Is there a homolytic substitution chemistry (SH2) of sulfones?

Article abstract of DOI:10.1021/jo050990c

A series of 2-alkylsulfonyl-2′-biphenyl radicals, in which the alkyl group is primary, secondary, or tertiary, were generated and the products of their reactions investigated. Dibenzothiophene S,S-dioxide was not identified among the products, which arose

Full text of DOI:10.1021/jo050990c

Is There a Homolytic Substitution Chemistry (SH2) of Sulfones?
David Crich,* Thomas K. Hutton, and Krishnakumar Ranganathan
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
dcrich@uic.edu
Received May 18, 2005
A series of 2-alkylsulfonyl-2′-biphenyl radicals, in which the alkyl group is primary, secondary, or
tertiary, were generated and the products of their reactions investigated. Dibenzothiophene S,S-
dioxide was not identified among the products, which arose mainly from intramolecular hydrogen
abstraction from the alkyl group or addition to the solvent, benzene. On this basis, it is concluded
that homolytic substitution at sulfonyl sulfur, if possible at all, is too slow to take precedence over
a number of competing decomposition pathways. Previous literature results suggesting the
possibility of intramolecular homolytic substitution at sulfonyl sulfur may be explained by
alternative processes.
Introduction
an initial aryl, vinyl, or alkyl radical is generated either
by halogen abstraction with a stannyl or silyl radical, by
reduction of a diazonium salt, or by radical addition to
an alkyne setting the stage for a cyclization reaction
involving SH2 at sulfur with cleavage of the exocyclic bond
and expulsion of an alkyl or aryl radical. In his pioneering
study, Kampmeier demonstrated that intramolecular
homolytic substitution also takes place at sulfur(IV) in
sulfoxides in substrates such as 3.2b Beckwith and Boate
later showed the sulfoxide reaction is not only consider-
ably faster than that of the corresponding sulfide but also
that it takes place with clean inversion of configuration
at sulfur.7 Sulfone 4, on the other hand, was reported by
Kampmeier not to take part in intramolecular homolytic
Bimolecular homolytic substitution (SH2) at sulfur(II)
with displacement of a carbon radical is a well-known
phenomenon, albeit a relatively slow one.1 When ren-
dered intramolecular the process is much more efficient,
as first demonstrated by Kampmeier and co-workers on
photolysis of the aryl iodides 1 and 2.2 Related systems,
based on 1 and 2, may be incorporated into radical chain
reactions where they provide convenient sources of acyl
and alkyl radicals,3 as demonstrated by applications in
synthetic and mechanistic studies involving complex
carbohydrates, nucleotides, and other natural products.4,5
Vinyl radicals generated in the course of chain reactions
have also been shown to undergo efficient intramolecular
homolytic substitution at sulfur.6 In each of the systems,
(4) (a) Beckwith, A. L. J.; Boate, D. R. J. Org. Chem. 1988, 53, 9.
(b) Crich, D.; Hwang, J.-T.; Yuan, H. J. Org. Chem. 1996, 61, 6189. (c)
Crich, D.; Yao, Q. Tetrahedron 1998, 54, 305. (d) De Boeck, B.;
Pattenden, G. Tetrahedron Lett. 1998, 6975. (e) Bashir, N.; Murphy,
J. A. Chem. Commun. 2000, 627. (f) Harrowven, D. C.; Hannam, J.
C.; Lucas, M. C.; Newman, N. A.; Howes, P. D. Tetrahedron Lett. 2000,
41, 9345. (g) Crich, D.; Suk, D.-H.; Hao, X. Tetrahedron 2002, 58, 5789.
(h) Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.;
Strazzari, S.; Zanardi, G. Org. Lett. 2002, 4, 3079. (i) Crich, D.; Yao,
Q. Org. Lett. 2003, 5, 2189. (j) Crich, D.; Yao, Q. J. Am. Chem. Soc.
2004, 126, 8232.
