Radical additions of TEMPO to ketenes: Correlation of free radical and nucleophilic reactivity

Article abstract of DOI:10.1021/ol990628i

Formula presented Tetramethylpiperidinyloxy (TEMPO, TO^.) reacts with a variety of ketenes R¹R²C=C=O by rate-limiting attack on carbonyl carbon to give the 1,2-bis(adducts) R¹R²C(OT)CO₂T. The α,β-unsaturated ketenes (E)-PhCH=CHCH=C=O (8b) and PhC≡CCH=C=O (8c) give the 1,4-bis(adducts) PhCH(OT)CH=CHCO₂T and PhC(OT)=C=CHCO₂T. The ketenes may be generated in situ for these reactions in the presence of TEMPO by either dehydrochlorination of R¹R²CHCOCI with Et₃N or Wolff rearrangement. Ketenes PhCH=C=O (8a), 8b, and 8c had not previously been observed as long-lived species at room temperature, but when formed by photochemical Wolff rearrangement, these could be characterized in solution by conventional IR spectroscopy and used for kinetic studies for reaction with TEMPO using UV detection. The reactions of six ketenes with TEMPO in hydrocarbon solvents follow second-order kinetics, with a range of 2.5 × 10⁵ in the rate constants, which are correlated with unit slope with the corresponding rate constants for hydration.

Full text of DOI:10.1021/ol990628i

ORGANIC
LETTERS
1
999
Vol. 1, No. 5
93-696
Radical Additions of TEMPO to
Ketenes: Correlation of Free Radical
and Nucleophilic Reactivity
6
Annette D. Allen, Bernice Cheng, Michael H. Fenwick, Wen-wei Huang,
Sharif Missiha, Daryoush Tahmassebi, and Thomas T. Tidwell*
Department of Chemistry, UniVersity of Toronto, Toronto, Ontario, Canada M5S 3H6
ttidwell@chem.utoronto.ca
Received April 30, 1999
ABSTRACT
•
1 2
Tetramethylpiperidinyloxy (TEMPO, TO ) reacts with a variety of ketenes R R CdCdO by rate-limiting attack on carbonyl carbon to give the
1
2
1
,2-bis(adducts) R R C(OT)CO
PhCH(OT)CHdCHCO T and PhC(OT)dCdCHCO
either dehydrochlorination of R R CHCOCl with Et
2
T. The r,â-unsaturated ketenes (E)-PhCHdCHCHdCdO (8b) and PhCtCCHdCdO (8c) give the 1,4-bis(adducts)
T. The ketenes may be generated in situ for these reactions in the presence of TEMPO by
N or Wolff rearrangement. Ketenes PhCHdCdO (8a), 8b, and 8c had not previously been
2
2
1
2
3
observed as long-lived species at room temperature, but when formed by photochemical Wolff rearrangement, these could be characterized
in solution by conventional IR spectroscopy and used for kinetic studies for reaction with TEMPO using UV detection. The reactions of six
5
ketenes with TEMPO in hydrocarbon solvents follow second-order kinetics, with a range of 2.5 × 10 in the rate constants, which are correlated
with unit slope with the corresponding rate constants for hydration.
Free radical additions to ketenes1,2 have received only
scattered attention since the original observation by Staudinger
that Ph
2 2
CdCdO (1) was sensitive to O , which implies that
ketenes are reactive with free radicals. Recent theoretical
studies at the B3LYP/6-31G*//B3LYP/6-31G* level of the
possible reaction pathways shown in eq 1 support this
Experimental studies with the stable free radical 2,2,6,6-
tetramethylpiperidinyloxy (TEMPO, TO ) have confirmed
2a
•
2
b
these predictions.
Thus, the persistent ketene Ph
reacts readily with TEMPO, and exposure of the product to
gives peroxide 6 by the proposed mechanism shown (eq
2
CdCdO
O
3
2
2
c
), while the bisketene (Me
form bis(trimethylsilyl) maleic anhydride.
3 2
SiCdCdO) (7) and TEMPO
2
b
(
1) (a) Tidwell, T. T. Ketenes; Wiley: New York, 1995. (b) Michael J.
V.; Nava, D. F.; Payne, W. A.; Stief, L. J. J. Chem. Phys. 1979, 70, 5222-
227. (c) Itzel, H.; Fischer, H. HelV. Chim. Acta 1976, 59, 880-901. (d)
5
Oehlers, C.; Temps, F.; Wagner, H. G.; Wolf, M. Ber. Bunsen-Ges. Phys.
Chem. 1992, 96, 171-175. (e) Wallington, T. J.; Ball, J. C.; Straccia, A.
M.; Hurley, M. D.; Kaiser, E. W.; Dill, M.; Schneider, W. F.; Bilde, M.
Int. J. Chem. Kinet. 1996, 28, 627-635.
expectation and predict that the formations of acyl radicals
2
and enolic radicals 3 are exothermic by 32.6 and 54.7 kcal/
•
mol, respectively, for HO attachment. For the aminoxyl
radical H
(
2) (a) Sung, K.; Tidwell, T. T. J. Org. Chem. 1998, 63, 9690-9697.
•
2
NO attack at CH
2
is predicted to be endothermic
(b) Huang, W.; Henry-Riyad, H.; Tidwell, T. T. J. Am. Chem. Soc. 1999,
1
21, 3939-3943. (c) Zhao, D.; Allen, A. D.; Tidwell, T. T. J. Am. Chem.
by 7.5 kcal/mol, while carbonyl carbon attack is exothermic
by 18.7 kcal/mol (eq 2).2b
Soc. 1993, 115, 10097-10103. (d) Carter, J.; Fenwick, M. H.; Huang, W.;
Popic, V. V.; Tidwell, T. T. Can. J. Chem. 1999, 77, 806-809.
1
0.1021/ol990628i CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/08/1999

