A new radical clock for testing the possibility of electron transfer from carbanions

Full text of DOI:10.1021/jo951132r

J . Org. Chem. 1996, 61, 1153-1154
1153
Sch em e 1
A New Ra d ica l Clock for Testin g th e
P ossibility of Electr on Tr a n sfer fr om
Ca r ba n ion s
D
PhSO2
D2O
5
D
Li+
–
J ean-Marc Mattalia,† Michel Chanon,† and
Charles J . M. Stirling*,‡
BuLi
THF
PhSO2
PhSO2
PhSO2
URA CNRS 1411, Universite´ d’Aix-Marseille III, Faculte´ des
Sciences de Saint-J e´rome, Avenue Escadrille
Normandie-Niemen, 13397 Marseille Cedex 13, France, and
University of Sheffield, Department of Chemistry,
Sheffield S3 7HF, U.K.
1
1D
Sch em e 2
Cl
Cl
NCS
CCl4, 25 °C
M-CPBA
CH2Cl2, 0-5 °C
PhS
PhS
PhSO2
Received J une 22, 1995
2
3
4
Cyclopropylcarbinyl radical ring opening may be used
as an efficient tool for the study of carbanions possibly
involved in SET reactions. The question of involvement
of electron-transfer processes in organic reactions clas-
sically considered to be polar is an active field.1 In
biological systems, unexpected insights have been ob-
tained using free radical clocks.2
Sch em e 3
Cl
Bu3SnH
THF, AIBN, reflux
+
PhSO2
PhSO2
PhSO2
4
5
1
Carbanions may be involved in electron transfer mech-
anisms.3 Nevertheless, there is not, at this time, an
indisputable rule to predict if a carbanion is going to react
through a polar or through an electron-transfer pathway
when it reacts with an electrophilic reagent. In depth
experimental studies of this mechanistic area could bring
new insights on the fundamentals of reactivity.4
This result prompted us to examine the cyclopropyl-
methyl phenyl sulfone 4, the first radical clock involving
cyclopropylcarbinyl ring-opening and designed for the
study of carbanions in electron-transfer processes. Prepa-
ration of R-chlorocyclopropylmethyl phenyl sulfone (4)
was by chlorination of cyclopropylmethyl phenyl sulfide
(2) to give 3 and rapid oxidation with m-chloroperbenzoic
acid in CH2Cl2 (17%) (Scheme 2).
In kinetic competition, reduction of chloride 4 with a
slight excess of Bu3SnH (1.4 equiv) in THF with AIBN
as initiator gave the ring-opened product 5 (more stable
E isomer,7 70% isolated yield) and a small amount of
unrearranged product 1 (5%) (Scheme 3).
We have previously described free radical clocks of the
norbornenyl type (k ) 108-109 s-1, 80 °C) specifically
designed for the study of carbanions.5 The use of this
kind of radical probe is governed by the cyclization rate
(addition of a C-C centered R-sulfonyl radical to a double
bond). The fastest known free radical clocks are based
on the cleavage of strained C-C bonds (cyclopropylcarbi-
nyl radical ring opening). This ring opening could become
specific for the radical if rearrangement in the corre-
sponding carbanion was prevented by appropriate groups
known for their carbanion stabilizing properties (G )
NO2, CN, RSO2). Accordingly, as shown in Scheme 1,
the desired sulfone-stabilized carbanion was prepared
from 1, and after 45 min at 25 °C the mixture was
quenched with D2O. Only deuterated sulfone 1R-d was
observed (NMR). No deuterated ring-opened product
corresponding to 5 was formed (Scheme 1). Stabilization
by the phenylsulfonyl group evidently prevents cyclopro-
pyl ring opening.