(1) (a) Ingold, K. U.; Roberts, B. P. Free Radical Substitution
Reactions: Bimolecular Homolytic Substitutions at Saturated Multi-
valent Atoms; Wiley: New York, 1971. (b) Beckwith, A. L. J.; Ingold,
K. U. In Rearrangements in Ground and Excited States; de Mayo, P.,
Ed.; Academic Press: New York, 1980; Vol. 1, pp 162-310. (c)
Beckwith, A. L. J. Chem. Soc. Rev. 1993, 143. (d) Crich, D. In
Organosulfur Chemistry: Synthetic Aspects; Page, P., Ed.; Academic
Press: London, 1995; Vol. 1, p 49. (e) Schiesser, C. H.; Wild, L. M.
Tetrahedron 1996, 52, 13265. (f) Walton, J. C. Acc. Chem. Res. 1998,
31, 99. (g) Schiesser, C. H.; Wild, L. M. J. Org. Chem. 1999, 64, 1131.
(2) (a) Kampmeier, J. A.; Evans, T. R. J. Am. Chem. Soc. 1966, 88,
4096. (b) Kampmeier, J. A.; Jordan, R. B.; Liu, M. S.; Yamanaka, H.;
Bishop, D. J. In Organic Free Radicals; Pryor, W. A., Ed.; ACS
Symposium Series No. 69; American Chemical Society: Washington,
DC, 1978; p 275.
(5) For kinetic studies see ref 4a and: (a) Franz, J. A.; Roberts, D.
H.; Ferris, K. F. J. Org. Chem. 1987, 52, 2256. (a) Beckwith, A. L. J.;
Duggan, S. A. M. J. Chem. Soc., Perkin Trans. 2 1994, 1509.
(6) (a) Ooi, T.; Furuya, M.; Sakai, D.; Hokke, Y.; Maruoka, K. Synlett
2001, 541. (b) Benati, L.; Calestani, G.; Leardini, R.; Minozzi, M.;
Nanni, D.; Spagnolo, P.; Strazzari, S. Org. Lett. 2003, 5, 1313. (c)
Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.; Scialpi, R.; Spagnolo,
P.; Zanardi, G. Synlett 2004, 987.
(3) (a) Tada, M.; Matsumoto, M.; Nukamura, T. Chem. Lett. 1988,
199. (b) Crich, D.; Yao, Q. J. Org. Chem. 1996, 61, 3566. (c) Crich, D.;
Hao, X. J. Org. Chem. 1997, 62, 5982. (d) Ooi, T.; Furuya, M.; Sakai,
D.; Maruoka, K. Adv. Synth. Catal. 2001, 343, 166.
(7) Beckwith, A. L. J.; Boate, D. R. J. Chem. Soc., Chem. Commun.
1986, 189.
10.1021/jo050990c CCC: $30.25 © 2005 American Chemical Society
Published on Web 08/20/2005
7672
J. Org. Chem. 2005, 70, 7672-7678

Homolytic Substitution Chemistry (SH2) of Sulfones
SCHEME 2. Intramolecular Hydrogen Abstraction
â to a Sulfonyl Group
substitution at sulfur, with dehalogenation being the only
observed reaction on photolysis in cyclohexane.2b
No further reports on homolytic substitution at sulfur
in sulfones appeared8 until the publication of two pro-
vocative articles from Van Dort and Fuchs in 1997.9 The
first of these describes a very interesting process in which
o-allylstannyl-substituted aryl alkyl sulfones 5 undergo
homolytic cleavage of the alkyl group with release of a
polymeric stannyl sulfinate 9.9a The reaction was con-
sidered to proceed by homolytic displacement of the
stannyl radical from the allylstannane 5 followed by
homolytic substitution at sulfonyl sulfur with displace-
ment of the alkyl radical. The hypothetical four-mem-
bered stannyl sulfone 8 generated as a byproduct in this
cyclization then undergoes polymerization to form the
observed byproduct 9 (Scheme 1).
by bromine abstraction from the silylmethyl bromides 10
with a stannyl radical, abstract a hydrogen atom from a
position â to a sulfone through an eight-membered cyclic
transition state leading to a â-sulfonyl radical 12. As is
typical for such radicals, elimination of the sulfonyl
radical ensues leading, after chain transfer, to the
o-trimethylsilylbenzenesulfinic acid 14 which ultimately
consumes a further equivalent of the stannane to give a
stannyl sulfinate 15 (Scheme 2). All sulfones employed
in this study were tertiary allylic, thereby excluding the
otherwise preferential hydrogen abstraction from the
R-position of the sulfone through a seven-membered cyclic
transition state.
