Enol ether radical cation reaction kinetics. Laser flash photolysis calibration of radical cation clocks [15]

Full text of DOI:10.1021/ja015639x

4364
J. Am. Chem. Soc. 2001, 123, 4364-4365
Enol Ether Radical Cation Reaction Kinetics. Laser
Flash Photolysis Calibration of Radical Cation
Clocks
John H. Horner* and Martin Newcomb*
Department of Chemistry, Wayne State UniVersity
Detroit, Michigan 48202
ReceiVed February 6, 2001
Synthetic applications of radical reactions in organic chemistry
increased rapidly in the past two decades largely due to the mild
conditions of many radical conversions and a growing under-
standing of radical kinetics, much of which was obtained with
1
Figure 1. (A) Time-resolved growth spectrum at 20 ns intervals from
1 ns after photolysis of 1a in acetonitrile at 21 °C. (B) Signal at 335
nm following photolysis of 1b in acetonitrile at -20 °C. The initial
bleaching is from destruction of the precursor.
radical clocks that permit one to “time” reactions. Although not
6
widely applied in synthesis as yet, radical cations offer attractive
features that include enhanced radical reactivity and attenuated
cation reactivity. The development of radical cations as routine
synthetic tools will require both specific methods for their
production and kinetic information. In regard to the former, recent
advances in the production of radical cations under non-oxidative
conditions by heterolytic fragmentation of radicals are especially
Scheme 1
2
noteworthy. In this work, we report the calibration of enol ether
3
radical cation clocks using laser flash photolysis (LFP) methods
and kinetic information about the heterolysis of â-phosphate
radicals and the evolution of diffusively free enol ether radical
cations from the initially formed ion pairs.
The reaction sequence we studied is shown in Scheme 1.
4
Photolysis of PTOC esters 1 (Nd:YAG, 355 nm) gives the
2-pyridinethiyl radical and acyloxyl radicals that decarboxylate
to give R-methoxy-â-(diethylphosphatoxy)alkyl radicals (2). Het-
erolytic cleavage of radicals 2 (loss of diethyl phosphate) gives
the target enol ether radical cations 3 that cyclize to the distonic
radical cations 4. The cyclizations of 3 to 4 are the “clock”
reactions, but a UV-observable element was necessary for direct
kinetic studies. Thus, we incorporated a reporter group, the 2,2-
5
diphenylcyclopropylcarbinyl unit. Ring openings of radicals 4
give diphenylalkyl radicals 5 that are readily detected by their
characteristic UV absorbances. The photochemical cleavages and
decarboxylation steps of precursors 1 are very fast, producing
radicals 2 in less than 1 ns. Similarly, the ring-opening reactions
Table 1. a Rate Constants and Yields for Enol Ether Radical Cation
6
of radicals 4 will occur on the picosecond time scale. Thus, the
Reactions
measured kinetics are either for the heterolysis reactions of 2,
the cyclizations of 3, or both. We note that the fast ring openings
of radicals 4 to 5 preclude reversion of 4 to 3 that might occur
with simple enol ether radical cations.
Photolyses of PTOC esters 1 in acetonitrile (ACN) or in
solutions of ACN containing 2,2,2-trifluoroethanol (TFE) were
followed by evolution of an absorbance centered at 335 nm from
diphenylalkyl radicals 5 (Figure 1A). At 21 ( 1 °C, all traces
displayed first-order growth; the kinetic results are listed in Table
solventb
1a
1b
1cc
7
7
0
% TFE
3.0 × 10 (65)
1.7 × 10 (25)
7
7
0.5% TFE
1.0% TFE
2.5% TFE
8.0 × 10 (80)
3.9 × 10 (80)
7
5
4.5 × 10 (90)
2 × 10 (10)
8
d
7
5
>2 × 10 (95)
5.5 × 10 (100)
1 × 10 (20)
a
Reactions conducted at (21 ( 1) °C. Observed rate constants in
-1
units of s . Percent yields of products 5 ((5%) in parentheses.
Percentage of 2,2,2-trifluoroethanol in acetonitrile. Rate constants
for 1c are upper limits; see text. d Instrument limit.
b
c
1. Yields of radicals 5 given in Table 1 were determined by
comparison of the ultimate intensity of the 335 nm signal from 5
to the initial intensity of the 490 nm signal from the byproduct
of the photolysis, the 2-pyridinethiyl radical. Reduced yields of
(
1) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317-323.
7
Newcomb, M. Tetrahedron 1993, 49, 1151-1176.
(
2) Crich, D.; Huang, X.; Newcomb, M. Org. Lett. 1999, 1, 225-227. Crich,
5a and 5b must result from reactions within the initially produced
ion pair because these radicals were stable over several micro-
seconds of the LFP experiments. We speculate that the destructive
reaction is deprotonation of radical cation 3 by phosphate anion
to give an allylic radical because recombination of 3 with
phosphate would give radical 2 in a nondestructive process. Low
yields of 5c were due to reactions of the diffusively free radical
cation (see below).