Increasing the excess of Bu3SnH yielded increasing
amounts of 1. The second-order reaction can be treated
as a pseudo-first-order process, and the rate constant of
the ring opening of the R-sulfonyl radical can be esti-
8
mated, the relation being k ) kH [5]/[1] - [Bu3SnH]0
where [Bu3SnH]0 is the initial concentration of reductant
and kH is the rate constant for the abstraction of H• from
Bu3SnH by the C-centered R-sulfonyl radical. Since the
effect of the phenylsulfonyl group on this radical is weak,9
for kH and the Arrhenius parameters we used the values
calculated by Ingold and co-workers for a secondary
radical (3 × 106 M-1 s-1, 80 °C).10 From these results, in
refluxing cyclohexane or benzene, ring opening of the
R-sulfonyl cyclopropylmethyl radical was estimated to
have k ) 107 s-1 (80 °C). The radical undergoes ring
opening more slowly than does the parent R-methylcy-
clopropylcarbinyl radical (secondary to primary radical
rearrangement, k80 °C ) 2.2 × 108 s-1). Previous studies
of substituted cyclopropylcarbinyl radicals with stabiliz-
† Universite´ d’Aix-Marseille III.
‡ University of Sheffield.
(1) Ashby, E. C. Acc. Chem. Res. 1988, 21, 414.
(2) (a) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317. (b)
Ingold, K. U.; Lusztyk, J .; Bowry, V. W. J . Am. Chem. Soc. 1991, 113,
5687. (c) Ingold, K. U.; Bowry, V. W. J . Am. Chem. Soc. 1991, 113,
5699. (d) Martin-Esker, A. A.; J ohnson, C. C.; Horner, J . H., Newcomb,
M. J . Am. Chem. Soc. 1994, 116, 9174. (e) For
a review of the
cyclopropyl group in studies of enzymes see: Suckling, C. J . Angew.
Chem., Int. Ed. Engl. 1988, 27, 537. (f) Newcomb, M.; Chestney, D. L.
J . Am.. Chem. Soc. 1994, 116, 9753.
(3) (a) Guthrie, R. D. In Comprehensive Carbanion Chemistry;
Buncel, E., Durst, D., Eds.; Elsevier: New York, 1980; Part A, Chapter
5. (b) Chung, S. K.; Dunn, L. B., J r. J . Org. Chem. 1984, 49, 935. (c)
Liotta, D.; Saindane, M.; Waykole, L J . Am. Chem. Soc. 1991, 105,
2922.
(7) (a) J ulia, M.; Rolando, C.; Verpeaux, J .-N. Tetrahedron Lett.
1982, 23, 4319. (b) Champagne, P. J .; Renaud, R. N. Can. J . Chem.
1980, 58, 1101.
(8) Newcomb, M. Tetrahedron 1993, 49, 1151.
(9) (a) Clark, T. In Sulfur-Centered Reactive Intermediates in
Chemistry and Biology; Chatgilialoglu, C., Asmus, K. D., Eds.; NATO
ASI Series 197; Plenum Press: New York, 1990; p 14. (b) Carton, P.
M.; Gilbert, B. C.; Laue, H. A. H.; Norman, R. O. C.; Sealy, R. C J .
Chem. Soc., Perkin Trans. 2 1975, 1245.
(4) Chanon, M; Rajzmann, M.; Chanon, F. Tetrahedron 1990, 46,
6193.
(5) (a) Vacher, B.; Samat, A.; Allouche, A.; Laknifli, A.; Baldy, A.;
Chanon, M. Tetrahedron 1988, 44, 2925. (b) Vacher, B.; Samat, A.;
Chanon, M. Tetrahedron Lett. 1985, 26, 5129.
(6) Newcomb, M.; J ohnson, C. C.; Manek, M. B.; Varick, T. R. J .
Am. Chem. Soc. 1992, 114, 10915.
(10) Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J . C. J . Am. Chem.
Soc. 1981, 103, 7739.
(11) (a) Beckwith, A. L. J .; Moad, G. J . Chem. Soc., Perkin Trans.
2 1980, 1473. (b) Beckwith, A. L. J .; Bowry, V. W. J . Am. Chem. Soc.
1994, 116, 2710.
