Rhodium-Catalyzed Rearrangement of α-Diazo Thiol Esters to Thio-Substituted Ketenes. Application in the Synthesis of Cyclobutanones, Cyclobutenones, and β-Lactams

Article abstract of DOI:10.1021/jo000227c

Exposure of α-diazo thiol esters (1) to the action of catalytic rhodium(II) acetate leads to a remarkably facile "thia-Wolff rearrangement", producing thio-substituted ketenes which combine with a variety of ketenophiles to provide access to α-thiocyclobutanones, cyclobutenones, and β-lactams. Reductive desulfurization of these cycloadducts takes place under mild conditions and in excellent yield, and this sequence thus represents a useful new alternative to the existing dichloroketene-based methodology for the synthesis of four-membered carbocycles and heterocycles.

Full text of DOI:10.1021/jo000227c

J . Org. Chem. 2000, 65, 4375-4384
4375
Rh od iu m -Ca ta lyzed Rea r r a n gem en t of r-Dia zo Th iol Ester s to
Th io-Su bstitu ted Keten es. Ap p lica tion in th e Syn th esis of
Cyclobu ta n on es, Cyclobu ten on es, a n d â-La cta m s
Michael D. Lawlor, Thomas W. Lee, and Rick L. Danheiser*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Received February 18, 2000
Exposure of R-diazo thiol esters (1) to the action of catalytic rhodium(II) acetate leads to a
remarkably facile “thia-Wolff rearrangement”, producing thio-substituted ketenes which combine
with a variety of ketenophiles to provide access to R-thiocyclobutanones, cyclobutenones, and
â-lactams. Reductive desulfurization of these cycloadducts takes place under mild conditions and
in excellent yield, and this sequence thus represents a useful new alternative to the existing
dichloroketene-based methodology for the synthesis of four-membered carbocycles and heterocycles.
In tr od u ction
employed as a ketene equivalent, since this electrophilic
ketene reacts well with many types of unactivated
multiple bonds, and the resultant cycloadducts undergo
facile dechlorination under mild conditions.4-6
Once regarded merely as theoretical curiosities, four-
membered ring compounds are recognized today as a
class of molecules of great practical significance.1 The
â-lactam ring system constitutes the key structural unit
in several clinically important classes of antibiotics, and
four-membered carbocycles play a prominent role as
intermediates for the synthesis of both cyclic and acyclic
organic compounds. Cyclobutanones and cyclobutenones,
in particular, have found wide application in organic
synthesis, participating in ring expansion and ring cleav-
age processes that give rise to diverse classes of complex
organic molecules.2 For example, research in our labora-
tory has demonstrated that the thermal electrocyclic
cleavage of cyclobutenones provides convenient access to
vinylketenes, which function as valuable synthetic build-
ing blocks for the efficient construction of six- and eight-
membered carbocyclic rings.3
Herein we report a new method for the generation of
thio-substituted ketenes as well as their surprisingly
facile cycloaddition with both activated and unactivated
alkenes and alkynes. As outlined in Scheme 1, we have
found that exposure of R-diazo thiol esters (1) to the
action of catalytic rhodium(II) acetate leads to a remark-
ably facile “thia-Wolff rearrangement”, producing thio-
substituted ketenes which combine with a variety of
ketenophiles to provide access to R-thiocyclobutanones,
cyclobutenones, and â-lactams. Reductive desulfurization
of these cycloadducts takes place under mild conditions
and in excellent yield, and this sequence thus represents
a useful new alternative to the existing dichloroketene-
based methodology for the synthesis of four-membered
carbocycles and heterocycles.
The [2 + 2] cycloaddition of ketenes with alkenes and
alkynes constitutes the most popular method for the
synthesis of cyclobutanones and cyclobutenones.4 Unfor-
tunately, however, this process is truly general only for
highly nucleophilic ketenophiles such as conjugated
dienes and enol ethers. In general, unactivated alkenes
and alkynes fail to react in good yield with either alkyl-
or aryl-substituted ketenes, or with ketene itself. To
circumvent this limitation, dichloroketene is usually
Resu lts a n d Discu ssion
P r ep a r a tion of r-Dia zo Th iol Ester s. Four R-diazo
thiol esters (6a -d ) incorporating different thiol groups
were prepared in order to examine the effect of electronic
and steric factors on the thia-Wolff rearrangement and
[2 + 2] cycloaddition of the resultant thio-substituted
ketenes. For the synthesis of the requisite R-diazo thiol
esters,7 we chose to employ the “detrifluoroacetylative”
diazo transfer strategy previously developed in our
laboratory.8 Thus, treatment of thiol esters 5a -d 9 with
1.05 equiv of lithium hexamethyldisilazide in THF at -78
°C furnishes the corresponding lithium enolates, which
are acylated by exposure to 1.2 equiv of trifluoroethyl
(1) For a comprehensive review of the chemistry of four-membered
carbocycles, see Methods of Organic Chemistry (Houben-Weyl); de
Meijere, A., Ed.; Thieme: Stuttgart, Germany, 1997; Vol. E17e and f.
(2) For reviews, see: (a) Bellus, D.; Ernst, B. Angew. Chem., Int.
Ed. Engl. 1988, 27, 797. (b) Wong, H. N. C.; Lau, K.-L.; Tam, K.-F.
Top. Curr. Chem. 1986, 133, 83. (c) Trost, B. M. Top. Curr. Chem. 1986,
133, 3. (c) Lee-Ruff, E. In Advances in Strain in Organic Chemistry;
Halton, B., Ed.; J ai Press: London, 1991; Vol. 1, pp 167-213. (d) Moore,
H. W.; Yerxa, B. R. In Advances in Strain in Organic Chemistry;
Halton, B. Ed.; J ai Press: London, 1995; Vol. 4, pp 81-162.
(3) (a) Danheiser, R. L.; Martinez-Davila, C.; Sard, H. Tetrahedron
1981, 37, 3943. (b) Danheiser, R. L.; Gee, S. K.; Sard, H. J . Am. Chem.
Soc. 1982, 104, 7670. (c) Danheiser, R. L.; Gee, S. K. J . Org. Chem.
1984, 49, 1672. (d) Loebach, J . L.; Bennett, D. M.; Danheiser, R. L. J .
Org. Chem. 1998, 63, 8680. (e) Bennett, D. M.; Okamoto, I.; Danheiser,
R. L. Organic Lett. 1999, 1, 641 and references therein.
(4) For recent reviews, see: (a) Hyatt, J . A.; Raynolds, P. W. Org.
Reactions 1994, 45, 159. (b) Tidwell, T. T. Ketenes; Wiley: New York,
1995. (c) Schaumann, E.; Scheiblich, S. In Methoden der Organischen
Chemie (Houben-Weyl); Kropf, E., Schaumann, E., Eds.; Thieme:
Stuttgart, Germany, 1993; Vol. E15, Parts 2 and 3. (d) Lee-Ruff, E. In
Methods of Organic Chemistry (Houben-Weyl); de Meijere, A., Ed.;
Thieme: Stuttgart, Germany, 1997; Vol. E17e, pp 190-219.
(5) Reviewed in: Brady, W. T. Tetrahedron 1981, 37, 2949.
(6) Keteniminium salts are more electrophilic than ketenes and
sometimes engage in satisfactory [2 + 2] cycloadditions with unacti-
vated olefins. See: ref 4d and Schmit, C.; Falmagne, J . B.; Escudero,
J .; Vanlierde, H.; Ghosez, L. Organic Syntheses; Wiley: New York,
1993; Collect. Vol. VIII, pp 306-309 and references therein.
(7) For reviews of the chemistry of R-diazo carbonyl compounds,
see: (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; Wiley: New
York, 1998. (b) Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091. (c)
Regitz, M.; Maas, G. Diazo Compounds: Properties and Synthesis;
Academic Press: Orlando, FL, 1986.
(8) (a) Danheiser, R. L.; Miller, R. F.; Brisbois, R. G.; Park, S. Z. J .
Org. Chem. 1990, 55, 1959. (b) Danheiser, R. L.; Miller, R. F.; Brisbois,
R. G. Org. Synth. 1995, 73, 134.
10.1021/jo000227c CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/08/2000

4376 J . Org. Chem., Vol. 65, No. 14, 2000
Lawlor et al.
Ta ble 1. P r ep a r a tion of Cyclobu ta n on es a n d â-La cta m s
fr om r-Dia zo Th iol Ester s
Sch em e 1
trifluoroacetate at -78 °C for 10 min. Treatment of the
resulting R-trifluoroacetyl thiol esters with 1.5 equiv of
MsN3 in the presence of 1.0 equiv of water and 1.5 equiv
of Et3N in acetonitrile (25 °C, 2.5 h) then affords the
desired diazo compounds 6a -d in good to excellent yield
after chromatographic purification (eq 1).
[2 + 2] Cycloa d d ition Rea ction s. Optimal conditions
for the thia-Wolff rearrangement and [2 + 2] cycloaddi-
tion were developed by examining the generation of
(phenylthio)ketene from 6b and its subsequent addition
to methylenecyclohexane, with the latter serving as a
representative “unactivated” ketenophile. As formulated
in eq 2, best results were obtained by using rhodium(II)
acetate7,10 (0.02 equiv) to promote the novel thia-Wolff
rearrangement. Copper(I) and copper(II) trifluoromethane-
sulfonate were found to be less effective catalysts for this
transformation, and in the absence of catalyst (under
otherwise identical conditions) the purely thermal Wolff
rearrangement proceeded inefficiently to afford cycload-
duct 8 in only 31% yield. Not surprisingly, the optimal
temperature for these reactions was found to depend on
the reactivity of the ketenophile. Cycloadditions involving
the more nucleophilic ketenophiles proceed smoothly in
refluxing dichloromethane (40 °C), while reactions with
less reactive cycloaddition partners are best accomplished
in 1,2-dichloroethane (83 °C). As is standard for ketene
cycloadditions, an excess (3.5-10 equiv) of the keteno-
a
The diazo thiol ester is treated with 0.02 equiv of Rh2(OAc)4
and 5 equiv of alkene (10 equiv in entries 6, 7, and 8) or 3.5 equiv
of imine (entry 13). Procedure A: reaction in 1,2-dichloroethane
at 83 °C for 3 h. Procedure B: reaction in dichloromethane at 40
°C for 3 h. Ar ) 2,4,6-trimethylphenyl (mesityl). Isolated yield
and ratio of diastereoisomers.
b
c
phile component is best employed, and the optimal pro-
tocol involves slowly adding a solution of the diazo thiol
ester to a solution of the ketenophile and catalyst in order
to minimize competition from ketene dimerization.