SCHEME 1. Mechanism for the Release of Alkyl
Radicals from Sulfones 5 According to Van Dort
and Fuchs
Identical chemistry is reported for a second system 16
albeit with hydrogen atom abstraction by an aryl radical,
via a nine-membered cyclic transition state.9b
The dichotomy arises when a secondary radical, closely
related to 11, but generated by addition of tris(trimeth-
ylsilyl radical) to an allylsilane, undergoes apparent
intramolecular homolytic substitution at sulfonyl sulfur,
rather than hydrogen atom abstraction, with release of
an alkyl radical and formation of a silacyclic sulfone
(Scheme 3).9b By way of explanation, Van Dort and Fuchs
postulate that the difference in reactivity between radical
11 (Scheme 2) and radical 18 (Scheme 3) may result from
the additional stability afforded to radical 18 by the
presence of two â-silyl groups.
Intrigued by these seemingly contradictory results, and
prompted by the need to identify a new radical precursor
in our laboratory, we set out to conduct a further
investigation into the possibility of homolytic substitution
at sulfur in sulfones on which we now report.
The second paper of the two reports an interesting
dichotomy.9b A series of silylmethyl radicals 11, generated
(8) Reviews on the free radical chemistry of sulfones and sulfonyl
radicals do not mention homolytic substitution at sulfur: (a) Patai,
S., Rapoport, Z., Stirling, C. J. M., Eds. The Chemistry of Sulfones and
Sulfoxides; Wiley: New York, 1988; p 1210. (b) Simpkins, N. S.
Sulphones in Organic Synthesis; Pergamon: Oxford, 1993. (c) Bertrand,
M. P. Org. Prep. Proc. Int. 1994, 26, 257. (d) Chatgilialoglu, C.;
Bertrand, M. P.; Ferreri, C. In S-Centered Radicals; Alfassi, Z. B., Ed.;
Wiley: Chichester, 1999; p 311.
(9) (a) Van Dort, P. C.; Fuchs, P. L. J. Org. Chem. 1997, 62, 7137.
(b) Van Dort, P. C.; Fuchs, P. L. J. Org. Chem. 1997, 62, 7142.
J. Org. Chem, Vol. 70, No. 19, 2005 7673

Crich et al.
SCHEME 5. Preparation of Anilinosulfone 33
SCHEME 3. Mechanism for the Release of Alkyl
Radicals from Sulfones 17 According to Van Dort
and Fuchs
TABLE 1. Sandmeyer Reactions
SCHEME 4. Preparation of Anilinosulfones 27 and
28
Preparation of Substrates
A biphenyl system related to the one originally em-
ployed in the sulfide series by Kampmeier (1) was
selected for this investigation on the grounds that any
cyclization would be enhanced by the presence of only
two rotating single bonds, as was clearly recognized by
Kampmeier.2,10 Primary and secondary 2-alkylsulfonyl-
2′-aminobiphenyls (27 and 28) were prepared by crossed
Ullmann protocols from the known iodosulfide 2111 and
from 22, at the level of the sulfide oxidation state as
outlined in Scheme 4. Subsequent oxidation of the sulfide
with m-CPBA afforded the corresponding sulfones and
treatment with zinc and calcium chloride in ethanol11
effected reduction of the nitro groups in the presence of
the sulfones.
a Key: (A) NaNO2, HCl, H2O, KI; (B) NaNO2, HCl, CH2Cl2, KI.
a Pd-catalyzed aryl iodide/thiol cross-coupling13 proved
more profitable, permitting installation of the tert-butyl
sulfide moiety to the biphenyl system. Oxidation with
m-CPBA then afforded the nitrosulfone 32 which, on
treatment with stannous chloride, finally yielded the
desired anilinosulfone 33 (Scheme 5).
