcd for C12
found 207.1015.
-Met h oxy-2-m et h yl-3-p-a cet oxyp h en ylcyclobu t a n -1-
14 3
H O
2
on e (2g). To a solution of 100 mg (0.45 mmol) of 2f in 5 mL of
tetrahydrofuran was added 150 µL (1.06 mmol) of triethy-
lamine, 50 µL (0.53 mmol) of acetic anhydride, and a few
crystals of DMAP, and the resulting solution was stirred at
room temperature for 16 h. The reaction was diluted with 5
HPLC separations were conducted on a Microsorb (5 µM
particle size) 25 cm × 21.4 mm i.d. column. HPLC conditions
for the separation of 3i/4i: 10% EtOAc/Hex at 10 mL/min flow
rate. For the separation of 3s/4s: 5% EtOAc/Hex at 8 mL/min
flow rate.
mL of brine and then extracted into Et
combined organic layers were washed with saturated aqueous
NaHCO , filtered, and then
2
O (2 × 10 mL). The
3
(3 × 15 mL), dried over MgSO
4
concentrated in vacuo. After chromatography (20% EtOAc/
1
Hex), 62 mg (51%) of 2g was obtained as an oil: H NMR δ
Gen er a l P r oced u r e for th e P h otoch em ica l [2 + 2]
Rea ction for th e F or m a tion of Cyclobu ta n on es. A solu-
7
1
3
.22 (d, J ) 8.2 Hz, 2H), 7.10 (d, J ) 8.7 Hz, 2H), 3.90 (t, J )
0.3 Hz, 1H), 3.50 (s, 3H), 3.16 (dd, J ) 10.4, 17.3 Hz, 1H),
tion of the carbene complex and olefin in degassed CH
2
Cl
2
in
13
.01 (dd, J ) 10.2, 17.3 Hz, 1H), 2.31 (s, 3H), 1.04 (s, 3H);
C
a Pyrex pressure tube was saturated with CO (80 psi, three
cycles) and then photolyzed under 80 psi of CO at 35 °C for
NMR δ 208, 168, 149, 134, 128, 121, 95, 53, 42, 38, 21, 16; IR
-1
(
neat) ν 1774, 1754 cm . Anal. Calcd for C14
H, 6.50. Found: C, 67.60; H, 6.35.
-Meth oxy-2-m eth yl-3-p-tr iflu or om eth a n esu lfon ylcy-
clobu ta n -1-on e (2h ). To a solution of 108 mg (0.52 mmol) of
f in 5 mL of tetrahydrofuran was added 180 µL (1.30 mmol)
16 4
H O : C, 67.73;
4
-20 h. Photolysis reactions were carried out by placing the
tube at a distance of 10 cm from a Conrad-Hanovia 7825
medium-pressure mercury lamp operating at 450 W, which
was placed in a water-cooled Pyrex immersion well. A Conrad-
Hanovia 7830-C power supply was used. After the reaction
was complete, the crude mixture was concentrated in vacuo
and the slurry triturated with methanol (4-6 mL). The
2
2
of triethylamine, 132 µL (0.78 mmol) of trifluoromethane
sulfonic anhydride, and a few crystals of DMAP, and the
resulting solution was stirred at room temperature for 16 h.
The reaction was diluted with 5 mL of brine and then extracted
(
11) (a) de Azevedo, M. B. M.; Greene, A. E. J . Org. Chem. 1995,
0, 4940. (b) Nebois, P.; Greene, A. E. J . Org. Chem. 1996, 61, 5210.
12) Bao, J .; Wulff, W. D.; Dominy, J . B.; Fumo, M. J .; Grant, E. B.;
into Et
washed with saturated aqueous NaHCO
over MgSO , filtered, and then concentrated in vacuo. After
chromatography (20% EtOAc/Hex), 2h was obtained as an
oil: 1H NMR δ 7.27 (br s, 5H), 3.90 (t, J ) 10.2 Hz, 1H), 3.50
(s, 3H), 3.13 (dd, J ) 10.4, 17.4 H, 1H), 3.01 (dd, J ) 10.1,
2
O (2 × 10 mL). The combined organic layers were
6
3
(3 × 15 mL), dried
(
4
Rob, A. C.; Whitcomb, M. C.; Yeung, S.-M.; Ostrander, R. L.; Rheingold,
A. L. J . Am. Chem. Soc. 1996, 118, 3392.
(13) Soderberg, B. C.; Hegedus, L. S.; Sierra, M. A. J . Am. Chem.
Soc. 1990, 112, 4364.