Table 1 delineates the scope of this approach to the
synthesis of R-thiocyclobutanones and â-lactams. As
illustrated in entries 1-4, aryl thiol esters are superior
substrates for the reaction as compared to the tert-
butylthio derivative 6d , and the mesityl thiol ester 6a
has proven to be particularly effective in reactions with
less ketenophilic alkenes (see entries 7 and 8, and 9 and
10). With the more reactive ketenophiles, however, nearly
identical results are obtained using either the mesityl
R-diazo thiol ester 6a or the more readily available
(9) Thiol esters 5a , 5c, and 5d were prepared by acylation of the
appropriate thiol with acetyl chloride in CH2Cl2-pyridine according
to the general procedure described in Danheiser, R. L.; Nowick, J . S.
J . Org. Chem. 1991, 56, 1176. S-Phenyl thioacetate (5b) is com-
mercially available. The thiols required for the preparation of 5a and
5c were synthesized by reduction of the corresponding commercially
available arylsulfonyl chlorides using the general procedure of Caesar,
P. D. In Organic Syntheses; Wiley: New York, 1963; Collect. Vol. IV,
pp 695-697.
(10) Review: Adams, J .; Spero, D. M. Tetrahedron 1991, 47, 1765.

Rh-Catalyzed Rearrangement of R-Diazo Thiol Esters
J . Org. Chem., Vol. 65, No. 14, 2000 4377
Ta ble 2. P r ep a r a tion of Cyclobu ten on es fr om r-Dia zo
thiophenyl ester 6b (see entries 1 and 2, and 5 and 6).
The efficiency of the reaction of 6a with unactivated
alkenes is especially notable and compares favorably with
results obtained previously employing dichloroketene.
For example, addition of dichloroketene to methylenecy-
clohexane is reported to proceed in 55% yield,11 while up
to 81% of the desired [2 + 2] cycloadduct is produced in
the reaction of (mesitylthio)ketene with this olefin (entry
2). The improved yields observed in cycloadditions in-
volving (mesitylthio)ketene are likely due to the shielding
effect of the bulky thioaryl group which may suppress
side reactions of the ketene such as dimerization, al-
though contributions by subtle electronic effects cannot
be excluded.
Th iol Ester s
The regio- and stereochemical outcome of the reactions
recorded in Table 1 are consistent with predictions based
on trends previously observed in other ketene [2 + 2]
cycloadditions.4 Reactions involving cyclic alkenes (e.g.,
12 and 21) proceed with a strong preference for products
in which the substituent derived from the monosubsti-
tuted ketene has an endo orientation on the new bicyclic
system. In the case of acyclic olefins (e.g., 15), the major
products are trans-substituted cyclobutanones, and the
trans-substituted â-lactam is the exclusive product ob-
tained in the reaction of imine 24.12 Stereochemical
assignments for these cycloadducts are based primarily
1
on H NMR studies; it is well documented that the vicinal
a
The diazo thiol ester is treated with 0.02 equiv of Rh2(OAc)4
coupling constant for protons attached at C2 and C3 in
cyclobutanones is larger in the case of cis-substituted
isomers.13-15 Additional support for the stereochemical
assignment in entry 8 was obtained through an equili-
bration study. Thus, exposure of a 3.5:1 mixture of 17a
and 17b to 1.1 equiv of LiOMe in MeOH (25 °C, 11 h)
resulted in the formation of a 9.4:1 mixture enriched in
the thermodynamically favored trans-substituted isomer
17a .
Table 2 summarizes the results of our studies on the
cycloaddition of (arylthio)ketenes with acetylenic keteno-
philes. Once again, (mesitylthio)ketene displays superior
reactivity to (phenylthio)ketene, especially in reactions
with unactivated ketenophiles such as 4-octyne (entries
1 and 2). Although addition to methoxypropyne was
found to be an efficient process, cycloadditions of (arylth-
io)ketenes with less-activated acetylenes do not proceed
as efficiently as the corresponding reactions of dichlo-
roketene,16 and attempted addition to phenylacetylene
resulted in a complex mixture of products.
and 3.5-5 equiv of alkyne. Procedure A: reaction in 1,2-dichlo-
roethane at 83 °C for 3 h. Procedure B: reaction in dichlo-
b
romethane at 40 °C for 3 h. Ar ) 2,4,6-trimethylphenyl (mesityl).
c Isolated yield.
“thia-Wolff rearrangement” to generate ketene 4. Orig-
inally discovered in 1912, the Wolff rearrangement17 is
widely employed today as a method for the homologation
of carboxylic acids (the Arndt-Eistert reaction), the ring
contraction of cyclic ketones, and the in situ generation
of ketenes for trapping in [2 + 2] cycloadditions.18 The
Wolff rearrangement is commonly effected by thermolysis
or irradiation of R-diazo carbonyl compounds, or by
reaction with silver salts. It is well established that rho-
dium carbenes derived from R-diazo carbonyl compounds
generally do not rearrange to ketenes, and in fact these
species play an important role as synthetic intermediates
that undergo efficient C-H, O-H, and N-H insertion
reactions, react with heteroatom nucleophiles to form
ylides, and combine with alkenes and alkynes in cycloaddi-
tions leading to cyclopropanes and cyclopropenes.7a,b,10,19
Few reports have appeared previously describing Wolff
rearrangements of R-diazo carbonyl compounds promoted
by rhodium carboxylates.20,21 We suggest that the un-
usual facility of the Wolff rearrangement of 2 is due to
the ability of the thiol ester sulfur to capture the rhodium
carbenoid in a process leading to the cyclic sulfonium
ylide 3. The formation of cyclic sulfonium ylides by
intramolecular attack of sulfides on rhodium carbenes
Discu ssion of Mech a n ism . As outlined in Scheme
1, we propose that the conversion of R-diazo thiol esters
to thio-substituted ketenes proceeds via the initial forma-
tion of a rhodium carbenoid 2, followed by subsequent
(11) Dunkelblum, E. Tetrahedron 1976, 32, 975.
(12) For a discussion of the stereochemical course of imine-ketene
cycloadditions, see: Georg, G. I.; Ravikumar, V. T. In The Organic
Chemistry of â-Lactams; Georg, G. I., Ed.; VCH: New York, 1993; pp
295-368.
(13) For examples, see: (a) Rey, M.; Roberts, S.; Dieffenbacher, A.;
Dreiding, A. S. Helv. Chim. Acta 1970, 53, 417. (b) DoMinh, T.; Strausz,
O. P. J . Am. Chem. Soc. 1970, 92, 1766. (c) Rey, M.; Roberts, S. M.;
Dreiding, A. S.; Roussel, A.; Vanlierde, H.; Toppet, S.; Ghosez, L. Helv.
Chim. Acta. 1982, 65, 703.
(14) The stereochemistry of 13a was established by comparison of
1H NMR data with that previously reported for this compound: see
Michel, P.; O’Donnell, M.; Biname, R.; Hesbain-Frisque, A. M.; Ghosez,
L.; Declercq, J . P.; Germain, G.; Arte, E.; Van Meerssche, M. Tetra-
hedron Lett. 1980, 21, 2577.
(16) For example, see: Danheiser, R. L.; Savariar, S. Tetrahedron
Lett. 1987, 28, 3299.
(17) For reviews, see: ref 7 and (a) Zollinger, H. Diazo Chemistry
II: Aliphatic, Inorganic, and Organometallic Compounds; VCH: New
York, 1995. (b) Gill, G. B. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Pattenden, G., Eds.; Pergamon Press: New York,
1991; Vol. 3, pp 887-912. (c) Ando, W. In The Chemistry of the
Diazonium and Diazo Groups; Patai, S., Ed.; Wiley: New York, 1978;
Part 1, Chapter 9, pp 458-475. (d) Meier, H.; Zeller, K.-P. Angew.
Chem., Int. Ed. Engl. 1975, 14, 32.
(15) A similar trend has been observed for 3,4-disubstituted â-lac-
tams. See Bachi, M. D.; Goldberg, O. J . Chem. Soc., Perkin Trans. 1
1972, 2332.
(18) For examples in the context of an aromatic annulation strategy,
see: Danheiser, R. L.; Brisbois, R. G.; Kowalczyk, J . J .; Miller, R. F.
J . Am. Chem. Soc. 1990, 112, 3093.

4378 J . Org. Chem., Vol. 65, No. 14, 2000
Lawlor et al.
is well documented in the literature,22 although we are
not aware of any prior examples that involve thiol esters
or that lead to the formation of three-membered rings.23
phenylthioacetyl chloride with 1 equiv of Et3N in the
presence of excess cyclopentadiene (25 °C, 29 h) afforded
13a ,b in only 13% yield (eq 3). Note that this cycloadduct
Several prior reports have described the generation of
thio-substituted ketenes via the photochemical Wolff
rearrangement,24 and we therefore investigated the
feasibility of preparing R-thiocyclobutanones and cy-
clobutenones by irradiation of R-diazo thiol esters in the
presence of alkene and alkyne ketenophiles. Unfortu-
nately, this photochemical reaction has not proven to be
an efficient process. For example, irradiation (300 nm)
of a solution of diazo thiol ester 6b and methylenecyclo-
hexane in benzene led to polymeric products with no
cyclobutanone detectable by 1H NMR analysis of the
crude product mixture.
is obtained in nearly quantitative yield when (phenylth-
io)ketene is generated via the thia-Wolff rearrangement
strategy (Table 1, entry 5). Similarly, less than 5% of the
desired cycloadduct was obtained from the reaction of
phenylthioacetyl chloride with triethylamine (1,2-dichlo-
roethane, reflux) in the presence of 10 equiv of the
unactivated olefin 4-phenyl-1-butene (15).
Several factors may contribute to the exceptional
efficiency of the [2 + 2] cycloadditions of ketenes gener-
ated via the thia-Wolff rearrangement. In our procedure,
the thio-substituted ketenes are likely generated in low
effective concentration, which should work to minimize
dimerization and polymerization of these reactive inter-
mediates. Also significant may be the fact that in this
method the ketenes are generated in the absence of
substances that might promote decomposition, such as
the amine hydrochlorides and Lewis acidic metal salts
(e.g., ZnCl2) that are present when ketenes are generated
via the classical dehydrohalogenation and reductive
dechlorination procedures. Finally, we cannot exclude the
possibility that rhodium may play a role by remaining
complexed to the thio-substituted ketene, thereby facili-
tating subsequent [2 + 2] cycloaddition reactions.
Syn t h et ic Tr a n sfor m a t ion s of r-Th iocyclob u -
ta n on es. The limited utility of ketene itself in [2 + 2]
cycloaddition reactions has stimulated the search for
electrophilic ketene equivalents that engage in efficient
cycloadditions with alkenes and alkynes and furnish
products that can easily be transformed to simple cy-
clobutanones and cyclobutenones. Due largely to pioneer-
ing work by Brady and Ghosez, dichloroketene stands
uncontested today as the most efficacious ketene equiva-
lent for [2 + 2] cycloadditions.4,5 Our discovery that
(arylthio)ketenes generated via the rhodium-catalyzed
thia-Wolff rearrangement engage in cycloadditions with
efficiency rivaling and even surpassing that of dichlo-
roketene suggested to us that this class of ketenes might
also play an important role in the synthesis of four-
membered carbocycles and heterocycles. Key to this
expectation was the assumption that excision of thioaryl
substituents from the resulting [2 + 2] cycloadducts could
be achieved under mild conditions and in high yield.