0022-3263/96/1961-1153$12.00/0 © 1996 American Chemical Society

1154 J . Org. Chem., Vol. 61, No. 3, 1996
Notes
extracted with three portions of CH2Cl2. The combined organic
extracts were washed with Na2S2O5, saturated aqueous NaHCO3
(three times), and water. Drying over Na2SO4 was followed by
evaporation. The crude product was flash chromatographed on
silica gel (elution: 10%, 20%, 30%, and 40% ethyl acetate in
cyclohexane) to yield sulfone 1 (1.64 g, 65% yield) as a transpar-
ent oil. 1H NMR: 7.49-7.94 (m, 5H), 2.99 (d, J ) 7 Hz, 2H),
0.97 (m, 1H), 0.52 (m, 2H), 0.09 (m, 2H). IR (cm-1): 1148 (SO2),
1303 (SO2). Anal. Calcd for C10H12SO2: C, 61.22; H, 6.12; S,
16.32. Found: C, 60.94; H, 6.10; S, 16.57.
Ch a r t 1
r-Meth ylcyclop r op ylm eth yl P h en yl Su lfon e (4). N-Chlo-
rosuccinimide (1.37 g, 0.01 mol) was added to a solution of sulfide
1 (1.67 g, 0.01 mol) in CCl4 (33 mL). After being stirred at room
temperature for 4.5 h, the solution was filtered and the solvent
was evaporated at room temperature. The oil obtained was
dissolved in CH2Cl2 (120 mL), and 12.05 g of m-CPBA (48%, 3
equiv) was added at 0-5 °C. After being stirred for 1.5 h at 0
°C, the mixture was filtered. The filtrate was washed with 10%
aqueous Na2S2O5, 10% aqueous K2CO3 (six times), and water.
Drying over Na2SO4 was followed by evaporation, and a few
drops of ethanol were added to the crude product. Chloro sulfone
4 crystallized on standing at -5 °C. The crystals were washed
with EtOH at -20 °C, (0.39 g, 17% yield): mp ) 57-58.4 °C;
1H NMR 7.58 (m, 2H), 7.71 (m, 1H), 7.98 (m, 2H), 4.23 (d, J )
9.0, 1H), 1.37 (m, 1H), 0.60-0.90 (m, 3H), 0.44 (m, 1H); IR
ing groups such as R-CO2Me, R-NO2, R-Ph, O- (ketyl), or
R-CO2tBu also showed dramatic decreases in ring-open-
ing rates2e,11b,12 but the decrease of the rate constant was
unexpected with the phenylsulfonyl group since this
substituent has no capacity for radical delocalization.9
This result could be explained by nonbonded interactions
between R-phenylsulfonyl and ring C-H groups disfavor-
ing the transition-state geometry which is necessary for
orbital overlap between the SOMO and the C-C bond
which is to be cleaved (Chart 1).2b The stereoselectivity
(E isomer formation, transoid transition state) of the ring
opening is also determined by steric repulsions between
the R-phenylsulfonyl substituent and the ring in the
cisoid versus transoid transition state (Chart 1).2b,11b
Nevertheless, the R-sulfonylcyclopropylcarbinyl radical
ring opening remains efficient and may be used as a
mechanistic tool in SET process studies involving R-sul-
fonylcarbanion species.
(cm-1): 1320 (SO2)(s), 1150 (SO2)(s). Anal. Calcd for C10H11
-
ClSO2:C, 52.06; H, 4.77; Cl, 15.40; S, 13.88. Found: C, 52.21;
H, 4.85; Cl, 15.25; S, 13.96.