Diazomethane Ring Expansion
J . Org. Chem., Vol. 64, No. 9, 1999 3309
1
1
7.4 Hz, 1H), 0.99 (s, 3H); 13C NMR δ 207, 148, 138, 129, 121,
16, 95, 53, 42, 38, 16; IR (neat) ν 1784 cm-1
-Meth oxy-2-m eth yl-3-p-m eth oxyp h en ylcyclobu ta n -1-
on e (2i). From 610 mg (2.43 mmol) of 1 and 393 mg (2.92
mmol) of p-methoxystyrene in 25 mL of CH Cl was obtained
3-r-Meth ylben zyloxy-2-m eth oxy-2-m eth ylcyclobu ta n -
1-on e (2r ). From 284 mg (1.13 mmol) of 1 and 185 mg (1.25
.
mmol) of R-methylbenzyl vinyl ether16 in 10 mL of CH
Cl was
2 2
2
obtained after chromatography (20% EtOAc/Hex), 182 mg
(68%) of 2r as an inseparable 1:1 mixture of diasteroisomers:
2
2
1
after chromatography (20% EtOAc/Hex), 320 mg (59%, 96/4
H NMR δ 7.45-7.23 (m, 10H), 4.62-4.44 (m, 2H), 4.27-4.12
1
syn/anti) of 2i as a white solid. syn-2i: mp 33-35 °C; H NMR
(m, 2H), 3.35 (s, 3H), 3.22 (s, 3H), 3.01-2.59 (m, 4H), 1.52 (s,
3H), 1.50 (d, J ) 5.2 Hz, 6H), 1.41 (s, 3H).
3-(2,4,6-Tr iisop r op ylb en zyloxy)-2-m et h oxy-2-m et h yl-
cyclobu ta n -1-on e (2s). From 135 mg (0.54 mmol) of 1 and
δ 7.14 (d, J ) 8.7 Hz, 2H), 6.92 (d, J ) 8.6 Hz, 2H), 3.85 (t, J
)
10.5 Hz, 1H), 3.82 (s, 3H), 3.50 (s, 3H), 3.15 (dd, J ) 10.4,
1
7.3 Hz, 1H), 2.99 (dd, J ) 10.3, 17.3 Hz, 1H), 1.02 (s, 3H);
1
3
16
C NMR δ 208, 158, 129, 128, 114, 95, 55, 52, 42, 38, 16; IR
168 mg (0.65 mmol) of 2,4,6-triisopropylbenzyl vinyl ether
film) ν 1779 cm - . Anal. Calcd for C13
1
H
O
: C, 70.89; H,
2 2
Cl was obtained after chromatography (10%
(
16
3
in 10 mL of CH
EtOAc/Hex) 134 mg (72%) of 2s as an oil: H NMR δ 7.05 (s,
H), 4.72 (d, J ) 10.6 Hz, 1H), 4.61 (d, J ) 10.3 Hz, 1H), 4.38
t, J ) 8.0 Hz, 1H), 3.43 (s, 3H), 3.44-3.25 (m, 2H), 3.05 (dd,
J ) 8.1, 17.9 Hz, 1H), 2.97-2.87 (m, 2H, CH(CH ), 1.45 (s,
H), 1.28 (m, 18H); 13C NMR δ 207, 149, 148, 128, 121, 95, 71,
1
7
.32. Found: C, 70.74; H, 7.30.
-P h en ylth io-2-m eth oxy-2-m eth ylcyclobu tan -1-on e (2j).
From 620 mg (2.47 mmol) of 1 and 0.36 mL (2.72 mmol) of
phenyl vinyl sulfide in 25 mL of CH Cl was obtained after
2
(
3
3 2
)
2
2
3
chromatography (20% EtOAc/Hex), 316 mg (58%) of 2j as a
-
1
1
65, 52, 46, 34, 29, 25, 24, 13; IR (neat) ν 1784 cm ; HRMS
FAB) calcd for C22 345.2429, found 345.2439.
3-r-Meth yl-(2,4,6-tr iisop r op yl)ben zyloxy-2-m eth oxy-2-
m eth ylcyclobu ta n -1-on e (2t). From 180 mg (0.72 mmol) of
and 237 mg (0.86 mmol) of R-methyl-2,4,6-triisopropylbenzyl
pale yellow oil: H NMR δ 7.44-7.18 (m, 5H), 4.00 (t, J ) 9.8
(
34 3
H O
Hz, 1H), 3.40 (s, 3H), 3.24 (dd, J ) 10, 18 Hz, 1H), 2.85 (dd, J
1
3
)
1
9.5, 18 Hz, 1H), 1.48 (s, 3H); C NMR δ 206, 136, 129, 128,
1
26, 96, 52, 47, 39, 16; IR (neat) ν 1784 cm - . Anal. Calcd for
S: C, 64.84; H, 6.35. Found: C, 64.94, H, 6.20.