A wide variety of reagents are available for the
reductive cleavage of carbon-sulfur bonds, including
Raney nickel, zinc metal, tributyltin hydride, nickel
boride, various metal complex reducing agents, and
several alkali metals.27 Table 3 summarizes the results
of our study of the desulfurization of R-thiocyclobutanone
cycloadducts 22 and 23. As expected, both substrates
undergo smooth desulfurization upon exposure to either
tributyltin hydride or activated zinc dust. For the latter
Few examples of [2 + 2] cycloadditions involving thio-
substituted ketenes have been described previously. To
our knowledge, Ghosez has reported the only prior
example of a [2 + 2] cycloaddition involving (phenylthio)-
ketene, namely the addition of this ketene to cyclopen-
tadiene to afford the expected bicyclo[3.2.0]butanone in
undesignated yield.14 Several cycloadditions involving
alkyl(phenylthio)ketenes with activated alkenes and imi-
nes have been reported.25 In these prior studies, the thio-
substituted ketenes were generated via the triethylamine-
promoted dehydrohalogenation of acyl chlorides,25a-c or
by photochemical rearrangement of Fischer chromium-
carbene complexes.25d-e In the latter process, cycloaddi-
tion is believed to involve a chromium-ketene complex
rather than a free ketene.26 Interestingly, our results
suggest that cycloadditions involving thio-substituted
ketenes generated by the rhodium-catalyzed decomposi-
tion of R-diazo thiol esters proceed more efficiently than
reactions involving the same ketenes produced via the
standard dehydrohalogenation protocol. For example, we
found that treatment of an ether solution of 1 equiv of
(19) Reviews: (a) Doyle, M. P. In Comprehensive Organometallic
Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Hegedus, L.
S., Eds.; Pergamon Press: New York, 1995; Vol. 12, Chapter 5.2, pp
387-468. (b) Davies, H. M. L. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press:
New York, 1991; Vol. 4, pp 1031-1067. (c) Taber, D. F. In Compre-
hensive Organic Synthesis; Trost, B. M., Fleming, I., Pattenden, G.,
Eds.; Pergamon Press: New York, 1991; Vol. 3, pp 1045-1062.
(20) (a) Taylor, E. C.; Davies, H. M. L. Tetrahedron Lett. 1983, 24,
5453. (b) Pirrung, M. C.; Morehead, A. T., J r. J . Am. Chem. Soc. 1994,
116, 8991. (c) Yong, K.; Salim, M.; Capretta, A. J . Org. Chem. 1998,
63, 9828. (d) Lee, Y. R.; Suk, J . Y.; Kim, B. S. Tetrahedron Lett. 1999,
40, 8219.
(21) Marsden has recently observed that R-silyl-R-diazo ketones (but
not esters) undergo Wolff rearrangement when heated in the presence
of catalytic rhodium(II) octanoate. In this case the anomalous rear-
rangement pathway (here involving alkyl or aryl group migration) is
most likely facilitated by the ability of the silyl group to stabilize the
resulting â-acylium cation intermediate. See Marsden, S. P.; Pang, W.-
K. J . Chem. Soc., Chem. Commun. 1999, 1199.
(22) Reviewed in chapter 7 of ref 7a and Padwa, A.; Hornbuckle, S.
F. Chem. Rev. 1991, 91, 263.
(23) For examples of cyclizations leading to four-membered cyclic
sulfonium ylides, see: Davies H. M. L.; Crisco, L. V. T. Tetrahedron
Lett. 1987, 28, 371.
(24) (a) Hixson, S. S.; Hixson, S. H. J . Org. Chem. 1971, 37, 1279.
(b) Georgian, V.; Boyer, S. K.; Edwards, B. J . Org. Chem. 1980, 45,
1686. (c) J ones, J .; Kresge, A. J . J . Org. Chem. 1992, 57, 6467.
(25) (a) Ishida, M.; Minami, T.; Agawa, T. J . Org. Chem. 1979, 44,
2067. (b) Palomo, C.; Cossio, F. P.; Odriozola, J . M.; Oiarbide, M.;
Ontoria, J . M. Tetrahedron Lett. 1989, 30, 4577. (c) Palomo, C.; Cossio,
F. P.; Odriozola, J . M.; Oiarbide, M.; Ontoria, J . M. J . Org. Chem. 1991,
56, 4418. (d) Ko¨bbing, S.; Mattay, J . Tetrahedron Lett. 1992, 33, 927.
(e) Ko¨bbing, S.; Mattay, J .; Raabe, G. Chem. Ber. 1993, 126, 1849.
(26) Hegedus and co-workers discovered this method for the genera-
tion of metal-ketene complexes from Fischer carbenes and have
systematically investigated the chemistry of these species. For a review,
see Hegedus, L. Tetrahedron 1997, 53, 4105.
(27) For reviews, see: (a) Caube`re, P.; Coutrot, P. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
New York, 1990; Vol. 8, pp 835-847. (b) Block, E. In Chemistry of
Ethers, Hydroxyl Groups and Their Sulphur Analogues; Patai, S., Ed.;
Wiley: New York, 1980; pp 585-608.

Rh-Catalyzed Rearrangement of R-Diazo Thiol Esters
Ta ble 3. Red u ction of r-Th iocyclobu ta n on es
J . Org. Chem., Vol. 65, No. 14, 2000 4379
and a less polar solvent. Thus, treatment of 8 with
lithium tert-butoxide in THF followed by excess methyl
iodide afforded the desired alkylation product 32 in good
yield after chromatographic purification (eq 4).
Similar conditions also proved effective for the regi-
oselective C-alkylation of the bicyclic adduct obtained
from [2 + 2] cycloaddition of (phenylthio)ketene with
cyclopentadiene. As outlined in Scheme 2, methylation
and benzylation of the lithium enolate derived from 13a
proceed in excellent yield to furnish products in which
alkylation has occurred mainly from the less sterically
encumbered convex (exo) face of the bicyclic system.
Reduction with tributyltin hydride then affords the
expected cyclobutanones in which the predominant prod-
uct has the R-alkyl substituent in the endo orientation
due to the preference for delivery of hydrogen to the
convex face of the bicyclic intermediate radical.33 Note
that this sequence provides an alternative route to 35
which is only produced in 33% yield via the cycloaddition
of methylketene with cyclopentadiene.34
a
Procedure A: reduction with 1.2-1.7 equiv of Bu3SnH and
cat. AIBN in toluene at reflux for 1 h. Procedure B: reduction
with 20-25 equiv of Zn dust in aqueous THF in the presence of
NH4Cl at reflux for 25-42 h.
reduction, the method of Holton28 proved optimal. Thus,
treatment of either 22 or 23 with excess activated zinc
dust in a 1:1 mixture of THF and aq saturated NH4Cl
solution (reflux, 25-42 h) led to the smooth formation of
cyclobutanone 31 in excellent yield after purification by
column chromatography.
We next turned our attention to the analogous reduc-
tion of R-(thioaryl)cyclobutenones. Dechlorination of 4,4-
dichlorocyclobutenones cannot be achieved under con-
ventional conditions using either tin hydride reagents or
zinc metal,29 but can be accomplished in good yield by
employing the protocol developed independently in our
laboratory30 and that of Dreiding.31 Unfortunately, to date
our attempts to effect reduction of R-thiocyclobutenone
28 under a variety of conditions have led to a complex
mixture of products together with unreacted starting
material.
Regioselective Alk yla tion of r-Th iocyclobu -
ta n on es. Like ketene itself, alkyl-substituted ketenes are
known to be very poor partners for cycloaddition with
unactivated olefins. We reasoned that (arylthio)ketenes
might have the capacity to function as useful alkylketene
equivalents, provided that the R-thiocyclobutanone cy-
cloadducts could be alkylated regioselectively32 and that
the resulting substituted sulfides would undergo efficient
desulfurization.
Optimal conditions for the alkylation of R-thiocyclobu-
tanones were developed employing the cycloadduct 8
derived from methylenecyclohexane, a particularly chal-
lenging substrate for alkylation due to the adjacent
quaternary center. In the event, attempted alkylation of
8 with methyl iodide using potassium tert-butoxide as
base in DMF led to the desired substituted cyclobutanone
accompanied by a significant amount of a byproduct
resulting from O-alkylation of the intermediate enolate.
Better results were obtained by using the lithium enolate
Experiments aimed at extending the scope of this
strategy to include less reactive alkylating agents thus
far have not been fruitful. Attempted alkylation of both
8 and 13a with 1-iodo-3-phenylpropane under the condi-
tions described above gave complex mixtures including
the desired cyclobutanones as well as products of O-
alkylation.
Oxid a tion of r-Th iocyclobu ta n on es. We anticipate
that a variety of functionalized four-membered car-
bocycles should be available via further synthetic elabo-
ration of the products of (arylthio)ketene cycloadditions.
For example, oxidation at the R position of the cyclobu-
tanone ring can be readily achieved by Pummerer rear-
rangement of the sulfoxide derived from R-thiocyclobu-
tanone 8 (Scheme 3). Either sodium periodate or m-CPBA
chemoselectively transforms 8 to the corresponding sul-
foxide (37),35 and exposure of 37 to the action of catalytic
p-toluenesulfonic acid in Ac2O-toluene then provides the
desired Pummerer rearrangement36 product 38 in excel-
lent yield.
Rin g Exp a n sion of r-Th iocyclobu ta n on es. Ring
strain renders cyclobutanones exceptionally reactive as
substrates in many ring expansion reactions,37 and in fact
the products of dichloroketene cycloadditions have found
extensive use in the synthesis of cyclopentanones.38 Our
(33) The stereochemistry of 35a and 35b was assigned by 1H NMR
analysis as previously described by: (a) Rey, M.; Roberts, S.; Dieffen-
bacher, A.; Dreiding, A. S. Helv. Chim. Acta 1970, 53, 417. (b) Brady,
W. T.; Hoff, E. F., J r.; Roe, J ., R.; Parry, J ., F. H. J . Am. Chem. Soc.
1969, 91, 5679.
(28) Holton, R. A.; Crouse, D. J .; Williams, A. D.; Kennedy, R. M. J .
Org. Chem. 1987, 52, 2317.
(29) Hassner, A.; Dillon, J . L., J r. J . Org. Chem. 1983, 48, 3382.
(30) (a) Reference 16. (b) Danheiser, R. L.; Savariar, S.; Cha, D. D.