refluxing of the mixture in toluene gave the adduct 10a of
,2-addition of two TEMPO molecules (eq 5). The structure
1
of 10a follows from the spectral properties, including the
-
1
1
CdO band in the IR at 1750 cm , and the H NMR
spectrum, with the CHO signal at δ 5.23, and there are eight
cleanly resolved CH
the conformational properties of the piperidinyloxy groups
but also to the diastereotopic nature of the CMe units. The
structure of 10a was confirmed by its X-ray structure. Initial
attack of TEMPO on the carbonyl carbon of 8a to give the
enolic radical 11a is expected by analogy with the results
3
singlets, as expected not only due to
8
The use of nitroxyl radicals as radical traps is widely
practiced,3 and the examination of their reactions with
nonradical species is also attracting increasing attention.
Thus, the kinetics of hydrogen abstraction from various
-5
2
•
4a
substrates by (CF
has been found to abstract H atoms from methylbenzenes at
20 °C.4b The reversible reactions of TEMPO with benzyl
3 2
) NO have been measured, and TEMPO
2
from Ph CdCdO (eq 3), followed by capture by the second
4c
1
TEMPO molecule as documented for other enolic radicals.
Generation of the 1-naphthyl analogue of 8a by Wolff
rearrangement and trapping as the TEMPO adduct corre-
radicals have also found extensive application in living free
radical polymerization.5
2
d
There have been many recent kinetic studies of radical
sponding to 10a has also been reported.
6
2b
additions to alkenes, and the discovery of the reaction of
TEMPO with Ph CdCdO and with the bis(ketene) 7
The photochemical Wolff rearrangement of diazoketones
9b,9b 9c, and others
9a
10a,11
to give ketenes 8b, 8c, 12,
9a
9a
10b
2
1
1
suggests an opportunity to extend the study of TEMPO
reactions to include other ketenes and activated alkenes.
Reported herein are our studies of the scope of the reaction
with ketenes, which also reveal that a number of highly
reactive ketenes may be generated by Wolff rearrangement
for direct observation using conventional spectroscopy at
ambient temperature.
and 13 for trapping with TEMPO was also successful and
led to the bis(adducts) 10b,c, 14, and 15 (Table 1).12
Table 1. Capture of Ketenes by TEMPO
Phenylketene (8a) is the prototype of a reactive, nonper-
sistent ketene and was first generated by Zn dechlorination
7a
of PhCHClCOCl by Staudinger in 1911. However, strenu-
ous efforts to isolate this ketene were unsuccessful, although
there was evidence from trapping experiments of its presence
7
a
in solution. Since that time this ketene has been generated
in situ for preparative or mechanistic studies, including
cycloadditions,7b hydration, and amination. Wolff rear-
rangement of diazoketones such as 9a-c provides a conve-
nient route to highly reactive ketenes such as 8a-c.
7c
7d
a
Yields not optimized. b Similar spectrum published in ref 10b. c Ref-
erence 12.
Diazoacetophenone (9a) proved to be a suitable precursor
of PhCHdCdO (8a) for in situ trapping with TEMPO, as
3
The dehydrochlorination of acyl chlorides with Et N is a
long established route to ketenes, and this procedure carried
9a was inert to TEMPO at room temperature but upon
1a
(
3) (a)Volodarsky, L. B.; Reznikov, V. A.; Ovcharenko, V. I. Synthetic
Chemistry of Stable Nitroxides; CRC Press: Boca Raton, FL, 1994. (b)
Keana, J. F. W. Chem. ReV. 1978, 78, 37-64. (c) Aurich, H. G. Nitroxides.
In Nitrones, Nitronates, Nitroxides; Patai, S., Rappoport, Z., Eds.; Wiley:
New York, 1989; Chapter 4.
(5) (a) Kothe, T.; Marque, S.; Martschke, R.; Popov, M.; Fischer, H. J.
Chem. Soc., Perkin Trans. 2 1998, 1553-1559. (b) Hawker, C. J. Acc.
Chem. Res. 1997, 30, 373-382. (c) Kazmaier, P. M.; Daimon, K.; Georges,
M. K.; Hamer, G. K.; Veregin, R. P. N. Macromolecules 1997, 30, 2228-
2231. (d) Benoit, D.; Chaplinski, V.; Braslau, R.; Hawker, C. J. J. Am.
Chem. Soc. 1999, 121, 3904-3920.
(6) (a) Zytowski, T.; Fischer, H. J. Am. Chem. Soc. 1997, 119, 12869-
12878. (b) Avila, D. V.; Ingold, K. U.; Lusztyk, J.; Dolbier, W. R., Jr.;
Pan, H.-Q.; Muir, M. J. Am. Chem. Soc. 1994, 116, 99-104.
(
4) (a) Doba, T.; Ingold, K. U. J. Am. Chem. Soc. 1984, 106, 3958-
3
1
963. (b) Connolly, T. J.; Scaiano, J. C. Tetrahedron Lett. 1997, 38, 1133-
136. (c) Braslau, R.; Burrill, L. C., II; Siano, M.; Naik, N.; Howden, R.
K.; Mahal, L. K. Macromolecules 1997, 30, 6445-6450. (d) Barton, D. H.
R.; Le Gloahec, V. N.; Smith, J. Tetrahedron Lett. 1998, 39, 7483-7486.
694
Org. Lett., Vol. 1, No. 5, 1999