-Su lfoxyp h e n yl-2-m e t h oxy-2-m e t h ylcyclob u t a n -1-
1
12 14 2
C H O
1
6
2 2
vinyl ether in 10 mL of CH Cl was obtained after chroma-
3
1
4
tography (5% EtOAc/Hex) 173 mg (67%) of 2t as an 86:14
mixture of diastereoisomers. Major: 1H NMR δ 7.11-6.95 (br
s, 2H), 5.19 (q, J ) 7.0 Hz, 1H), 4.25 (t, J ) 8.0 Hz, 1H), 3.97-
on e (2k ). Following the procedure of Quallich and Lackey,
to a solution of 86 mg (0.30 mmol) of 2j in 2 mL of acetone
was added a solution of 290 mg (0.46 mmol) of oxone in 1.5
mL of water and the cloudy slurry stirred at room temperature
for 1 h. The reaction was diluted with 4 mL of 10% aqueous
3
2
3
.82 (m, 1H), 3.36 (s, 3H), 3.30-3.19 (m, 1H), 2.96-2.85 (m,
H, H ), 2.80 (dd, J ) 4.0, 8.7 Hz, 1H), 1.62 (d, J ) 6.9 Hz,
H), 1.50 (s, 3H), 1.26 (d, J ) 6.9 Hz, 12H), 1.18 (d, J ) 7.0
4
NaHSO
3
and then extracted into CH
2
Cl
2
(2 × 5 mL). The
1
3
Hz, 6H); C NMR δ 208, 147, 136, 132, 95, 73, 68, 53, 46, 34,
2
C H O
23 36 3
combined organic layers were dried over MgSO
4
, filtered, and
-
1
9, 25, 24, 14; IR (neat) ν 1779 cm ; HRMS (FAB) calcd for
359.2586, found 359.2584.
Gen er a l P r oced u r e for th e Rin g-Exp a n sion Rea ction s
then concentrated in vacuo, affording 72 mg (77%) of 2k (>95%
1
purity): H NMR δ 7.96-7.89 (m, 2H), 7.74-7.57 (m, 3H), 3.85
(
3
t, J ) 9.7 Hz, 1H), 3.50 (dd, J ) 9.7, 17.7 Hz, 1H), 3.40 (s,
H), 2.98 (dd, J ) 9.8, 17.8 Hz, 1H), 1.78 (s, 3H); 1 C NMR δ
3
of Cyclobu ta n on es. Freshly prepared diazomethane was
bubbled through a solution of cyclobutanone in 2-4 mL of
tetrahydrofuran at 0 °C. The yellow solution remained at 0
2
cm
01, 140, 134, 129, 127, 96, 57, 52, 43, 14; IR (neat) ν 1789
-
1
.
°
C for 30-60 min and then was slowly warmed to ambient
2
-Meth oxy-2-m eth yl-3-((S)-4-p h en yl-2-oxa zolid in yl)cy-
temperature and concentrated in vacuo once the yellow color
had dissipated. The ratio of cyclopentanones was obtained from
the crude reaction mixtures by H NMR spectroscopy and GLC
clobu ta n -1-on e (2m ). From 320 mg (1.27 mmol) of 1 and 363
mg (1.91 mmol) of 3-vinyl-(S)-4-phenyl-2-oxazolidinone15 in 14
1
mL of CH
2
Cl
2
was obtained after chromatography (40% EtOAc/
+31 (c 1.6,
); mp 130-132 °C; H NMR δ 7.48-7.39 (m, 3H), 7.36-
.29 (m, 2H), 4.87 (dd, J ) 5.4, 8.7 Hz, 1H), 4.70 (t, J ) 8.7
Hz, 1H), 4.25 (dd J ) 5.5, 8.8 Hz, 1H), 4.18 (t, J ) 10 Hz, 1H),
analysis. Purification was achieved by either chromatography
on silica gel or vacuum distillation (Kugelrohr).