Organic Syntheses; Wiley: New York, 1993; Collect. Vol. VIII, pp 82-
86.
(31) Ammann, A. A.; Rey, M.; Dreiding, A. S. Helv. Chim. Acta 1987,
70, 321.
(32) For examples of the regioselective alkylation of R-thiocyclobu-
tanones, see: (a) Coates, R. M.; Pigott, H. D.; Ollinger, J . Tetrahedron
Lett. 1974, 3955. (b) Cohen, T.; Ouellette, D.; Pushpananda, K.;
Senaratne, A.; Yu, L.-C. Tetrahedron Lett. 1981, 22, 3377.
(34) Brady, W. T.; Hoff, E. F., J r. J . Org. Chem. 1970, 35, 3733.
(35) For
a review of methods for the oxidation of sulfides to
sulfoxides, see Madesclaire, M. Tetrahedron 1986, 42, 5459.
(36) For reviews, see: (a) Grierson, D. S.; Husson, H. P. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: New York, 1991; Vol. 6; pp 924-946. (b) Kennedy,
M.; McKervey, M. A. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 7, pp
193-206. (c) De Lucchi, O.; Miotti, U.; Modena, G. Org. React. 1991,
40, 157.

4380 J . Org. Chem., Vol. 65, No. 14, 2000
Lawlor et al.
Sch em e 2
Attempted ring expansion37 of R-thiocyclobutanones
Sch em e 3
such as 8 employing diazomethane either alone or in the
presence of boron trifluoride etherate led only to the
recovery of the cyclobutanone in near-quantitative yield.
On the other hand, similar reaction with ethyl diazoac-
etate rapidly produced the desired cyclopentanone 40 in
good yield as a 1:1 mixture of diastereomers (Scheme 4).
NMR studies confirmed the identity of the product as the
expected cyclopentanone resulting from predominant
migration of the less-substituted carbon atom37 in the
four-membered ring.
Con clu sion
R-Diazo thiol esters undergo a remarkably facile “thia-
Wolff rearrangement” in the presence of catalytic rhod-
ium(II) acetate to produce (arylthio)ketenes which com-
bine with a variety of ketenophiles to provide access to
R-thiocyclobutanones, cyclobutenones, and â-lactams.
Reductive desulfurization of these cycloadducts takes
place under mild conditions and in excellent yield, and
this sequence thus represents a useful new alternative
to the existing dichloroketene-based methodology for the
synthesis of four-membered carbocycles and heterocycles.
Sch em e 4
Exp er im en ta l Section
Ma ter ia ls. Commercial grade reagents and solvents were
used without further purification except as indicated below.
Acetonitrile, boron trifluoride etherate, dichloromethane, 1,2-
dichloroethane, diisopropylamine, 1,1,1,3,3,3-hexamethyldisi-
lazane, pyridine, toluene, and triethylamine were distilled from
calcium hydride. THF was distilled from sodium benzophenone
ketyl or dianion. Acetyl chloride was distilled from quinoline.
N,N-Dimethylformamide was sequentially dried in three
stages over activated 3 Å molecular sieves. Tributyltin hydride
was distilled under reduced pressure. Methyl iodide was
passed through a short column of neutral alumina or distilled
immediately prior to use. Molecular sieves were heated at 90
°C under vacuum for 12 h and stored in a desiccator jar until
use. 4-Phenyl-1-butene and 2-methyl-4-phenyl-1-butene were
prepared by Wittig methylenation of the corresponding car-
bonyl compounds. Zinc metal was activated by the procedure
of Nozoe et al.39
Gen er a l P r oced u r es. All reactions were performed in
flame-dried glassware under a positive pressure of argon and
stirred magnetically unless otherwise indicated. Air- and
moisture-sensitive liquids and solutions were transferred via
syringe or cannula and were introduced into reaction vessels
through rubber septa. Reaction product solutions and chro-
matography fractions were concentrated using a Bu¨chi rotary
evaporator at approximately 20 mmHg and then at ca. 0.1
mmHg (vacuum pump) unless otherwise indicated. Column
chromatography was performed using 230-400 mesh Merck
or Baker silica gel. Melting points and boiling points are
uncorrected.
exploratory studies suggest that R-thiocyclobutanones
may prove to be equally valuable as intermediates for
the synthesis of five-membered rings. As outlined in
Scheme 4, Baeyer-Villiger rearrangement of 8 to the
five-membered lactone 39 occurs smoothly on exposure
to hydrogen peroxide in methanol at room temperature.
Interestingly, the exclusive product in this reaction is the
lactone produced by migration of the phenylthio-substi-
tuted carbon atom.
(37) For reviews of ring expansion methods, see: (a) Wovkulich, P.
M. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: New York, 1991; Vol. 1, pp 843-899. (b) Hesse, M.
Ring Enlargement in Organic Chemistry; VCH: Weinheim, 1991. (c)
Gutsche, C. D.; Redmore, D. Carbocyclic Ring Expansions Reactions;
Academic Press: New York, 1968. (d) Haufe, G.; Mann, G. The
Chemistry of Alicyclic Compounds; Elsevier: Berlin, 1989; pp 240-
372.
(38) (a) Greene, A. E.; Depre´s, J .-P. J . Am. Chem. Soc. 1979, 101,
4003. (b) Au-Yeung, B.-W.; Fleming, I. J . Chem. Soc., Chem. Commun.
1977, 81.
(39) Tsuda, K.; Ohki, E.; Nozoe, S. J . Org. Chem. 1963, 28, 783.

Rh-Catalyzed Rearrangement of R-Diazo Thiol Esters
J . Org. Chem., Vol. 65, No. 14, 2000 4381
2,4,6-Tr im eth ylben zen eth iol.40 Zinc-mercury amalgam
was prepared by the following procedure. A 500-mL, one-
necked, round-bottomed flask equipped with an argon inlet
adapter was charged with mercury(II) chloride (7.48 g, 27.6
mmol), 112 mL of water, and concentrated hydrochloric acid
(3.8 mL, 45.9 mmol). The resulting clear solution was stirred
rapidly as zinc dust (37.4 g, 572 mmol) was added. The reaction
mixture was stirred at 25 °C for 15 min and then filtered
through a Bu¨chner funnel. The resulting gray amalgam was
washed sequentially with 100 mL of water containing five
drops of concentrated hydrochloric acid, 100 mL of ethanol,
and 150 mL of diethyl ether. The amalgam was not allowed
to dry completely. A 500-mL, three-necked, round-bottomed
flask equipped with a reflux condenser fitted with an argon
inlet adapter, a glass stopper, and a mechanical stirrer was
charged with a 33% solution of sulfuric acid that was prepared
from concentrated sulfuric acid (63 mL, 610 mmol) and 119
mL of water. 2,4,6-Trimethylbenzenesulfonyl chloride (10 g,
45.7 mmol) was added, and the freshly prepared Zn-Hg
amalgam was added in portions over ca. 1 min (exothermic
reaction). The reaction mixture was heated at reflux for 4 h
(during which time a white precipitate formed) and then was
allowed to stand at 25 °C for 12 h. The resulting mixture was
filtered through a Bu¨chner funnel with the aid of four 100-
mL portions of warm diethyl ether. The aqueous phase was
separated and extracted with two 100-mL portions of diethyl
ether, and the combined organic phases were washed with two
100-mL portions of water and 100 mL of brine, dried over
MgSO4, filtered, and concentrated to give 4.52 g of a cloudy,
pale yellow oil. Distillation through a Vigreux column at
reduced pressure afforded 3.78 g (54%) of the thiol as a
colorless liquid with properties consistent with those previ-
ously reported for this compound.
mmol) was added rapidly in one portion. The reaction mixture
was stirred at -78 °C for 10 min and then partitioned between
40 mL of 5% HCl solution and 50 mL of diethyl ether. The
aqueous phase was separated and extracted with two 40-mL
portions of ether, and the combined organic phases were
washed with 45 mL of brine and concentrated to afford 2.25 g
of a yellow oil which was immediately dissolved in 25 mL of
acetonitrile and transferred via cannula to a 100-mL, three-
necked, round-bottomed flask equipped as described above.
Water (0.118 mL, 0.118 g, 6.55 mmol) and triethylamine (1.40
mL, 1.02 g, 10.0 mmol) were added rapidly, and then a solution
of methanesulfonyl azide (1.15 mL, 1.20 g, 9.89 mmol) in 28
mL of acetonitrile was added over 20 min. The resulting yellow
solution was stirred at 25 °C for 2.5 h and then concentrated
to a volume of ca. 10 mL. The residue was diluted with 50 mL
of diethyl ether and washed with three 40-mL portions of 10%
NaOH solution and 40 mL of brine, dried over MgSO4, filtered,
and concentrated to afford 1.18 g of an orange oil. Column
chromatography on 70 g of silica gel (gradient elution with
5-10% ethyl acetate-hexane) provided 0.885 g (76%) of
R-diazo thiol ester 6b as a yellow oil: IR (film) 3090, 3060,
2260, 2100, and 1625 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.38-
7.52 (m, 5 H), and 5.25 (s, 1 H); 13C NMR (75 MHz, CDCl3) δ
184.1, 135.3, 129.8, 129.3, 127.3, and 54.2.
S-2,4,6-Tr im et h ylp h en yl 2-Dia zoet h a n et h ioa t e (6a ).
Reaction of thiol ester 5a (1.0 g, 5.15 mmol) with LiHMDS
(5.46 mmol) and 2,2,2-trifluoroethyl trifluoroacetate (0.83 mL,
1.22 g, 6.20 mmol) in 26 mL of THF according to the general
procedure provided 1.88 g of a yellow oil which was diluted
with 24 mL of acetonitrile and treated with water (0.093 mL,
0.093 g, 5.16 mmol), triethylamine (1.10 mL, 0.799 g, 7.89
mmol), and a solution of MsN3 (0.90 mL, 0.938 g, 7.74 mmol)
in 20 mL of acetonitrile at 25 °C for 2.5 h to afford 1.2 g of a
yellow solid. Column chromatography on 60 g of silica gel
(gradient elution with 2.5-5% ethyl acetate-hexane) provided
1.01 g (89%) of R-diazo thiol ester 6a as a pale yellow solid:
mp 91.5-93 °C; IR (CCl4) 3100, 3010, 2960, 2940, 2910, 2840,
2100, 1630, and 1600, cm-1; 1H NMR (300 MHz, CDCl3) δ 7.00
(s, 2 H), 5.18 (s, 1 H), 2.39 (s, 6 H), and 2.30 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 184.4, 143.2, 140.5, 129.4, 123.6, 53.3, 21.8,
and 21.1.