With a series of anilines in hand, formation of the
desired iodobiphenyl systems was attempted via the
Sandmeyer reaction, with the results set out in Table 1.
Iodination of the primary alkyl aminosulfone 27 pro-
ceeded without incident to give the aryl iodide 34 in a
yield of 49%. However, the secondary alkyl aminosulfone
28 gave none of the expected aryl iodide, instead affording
the 2-iodo-2-propyl sulfone 35 as the only isolated
Attempted preparation of the corresponding biphenyl
tert-butyl sulfone via a similar crossed Ullmann reaction
was unsuccessful, and an alternative method was sought.
Iodination of 2-nitro-2′-aminobiphenyl 2912 followed by
(10) Interestingly, in his very first paper on this subject2a Kamp-
meier reports in a footnote that the sulfone corresponding to 1 (R )
Me) was prepared but no comment was made on any chemistry of this
sulfone.
(11) Hori, M.; Shimizu, H.; Matsuo, K.; Kataoka, T. Chem. Pharm.
Bull. 1984, 32, 4360.
(12) Heck, R. F.; Terpko, M. O. J. Org. Chem. 1980, 45, 4992.
(13) (a) Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J.-i. Bull. Chem.
Soc. Jpn. 1980, 53, 1385. (b) Kondo, T.; Mitsudo, T. Chem. Rev. 2000,
100, 3205.
7674 J. Org. Chem., Vol. 70, No. 19, 2005

Homolytic Substitution Chemistry (SH2) of Sulfones
TABLE 2. Radical Reactions
Radical Reactions
The two iodosulfones 34 and 37 were treated with
tributyltin hydride, with AIBN initiation, in benzene at
reflux in the usual manner with the results presented
in Table 2. In the absence of an aryl iodide in the
secondary alkyl sulfone case, the results obtained from
the Sandmeyer reaction of the amine 28 were taken as
indicative of the behavior of the corresponding aryl
radical and are thus reproduced in Table 2. All radical
reactions were relatively complex, and only major prod-
ucts were identified. Nevertheless, with the aid of an
authentic sample16 and examination the crude reaction
mixtures, it is possible to state that simple homolytic
attack at sulfonyl sulfur with expulsion of an alkyl radical
and formation of dibenzothiophene S,S-dioxide 38 did not
take place for any of the substrates.
The primary and secondary systems exhibited similar
fundamental behavior, namely hydrogen abstraction from
the R-position of the sulfone through a seven-membered
cyclic transition state. In the primary case, conducted in
the presence of tributyltin hydride in hot, dilute benzene
solution, the alkyl radical formed on intramolecular
hydrogen abstraction underwent oxidative cyclization
onto the second aromatic ring leading eventually to the
known17 cyclic sulfone 39. The oxidation of intermediate
cyclohexadienyl radicals under these conditions is typical
and is currently thought to be achieved by means of the
azo initiator.18,19 In the secondary case, with aryl radical
generation from the amine 28 via electron transfer to
the corresponding diazonium ion and the Sandmeyer
reaction,3c,20 the secondary alkyl radical formed on in-
tramolecular hydrogen atom transfer was trapped with
iodine to give 35 as the major product. It may be that in
the case of the secondary radical derived from 28,
cyclization to a product corresponding to 39 is retarded
by the bulk of the attacking radical or, simply, that the
high concentration of iodide under the Sandmeyer condi-
tions ensures trapping of the alkyl radical before this
cyclization can take place. Whatever the reason for the
divergent nature for the final products, it is clear that
both 35 and 39 arise from the same primary process of
intramolecular hydrogen atom abstraction through a
seven-membered transition state. Furthermore, this
a Key: (A) Bu3SnH, AIBN, C6H6, ∆; (B) NaNO2, HCl, KI.