Hex) 187 mg (53%) of 2m as a white solid: [R]
D
1
CHCl
7
3
Bu tylcyclop en ta n on es (3a /4a ). From 110 mg (0.64 mmol)
of 2a , 3a /4a as an inseparable 59:41 mixture of products, after
vacuum distillation (Kugelrohr, 70 °C/0.7 mmHg), 72 mg
(61%). The product ratio was determined by integration of the
3
1
1
.47 (dd, J ) 9.1, 18 Hz, 1H), 3.14 (s, 3H), 2.71 (dd, J ) 10.2,
13
8 Hz, 1H), 1.43 (s, 3H); C NMR δ 206, 157, 138, 129.4, 129.3,
R-OCH
3
resonances in the 1H NMR spectrum: 3a , 3.26 (s);
a , 3.24 (s).
26, 96, 70, 61, 52, 48, 42, 14; IR (film) ν 1794, 1723 cm-1
;
4
4
HRMS (FAB) calcd for C15H17NO 276.1235, found 276.1229.
Tr im eth ylsilylm eth ylen ecyclopen tan on es (3b/4b). From
1 mg (0.45 mmol) of 2b, 3b/4b as an inseparable 59:41
3
-ter t-Bu toxy-2-m eth oxy-2-m eth ylcyclobu tan -1-on e (2p).
From 270 mg (1.07 mmol) of 1 and 1.5 mL (10.79 mmol) of
tert-butyl vinyl ether in 10 mL of CH Cl was obtained after
vacuum distillation (Kugelrohr, 125 °C/0.7 mmHg) 102 mg
9
mixture of products, after vacuum distillation (Kugelrohr, 80
C/0.7 mmHg), 65 mg (67%). The product ratio was determined
2
2
°
1
by integration of the R-CH
spectrum: 3b, 1.05 (s); 4b, 1.15 (s).
3
resonances in the H NMR
1
(
51%) of 2p as an oil: H NMR δ 4.40 (t, J ) 8.0 Hz, 1H), 3.39
(s, 3H), 2.91 (dd, J ) 8.5, 18 Hz, 1H), 2.80 (dd, J ) 7.7, 18 Hz,
Bicyclo[3.3.0]h ep ta n on es (3c/4c). From 80 mg (0.51
mmol) of 2c, 3c/4c as a 91:9 mixture of products, after vacuum
distillation (Kugelrohr, 110 °C/0.7 mmHg), 63 mg (72%). 3c:
1
3
1
4
1
H), 1.38 (s, 3H), 1.24 (s, 9H); C NMR δ 209, 95, 74, 63, 52,
8, 28, 14; IR (neat) ν 1779 cm-1; HRMS (CI) calcd for C10
87.1334, found 187.1327.
18 3
H O
1
H NMR δ 3.15 (s, 3H), 2.85-2.65 (m, 2H), 2.41 (dd, J ) 7.8,
3
-Ben zyloxy-2-m eth oxy-2-m eth ylcyclobu tan -1-on e (2q).
1
1
3
7.9 Hz, 1H), 2.05-1.90 (m, 1H), 1.80-1.50 (m, 4H), 1.45-
From 570 mg (2.27 mmol) of 1 and 611 mg (4.55 mmol) of
benzyl vinyl ether in 25 mL of CH
chromatography (10% EtOAc/Hex), 414 mg (82%) of 2q as an
oil: H NMR δ 7.42-7.29 (m, 5H), 4.66 (d, J ) 12.1 Hz, 1H),
4
3
1
7
13
.30 (m, 2H), 1.15 (s, 3H); C NMR δ 213, 84, 52, 51, 42, 35,
1
6
2
Cl
2
was obtained after
-1
3, 27, 25, 13; IR (neat) ν 1739 cm ; HRMS (EI) calcd for
10 16 2
C H O 168.1150, found 168.1149.
1
Bicyclo[3.3.0]h ep ten on es (3d /4d ). From 58 mg (0.38
mmol) of 2d , 3d /4d as a 91:9 mixture of products, after vacuum
distillation (Kugelrohr, 110 °C/0.7 mmHg), 43 mg (68%). 3d :
.59 (d, J ) 11.8 Hz, 1H), 4.35 (t, J ) 7.6 Hz, 1H), 3.40 (s,
H), 2.96 (dd, J ) 8.1, 18 Hz, 1H), 2.88 (dd, J ) 8, 18 Hz, 1H),
1
3
.47 (s, 3H); C NMR δ 207, 137, 128, 127.9, 127.7, 95, 72,
1
H NMR δ 5.79-5.74 (m, 1H), 5.51-5.46 (m, 1H), 3.27 (d, 1H,
-
1
0, 52, 46, 13; IR (neat) ν 1779 cm ; HRMS (CI) calcd for
J ) 8.8 Hz), 3.15 (s, 3H), 2.80 (dd, J ) 10.6, 19 Hz, 1H), 2.74-
2
1
13 16 3
C H O 221.1177, found 221.1167.
