Treasures from the Free Radical Renaissance Period - Miscellaneous hexenyl radical kinetic data

Article abstract of DOI:10.1039/c0ob00708k

Rate constant data and Arrhenius parameters have been determined for a series of substituted hexenyl radicals of differing electronic and steric demand. Electron-withdrawing groups (CF₃, CO₂Et) directly attached to the radical centre slighly accelerate 5-exo ring-closure (k _cis + k_trans ～ 2.1 × 10⁵ s ^-1 at 25°) relative to donating groups (OMe; 1.6 × 10 ⁵ s^-1 at 25°). Sterically demanding groups (tert-Bu), as expected, slow the cyclization process (1 × 10⁵ s ^-1). These observations are consistent with subtle changes in activation energy for 5-exo ring-closure. Interestingly, the nature of the solvent would appear to have a significant influence on this chemistry with the cis/trans stereoselectivity sometimes improved as the solvent polarity is increased. Except for the system containing the CF₃ (electron-withdrawing) group which displays an increase in the cyclization/capture rate constant (k_c/k_H), a general decrease in the k_c/k_H ratio as solvent polarity is increased is noted; these changes have been speculated to arise mainly from changes in k_H in the various solvents employed.

Full text of DOI:10.1039/c0ob00708k

Organic &
Biomolecular
Chemistry
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Volume 9 | Number 6 | 21 March 2011 | Pages 1669–2008
ISSN 1477-0520
FULL PAPER
Beckwith et al.
Treasures from the Free Radical
Renaissance Period – Miscellaneous
hexenyl radical kinetic data
1477-0520(2011)9:6;1-C