product. Formation of this compound can be rationalized
as proceeding via a radical mechanism, discussion of
which is deferred to the following section. Under the
classical Sandmeyer conditions, in dilute hydrochloric
acid, the tert-butyl sulfone 33 provided none of the
desired iodide, but gave the cyclic sultine 3614 as the only
isolated product. Formation of the desired iodide 37 was
eventually achieved in high yield through the use of a
biphasic CH2Cl2/hydrochloric acid system for the Sand-
meyer reaction. We speculate that this change in product
may be due to two different mechanisms operating in the
two solvent systems. In the monophasic aqueous system
it may be that an intramolecular nucleophilic attack by
the sulfonyl oxygen competes with the classical Sandm-
eyer process,15 but that this component is suppressed in
the organic phase of the biphasic conditions. The fact that
we only observed this process with the tertiary system
33 suggests that it is either facilitated by the highly
substituted nature of the system, as is common for
cyclizations in general, or by a concerted loss of the tert-
butyl cation.
(16) Noyori, R.; Zheng, X.; Aoki, M.; Hyodo, M.; Sato, K. Tetrahedron
2001, 57, 2469.
(17) Pagani, G.; Bradamante, S. J. Chem. Soc., Perkin Trans. 1 1973,
163.
(18) (a) Beckwith, A. L. J.; Bowry, V. W.; Bowman, W. R.; Mann,
E.; Parr, J.; Storey, J. M. D. Angew. Chem., Int. Ed. Engl. 2004, 43,
95. (b) Engel, P. S.; Wu, W.-X. J. Am. Chem. Soc. 1989, 111, 1830. (c)
Curran, D. P.; Yu, H.; Liu, H. Tetrahedron 1994, 50, 7343. (d) Curran,
D. P.; Liu, H. J. Chem. Soc., Perkin Trans. 1 1994, 1377.
(19) For related reactions involving intramolecular hydrogen ab-
straction by an aryl radical followed by cyclization onto the aromatic
ring, see: Storey, J. M. D. Tetrahedron Lett. 2000, 41, 8173.
(20) (a) Beckwith, A. L. J.; Meijs, G. F. J. Org. Chem. 1987, 52, 1922.
(b) Murphy, J. A. In Radicals in Organic Synthesis; Renaud, P., Sibi,
M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 1, p 298. (c) Bashir,
N.; Patro, B.; Murphy, J. A. Adv. Free Radical Chem. 1999, 2, 123.
(14) Squires, T. G.; Venier, C. G.; Hodgson, B. A.; Chang, L. W.;
Davis, F. A.; Panunto, T. W. J. Org. Chem. 1981, 46, 2373.
(15) A recent discussion of the mechanisms of substitution of arene
diazonium ions: Ussing, B. R.; Singleton, D. A. J. Am. Chem. Soc. 2005,
127, 2888.
J. Org. Chem, Vol. 70, No. 19, 2005 7675

Crich et al.
SCHEME 6. Formation of Sultine 36
SCHEME 7. Possible 1,5-Hydrogen Migrations in
Radical 42
process is significantly favored over homolytic attack at
sulfur and hydrogen atom abstraction of a more remote
hydrogen through an eight-membered transition state as
postulated by Van Dort and Fuchs for the formation of
radical 12 (Scheme 2).9
With the tertiary iodide 37, hydrogen atom abstraction
through a seven-membered transition state to yield a
sulfone-stabilized alkyl radical is not possible, and the
reaction mixture was considerably more complex, per-
haps reflecting the absence of any one facile pathway for
the initial aryl radical. The main product identified was
the sultine 36 which, in this case, must arise by radical
attack at the sulfonyl oxygen with expulsion of a tert-
butyl radical (Scheme 6). This process is the open-shell
equivalent of the cationic mechanism proposed above for
the formation of 36 under the monophasic Sandmeyer
conditions.