.59 (m, 2H, H ), 2.15 (d, 1H, J ) 16.8 Hz), 1.83 (dd, J ) 5.5,
5
13
9.1 Hz, 1H), 1.20 (s, 3H); C NMR δ 215, 133, 128, 82, 59,
-
1
(
(
14) Quallich, G. J .; Lackey, J . W. Tetrahedron Lett. 1990, 31, 3685.
15) For the synthesis of 3-vinyl-(S)-4-phenyl-2-oxazolidinone, see
51, 43, 40, 33, 13; IR (neat) ν 1738 cm ; HRMS (EI) calcd for
166.0993, found 166.0998.
P h en ylcyclop en ta n on es (3e/4e). From 88 mg (0.46 mmol)
10 14 2
C H O
ref 5.
(16) For the synthesis of vinyl ethers, see: Watanabe, W. H.; Conlon,
of 2e, 3e/4e as an inseparable 72:28 mixture of products, after
chromatography (10% EtOAc/Hex), 74 mg (79%). The product
L. E. J . Am. Chem. Soc. 1957, 79, 2828.
(17) Mr. Brian Brown is gratefully acknowledged for providing
samples of 5a and 5b.
ratio was determined by integration of the R-OCH
3
and R-CH
3

3
310 J . Org. Chem., Vol. 64, No. 9, 1999
Reeder and Hegedus
resonances in the 1H NMR spectrum: 3e, 3.40 (s), 0.90 (s);
IR (neat) ν 1744 cm-1. Anal. Calcd for C10
8.75. Found: C, 65.16; H, 8.74.
16 3
H O : C, 65.19; H,
4
e, 3.29 (s), 1.01 (s).
p-Hyd r oxyp h en ylcyclop en ta n on es (3f/4f). From 78 mg
ter t-Bu toxycyclop en ta n on es (3p /4p ). From 50 mg (0.27
mmol) of 2p , 3p /4p as a 62:38 mixture of products which were
(
0.38 mmol) of 2f, 3f/4f as an inseparable 71:29 mixture of
products, after chromatography (30% EtOAc/Hex), 63 mg
76%). The product ratio was determined by integration of the
separable by chromatography (10% Et
2
O/Hex). The product
and R-CH
(
ratio was determined by integration of the R-OCH
3
3
1
1
1
R-OCH
.40 (s), 0.89 (s); 4f, 3.27 (s), 1.00 (s).
p-Acetoxyp h en ylcyclop en ta n on es (3g/4g). From 45 mg
0.18 mmol) of 2g, 3g/4g as an inseparable 66:43 mixture of
products. The product ratio was determined by integration of
3
and R-CH
3
resonances in the H NMR spectrum: 3f,
resonances in the H NMR. 3p : H NMR δ 3.99 (m, 1H), 3.29
(s, 3H), 2.43-2.12 (m, 3H), 1.81-1.69 (m, 1H), 1.20 (br s, 9H),
3
1
1.19 (s, 3H). 4p : H NMR δ 4.01 (d, J ) 5.2 Hz, 1H), 3.21 (s,
(
3H), 2.67 (dd, J ) 5.5, 18 Hz, 1H), 2.38 (d, J ) 18 Hz, 1H),
2.27 (d, J ) 17.7 Hz, 1H), 2.15 (d, J ) 18.1 Hz, 1H), 1.34 (s,
3H), 1.19 (s, 9H).
Ben zyloxycyclop en ta n on es (3q/4q). From 83 mg (0.38
mmol) of 2q, 3q/4q as an inseparable 72:28 mixture of
products, after chromatography (10% EtOAc/Hex), 74 mg
1
the R-OCH
g, 3.40 (s), 0.89 (s); 4g, 3.29 (s), 1.01 (s).
p -Tr iflu or om et h a n esu lfon ylp h en ylcyclop en t a n on es
3h /4h ). From 45 mg (0.13 mmol) of 2h , 3h /4h as an insepa-
rable 77:23 mixture of products. The product ratio was
resonances in the
3
3
and R-CH resonances in the H NMR spectrum:
3
(
(84%). The product ratio was determined by integration of the
1
determined by integration of the R-OCH
3
R-OCH
3
and R-CH
3
resonances in the H NMR spectrum: 3q,
1
H NMR spectrum: 3h , 3.39 (s); 4h , 3.25 (s).