D.; Huang, X.; Newcomb, M. J. Org. Chem. 2000, 65, 523-529. Bales, B.
C.; Horner, J. H.; Huang, X.; Newcomb, M.; Crich, D.; Greenberg, M. M. J.
Am. Chem. Soc. 2001, 123, 3623-3629.
(
3) Intramolecular cycloadditions that can serve as clocks for substituted
styrene radical cations have been reported. See: Schepp, N. P.; Shukla, D.;
Sarker, H.; Bauld, N. L.; Johnston, L. J. J. Am. Chem. Soc. 1997, 119, 10325-
1
2
0334.
(
4) Synthetic details will be reported. The acronym PTOC is for pyridine-
-thioneoxycarbonyl.
(
5) Newcomb, M.; Tanaka, N.; Bouvier, A.; Tronche, C.; Horner, J. H.;
Musa, O. M.; Martinez, F. N. J. Am. Chem. Soc. 1996, 118, 8505-8506.
(
6) Newcomb, M.; Johnson, C. C.; Manek, M. B.; Varick, T. R. J. Am.
(7) Alam, M. M.; Watanabe, A.; Ito, O. J. Org. Chem. 1995, 60, 3440-
3444.
Chem. Soc. 1992, 114, 10915-10921.
1
0.1021/ja015639x CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/17/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 18, 2001 4365
Table 2. Arrhenius Parameters for Enol Ether Radical Cation
Reactions
the yields of 5a and 5b. In the more highly polar solvent mixtures,
2.5% TFE in ACN, ion pair escape was faster than reaction of
solventa
Arrhenius function (log k, s)b
diethyl phosphate anion with radical cations 3. The yields of 5 in
the 0.5% TFE solutions indicate that escape was about 4 times
faster than deprotonation in this reduced polarity mixture. In ACN,
the higher yield of 5a (65%) compared to 5b (25%) suggests that
the cyclization of 3a was competitive with the deprotonation
reaction. Using the estimate (see above) that cyclization of 3a
precursor
1
a
0% TFE
(9.71 ( 0.10) - (2.94 ( 0.12)/θ
(9.10 ( 0.11) - (1.57 ( 0.14)/θ
(10.47 ( 0.17) - (4.23 ( 0.21)/θ
(10.52 ( 0.12) - (3.82 ( 0.15)/θ
0
.5% TFE
0% TFE
.5% TFE
1
b
2
a
Percent of TFE in ACN. b Errors are 2σ; θ ) 2.313RT (kcal/mol).
9
-1
has a rate constant of about 1 × 10 s , the rate constant for
deprotonation of 3a by diethyl phosphate anion is also about 1
9
-1
The 6-exo cyclization of radical cation 3b was readily
characterized. In ACN at low temperatures, the kinetic traces
clearly displayed a convolution of two processes with similar rate
constants (Figure 1B), indicating that both the heterolysis and
cyclization reactions were being monitored. Arrhenius functions
for the b system were determined in the temperature range -30
to 50 °C in ACN and in ACN containing 2.5% TFE (Table 2).
The log A term was unchanged in the two solvents and was
consistent with that expected for a 6-exo cyclization.8 The
increased reactivity of the enol ether radical cation in comparison
to an alkyl radical is a result of the considerably reduced activation
energy; the rate constant for cyclization of the 6-heptenyl radical
× 10 s . From the yield of 5b, ion pair escape in ACN is about
8 -1
1/3 as fast as the deprotonation reaction, or about 3 × 10 s .
The construction of functionalized cyclic products via enol ether
radical cations has been demonstrated by Moeller and co-
workers,12 and one of the objectives of this work was to provide
kinetic information about enol ether radical cation reactions that
is useful for synthetic applications. Some general observations
in that regard are possible. If the radical heterolysis entry to enol
ether radical cations from â-phosphatoxyalkyl radicals is being
used, the solvent polarity should be great enough to permit
efficient escape of the radical cation from the first-formed ion
T
pair. The measured E (30) value for 2.5% TFE in ACN is about
3
-1 9
13
at ambient temperature is about 5 × 10 s . The slight reduction
56, similar in polarity to methanol, and solvents or mixtures
of E for cyclization of 3b with increased solvent polarity, a
a
with this E (30) value or greater should permit efficient ion pair
T
escape.14 Because the reporter group employed in this study was
feature not found in related radical cyclizations, reflects increasing
concentration of charge in the transition state as radical cation 3
evolves to distonic radical cation 4, a true oxonium ion.