out in the presence of TEMPO also proved successful for
the in situ trapping of ketenes (eq 6).
Et N
2TO
•
3
RCH COCl
8 RCHdCdO
a,b,d,e
8 RCH(OT)CO T
(6)
2
2
8
1
0a,b,d,e
R ) Ph, 8a, 10a (30%); R ) PhCHdCH, 8b,
1
3a-c
10b (28%); R ) t-Bu,
8d, 10d (16%);
3d
R ) PhO, 8e, 10e (58%)
7d
7c,9a
Kinetic studies of amination and hydration
of reactive
ketenes, including 8a-c, were previously carried out using
in situ generation of the ketenes by Wolff rearrangement
using flash photolysis of diazo ketones. However, this
methodology may be complicated for studies of ketene
reactions with TEMPO, which has a strong UV/visible
chromophore. We have circumvented this obstacle by finding
that solutions of these ketenes may be generated separately
by Wolff rearrangements in hydrocarbon solvents, and these
are surprisingly long-lived, permitting their spectral charac-
terization and use. Thus, photolysis of diazo ketones 9a-c
and 2-diazocyclohexanone in isooctane gave solutions of
ketenes 8a-c and 12, whose characteristic ketenyl IR bands
Figure 1. Comparative reactivity of ketenes with TEMPO and
O.
H
2
eu found for the reaction of 7 with TEMPO. This is
reasonable for these bimolecular reactions proceeding by
similar mechanisms.
Solutions of the ketenes 8a-c and 12 were prepared by
photochemical Wolff rearrangements, and their reaction rates
with TEMPO were measured using conventional UV. All
the ketenes showed good first-order dependences on
(Table 1) and UV spectra could be measured by conventional
means and are in good agreement with literature results.
Measurement of the rates of reaction of the long-lived
ketenes 1 and 7 with excess TEMPO was successful, as
determined by observation of the decrease in the ketene
chromophores by UV (Table 2). Interestingly the theoretically
[TEMPO]; the derived second-order rate constants are
summarized in Table 2, and full kinetic data are given in
Table 3 (Supporting Information).
The rate constants for the reactions of the ketenes with
5
TEMPO show a variation of 2.5 × 10 with ketene structure.
There have been extensive studies of the hydration reactivi-
2
c,7c,9a,13a-c
ties of ketenes in H
CN,
2
O
and for amination in CH
3
-
Table 2. Rate Constants for Ketene Reaction with TEMPO at
7d,14a
and both these reactions also show large variations
2
5 °Ca
in reactivity with ketene structure. Theoretical studies of
ketene hydration and amination favor rate-limiting in-plane
nucleophilic attack on the carbonyl carbon, with hydrogen
ketene
k2TEMPO (M-1 s-1
)
Ph2CdCdO (1)
0.357
1.50 × 10
1.26
18.4
37.4
-
4 b
2
bonding interactions involving other H O or amine molecules
(Me3SiCdCdO)2 (7)
coordinating with the nucleophile and the ketenyl
PhCHdCdO (8a )
E)-PhCHdCHCHdCdO (8b)
PhCtCCHdCdO (8c)
1
a,14b-e
(
oxygen.
The most extensive set of ketene reactivity data is for
hydration, and correlation of log kTEMPO for the reaction of
the ketenes with TEMPO (25 °C) with the corresponding