Gen er a l P r oced u r e for Gen er a tion of Th iok eten es
a n d Cycloa d d ition . 2-(P h en ylth io)sp ir o[3.5]n on a n -1-on e
(8). A 25-mL, two-necked, round-bottomed flask equipped with
a rubber septum and a reflux condenser fitted with a rubber
septum and inlet needle was charged with rhodium(II) acetate
(0.010 g, 0.023 mmol), 3.5 mL of dichloroethane, and methyl-
enecyclohexane (0.680 mL, 0.544 g, 5.66 mmol). The rubber
septum was replaced with a glass stopper, and the green
reaction mixture was heated at reflux while a solution of
R-diazo thiol ester 6b (0.202 g, 1.13 mmol) in 2.5 mL of
dichloroethane was added dropwise via syringe pump (through
the reflux condenser) over 2.25 h. An additional 1.5 mL of
dichloroethane was used to rinse the syringe and was added
to the reaction mixture over ca. 5 min. The reaction mixture
was cooled to 25 °C and then concentrated to afford 0.279 g of
a brown oil. Column chromatography on 28 g of silica gel
(gradient elution with 2.5-5% ethyl acetate-hexane) gave
0.219 g of cyclobutanone 8 (78%) as a yellow oil: IR (film) 3040,
2920, 2840, 1770, and 1580 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.43-7.47 (m, 2 H), 7.19-7.31 (m, 3 H), 4.19 (app s, 1 H),
2.89 (d, J ) 18.2 Hz, 1 H), 2.75-2.85 (d of m, J ) 17.8 Hz, 1
H), 1.54-1.83 (m, 7 H), and 1.24-1.43 (m, 3 H); 13C NMR (75
MHz, CDCl3) δ 204.6, 135.4, 130.5, 129.0, 126.8, 69.2, 54.6,
38.3, 37.2, 32.2, 25.4, 24.2, and 23.1.
S-2,4,6-Tr im eth ylp h en yl Eth a n eth ioa te41 (5a ). A 100-
mL, three-necked, round-bottomed flask equipped with an
argon inlet adapter, glass stopper, and a rubber septum was
charged with 2,4,6-trimethylbenzenethiol (1.81 g, 11.9 mmol),
35 mL of dichloromethane, and pyridine (1.15 mL, 1.12 g, 14.2
mmol) and cooled to 0 °C. Acetyl chloride (1.0 mL, 1.10 g, 14.1
mmol) was added slowly via syringe over ca. 8 min. The
resulting mixture was stirred at 0 °C for 10 min and then at
25 °C for 2 h. The resulting cloudy white mixture was poured
into 20 mL of water, and the aqueous phase was separated
and extracted with two 10-mL portions of dichloromethane.
The combined organic phases were washed with 20 mL of
brine, dried over MgSO4, filtered, and concentrated to afford
2.38 g of a pale yellow oil. Column chromatograpy on 48 g of
silica gel (gradient elution with 0-2.5% ethyl acetate-hexane)
provided 2.21 g (96%) of thiol ester 5a as a white solid: mp
54.5-55.5 °C; IR (CCl4) 3020, 2960, 2940, 2910, 2840, 1700,
and 1600 cm-1 1H NMR (300 MHz, CDCl3) δ 6.98 (s, 2 H),
;
2.41 (s, 3 H), 2.31 (s, 6 H), and 2.29 (s, 3 H); 13C NMR (75
MHz, CDCl3) δ 193.8, 142.4, 139.9, 129.2, 123.9, 30.1, 21.5,
and 21.1.
Gen er a l P r oced u r e for Dia zo Tr a n sfer . S-P h en yl 2-Di-
a zoeth a n eth ioa te (6b). A 100-mL, three-necked, round-
bottomed flask equipped with an argon inlet adapter, rubber
septum, and a pressure-equalizing addition funnel fitted with
a rubber septum was charged with 1,1,1,3,3,3-hexamethyld-
isilazane (1.50 mL, 1.15 g, 7.11 mmol) and 18 mL of THF and
then cooled at 0 °C while n-BuLi (2.40 M in hexane, 2.90 mL,
6.96 mmol) was added rapidly dropwise. The resulting solution
was stirred at 0 °C for 15 min, and then cooled at -78 °C while
a solution of phenyl thioacetate (0.89 mL, 1.0 g, 6.57 mmol)
in 14 mL of THF was added dropwise over 15 min. The
reaction mixture was stirred at -78 °C for 30 min, and then
2,2,2-trifluoroethyl trifluoroacetate (1.10 mL, 1.61 g, 8.21
2-(2,4,6-Tr im eth ylph en ylth io)spir o[3.5]n on an -1-on e (9).
Reaction of R-diazo thiol ester 6a (0.100 g, 0.454 mmol) with
methylenecyclohexane (ca. 87% purity, 0.310 mL, 0.216 g, 2.24
mmol) and rhodium(II) acetate (0.004 g, 0.009 mmol) in 5 mL
of dichloroethane for 3 h according to the general procedure
provided 0.150 g of a green oil. Column chromatography on
15 g of silica gel (gradient elution with 0-1% ethyl acetate-
hexane) yielded 0.106 g (81%) of 9 as a pale yellow solid: mp
(40) For recent alternative procedures for the preparation of this
thiol, see: (a) Blower, P. J .; Dilworth, J . R.; Hutchinson, J . P.; Zubieta,
J . A. J . Chem. Soc., Dalton Trans. 1985, 1533. (b) Garratt, D. G.;
Beaulieu, P. L. Can. J . Chem. 1980, 58, 2737.
(41) For previous reports of the preparation of 5a , see: (a) Kuliev,
A. M. J . Org. Chem. USSR 1978, 14, 2437. (b) Petrillo, G. Novi; M.;
Garbarino, G.; Filiberti, M. Tetrahedron Lett. 1988, 29, 4185.
89-90 °C; IR (CCl4) 3020, 2920, 2850, 1780, and 1600 cm-1
1H NMR (300 MHz, CDCl3) δ 6.92 (s, 2 H), 3.62 (s, 1 H), 2.83
;

4382 J . Org. Chem., Vol. 65, No. 14, 2000
Lawlor et al.
(d, J ) 17.3 Hz, 1 H), 2.66 (d, J ) 17.0 Hz, 1 H), 2.53 (s, 6 H),
(300 MHz, CDCl3) δ 7.17-7.33 (m, 8 H, 20a , 20b), 7.14 (d, J
) 6.6 Hz, 2 H, 20a ), 6.92 (s, 4 H, 20a , 20b), 3.80 (app t, J )
2.4 Hz, 1 H, 20a ), 3.73 (app t, J ) 2.1 Hz, 1 H, 20b), 2.93 (dd,
J ) 16.8, 2 Hz, 1 H, 20b), 2.57-2.86 (m, 6 H, 20a , 20b), 2.53
(s, 12 H, 20a , 20b), 2.25 (s, 6 H, 20a , 20b), 2.15 (d of t, J )
12.4, 5.1 Hz, 1 H, 20b), 1.80-2.02 (m, 2 H, 20a ; m, 1 H, 20b),
1.48 (s, 3 H, 20b), and 1.39 (s, 3 H, 20a ); 13C NMR (75 MHz,
CDCl3) δ 204.3, 204.1, 142.9, 142.7, 141.8, 141.5, 138.7, 129.5,
129.2, 129.1, 128.5, 128.3, 128.2, 126.0, 71.9, 70.9, 55.5, 54.5,
43.7, 38.5, 36.0, 35.7, 32.1, 31.6, 26.0, 22.1, and 21.0.
2-(P h en ylth io)-1,2,2a ,7a -tetr a h yd r o-7H-cyclobu t[a ]in -
d en -1-on e (22). Reaction of R-diazo thiol ester 6b (0.298 g,
1.67 mmol) with indene (1.0 mL, 0.996 g, 8.57 mmol) and
rhodium(II) acetate (0.015 g, 0.034 mmol) in 11 mL of
dichloroethane for 2.5 h according to the general procedure
provided a brown oil. Column chromatograpy on 45 g of silica
gel (gradient elution with 5-10% ethyl acetate-hexane)
provided 0.316 g of a pale yellow solid which was recrystallized
from ethyl acetate-hexane to afford 0.214 g (48%) of 22 as
pale yellow crystals: mp 94-96 °C; IR (CCl4) 3060, 3020, 2950,
2910, 2840, 1770, and 1670 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.20-7.42 (m, 9 H), 4.98 (dd, J ) 9.0, 3.8 Hz, 1 H), 4.41 (app
t, J ) 8.3 Hz, 1 H), 4.08-4.15 (m, 1 H), 3.36 (d, J ) 16.5 Hz,
1 H), and 3.12 (dd, J ) 16.6, 9.8 Hz, 1 H); 13C NMR (75 MHz,
CDCl3) δ 208.7, 143.8, 139.0, 135.7, 130.0, 129.0, 128.3, 127.6,
126.7, 126.6, 125.5, 65.6, 60.3, 43.5, and 34.4.
2-(2,4,6-Tr im eth ylp h en ylth io)-1,2,2a ,7a -tetr a h yd r o-7H-
cyclobu t[a ]in d en -1-on e (23). Reaction of R-diazo thiol ester
6a (0.302 g, 1.37 mmol) with indene (0.80 mL, 0.797 g, 6.86
mmol) and rhodium(II) acetate (0.012 g, 0.027 mmol) in 10
mL of dichloroethane for 2.75 h according to the general
procedure provided 1.1 g of an oil. Column chromatography
on 22 g of silica gel (gradient elution with 5-20% ethyl
acetate-hexane) gave 0.335 g of a pale yellow solid which was
recrystallized from ethyl acetate-hexane to afford 0.244 g
(58%) of 23 as fluffy white crystals: mp 165.5-167.5 °C; IR
(CCl4) 3050, 3010, 2940, 2900, 2840, and 1750 cm-1; 1H NMR
(300 MHz, CDCl3) δ 7.58-7.61 (m, 1 H), 7.24-7.30 (m, 3 H),
6.93 (s, 2 H), 4.34 (dd, 9.4, 3.0 Hz, 1 H), 4.29 (app t, J ) 9.4
Hz, 1 H), 3.90-3.96 (br t, 1 H), 3.34 (d, J ) 16.5 Hz, 1 H),
3.08 (dd, J ) 16.7, 9.7 Hz, 1 H), 2.55 (s, 6 H), and 2.25 (s, 3
H); 13C NMR (75 MHz, CDCl3) δ 209.2, 143.8, 142.6, 139.4,
138.5, 130.6, 129.0, 128.1, 127.8, 126.6, 125.4, 67.9, 59.6, 43.8,
34.4, 22.3, and 21.0.
2.25 (s, 3 H), 1.54-1.89 (m, 7 H), and 1.31-1.44 (m, 3 H); 13
C
NMR (75 MHz, CDCl3) δ 204.6, 142.9, 138.5, 129.4, 129.1, 70.8,
53.9, 37.9, 36.9, 32.0, 25.4, 24.3, 23.1, 22.1, and 20.9. Anal.
