Kinetics of the Oxiranylcarbinyl Radical Rearrangement

Full text of DOI:10.1021/jo962054q

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J . Org. Chem. 1997, 62, 1572-1573
Sch em e 1
Kin etics of th e Oxir a n ylca r bin yl Ra d ica l
Rea r r a n gem en t
Venkat Krishnamurthy and Viresh H. Rawal*,1
Department of Chemistry, The Ohio State University,
Columbus, Ohio 43210, and Department of Chemistry,
The University of Chicago, Chicago, Illinois 60637
We took advantage of Newcomb’s competition method
to determine the rate of the oxiranylcarbinyl radical
rearrangement,11,23 which involves the use of Barton’s
PTOC esters [((pyridine-2-thione)oxy)carbonyl] as radical
precursors24 and hydrogen atom transfer from thiophenol
or benzeneselenol as the basis reaction. The rates for
trapping of alkyl radicals by PhSH and PhSeH are ∼108
M-1 s-1 and ∼109 M-1 s-1, respectively, and are known
to be relatively insensitive to radical structure.11,23,25,26
Received November 4, 1996
How fast is the oxiranylcarbinyl radical rearrangement
(1 f 2, Scheme 1)? All indications to date are that it is
very fast. The first hint of this was the report that
reduction of epibromohydrin with tin hydride afforded
only allyl alcohol and none of the direct reduction
product, propene oxide.2,3 A competition experiment
showed the hexenyl radical cyclization (k ) 2.3 × 105 s-1
at 25 °C)4 to be no match for the radical-induced epoxide
fragmentation.5,6 Attempted observation of the oxiran-
ylcarbinyl radical by ESR proved unsuccessful, as its
rearrangement to the allyloxy radical (e.g., 2) was rapid,
even at 128 K.7-10 On the basis of these observations,
the rate of the fragmentation was estimated to be >4 ×
Sch em e 2
108 s-1 10
In systems where the oxiranylcarbinyl radical
.
is allowed to compete directly with the well-studied
cyclopropylcarbinyl radical rearrangement (k ) 1.0 × 108
at 25 °C),11,12 only products from epoxide fragmentation
are observed.13-15 By assuming the reverse reaction (2
f 1) to be relatively slow, an assumption that turns out
to be not quite correct,16 a lower limit for the forward
rearrangement was set at 1 × 1010 s-1 at 70 °C.14 Our
long-standing interest in the synthetic potential of radi-
cal-induced epoxide fragmentations17-21 prompted us to
examine the rate of this rearrangement more precisely.
We describe here the results of our investigations, which
allowed the direct determination of this rate.22
A cyclohexyl-substituted oxiranylcarbinyl radical pre-
cursor was selected, since the products from its reduction
or rearrangement would be less volatile than those from
the parent system. The necessary PTOC ester was
prepared in four steps as shown in Scheme 2. The
enolate of benzylcrotonate [2.0 equiv, LDA (2.0 equiv),
HMPA 3.0 equiv, in THF, -78 °C] was treated slowly
with a THF solution of 1,5-dibromopentane to afford the
spiro-bisalkylation product 5 in 77% yield.27 Epoxidation
of the alkene with m-CPBA followed by hydrogenolysis
of the benzyl group gave epoxycyclohexanecarboxylic acid
6. Treatment of the acid with triphenylphosphine and
2,2′-dithiobis(pyridine N-oxide) in CH2Cl2 at -5 °C gave
a bright yellow solution containing PTOC ester 7.24
Removal of the solvent in vacuo, with the bath temper-
ature maintained below 35 °C, gave the crude PTOC ester
in quantitative yield. Ester 7 is photolabile, although it
can be purified by column chromatography in subdued
lighting, but with considerable loss of the product (32%
yield). In practice, the crude PTOC ester was found to
(1) Current address: Department of Chemistry, The University of
Chicago, 5735 S. Ellis Ave., Chicago, IL 60637.
(2) Kuivila, H. G. Acc. Chem. Res. 1968, 1, 299-305.
(3) Krosley, K. W.; Gleicher, G. J .; Clapp, G. E. J . Org. Chem. 1992,
57, 840-844.
(4) Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J . C. J . Am. Chem.
Soc. 1981, 103, 7739-7742.
(5) J ohns, A.; Murphy, J . A.; Patterson, C. W.; Wooster, N. F. J .
Chem. Soc., Chem. Commun. 1987, 1238-1240.
(6) Dickinson, J . M.; Murphy, J . A.; Patterson, C. W.; Wooster, N.
F. J . Chem. Soc., Perkin Trans. 1 1990, 1179-1184.
(7) Davies, A. G.; Muggleton, B. J . Chem. Soc., Perkin Trans. 2 1976,
502-510.
(8) Davies, A. G.; Tse, M.-W. J . Organomet. Chem. 1978, 155, 25-
30.
(9) Davies, A. G.; Hawari, J . A.-A.; Muggleton, B.; Tse, M.-W. J .
Chem. Soc., Perkin Trans. 2 1981, 1132-1137.
(10) Laurie, D.; Nonhebel, D. C.; Suckling, C. J .; Walton, J . C.
Tetrahedron 1993, 49, 5869-5872.
(11) Newcomb, M.; Glenn, A. G. J . Am. Chem. Soc. 1989, 111, 275-
277.
(12) Bowry, V. W.; Lusztyk, J .; Ingold, K. U. J . Am. Chem. Soc. 1991,
113, 5687-5698.
(13) Ayral-Kaloustian, S.; Agosta, W. C. J . Org. Chem. 1983, 48,
1718-1725.
(22) Taken from the Ph.D. thesis of Venkat Krishnamurthy, The
Ohio State University, 1995.