The formation of the simple deiodination product 40
is not unexpected in a tin hydride mediated radical
reaction, but the isolation of appreciable amounts of
phenylated products 41 deserves comment. Phenyl radi-
cals add to benzene with a rate constant of 4.5 × 105 M-1
s-1 at 25 °C,21 which is small when compared to the rate
of trapping by tributyltin hydride which approaches the
diffusion controlled limit.22 However, in neat benzene
(11.2 M) as solvent, an effective first-order rate constant
of 5 × 106 s-1 is reached which is comparable with many
alkyl radical cyclizations, if not yet aryl and vinyl radical
cyclizations.23 Thus, in reality, for reactions generating
aryl radicals with no effective reaction pathways and in
the presence of only low concentrations of stannane it
should not be surprising to see phenylated products
arising from reaction with the solvent benzene. As
discussed above for the formation of 39, rearomatization
of the intermediate cyclohexadienyl radical presumably
involves the AIBN used as initiator.18,24 Compound 41
was the only isolated product from a mixture containing
at least two apparently related substances. Owing to
difficulties with separation, we are not able to determine
whether the mixture is one of atropisomers or regio-
isomers arising from 1,5-hydrogen atom migration at the
level of radical 42 (Scheme 7)25 or both.26
a further pathway for the decomposition of radical 42,
similar to the one postulated by Van Dort and Fuchs,
for radical 11 in Scheme 2,9 leading to the biphenyl
sulfonyl radical 45 after loss of isobutylene. However,
while a minor fraction containing several des-tert-butyl
products was obtained,27 the obvious product of chain
transfer with the stannane, 2-biphenylsulfinic acid 46,28
was not among them.
Discussion
Our results clearly show that homolytic substitution
at sulfur in sulfones is not a facile process, in line with
the original comments of Kampmeier.2 When intramo-
lecular hydrogen atom abstraction adjacent to the sulfone
is possible this is the predominant process. When such
hydrogen atom abstractions adjacent to the sulfone are
blocked, as in the case of the tertiary system 37, other
processes dominate, including attack at sulfonyl oxygen
and addition to the solvent. These results obviously are
in contrast with the results of Van Dort and Fuchs,9
especially for the systems presented in Schemes 1 and
(25) (a) Karady, S.; Abramson, N. L.; Dolling, U.-H.; Douglas, A.
W.; McManemin, G. J.; Marcune, B. J. Am. Chem. Soc. 1995, 117, 5425.
(b) Cummins, J. M.; Dolling, U.-H.; Douglas, A. W.; Karady, S.;
Leonard, W. R.; Marcune, B. F. Tetrahedron Lett. 1999, 40, 6153. (c)
Chandler, S. A.; Hanson, P.; Taylor, A. B.; Walton, P. H.; Timms, A.
W. J. Chem. Soc., Perkin Trans. 2 2001, 214. (d) Karady, S.; Cummins,
J. M.; Dannenberg, J. J.; del Rio, E.; Dormer, P. G.; Marcune, B. F.;
Reamer, R. A.; Sordo, T. L. Org. Lett. 2003, 5, 1175. (e) Gribble, G.
W.; Fraser, H. L.; Badenock, J. C. Chem. Commun. 2001, 805. (f) Qian,
X.; Cui, J.; Zhang, R. Chem. Commun. 2001, 2656.
We cannot categorically rule out hydrogen atom ab-
straction through an eight-membered transition state as
(21) Scaiano, J. C.; Stewart, L. C. J. Am. Chem. Soc. 1983, 105, 3609.
(22) Garden, S. J.; Avila, D. V.; Beckwith, A. L. J.; Bowry, V. W.;
Ingold, K. U.; Lusztyk, J. J. Org. Chem. 1996, 61, 805.
(23) (a) Ingold, K. U.; Griller, D. Acc. Chem. Res. 1980, 13, 317. (b)
Newcomb, M. Tetrahedron 1993, 49, 1151. (c) Newcomb, M. In Radicals
in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-VCH:
Weinheim, 2001; Vol. 1, p 317.