Using radical cyclization kinetics as a model, one expects a
previously shown to have only a minor effect on radical kinetics,
comparable to that of an alkyl group,5 the results with 3 should
apply to simpler systems. To a first approximation, one should
expect that an enol ether radical cation will cyclize or add to an
alkene that does not contain polar groups about 3 orders of
magnitude faster than the corresponding radical, but we caution
that enol ether radical cation additions to unsubstituted alkene
groups might be reversible. An interesting observation, especially
in regard to potential cascade reaction sequences, is that the
distonic radical cation formed upon reaction of the enol ether
radical cation has both substantially reduced radical reactivity and
substantially increased cation reactivity.15
,16
5
-exo cyclization to be about 50 times faster than a 6-exo
8
cyclization, and the rate constant for cyclization of 3a should
9
-1
be about 1 × 10 s at ambient temperature on the basis of the
rate constants found for 3b. The measured rate constants for the
10
5
-exo system must be those for the heterolysis of 2a. This
conclusion is consistent with the large kinetic acceleration
associated with increased solvent polarity. In addition, the log A
terms found in ACN and 0.5% TFE in ACN (Table 2) are too
small for a 5-exo cyclization and apparently are associated with
an entropic penalty of solvent reorganization in the heterolysis.
The observed rate constants for the 7-exo cyclization of enol
ether radical cation 3c in Table 1 are upper limits. The cyclization
reactions were so slow that other reactions of diffusively free 3c
were important as indicated both by the low yields of 5c and by
an observed reduction in the rate constants when increasingly
dilute solutions of PTOC ester 1c were studied. The kinetic values
for 3c are about 2 orders of magnitude smaller than those for the
Acknowledgment. We thank the National Science Foundation (CHE-
9981746) and the National Institutes of Health (GM-56511) for financial
support.
Supporting Information Available: Tables of rate constants for the
functions in Table 2 (PDF). This material is available free of charge via
the Internet at http://pubs.acs.org.
JA015639X
6
-exo cyclization of 3b, and they are consistent with that expected
from radical kinetics. The rate constant for reaction of the
(11) Gugger, A.; Batra, R.; Rzadek, P.; Rist, G.; Giese, B. J. Am. Chem.
Soc. 1997, 119, 8740-8741. Newcomb, M.; Miranda, N.; Huang, X.; Crich,
D. J. Am. Chem. Soc. 2000, 122, 6128-6129.
-
1 9
7-octenyl radical is only about 100 s .
Semiquantitative information about the rates of conversion of
the first-formed ion pairs to diffusively free ions is provided by
(
12) Moeller, K. D.; Tinao, L. V. J. Am. Chem. Soc. 1992, 114, 1033-
1041. Tinao-Woolridge, L. V.; Moeller, K. D.; Hudson, C. M. J. Org. Chem.
1
994, 59, 2381-2389. Frey, D. A.; Reddy, H. K.; Moeller, K. D. J. Org.
(8) Johnson, C. C.; Horner, J. H.; Tronche, C.; Newcomb, M. J. Am. Chem.
Chem. 1999, 64, 2805-2813.
Soc. 1995, 117, 1684-1687. Newcomb, M.; Horner, J. H.; Filipkowski, M.
A.; Ha, C.; Park, S. U. J. Am. Chem. Soc. 1995, 117, 3674-3684. Newcomb,
M.; Choi, S. Y.; Horner, J. H. J. Org. Chem. 1999, 64, 1225-1231.
(13) Reichardt, C. Chem. ReV. 1994, 94, 2319-2358.
(14) Methanol should be an excellent solvent because it will react “slowly”
1
5
with an enol ether radical cation. In addition, rapid reaction of methanol
with the distonic radical cation products could prevent reversible conversions.
(15) Rate constants at ambient temperature for enol ether radical cation
(
9) Beckwith, A. L. J.; Moad, G. J. Chem. Soc., Chem. Commun. 1974,
4
3
72-473. Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985, 41, 3925-
5
6
-1 -1
941.
reactions with water are in the 1 × 10 to 1 × 10
M
s
range; see:
(
10) The “heterolysis reaction” is a complex sequence of reactions involving
Newcomb, M.; Miranda, N.; Mousumi, S.; Huang, X.; Crich, D. Submitted
for publication.
bond breaking to give a contact ion pair (CIP), solvation to the solvent-
separated ion pair (SSIP), and escape of free ions. Heterolyses of related
R-methoxy-â-(diethylphosphatoxy) radical have rate constants similar to that
found for 2a.11
(16) Horner, J. H.; Tanaka, N.; Newcomb, M. J. Am. Chem. Soc. 1998,
120, 10379-10390. Furxhi, E.; Horner, J. H.; Newcomb, M. J. Org. Chem.
1999, 64, 4064-4068.