(23) Newcomb, M.; Glenn, A. G.; Williams, W. G. J . Org. Chem.
1989, 54, 2675-2681. For a recent application of the PTOC ester
methodology, see: Venkatesan, H.; Greenberg, M. M. J . Org. Chem.
1995, 60, 1053-1059.
(24) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron
1985, 41, 3901-3924.
(25) Franz, J . A.; Bushaw, B. A.; Alnajjar, M. S. J . Am. Chem. Soc.
1989, 111, 268-275.
(26) Newcomb, M. Tetrahedron 1993, 49, 1151-1176.
(27) The modified procedure described here allows the dialkylation
to be carried out in one step and in good yield. See: Brocksom, T. J .;
Constantino, M. G.; Ferraz, H. M. C. Synth. Commun. 1977, 7, 483-
493.
(14) Krosley, K. W.; Gleicher, G. J . J . Phys. Org. Chem. 1993, 6,
228-232.
(15) Unpublished work from this laboratory by Dr. Seiji Iwasa, 1992.
(16) Ziegler, F. E.; Petersen, A. K. J . Org. Chem. 1995, 60, 2666-
2667.
(17) Rawal, V. H.; Newton, R. C.; Krishnamurthy, V. J . Org. Chem.
1990, 55, 5181-5183.
(18) Rawal, V. H.; Iwasa, S. Tetrahedron Lett. 1992, 33, 4687-4690.
(19) Rawal, V. H.; Krishnamurthy, V. Tetrahedron Lett. 1992, 33,
3439-3442.
(20) Rawal, V. H.; Zhong, H. M. Tetrahedron Lett. 1993, 34, 5197-
5200.
(21) Rawal, V. H.; Krishnamurthy, V.; Fabre, A. Tetrahedron Lett.
1993, 34, 2899-2902.
S0022-3263(96)02054-3 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 6, 1997 1573
Sch em e 3
alcohol 11 and not the direct reduction product 12. So
as to maximize the amount epoxide 12, a high concentra-
tion of PhSH was used. Even at 5 M PhSH concentra-
tion, the amount of 12 was too small to be determined
by NMR. However, analysis of the reaction mixture by
GC, using authentic samples of 11 and 12 for comparison,
indicated 11 and 12 to be present reproducibly in a 57.5:1
ratio.28-30 It is noteworthy that this result represents
the first time that the oxiranylcarbinyl radical has been
trapped in the unrearranged form. Using the reported
rate constant of 1.1 × 108 s-1 at 25 °C for the hydrogen
abstraction from thiophenol by a tertiary alkyl radicals,25
the approximate rate for the rearrangement of 8 to 9 at
25-30 °C is 3.2 × 1010 s-1
.
be suitable for these studies, since it was identical by 1H
NMR with the purified sample and, more importantly,
the two samples gave identical results in the competition
experiments.
Our results show the oxiranylcarbinyl radical rear-
rangement to be quite fast, about 2 orders of magnitude
faster than the cyclopropylcarbinyl radical rearrange-
ment. The observed high rate for the rearrangement is
consistent with the results of high level computational
studies of J ackson and Lee, which predicted a low barrier
(<4.8 kcal/mol) for the C-O bond cleavage.31 More recent
calculations by Pasto suggest an even lower barrier for
this rearrangement.32
The kinetic studies were carried out using Newcomb’s
general protocol for the “PTOC/thiol method.”11,23 The
expected outcome of the photolysis is shown in Scheme
3. The equation used to analyze the rate of the frag-
mentation reaction (k1) was derived as shown in eqs 1-4.
A steady-state analysis for intermediate 9 (eq 2) gave the
relationship shown in eq 3. This equation can be simpli-
fied further by making the reasonable assumptions that
k-1 is smaller than k1 and that k3 is smaller than k2.
Under these conditions the second term drops out and
gives the simplified relationship shown in eq 4.
Ack n ow led gm en t. We thank the National Insti-
tutes of Health (R01-GM-45624) for financially support-
ing this work. Generous financial support, in the form
of faculty awards, from Eli Lilly, Pfizer, Merck, and
American Cyanamid are also gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral data of all new compounds employed in
this study (15 pages).
[11]/[12] ) k3[8]/k2[9]
[9] ) k1[8]/(k-1 + k2[10])
(1)
(2)
(3)
(4)
J O962054Q
(28) Complex reaction products were obtained using selenophenol
as the hydrogen donor. One problem appears to be the instability of
the reduced epoxide (12) to benzeneselenol.
(29) Newcomb, M.; Varick, T. R.; Ha, C.; Manek, M. B.; Yue, X. J .
Am. Chem. Soc. 1992, 114, 8158-8163.
(30) Newcomb, M.; J ohnson, C. C.; Manek, M. B.; Varick, T. R. J .
Am. Chem. Soc. 1992, 114, 10915-10921.
(31) J ackson, J . E.; Lee, J .-S. Unpublished results. We thank
Professor J ackson (Michigan State University) for sharing these
unpublished results with us (1993). This work was presented at the
205th American Chemical Society National Meeting, Denver, CO,
March 1993; paper no. 104. Details of the calculations can be found in
the Ph.D. dissertation of J .-S. Lee, Michigan State University, 1993.
(32) Pasto, D. J . J . Org. Chem. 1996, 61, 252-256.
[11]/[12] ) (k3[10]/k1) + (k-1k3/k1k2)
[11]/[12] ) k3[10]/k1
In the event, a solution of unpurified PTOC ester 7 in
a pressure tube was treated with a measured amount of
PhSH and irradiated with a sunlamp for 10 min. The
temperature of the reaction was maintained between 25
and 30 °C using a water bath. The H NMR of the crude
product showed only peaks corresponding to the allylic
1