Red u ction s of Ch lor osu lfon e 4 w ith Bu 3Sn H. F or m a -
t ion of 1-(P h en ylsu lfon yl)-1-b u t en e (5). Chlorosulfone 4
(0.093 g 0.4 mmol) and a few crystals of AIBN were dissolved in
degassed THF (4 mL) under an argon atmosphere (a slight
positive pressure of argon was maintained and additions were
performed by syringe). At reflux, Bu3SnH (0.15 mL, 1.4 equiv)
was added. The mixture was refluxed for 21 h, and after the
solvent was removed, the residue was dissolved in CH3CN (15
mL). The solution was washed three times with hexane and
evaporated to yield the crude product (99 mg). The ratio 5/2 )
95/5 was determined by 1H NMR. Flash chromatography on
silica gel (elution with 20% ethyl acetate in cyclohexane) afforded
the ring-opened reduction product 5 (E isomer, 0.055 g, 70%
yield) as an oil. Other reductions were performed at 80 °C for
1.5 h in refluxing cyclohexane [Bu3SnH]0 ) 0.16 M (5 equiv) and
0.27 M (8.4 equiv) when the ratio of 5/2 was 92/8. In refluxing
benzene, same results were obtained: for [Bu3SnH]0 ) 0.16 M
(5 equiv) the ratio of 5/2 was 94/6.14
Note a d d ed in p r oof: To illustrate an application of
this radical clock 1, we have run the reaction with CCl4
in a t-BuOK-t-BuOH medium. The dichlorosulfone 6
was isolated in 80% yield, showing that if electron
transfer to give the R-sulfonyl radical is involved, the
subsequent intermolecular reaction of the radical is faster
than ring fission.
Con clu sion s
These preliminary results open the way to a new
radical-probe family designed for the study of carbanions
possibly involved in SET reactions. There is potential
to trap intermediates of very short lifetime, and the
system is readily tunable with substituents in order to
increase the efficiency of this kind of radical probe. The
comparative stabilization of the carbanion by substitu-
ents present on the cyclopropyl group has to be kept in
mind.
Note Ad d ed in P r oof. Th e Ra d ica l Clock in Ha loge-
n a tion . Sulfone 1 (0.12 g, 0.6 mmol), finely ground KOH
(0.279 g), t-BuOH (2.6 mL), and CCl4 (2.6 mL) were stirred
for 113 h at 25 °C. Additional CCl4 (1 mL) and KOH (0.17 g
and 0.34 g) were added after 17 h and 96 h, respectively.
Addition of water and extraction (CH2Cl2) gave a crude product
whose 1H NMR spectrum showed no vinylic protons. Flash
chromatography (elution: cyclohexane then 10% ethyl acetate
in cyclohexane) gave halosulfone 6 (80%): mp 36-37.5 °C; 1H
NMR 8.08 (m, 2H), 7.74 (tt, J ) 7.5 and 1.7 Hz, 1H), 7.59 (m,
2H), 1.94 (m, 1H), 0.82 (m, 4H). Anal. Calcd for
C10H10Cl2SO2: C, 45.45; H, 3.79; Cl, 26.52; S, 12.12. Found:
C, 45.46; H, 3.64; Cl, 26.70; S, 12.33.
Exp er im en ta l Section
Cyclop r op ylm eth yl P h en yl Su lfon e 1. Sulfide 2 (2.10 g
0.0128 mol) was dissolved in acetic acid (39 mL). This solution
was heated to 60 °C, and then hydrogen peroxide was added
dropwise (8.3 mL, 0.085 mol of a 30% solution in water). The
mixture was kept at 100 °C for 1 h, and after being cooled to
room temperature, the solution was diluted with water and
Ack n ow led gm en t. We thank the Commission of the
European Communities Human and Capital Mobility
Fund and the University of Sheffield for support.
J O951132R
(12) (a) Russell, G. A.; Dedolph, D. F. J . Org. Chem. 1985, 50, 2498.
(b) Tanko, J . M.; Drumwright, R. E. J . Am. Chem. Soc. 1992, 114, 1844.
(13) For an alternative workup see: (a) Leibner, J . E.; J acobus, J .
J . Org. Chem. 1979, 44, 449. (b) Lemieux, R. P.; Beak, P. J . Org. Chem.
1990, 55, 5454.
(14) No bigger excess of Bu3SnH was used in order to prevent the
formation of a vinylstannane from sulfone 5: Watanabe, Y.; Ueno, Y.;
Araki, T.; Endo, T.; Okawara, M. Tetrahedron Lett. 1986, 27, 215.