3.40 (s), 1.29 (s); 4q, 3.20 (s), 1.41 (s).
p-Meth oxyp h en ylcyclop en ta n on es (3i/4i). From 67 mg
0.30 mmol) of 2i, 37 mg (52%) of 3i/4i as an 80:20 mixture of
products which were separable by HPLC (10% EtOAc/Hex).
r-Meth ylben zyloxycyclop en ta n on es (3r /4r ). From 68
mg (0.29 mmol) of the 1:1 mixture of 2r was obtained an
inseparable mixture of four products. The ratio of 3/4 was
determined by treatment of 18 mg (0.07 mmol) of this mixture
with 4 mg (0.08 mmol) of NaH (60% dispersion in mineral oil)
in 1.4 mL of THF at room temperature for 2 h. The reaction
(
1
3
2
i: H NMR δ 7.20 (d, J ) 8.6 Hz, 2H), 6.90 (d, J ) 8.7 Hz,
H), 3.82 (s, 3H), 3.57-3.51 (m, 1H), 3.40 (s, 3H), 2.59-2.45
(
m, 1H), 2.45-2.24 (m, 2H), 2.16-1.98 (m, 1H), 0.89 (s, 3H);
1
3
C NMR δ 218, 158, 131, 129, 113, 82, 55, 51, 45, 35, 22, 16;
was quenched with brine (5 mL) and then extracted using Et
(2 × 5 mL). The combined organic layers were washed with
saturated NH Cl (10 mL), dried over MgSO , filtered, and then
2
O
-
1
IR (neat) ν 1744 cm . Anal. Calcd for C14
18 3
H O : C, 71.77; H
7
.74. Found: C, 71.51; H, 7.53. 4i: 1H NMR δ 7.10 (d, J ) 7.6
4
4
Hz, 2H), 6.88 (d, J ) 7.2 Hz, 2H), 3.81 (s, 3H), 3.60 (t, J ) 7.7
Hz, 1H), 3.28 (s, 3H), 2.86 (dd, J ) 8.6, 18.9 Hz, 1H), 2.56 (d,
J ) 18.7 Hz, 1H), 2.54 (d, J ) 19.3 Hz, 1H), 2.41 (d, J ) 18.2
concentrated in vacuo, affording 3r and the elimination
1
product of 4r . Before the elimination reaction, the H NMR
spectrum exhibited resonances for the R-OCH
3
groups as
1
3
Hz, 1H), 1.01 (s, 3H); C NMR δ 216, 158, 131, 129, 113, 83,
5, 50, 49, 48, 43, 19; IR (neat) ν 1744 cm -1
P h en ylth iocyclop en ta n on es (3j/4j). From 61 mg (0.27
singlets at 3.24, 3.22, 3.10, and 3.08. After treatment with
base, the peaks at 3.24 and 3.10 remain, while those at 3.22
and 3.08 have decreased, suggesting that the ratio of 3r /4r
was 70:30.
5
.
mmol) of 2j, 3j/4j as an inseparable 80:20 mixture of products,
after chromatography (20% EtOAc/Hex), 60 mg (92%). The
2,4,6-Tr iisop r op ylben zyloxycyclop en ta n on es (3s/4s).
From 67 mg (0.19 mmol) of 2s, 32 mg (46%) of 3s/4s as a 68:
32 mixture of products that were separable by HPLC (5%
EtOAc/Hex). 3s: 1H NMR δ 7.03 (br s, 2H), 4.68 (d, J ) 10.3
Hz, 1H), 4.60 (d, J ) 10.2 Hz, 1H), 4.04 (t, J ) 5.1 Hz, 1H),
3.34-3.21 (m, 2H), 3.30 (s, 3H), 2.94-2.83 (m, 1H), 2.44-2.24
(m, 3H), 2.08-1.95 (m, 1H), 1.28 (s, 3H), 1.27 (d, J ) 6.6 Hz,
18H); 13C NMR δ 214, 148, 128, 121, 83, 82, 64, 51, 34, 33, 29,
product ratio was determined by integration of the R-OCH
3
1
and R-CH
.30 (s); 4j, 3.27 (s), 1.49 (s).