Calcd for C18H24OS: C, 74.95; H, 8.39. Found: C, 74.67; H, 8.44.
7-(P h en ylth io)bicyclo[3.2.0]h ept-2-en -6-on e (13a, 13b).14
A 100-mL, three-necked, round-bottomed flask equipped with
a reflux condenser fitted with a pressure-equalizing addition
funnel (fitted with a rubber septum and an inlet needle), glass
stopper, and a rubber septum was charged with rhodium(II)
acetate (0.086 g, 0.19 mmol), 35 mL of dichloromethane, and
freshly prepared cyclopentadiene (3.90 mL, 3.20 g, 48.4 mmol).
The green reaction mixture was heated at reflux while a
solution of R-diazo thiol ester 6b (1.74 g, 9.76 mmol) in 25 mL
of dichloromethane was added dropwise via the addition funnel
over ca. 2.5 h. The reaction mixture was cooled to 25 °C and
then concentrated to give a brown oil. Column chromatograpy
on 50 g of silica gel (gradient elution with 5-10% ethyl
acetate-hexane) followed by similar purification of mixed
fractions on 5 g of silica gel provided 2.02 g (96%) of cyclobu-
1
tanones 13a and 13b (92:8 by H NMR analysis) as a yellow
solid: mp 77-85 °C; IR (film) 3050, 3040, 3010, 2840, 1775,
1
and 1580 cm-1. For 13a : H NMR (300 MHz, CDCl3) δ 7.39-
7.43 (m, 2 H), 7.20-7.31 (m, 3 H), 5.93-5.97 (m, 1 H), 5.83-
5.89 (m, 1 H), 4.77-4.81 (m, 1 H), 3.87-3.97 (m, 2 H), 2.73-
2.82 (d of m, 1 H), and 2.44-2.56 (m, 1 H); 13C NMR (75 MHz,
CDCl3) δ 209.1, 135.5, 135.5, 129.9, 129.3, 129.0, 126.6, 65.6,
59.9, 44.5, and 35.2. Anal. Calcd for C13H12OS: C, 72.19; H,
5.59. Found: C, 71.95; H, 5.59.
7-en d o-(2,4,6-Tr im eth ylp h en ylth io)bicyclo[3.2.0]h ep t-
2-en -6-on e (14a , 14b). Reaction of R-diazo thiol ester 6a (0.123
mg, 0.558 mmol) with freshly prepared cyclopentadiene (0.46
mL, 0.377 g, 5.71 mmol) and rhodium(II) acetate (0.005 g,
0.011 mmol) in 4 mL of dichloromethane for 3 h according to
the general procedure provided 0.180 g of a green oil. Column
chromatography on 18 g of silica gel (gradient elution with
0-0.5% ethyl acetate-hexane) afforded 0.133 g (92%) of 14a
1
and 14b (98:2 by H NMR analysis) as a white solid: mp 77-
88 °C; IR (CCl4) 3040, 3010, 2940, 2910, 2840, 1775, and 1595
cm-1. For 14a : 1H NMR (300 MHz, CDCl3) δ 6.92 (s, 2 H),
5.96-5.98 (m, 2 H), 4.23 (dd, J ) 8.8, 2.3 Hz, 1 H), 3.84 (app
t, J ) 7.3 Hz, 1 H), 3.75 (app t, J ) 7.9 Hz, 1 H), 2.75 (d, J )
17.6 Hz, 1 H), 2.53 (s, 6 H), 2.42-2.51 (m, 1 H), and 2.25 (s, 3
H); 13C NMR (75 MHz, CDCl3) δ 209.7, 142.7, 138.5, 135.4,
130.1, 129.8, 129.0, 67.9, 59.4, 45.2, 35.1, 22.2, and 21.0.
3-(2-P h en yleth yl)-2-(2,4,6-tr im eth ylp h en ylth io)cyclob-
u ta n on e (17a , 17b). Reaction of R-diazo thiol ester 6a (0.200
g, 0.908 mmol) with 4-phenyl-1-butene (1.20 g, 9.08 mmol) and
rhodium(II) acetate (0.008 g, 0.018 mmol) in 7 mL of dichlo-
roethane for 3 h according to the general procedure provided
1.4 g of a brown-green oil. Excess alkene was removed by
column chromatography on 10 g of silica gel (gradient elution
with 0-2% ethyl acetate-hexane) which provided 0.250 g of
a brown oil. Column chromatography on 50 g of silica gel
(gradient elution with 1-5% ethyl acetate-hexane) yielded
0.183 g (62%) of cyclobutanones 17a and 17b (83:17 by 1H
NMR analysis): IR (film) 3080, 3060, 3020, 2920, 2840, 1775,
and 1595 cm-1. For 17a : 1H NMR (300 MHz, CDCl3) δ 7.19-
7.30 (m, 3 H), 7.11 (d, J ) 7.2 Hz, 2 H), 6.91 (s, 2 H), 4.09 (dt,
J ) 9.4, 2.7 Hz, 1 H, 17b), 3.77 (dt, J ) 6.7, 2.9 Hz, 1 H), 3.12
(ddd, J ) 17.5, 9.1, 2.7 Hz, 1 H), 2.51-2.66 (m, 3 H), 2.48 (s,
6 H), 2.25 (s, 3 H), 2.14-2.25 (m, 1 H), 1.91-2.07 (m, 1 H),
and 1.73-1.88 (m, 1 H); 13C NMR (75 MHz, CDCl3) δ 204.0,
143.2, 141.1, 138.9, 129.1, 128.5, 128.3, 127.9, 126.1, 64.9, 49.6,
37.1, 34.3, 33.1, 22.1, and 21.0.
tr a n s-1,4-Dip h en yl-3-(p h en ylth io)-a zetid in -2-on e (25).
Reaction of R-diazo thiol ester 6b (0.045 g, 0.253 mmol) with
N-benzylideneaniline (0.160 g, 0.883 mmol) and rhodium(II)
acetate (0.003 g, 0.007 mmol) in 2.25 mL of dichloromethane
for 3 h according to the general procedure provided a light
brown oil. Column chromatography on 10 g of silica gel
(gradient elution with 0-5% ethyl acetate-hexane) yielded
0.071 g (85%) of â-lactam 25 as an off-white solid: mp 116-
1
117 °C; IR (CCl4) 3060, 3030, 2920, 1760, and 1590 cm-1; H
NMR (300 MHz, CDCl3) δ 7.51 (d, J ) 7.2 Hz, 2 H), 7.17-7.35
(m, 12 H), 7.00-7.04 (m, 1 H), 4.81 (d, J ) 2.5 Hz, 1 H), and
4.26 (d, J ) 2.5 Hz, 1 H); 13C NMR (75 MHz, CDCl3) δ 163.3,
137.1, 136.2, 132.2, 132.1, 129.2, 129.0, 128.9, 128.0, 125.9,
124.3, 117.2, 62.9, and 61.4.
2-Me t h yl-3-p h e n yl-4-(2,4,6-t r im e t h ylp h e n ylt h io)cy-
clobu ten -1-on e (28). Reaction of R-diazo thiol ester 6a (0.155
g, 0.704 mmol) with 3-phenyl-2-propyne (0.425 mL, 0.394 g,
3.40 mmol) and rhodium(II) acetate (0.007 g, 0.016 mmol) in
5 mL of dichloroethane for 3 h according to the general pro-
cedure provided 0.535 g of a dark green oil. Column chroma-
tography on 53 g of silica gel (gradient elution with 5-10%
ethyl acetate-hexane) afforded 0.109 g (50%) of 28 as an
orange oil: IR (film) 3040, 3020, 2940, 2920, 2840, 1760, and
3-Meth yl-3-(2-p h en yleth yl)-2-(2,4,6-tr im eth ylp h en ylth -
io)cyclobu ta n on e (20a , 20b). Reaction of R-diazo thiol ester
6a (0.075 g, 0.340 mmol) with 2-methyl-4-phenyl-1-butene
(0.254 g, 1.74 mmol) and rhodium(II) acetate (0.003 g, 0.007
mmol) in 2.5 mL of dichloroethane for 3 h according to the
general procedure gave 0.389 g of a green oil. Column chroma-
tography on 30 g of silica gel (gradient elution with 0-5% ethyl
acetate-hexane) yielded 0.068 g (59%) of cyclobutanones 20a
and 20b (57:43 by 1H NMR analysis) as a yellow oil: IR (film)
1
1610 cm-1; H NMR (300 MHz, CDCl3) δ 7.65-7.68 (m, 2 H),
7.47-7.50 (m, 3 H), 6.92 (s, 2 H), 4.84 (q, J ) 2.0 Hz, 1 H),
2.46 (s, 6 H), 2.26 (s, 3 H), and 1.97 (d, J ) 1.8 Hz, 3 H); 13C
NMR (75 MHz, CDCl3) δ 187.7, 165.9, 143.7, 143.0, 138.7,
131.3, 131.2, 129.4, 129.1, 129.0, 127.8, 64.7, 22.3, 21.0, and
9.5.
3-Met h oxy-2-m et h yl-4-(p h en ylt h io)cyclob u t en -1-on e
(29). Reaction of R-diazo thiol ester 6b (0.101 g, 0.567 mmol)
1
3050, 3020, 2940, 2920, 2840, 1780, and 1600 cm-1; H NMR

Rh-Catalyzed Rearrangement of R-Diazo Thiol Esters
J . Org. Chem., Vol. 65, No. 14, 2000 4383
with 1-methoxypropyne (0.166 mL, 0.139 g, 1.98 mmol) and
rhodium(II) acetate (0.005 g, 0.011 mmol) in 5 mL of dichlo-
romethane for 3 h according to the general procedure gave
0.137 g of a brown oil. Column chromatography on 15 g of silica
gel (gradient elution with 20-30% ethyl acetate-hexane)
yielded 0.090 g (72%) of cyclobutenone 29 as a yellow oil: IR
stirred at 0 °C for 30 min, and then methyl iodide (0.110 mL,
0.251 g, 1.77 mmol) was added rapidly dropwise. The ice bath
was removed, the flask was wrapped with aluminum foil, and
the reaction mixture was stirred at 25 °C for 26 h. The
resulting yellow mixture was partitioned between 10 mL of
diethyl ether and 10 mL of saturated aqueous NH4Cl, and the
organic phase was separated and washed with 5 mL of water.
The combined aqueous layers were extracted with 5 mL of
diethyl ether, and the combined organic layers were washed
with 8 mL of brine, dried over MgSO4, filtered, and concen-
trated to provide 0.104 g of an oil. Column chromatography
on 13 g of silica gel (gradient elution with 0-2.5% ethyl
acetate-hexane) afforded 0.089 g (77%) of cyclobutanone 32
(contaminated with ca. 8% of O-alkylation product): IR (film)
1
(film) 3020, 2990, 2940, 2910, 2850, 1760, and 1620 cm-1; H
NMR (300 MHz, CDCl3) δ 7.47-7.50 (m, 2 H), 7.29-7.31 (m,
3 H), 4.59 (q, J ) 1.8 Hz, 1 H), 4.14 (s, 3 H), and 1.54 (d, J )
1.7 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 184.2, 176.1, 134.1,
130.8, 128.7, 128.2, 120.8, 62.7, 59.7, and 6.6. Anal. Calcd for
C
12H12O2S: C, 65.43; H, 5.49. Found: C, 65.22; H, 5.58.