(24) In other circumstances the aryl-substituted cyclohexadienyl
radicals, such as the ones implied in the formation of either 39 or 41,
may be trapped in stannane-mediated systems with catalytic diphenyl
diselenide, resulting in a synthetically useful process. (a) Crich, D.;
Hwang, J.-T. J. Org. Chem. 1998, 63, 2765. (b) Crich, D.; Sannigrahi,
M. Tetrahedron 2002, 58, 3319. (c) Crich, D.; Rumthao, S. Tetrahedron
2004, 60, 1513. (d) Crich, D.; Grant, D. J. Org. Chem. 2005, 70, 2384.
(26) Compound 41 is tentatively assigned as shown rather than as
regioisomer 44 on the basis of the number of chemically distinct
resonances in the 13C NMR spectrum.
(27) The main components of this mixture contained both an
electron-rich and an electron-poor aromatic ring, suggesting that they
are derived from opening of the sultine ring in 36.
(28) An authentic sample of 46 was prepared: Davies, W.; Middle-
ton, F. C. J. S.; Porter, Q. N. J. Chem. Soc. 1955, 1565.
7676 J. Org. Chem., Vol. 70, No. 19, 2005

Homolytic Substitution Chemistry (SH2) of Sulfones
SCHEME 8. Alternative Mechanism for the
Fragmentation of Radical 6
FIGURE 1. Structure 48 and the anticipated mass spectral
fragmentation pattern.
SCHEME 9. Mechanism for the Formation of 48
3, which as written imply homolytic attack at sulfur by
much less reactive radicals than the aryl radicals em-
ployed in our study. It may be that the alkyl and
stabilized alkyl radicals employed by Van Dort and
Fuchs, in contrast to our aryl radicals, enable them to
avoid the side reactions we encountered thereby provid-
ing time for the SH2 process. This is unlikely, however,
as the SH2 process itself would also be expected to be
slower with alkyl rather than aryl radicals. Rather, we
believe that alternative explanations exist for the results
of Van Dort and Fuchs that do not involve direct
homolytic substitution at sulfone sulfur. Thus, the chem-
istry reported in Scheme 1 may be explained as outlined
in Scheme 8 with formation of an unstable intermediate
47 rather than the benzo-fused four-membered ring 8
proposed originally.
The chemistry presented in Scheme 2 does not involve
homolytic attack at sulfur and the hydrogen atom
abstractions â to the sulfone are reasonable in the
absence of R-hydrogens. The alkyl nature of radical 11
explains the apparent absence of products arising from
radical addition to the solvent. On careful examination
of the data, we are led to the conclusion that the apparent
dichotomy between Schemes 2 and 3 discussed in the
Introduction is best explained by misidentification of
product 20. Thus, Van Dort and Fuchs identified this
product on the basis of its 1H and 13C NMR spectral data
as well as by the low-resolution mass spectrum.9b While
the NMR spectral data29 appears to be consistent with
structure 20, the mass spectrum is not. Thus, the
molecular formula of structure 20 is C20H42O2Si5S, lead-
ing to a nominal molecular weight of 486 amu. The
reported EI mass spectrum9b has m/z 349, 175, and 73
requiring a loss of a fragment(s) of 137 amu to give the
ion at m/z 349. The loss of a 137 amu fragment can only
be explained by cleavage of a SiMe3 group (73 amu) and
the elements of SO2 (64 amu), and while either of these
is conceivable individually, the combination or sequenc-
ing of the two is improbable in the context of structure
20. Rather, we believe that the data is better accom-
modated by the alternative structure 48 with the mass
spectral fragmentation indicated (Figure 1).
The formation of this structure is very readily ex-
plained by a homolytic substitution reaction involving
attack of the initial adduct 18 on the aromatic ring to
give a cyclohexadienyl radical 49, which then expels a
sulfonyl radical to give 48. Substantial precedent exists
for related homolytic aromatic substitution reactions,
including ones in which a sulfonyl radical is displaced
by an alkyl radical.30 Finally, facile loss of sulfur dioxide
from the sulfonyl radical31 would afford the alkyl radical
(Scheme 9).