Su lfoxyp h en ylcyclop en ta n on es (3k /4k ). From 72 mg
0.30 mmol) of 2k , 51 mg (67%) of 3k /4k as a 92:8 mixture of
3
resonances in the H NMR spectrum: 3j, 3.23 (s),
1
(
1
products. 3k : H NMR δ 7.95-7.85 (m, 2H), 7.70-7.50 (m, 3H),
3
.80-3.65 (m, 1H), 3.15 (s, 3H), 2.59-2.47 (m, 1H), 2.34-2.14
1
3
-1
(
6
m, 3H), 1.59 (s, 3H); C NMR δ 212, 139, 134, 129, 128, 82,
6, 51, 33, 19, 15; IR (neat) ν 1748 cm-1
P yr r olid in ylcyclop en ta n on es (3l/4l). From 76 mg (0.38
mmol) of 2l, 3l/4l as a 97:3 mixture of products, after
24.7, 24.5, 24.1, 23, 12; IR (neat) ν 1744 cm ; HRMS (FAB)
1
.
calcd for C23
H
36
O
3
359.2586, found 359.2597. 4s: H NMR δ
7.03 (s, 2H), 4.62 (d, J ) 10.3 Hz, 1H), 4.47 (d, J ) 10.3 Hz,
1H), 4.02 (d, J ) 5.1 Hz, 1H), 3.31-3.16 (m, 2H), 3.24 (s, 3H),
2.94-2.82 (m, 1H), 2.69 (dd, J ) 5.2, 18.7 Hz, 1H), 2.50 (d, J
) 18.6 Hz, 1H), 2.41 (d, J ) 17.9 Hz, 1H), 2.27 (d, J ) 17.9
Hz, 1H), 1.39 (s, 3H), 1.29-1.20 (m, 18 H); 13C NMR δ 215,
1
chromatography (10% CH
3
OH/Et
2
O), 72 mg (89%). 3l:
H
NMR δ 4.50 (m, 1H), 3.46-3.36 (m, 1H), 3.31-3.20 (m, 1H),
3
3
.25 (s, 3H), 2.49-2.33 (m, 5H), 2.10-1.91 (m, 3H), 1.14 (s,
13
H); C NMR δ 213, 175, 83, 56, 51, 46, 34, 31, 21, 18, 13; IR
149, 148, 128, 121, 83, 81, 64, 50, 46, 42, 34, 29, 24.7, 24.4,
-
1
-1
(
neat) ν 1744 cm . Anal. Calcd for C11
.11; N, 6.63. Found: C, 62.39; H, 7.92; N, 6.43.
-Meth oxy-2-m eth yl-3-((S)-4-p h en yl-2-oxa zolid in yl)cy-
H
17NO
3
: C, 62.54; H,
36 3
24.1, 16; IR (neat) ν 1749 cm ; HRMS (FAB) calcd for C23H O
8
359.2586, found 359.2574.
2
r-Me t h y l-2,4,6-t r iis o p r o p y lb e n zy lo x y c y c lo p e n t a -
n on es (3t/4t). From 54 mg (0.15 mmol) of 2t, 43 mg (76%) of
3t/4t as a 30:70 mixture of products that were separable by
clop en ta n -1-on e (3m ). From 98 mg (0.35 mmol) of 2m , 3m
as a single product, after chromatography (40% EtOAc/Hex),
1
1
8
7 mg (84%) of 3m as an oil: [R]
D
+96 (c 2.0, CHCl
3
); H NMR
chromatography (5% EtOAc/Hex). 3t: H NMR δ 7.09-6.91
δ 7.50-7.30 (m, 5H), 4.80 (t, J ) 7.5 Hz, 1H), 4.65 (t, J ) 8.6
Hz, 1H), 4.18 (dd, J ) 7.1, 8.7 Hz, 1H), 3.72-3.65 (m, 1H),
(m, 2H), 5.30 (q, J ) 6.7 Hz, 1H), 4.00 (m, 1H), 3.98-3.87 (m,
1H), 3.33 (s, 3H), 3.33-3.17 (m, 1H), 2.93-2.79 (m, 1H), 2.40-
1.97 (m, 3H), 1.77-1.62 (m, 1H), 1.55 (d, J ) 6.6 Hz, 3H),
3
(
1
.10 (s, 3H), 2.54-2.36 (m, 1H), 2.34-2.13 (m, 2H), 1.94-1.78
13
13
m, 1H), 1.20 (s, 3H); C NMR δ 211, 158, 138, 129.6, 129.5,
1.34-1.16 (m, 21H); C NMR δ 215, 147, 133, 123, 120, 83,
-
1
27, 82, 70, 61, 58, 51, 34, 23, 13; IR (neat) ν 1749 cm ; HRMS
290.1395, found 290.1389.