3-Met h oxy-2-m et h yl-4-(2,4,6-t r im et h ylp h en ylt h io)cy-
clobu ten -1-on e (30). Reaction of R-diazo thiol ester 6a (0.050
g, 0.227 mmol) with 1-methoxypropyne (0.066 mL, 0.055 g,
0.787 mmol) and rhodium(II) acetate (0.002 g, 0.005 mmol) in
1.9 mL of dichloromethane for 3 h according to the general
procedure provided a light brown oil. Column chromatography
on 6 g of silica gel (elution with 15% ethyl acetate-hexane)
gave 0.042 g (71%) of cyclobutenone 30 as a yellow oil: IR
1
3050, 2920, 2840, 1770, and 1580 cm-1; H NMR (300 MHz,
CDCl3) δ 7.49 (dd, J ) 7.7, 2.1 Hz, 2 H), 7.28-7.33 (m, 3 H),
3.43 (d, J ) 16.2 Hz, 1 H), 2.75 (d, J ) 16.4 Hz, 1 H), 2.03-
2.06 (m, 1 H), 1.23-1.76 (m, 9 H), and 1.23 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 205.4, 136.1, 134.1, 128.8, 128.7, 128.6,
128.5, 71.2, 53.2, 38.8, 34.5, 33.6, 32.5, 25.6, 23.8, 23.3, and
15.5.
1
(film) 3025, 2980, 2955, 2880, 1780, and 1640 cm-1; H NMR
7-Met h yl-7-(p h en ylt h io)b icyclo[3.2.0]h ep t -2-en -6-on e
(33a , 33b ). A 10-mL, two-necked, round-bottomed flask
equipped with an argon inlet adapter and rubber septum was
charged with lithium t-butoxide (0.068 g, 0.849 mmol) and 2.5
mL of THF and cooled at 0 °C while a solution of R-thiocy-
clobutanone 13a (0.153 g, 0.707 mmol) in 2.5 mL of THF was
added dropwise via cannula over ca. 10 min. The resulting
solution was stirred at 0 °C for 30 min, and methyl iodide
(0.175 mL, 0.399 g, 2.81 mmol) was then added rapidly
dropwise. The ice bath was removed, the flask was wrapped
in aluminum foil, and the orange reaction mixture was stirred
at 25 °C for 23 h and then partitioned between 10 mL of diethyl
ether and 10 mL of saturated aqueous NH4Cl. The organic
layer was separated and washed with 5 mL of water, and the
combined aqueous phases were extracted with 5 mL of diethyl
ether. The combined organic phases were washed with 10 mL
of brine, dried over MgSO4, filtered, and concentrated to give
0.163 g of an orange oil. Column chromatography on 16 g of
silica gel (gradient elution with 2.5-5% ethyl acetate-hexane)
afforded 0.142 g (87%) of cyclobutanones 33a and 33b (93:7
by 1H NMR analysis): IR (film) 3050, 2950, 2910, 2850, 1770,
and 1580 cm-1. For 33a : 1H NMR (300 MHz, CDCl3) δ 7.57-
7.60 (m, 2 H), 7.28-7.32 (m, 3 H), 5.90-5.96 (m, 2 H), 3.96-
4.03 (app t, 1 H), 3.46-3.51 (m, 1 H), 2.74-2.82 (m, 1 H), 2.46-
2.56 (app dd, 1 H), and 1.48 (s, 3 H); 13C NMR (75 MHz, CDCl3)
δ 212.6, 135.0, 134.9, 131.6, 129.8, 128.7, 128.0, 70.7, 57.7, 51.9,
34.6, and 22.9.
(300 MHz, CDCl3) δ 6.92 (s, 2 H), 4.30 (q, J ) 2.1 Hz, 1 H),
4.12 (s, 3 H), 2.52 (s, 6 H), 2.24 (s, 3 H), and 1.63 (d, J ) 1.8
Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 184.5, 177.0, 143.9,
138.8, 129.0, 127.0, 119.6, 63.5, 59.6, 22.1, 21.0, and 6.9.
1,2,2a ,7a -Tetr a h yd r o-7H-cyclobu t[a ]in d en -1-on e (31).42
P r oced u r e A: Tr ibu tyltin Hyd r id e Red u ction . A 10-mL,
one-necked, round-bottomed flask equipped with a rubber
septum and argon inlet needle was charged with sulfide 22
(0.094 g, 0.353 mmol) and 2.5 mL of toluene. The flask was
fitted with a reflux condenser, and the reaction mixture was
heated at reflux while a solution of tributyltin hydride (0.114
mL, 0.123 g, 0.424 mmol) and AIBN (0.006 g, 0.037 mmol) in
2.5 mL of toluene was added dropwise (through the condenser)
over 35 min. After 1 h, the reaction mixture was cooled to 25
°C and concentrated by rotary evaporation at 0 °C to afford
0.250 g of a yellow oil. Column chromatography on 20 g of silica
gel (gradient elution with 5-10% ethyl acetate-hexane)
provided 0.050 g (89%) of 31 as a colorless oil which solidified
upon storage at 0 °C: mp 33.5-36 °C; IR (film) 3060, 3010,
2940, 2900, 2840, and 1775 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.21-7.31 (m, 4 H), 4.03-4.06 (m, 2 H), 3.55-3.65 (m, 1 H),
3.30 (d, J ) 16.8 Hz, 1 H), 3.04-3.13 (m, 1 H), and 2.88 (d, J
) 17.7 Hz, 1 H); 13C NMR (75 MHz, CDCl3) δ 212.2, 144.5,
143.0, 127.4, 125.3, 125.0, 62.7, 55.6, 36.5, and 33.9. P r oce-
d u r e B: Zin c Red u ction . A 25-mL, one-necked, round-
bottomed flask equipped with a rubber septum and argon inlet
needle was charged with sulfide 22 (0.095 g, 0.357 mmol) and
4 mL of THF. Activated zinc dust (0.466 g, 7.13 mmol) was
added in one portion, followed by 4 mL of saturated aq NH4Cl
solution. The flask was fitted with a reflux condenser, and the
reaction mixture was heated at reflux with vigorous stirring
for 25 h. The resulting mixture was cooled to 25 °C and filtered
with the aid of diethyl ether. The combined filtrates were
washed with two 10-mL portions of saturated aqueous NaH-
CO3, and the combined aqueous phases were extracted with
10 mL of diethyl ether. The combined organic layers were
washed with 10 mL of brine, dried over MgSO4, filtered, and
concentrated by rotary evaporation at 0 °C to afford 0.088 g
of crude product. Column chromatography on 9 g of silica gel
(gradient elution with 5-10% ethyl acetate-hexane) furnished
0.047 g (84%) of 31 as an oil which solidified upon storage at
0 °C (this material was contaminated with <5% starting
7-exo-(P h en ylm eth yl)-7-(ph en ylth io)bicyclo[3.2.0]h ept-
2-en -6-on e (34). A 10-mL, two-necked, round-bottomed flask
equipped with an argon inlet adapter and a rubber septum
was charged with lithium tert-butoxide (0.070 mg, 0.874 mmol)
and 2.5 mL of THF and cooled at 0 °C while a solution of
R-thiocyclobutanone 13a (0.157 g, 0.726 mmol) in 2.5 mL of
THF was added dropwise via cannula over ca. 8 min. The
resulting orange solution was stirred at 0 °C for 30 min, and
benzyl bromide (0.345 mL, 0.496 g, 2.90 mmol) was then added
rapidly dropwise. The ice bath was removed, the flask was
wrapped in aluminum foil, and the reaction mixture was
stirred at 25 °C for 17 h and then partitioned between 10 mL
of saturated aq NH4Cl and 10 mL of diethyl ether. The organic
layer was separated and washed with 10 mL of water, and
the combined aqueous phases were extracted with 10 mL of
diethyl ether. The combined organic phases were washed with
8 mL of brine, dried over MgSO4, filtered, and concentrated
to give 0.402 g of an orange oil. Column chromatography on
25 g of silica gel (gradient elution with 2.5-5% ethyl acetate-
hexane) afforded 0.192 g (86%) of cyclobutanone 34 (contami-
nated with ca. 8% of O-alkylation product): IR (film) 3060,
1
material as determined by H NMR analysis).
2-Meth yl-2-(p h en ylth io)sp ir o[3.5]n on a n -1-on e (32). A
10-mL, two-necked, round-bottomed flask equipped with a
rubber septum and argon inlet needle was charged with
lithium tert-butoxide (0.043 g, 0.537 mmol) and 2 mL of THF
and cooled at 0 °C while a solution of R-thiocyclobutanone 8
(0.110 g, 0.446 mmol) in 1.5 mL of THF was added dropwise
via cannula over ca. 3 min. The resulting yellow solution was
1
3030, 2960, 2920, 2860, 1775, 1600, and 1580 cm-1; H NMR
(300 MHz, CDCl3) δ 7.66 (dd, J ) 8.2, 2.0 Hz, 2 H), 7.22-7.34
(m, 6 H), 7.10 (dd, J ) 8.1, 2.0 Hz, 2 H), 5.88 (s, 2 H), 3.63 (dd,
J ) 8.2, 1.3 Hz, 1 H), 3.10 (d, J ) 13.8 Hz, 1 H), 2.97 (d, J )
13.8 Hz, 1 H), 2.93 (ddd, J ) 9.7, 8.0, 1.6 Hz, 1 H), 2.66 (ddd,
J ) 18.1, 3.1, 1.7 Hz, 1 H), and 2.29 (ddd, J ) 18.1, 10.2, 2.1
(42) J effs, P. W.; Molina, G.; Cass, M. W.; Cortese, N. A. J . Org.
Chem. 1982, 47, 3871.

4384 J . Org. Chem., Vol. 65, No. 14, 2000
Lawlor et al.