Conclusion
The answer to the title question is a cautious no. Early
indications from Kampmeier2 together with the work
described here strongly suggest that homolytic attack at
sulfonyl sulfur, if it exists at all, is such a slow process
that competing reactions, be they inter- or intramolecu-
lar, always take precedence. Earlier work by Van Dort
and Fuchs,9 suggesting that homolytic displacement from
sulfonyl sulfur takes place, is open to alternative inter-
pretations which both remove the original dichotomies
and bring it in line with the work described here and
that of Kampmeier. The possibility that SH2 at sulfonyl
sulfur may occur in systems designed to prevent all
competing reactions cannot be excluded, as was found
(30) (a) Studer, A.; Bossart, M. In Radicals in Organic Synthesis;
Renaud, P., Sibi, M., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2, p 62.
(b) Loven, R.; Speckamp, W. N. Tetrahedron Lett. 1972, 13, 1567. (c)
Ko¨hler, H. J.; Speckamp, W. N. J. Chem. Soc., Chem. Commun. 1980,
142. (d) Motherwell, W. B.; Pennell, A. M. K. J. Chem. Soc., Chem.
Commun. 1991, 877. (e) da Mata, M. L. E. N.; Motherwell, W. B.;
Ujjainwalla, F. Tetrahedron Lett. 1997, 38, 137. (f) da Mata, M. L. E.
N.; Motherwell, W. B.; Ujjainwalla, F. Tetrahedron Lett. 1997, 38, 141.
(g) Studer, A.; Bossart, M. J. Chem. Soc., Chem. Commun. 1998, 19,
2127. (h) Caddick, S.; Shering, C. L.; Wadman, S. N. Tetrahedron 2000,
56, 465. (i) Aldabbagh, F.; Bowman, W. R. Tetrahedron 1999, 55, 4109.
(31) (a) Rosenstein, I. J. In Radicals in Organic synthesis; Renaud,
P., Sibi, M., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 1, p 50. (b) Le
Guyader, F.; Quicelet-Sire, B.; Seguin, S.; Zard, S. Z. J. Am. Chem.
Soc. 1997, 119, 7410. (c) Sire, B.; Seguin, S.; Zard, S. Z. Angew. Chem.,
Int. Ed. 1998, 37, 2864. (d) Bertrand, F.; Quiclet-Sire, B.; Zard, S. Z.
Angew. Chem., Int. Ed. 1999, 38, 1943. (e) Quiclet-Sire, B.; Zard, S. Z.
J. Am. Chem. Soc. 1996, 118, 1209.
(29) 1H NMR (CDCl3):9b 0.21 (s, 27H), 0.27 (s, 3H), 0.36 (s, 3H), 0.71
(dd, J ) 4.8, 14.5, 1H), 0.93 (dd, J ) 12.3, 14.3, 1H), 1.28 (dd, J ) 8.1,
14.5, 1H), 1.53 (dd, J ) 2.1, 14.3, 1H), 3.30 (dddd, J ) 2.1, 4.8, 8.1,
12.3, 1H), 7.21 (br, t, J ) 7.3, 1H), 7.28 (br, d, J ) 7.3, 1H), 7.35 (br,
t, J ) 7.3, 1H), 7.50 (br, d, J ) 7.3, 1H). 13C NMR (CDCl3): -1.6, -0.2,
1.5 (9 carbons), 20.2, 21.5, 43.6, 124.8, 125.8, 129.7, 131.8, 138.8, 159.6.
J. Org. Chem, Vol. 70, No. 19, 2005 7677

Crich et al.
to be the case for SH2 at sp3 carbon.32 However, it is
unlikely that any such highly engineered systems will
have broad synthetic utility.
Professor P. L. Fuchs, Purdue University, for a helpful
discussion and exchange of information.
Supporting Information Available: Full experimental
details and characterization data. This material is available
free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. WethanktheNSF(CHE9986200)
for partial support of this work. We are grateful to
(32) Johnson, M. D. Acc. Chem. Res. 1983, 16, 343.
JO050990C
7678 J. Org. Chem., Vol. 70, No. 19, 2005