Eth oxycyclopen tan on es (3n /4n ). From 95 mg (0.60 mmol)
79, 72, 52, 34.3, 34.2, 33, 25, 24.8, 24.5, 24.1, 22, 13; IR (neat)
-
1
(FAB) calcd for C16
H
19NO
4
38 3
ν 1748 cm ; HRMS (FAB) calcd for C24H O 373.2742, found
373.2730. 4t: 1H NMR δ 7.07-6.98 (m, 2H), 5.15 (q, J ) 6.3
Hz, 1H), 4.06 (m, 1H), 3.91-3.75 (m, 1H), 3.26 (s, 3H), 3.26-
3.14 (m, 1H), 2.92-2.79 (m, 1H), 2.51 (dd, J ) 6.2, 18.7 Hz,
1H), 2.41 (d, J ) 18.3 Hz, 1H), 2.34 (d, J ) 17.5 Hz, 1H), 2.16
(d, J ) 18.7 Hz, 1H), 1.55 (d, J ) 6.6 Hz, 3H), 1.47 (s, 3H),
1.33-1.14 (m, 18H); 13C NMR δ 215, 147, 134, 123, 120, 83,
of 2n , 3n /4n as an inseparable 67:33 mixture of products, after
vacuum distillation (Kugelrohr, 75°/0.7 mmHg), 72 mg (70%).
The product ratio was determined by integration of the
1
R-OCH
n , 3.20 (s).
Oxa bicyclo[4.3.0]octa n on es (3o/4o). From 80 mg (0.47
3
resonances in the H NMR spectrum: 3n , 3.28 (s);
4
-
1
79, 73, 50, 47, 44, 34, 24.2, 24.1, 22, 17; IR (neat) ν 1748 cm
HRMS (FAB) calcd for C24 373.2742, found 373.2745.
;
mmol) of 2o, 3o/4o as a 95:5 mixture of products, after vacuum
distillation (Kugelrohr, 75 °C/0.7 mmHg), 70 mg (81%). 3o:
38 3
H O
Meth ylben zyloxycyclop en ta n on es (6a /7a ). From 41 mg
1
17
H NMR δ 3.95-3.90 (m, 1H), 3.57 (d, J ) 3.1 Hz, 1H), 3.44-
(0.22 mmol) of 5a , 6a /7a as an inseparable 24:76 mixture of
3
(
1
.12 (m, 1H), 3.17 (s, 3H), 2.70-2.60 (m, 1H), 2.32 (s, 1H), 2.27
products. The product ratio was determined by integration of
d, J ) 2.3 Hz, 1H), 1.85-1.60 (m, 3H), 1.40-1.32 (m, 1H),
the R-CH
resonances in the 1H NMR spectrum (C
D ): 6a ,
3 6 6
1.02 (d, J ) 7.3 Hz); 7a , 0.68 (d, J ) 6.9 Hz).
1
3
.18 (s, 3H); C NMR δ 213, 82, 72, 67, 51, 36, 30, 23, 19, 10;

Diazomethane Ring Expansion
J . Org. Chem., Vol. 64, No. 9, 1999 3311
B e n zy lo x y m e t h y le n e d ip h e n y lo x a zo lid in y lc y c lo -
p en ta n on es (6b/7b). From 35 mg (0.08 mmol) of 5b,17 6b/7b
as an inseparable 36:64 mixture of products, after chroma-
tography (40% EtOAc/Hex), 20 mg (55%). The product ratio
on instruments supported by the National Institutes of
Health shared instrumentation grant GM49631.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
compounds 2a -c,f-k ,m ,p -t, 3a /4a , 3b/4b, 3c,d , 3e/4e, 3f/
2
was determined by integration of the -CH OBn- resonances
1
in the H NMR spectrum: 6b, 3.75 (d, J ) 3.6 Hz); 7b, 3.60
4
4
f, 3g/4g, 3h /4h , 3i, 4i, 3j/4j, 3k -m , 3n /4n , 3o, 3p /4p , 3q/
(d, J ) 5.1 Hz).
q, 3r /4r , 3s, 4s, 3t, 4t, 6a /7a , and 6b/7b and 13C NMR spectra
for compounds 2a -c,f-k ,m ,p ,q,s,t, 3c,d ,i, 4i, 3k -m , 3o, 3s,
Ack n ow led gm en t. Support for this research under
4
s, 3t, and 4t. This material is available free of charge via
Grant No. GM26178 from the National Institutes of
General Medical Sciences (Public Health Service) is
gratefully acknowledged. Mass spectra were obtained
the Internet at http://pubs.acs.org.
J O990226O