values of log k for hydration in H O gives the relationship
2
of eq 7 , as illustrated in Figure 1. The unit slope leads to
the interesting conclusion that the reactions of ketenes with
2 c
2
.98 × 10-
a
b
In isooctane unless noted. In mesitylene, extrapolated from data at
q
q
-1
-1
higher temperatures; ∆H ) 13.8 kcal/mol, ∆S ) -29.6 cal K
H2O rate.
M .
c
13c
(
10) (a) Tomioka, H.; Okuno, H.; Izawa, Y. J. Org. Chem. 1980, 45,
5278-5283. (b) Schulz, R.; Schweig, A. Z. Naturforsch. 1984, 39B, 1536-
540.
11) (a) Chapman, O. L.; Chang, C.-C.; Kolc, J.; Rosenquist, N. R.;
2
a
q
•
calculated ∆S value for attachment of HO to C
R
of CH
2
d
1
CdO is -32.3 eu, which is quite close to the value of -29.6
(
Tomioka, H. J. Am. Chem. Soc. 1975, 97, 6586-6588. (b) Spangler, R. J.;
(
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(12) The product 10b is obtained as an unseparated 2/1 or 3/1 mixture
of E/Z isomers by dehydrochlorination or Wolff rearrangement, respectively,
1
13
as identified by the 2-D H and C NMR spectra. The yield reported is for
the dehydrochlorination route. Products 10c-e, 14 and 15 are identified
by consistent NMR, MS, and IR spectra. See the Supporting Information
for details.
1
998, 120, 1827-1834.
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Soc., Perkin Trans. 2 1993, 1299-1304.
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(
(
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R. L.; Miller, R. F.; Brisbois, R. G.; Park, S. Z. J. Org. Chem. 1990, 55,
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1
1
Org. Lett., Vol. 1, No. 5, 1999
695

•
•
log kTEMPO ) (0.98 ( 0.08) log k - (3.30 ( 0.19)
(7)
for H
2
NO relative to HO and also with the steric barriers
H O
2
•
expected for reaction of TEMPO compared with H
2
NO .
TEMPO, which involve formation of a C-O bond, correlate
with the hydration reactivities, which also involve C-O bond
Acknowledgment. Financial support by the Natural
Sciences and Engineering Research Council of Canada and
the donation of diazo ketone 9b by Professor R. Danheiser
formation.
Attachment of H
•
dCdO is calculated2b
2
NO to C
R
of CH
2
to be 36.0 kcal/mol less favorable than the corresponding
(MIT) are gratefully acknowledged.
•
2a
attachment of HO , and experimentally the reaction of
TEMPO with ketenes shows appreciable barriers (Table 2).
This is consistent with the much lower reactivity calculated
Supporting Information Available: Experimental pro-
cedures, kinetic data, NMR spectra, and X-ray structural
information on 10a and an X-ray crystallographic file, in
CIF format. This material is available free of charge via the
Internet at http://pubs.acs.org.
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14) (a) Allen, A. D.; Tidwell, T. T. J. Org. Chem. 1999, 63, 266-271.
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6
1
8
(
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17-829.
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