Hz, 1 H); 13C NMR (75 MHz, CDCl3) δ 212.8, 136.2, 135.1,
134.6, 131.8, 130.1, 129.4, 128.9, 128.5, 128.0, 127.0, 74.9, 59.3,
48.3, 41.5, and 34.6.
the flask was fitted with a reflux condenser and heated at
reflux for 1 h. The resulting mixture was cooled to 25 °C and
concentrated to afford 0.113 g of an oil. Column chromatog-
raphy on 6 g of silica gel (gradient elution with 5-10% ethyl
acetate-hexane) provided 0.094 g (89%) of R-acetoxy sulfide
38 as a colorless oil: IR (film) 3040, 3000, 2920, 2840, 1780,
and 1745 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.29-7.44 (m, 5
H), 3.27 (d, J ) 16.5 Hz, 1 H), 2.71 (d, J ) 16.5 Hz, 1 H), 2.13-
2.21 (m, 2 H), 2.11 (s, 3 H), 1.67-1.84 (m, 3 H), 1.43-1.45 (m,
2 H), and 1.18-1.33 (m, 3 H); 13C NMR (75 MHz, CDCl3) δ
193.9, 168.6, 135.1, 129.3, 129.2, 128.9, 98.4, 49.8, 44.2, 32.6,
30.5, 25.3, 24.0, 22.5, and 21.2.
7-(P h en ylm et h yl)b icyclo[3.2.0]h ep t -2-en -6-on e (36a ,
36b). A 10-mL, one-necked, round-bottomed flask equipped
with a rubber septum and argon inlet needle was charged with
sulfide 33 (0.159 g, 0.519 mmol) and 4.5 mL of toluene. The
flask was fitted with a reflux condenser and heated at reflux
while a solution of tributyltin hydride (0.167 mL, 0.181 g, 0.621
mmol) and AIBN (0.009 g, 0.055 mmol) in 2.5 mL of toluene
was added dropwise (through the reflux condenser) over 35
min. After 20 min, the reaction mixture was cooled to 25 °C
and concentrated to afford 0.344 g of a colorless oil. Column
chromatography on 35 g of silica gel and then again on 10 g of
silica gel (gradient elution with 2.5-5% ethyl acetate-hexane)
provided 0.089 g (87%) of cyclobutanones 36a and 36b (88:12
by 1H NMR analysis): For 36a : IR (film) 3080, 3060, 3020,
La cton e 39. A 10-mL, one-necked, round-bottomed flask
equipped with a rubber septum and argon inlet needle was
charged with R-thiocyclobutanone 8 (0.060 g, 0.244 mmol), 3
mL of methanol, and then 30% aq hydrogen peroxide (0.110
mL, 0.033 g, 0.970 mmol). The reaction mixture was stirred
at 25 °C for 23 h and then partitioned between 8 mL of
dichloromethane and 8 mL of water. The aqueous phase was
saturated with sodium chloride and extracted with three 8-mL
portions of dichloromethane. The combined organic layers were
dried over MgSO4, filtered, and concentrated to provide 0.068
g of an oil. Column chromatography on 30 g of silica gel
(gradient elution with 5-10% ethyl acetate-hexane) afforded
0.046 g (72%) of 39 as a colorless oil: IR (film) 3020, 2900,
2820, and 1760 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.53-7.56
(m, 2 H), 7.29-7.36 (m, 3 H), 5.49 (s, 1 H), 2.62 (d, J ) 17.1
Hz, 1 H), 2.38 (d, J ) 17.6 Hz, 1 H), and 1.34-1.70 (m, 10 H);
13C NMR (75 MHz, CDCl3) δ 175.2, 132.9, 132.5, 129.2, 128.1,
96.6, 44.9, 40.0, 34.9, 31.6, 25.4, 22.7, and 22.7.
1
2940, 2910, 2840, 1770, and 1600 cm-1; H NMR (300 MHz,
CDCl3) δ 7.27-7.32 (m, 2 H), 7.17-7.24 (m, 3 H), 5.91-5.92
(m, 1 H), 5.74-5.79 (m, 1 H), 3.75-3.85 (m, 2 H), 3.59-3.66
(m, 1 H), 2.94 (dd, J ) 14.7, 5.0 Hz, 1 H), 2.63-2.72 (m, 1 H),
2.67 (dd, J ) ∼15, 5 Hz, 1 H), and 2.41 (dddd, J ) 17.1, 6.8,
3.9, 2.0 Hz, 1 H); 13C NMR (75 MHz, CDCl3) δ 214.3, 139.5,
135.1, 129.5, 128.5, 128.3, 126.1, 65.5, 59.4, 42.5, 34.1, and
30.6.
2-(P h en ylsu lfin yl)sp ir o[3.5]n on a n -1-on e (37). P r oce-
d u r e A: m -CP BA Oxid a tion . A 25-mL, two-necked, round-
bottomed flask equipped with an argon inlet adapter and a
rubber septum was charged with sulfide 8 (0.101 g, 0.410
mmol) and 5 mL of dichloromethane and cooled at 0 °C while
a solution of m-CPBA (85%, 0.083 g, 0.409 mmol) in 3 mL of
dichloromethane was added dropwise by syringe over 8 min.
The reaction mixture was stirred at 0 °C for 70 min and was
then partitioned between 40 mL of diethyl ether and 10 mL
of 10% aqueous Na2SO3. The organic phase was separated and
washed with two 10-mL portions of saturated aqueous NaH-
CO3 and 10 mL of brine, dried over MgSO4, filtered, and
concentrated to afford 0.110 g of a light brown oil. Column
chromatography on 10 g of silica gel (gradient elution with
20-30% ethyl acetate-hexane) gave 0.095 g (88%) of sulfoxide
37 as a colorless oil (60:40 mixture of diastereomers by 1H
NMR analysis): IR (film) 3040, 2920, 2840, 2220, and 1770
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.72-7.75 (m, 2 H), 7.63-
7.67 (m, 2 H), 7.50-7.57 (m, 6 H), 4.03 (app t, J ) 2.4 Hz, 1
H), 3.66 (dd, J ) 4.5, 2.3 Hz, 1 H), 3.08 (dd, J ) 17.1, 2.0 Hz,
1H), 2.97 (dd, J ) 17.5, 1.1 Hz, 1H), 2.82 (ddd, J ) 17.5, 3.0,
1.4 Hz, 1 H), 2.76 (dd, J ) 17.2, 4.6 Hz, 1 H), 2.22-2.29 (m, 2
H), 2.05-2.12 (m, 1 H), and 1.26-2.01 (m, 17 H); 13C NMR
(75 MHz, CDCl3) δ 198.6, 197.3, 142.7, 141.6, 131.6, 131.3,
129.2, 129.1, 125.0, 124.7, 87.0, 84.5, 58.9, 55.9, 39.1, 38.1, 38.0,
37.1, 32.2, 25.3, 25.1, 23.8, 23.5, and 22.9. Anal. Calcd for
2-(P h en ylth io)-2′-car beth oxyspir o[4.5]decan -1-on e (40a,
40b). A 10-mL, two-necked, round-bottomed flask equipped
with an argon inlet adapter and rubber septum was charged
with cyclobutanone 8 (0.048 g, 0.195 mmol) and 0.750 mL of
diethyl ether and was cooled at 0 °C while boron trifluoride
etherate (0.048 mL, 0.055 g, 0.390 mmol) was added in one
portion. To the resulting mixture was then added dropwise
over 10 min a solution of ethyl diazoacetate (0.041 mL, 0.044
g, 0.390 mmol) in 1.25 mL of diethyl ether by syringe down
the side of the flask (so that it would be cooled before contact
with the reaction mixture). The reaction mixture was stirred
at 0 °C for 1.5 h and then diluted with 5 mL of diethyl ether
and washed with 3-mL portions of saturated aqueous NaHCO3,
water, and then brine. The organic phase was dried over
MgSO4, filtered, and concentrated to provide 0.062 g of a yellow
oil. Column chromatography on 6 g of silica gel (gradient
elution with 5-10% ethyl acetate-hexane) afforded 0.043 g
(66%) of cyclopentanones 40a and 40b (1:1 by 1H NMR
analysis): IR (film) 3040, 2960, 2910, 2840, 1750, 1720, and
1
1660 cm-1; H NMR (300 MHz, CDCl3) δ 7.44-7.49 (m, 4 H),
7.24-7.33 (m, 6 H), 4.16-4.27 (m, 4 H), 3.53 (dd, J ) 9.6, 7.8
Hz, 1 H), 3.49 (s, 1 H), 3.48 (s, 1 H), 3.33 (app t, J ) 9.5 Hz,
1 H), 2.47 (two dd, J ) 13.5, 10.0 Hz, 2 H), 2.11 (dd, J ) 13.6,
8.0 Hz, 1 H), 2.06 (dd, J ) 14.4, 9.5 Hz, 1 H), 1.20-1.85 (m,
20 H), 1.29 (app t, J ) 7.7 Hz, 3 H), and 1.28 (app t, J ) 7.1
Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 206.0, 202.5, 169.6,
168.8, 134.3, 133.4, 132.3, 131.9, 129.0, 128.8, 128.1, 127.5,
66.2, 62.2, 61.6, 61.5, 50.4, 50.3, 42.0, 41.3, 36.6, 36.4, 34.0,
33.0, 31.1, 25.6, 25.4, 22.2, 22.1, 14.2, and 14.1.
C
15H18O2S: C, 68.67; H, 6.92. Found: C, 68.71; H, 7.01.
P r oced u r e B: Na IO4 Oxid a tion . A 10-mL, one-necked,
round-bottomed flask equipped with a rubber septum and
argon inlet needle was charged with sodium periodate (0.125
g, 0.584 mmol) and 1.25 mL of water and cooled at 0 °C while
a solution of sulfide 8 (0.096 g, 0.390 mmol) in 1.25 mL of
methanol was added dropwise via cannula. The resulting
cloudy white reaction mixture was stirred at 0 °C for 30 min
and then at 25 °C for 26 h. The resulting mixture was
partitioned between 10 mL of dichloromethane and 10 mL of
water, and the aqueous phase was separated and extracted
with three 10-mL portions of dichloromethane. The combined
organic phases were dried over MgSO4, filtered, and concen-
trated to afford 0.109 g of a yellow oil. Column chromatography
on 10 g of silica gel (gradient elution with 20-30% ethyl
acetate-hexane) yielded 0.078 g (76%) of sulfoxide 37 as an
off-white solid, mp 78-83 °C (60:40 mixture of diastereomers
Ack n ow led gm en t. We thank the National Insti-
tutes of Health (GM 28273) for generous financial
support. M.D.L. was supported in part by NIH training
grant CA 09112. T.W.L. was a J ames Flack Norris
Summer Undergraduate Research Scholar of the North-
eastern Section of the American Chemical Society and
a Pfizer Undergraduate Summer Research Fellow.
1
by H NMR analysis).
2-Acetoxy-2-(p h en ylth io)sp ir o[3.5]n on a n -1-on e (38). A
10-mL, one-necked, round-bottomed flask equipped with a
rubber septum and argon inlet needle was charged with a
solution of sulfoxide 37 (0.091 g, 0.35 mmol) in 3 mL of toluene.
Acetic anhydride (0.164 mL, 0.177 g, 1.74 mmol) and p-
toluenesulfonic acid (0.002 g, 0.001 mmol) were added, and
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
J O000227C