Organic &
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PAPER
Treasures from the Free Radical Renaissance Period – Miscellaneous hexenyl
radical kinetic data†‡
Athelstan L. J. Beckwith§a and Carl H. Schiesser*a,b,c
Received 13th September 2010, Accepted 2nd November 2010
DOI: 10.1039/c0ob00708k
Rate constant data and Arrhenius parameters have been determined for a series of substituted hexenyl
radicals of differing electronic and steric demand. Electron-withdrawing groups (CF3, CO2Et) directly
attached to the radical centre slighly accelerate 5-exo ring-closure (kcis + ktrans ~ 2.1 ¥ 105 s-1 at 25◦)
relative to donating groups (OMe; 1.6 ¥ 105 s-1 at 25◦). Sterically demanding groups (tert-Bu), as
expected, slow the cyclization process (1 ¥ 105 s-1). These observations are consistent with subtle
changes in activation energy for 5-exo ring-closure. Interestingly, the nature of the solvent would appear
to have a significant influence on this chemistry with the cis/trans stereoselectivity sometimes improved
as the solvent polarity is increased. Except for the system containing the CF3 (electron-withdrawing)
group which displays an increase in the cyclization/capture rate constant (kc/kH), a general decrease in
the kc/kH ratio as solvent polarity is increased is noted; these changes have been speculated to arise
mainly from changes in kH in the various solvents employed.
The Dark Ages, of course, were interspersed with significant
Introduction
contributions by Hey and Waters,6 Kharash,7 Walling8 and
others,9 but free radicals remained largely inaccessible to synthetic
chemists until their Renaissance during the period 1970–1990
in which the factors that control the reactivity, regiochemistry
and stereochemistry of radical reactions began to be teased out.
Ingold,10 Julia,11 Barton,12 Surzur,13 Davies,14 Fischer,15 Giese,16
Curran,17 Newcomb18 and one of us19 (as well as others) were all
significant contributors to the dramatic rise in our understanding
of free radical chemistry during this period, and to their general
acceptance in the wider chemistry community.20
A plethora of vital rate constant data became available, and
molecular modeling provided for the first time an explanation
for the exo/endo paradox associated with the ring-closure of the
5-hexenyl radical.21,22 Who would have thought that transition
state ring-strain is the primary driver for most alkenyl radical
ring-closures? As the implications of the Beckwith–Houk model
became more widely appreciated, so did the more-general use of
free radicals in synthesis.20
It is during this Renaissance Period that we asked key questions
in relation to the factors controlling w-alkenyl radical ring
closures. How important are steric factors during cyclization?
Is the geometry of the alkene important? What about electronic
demand on the radical centre – do electon-donating and electron-
withdrawing groups play important roles? What about solvent
effects?
While some of our investigations toward answering these
questions have been published,23 some required key kinetic data
to become available in the post-Renaissance period for meaningful
conclusions to be drawn. We now report miscellaneous kinetic
data that contribute to our further understanding of radical
There was a time when free radicals were scorned by organic
chemists and when “practically every organic text book written”
contained a statement that free radicals were “incapable of an inde-
pendent existence”.1 Except for polymer chemistry, these reactive
species were mostly regarded as poorly-understood curiosities,
often scape-goats for unwanted outcomes during synthesis, or
when the practitioner required that elusive explanation for his
or her unwanted observation. Those were the Dark Ages of free
radical chemistry, the lengthy period between the “discovery” of
organic free radicals by Gomberg in 1900 and their resurgence
some seventy or so years later.2,3
Many of us appreciate that there was a brief period of
enlightenment before the Dark Ages; Marcellin Berthelot devotes
a section to radicaux in his La Synthe`se Chimique, published in
1887,4 and Wurtz was generating alkyl radicals as early as 1855.5
aResearch School of Chemistry, Australian National University, Canberra,
ACT, 0200, Australia
bCurrent address: School of Chemistry, Bio21 Molecular Science and
Biotechnology Institute, The University of Melbourne, Victoria, 3010,
Australia. E-mail: carlhs@unimelb.edu.au; Fax: +61 3 9347 8189; Tel: +61
3 8344 2432
cARC Centre of Excellence for Free Radical Chemistry and Biotechnology,
Australia
† In memory of Athel Beckwith who contributed significantly to enlight-
enment during the Free Radical Renaissance period.
‡ Electronic supplementary information (ESI) available: Procedures for
the preparation of 1b-H, 2b-H, 3b-H, 3c-H, 4a-H, 4b-H, 7-H, 8-H, 25-H
and 27; derivation of eqn (6) kinetic data for the cyclization of 1a, 1b, 1c, 6
and 24 under various reaction conditions. See DOI: 10.1039/c0ob00708k
§ Deceased May 2010
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ring-closure chemistry and go some way to answering the ques-
tions presented above.
Results
Scheme 3 Reagents and conditions: (a) NaH, NCS, DMF, 81%; (b)
NaOH, EtOH, reflux; (c) ꢀ, neat; (d) SOCl2 (e) EtOH. 69% over four
steps.
Some of the issues raised above could be addressed through the
determination of kinetic parameters of appropriately substituted
hexenyl radicals. Accordingly, we chose to explore the ring-closure
chemistry of radicals 1, 4 and 6 as depicted Scheme 1. Rate
constants for cyclization (kcis, ktrans, kc; Scheme 1) were determined
through the use of standard free radical competition kinetics as
decribed previously by us,24 as well as others and is illustrated in
Scheme 2 using radical 4b as an example. We appreciate that kinetic
data for radicals 1a and 1b have been published by Newcomb,25
however, the work presented in this paper predates those reports
and provides solvent effect data not previously made available; it
is therefore instructive to compare our results with those other
seminal contributions to the field.
Scheme 4 Reagents and conditions: (a) NaOMe, 91%; (b) SOCl2 (c)
1-hydroxy-5-methyl-(1H)-thiazolin-2-thinone. 24% over two steps.
Scheme 5 Reagents and conditions: (a) CF3CO2Et, 56%; (b) PhOC(S)Cl,
pyridine, 67%.
Scheme 6 Reagents and conditions: (a) ethylene glycol, NaH, 75%; (b)
PBr3, 38%.
Scheme 1
Scheme 7 Reagents and conditions: (a) 2-hydroxytetrahydropyran; 47%;
(b) PDC; (c) n-butylmagnesium bromide, 40% over two steps; (d)
PhOC(S)Cl, pyridine, 74%.
Scheme 2
Preparation of Radical Precursors
In order to facilitate this study, precursors to the radicals of interest
were required, and these were prepared as described below. To that
end chloride (9), thiohydroxamic ester (10), thionocarbonates (11,
12) and bromides (13, 14) were prepared following the procedures
outlined in Schemes 3–7.
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Table 1 Rate data and Arrhenius functions for the 5-exo cyclizations of substituted 5-hexenyl radicals
a
b
a
b
Entry
Radical
Solvent
kcis
fcis
ktrans
ftrans
1
2
3
4
5
6
7
8
1a
benzene
benzene
benzene
THF
hexane
hexane
hexane
hexane
hexane
cyclopropane
benzene
1.0 ¥ 105
7.1 ¥ 104
8.1 ¥ 104
8.9 ¥ 104
1.2 ¥ 105
4 ¥ 106
(8.6 0.6)–(4.9 0.6)/q
1.1 ¥ 105
1.3 ¥ 105
7.7 ¥ 104
1.1 ¥ 105
9.4 ¥ 104
(8.5 0.6)–(4.7 0.6)/q
(10.1 0.6)–(7.1 0.9)/q
(9.6 0.4)–(6.3 0.5)/q
d
1ac
1b
11.7–8.7/q
(9.9 0.6)–(6.8 0.9)/q
1bc
1c
10.8–7.5/q
d
(9.4 0.4)–(5.9 0.5)/q
4ae
4bd
6
n.d.f
4 ¥ 106
n.d.f
7.8 ¥ 104
7.3 ¥ 104
7.3 ¥ 104
4 ¥ 104
(10.2 0.4)–(7.3 0.5)/q
(8.9 0.4)–(5.5 0.5)/q
(9.3 0.3)–(5.6 0.5)/q
(9 1)–(6 1.5)/q
1.4 ¥ 105
2.6 ¥ 104
(10.0 0.4)–(6.6 0.5)/q
(10.8 0.4)–(8.7 0.5)/q
9
10
11
23g
24e,h
24e
a Rate constants (s-1) at 25◦ calculated from Arrhenius function. b Arrhenius function in kcal mol-1; q = 2.3RT; Errors expressed to 2s. c Ref. 25 d Combined
Arrhenius function for kcis + ktrans
e Cyclization data (kc) only; no stereochemistry for this radical. f Not determined, see text; Rate constants determined
from experiment performed at 25◦. g Ref. 23; note that the cis and trans products (2, 3) were originally incorrectly assigned (see ref. 23). h Ref. 31.
.
Diethyl hex-5-en-1,1-dicarboxylate (15)26 was treated with
sodium hydride, followed by N-chlorosuccinimide to afford the
corresponding chloride (16) in 81% yield. Saponification followed
by decarboxylation and subsequent re-esterification afforded the
required precursor (9) to radical 1a (Scheme 3).
Kinetic Experiments
With the required radical precursors in hand, we next turned our
attention to their ring-closure chemistry. Approximately 10 mol%
of the required precursor was added to a pre-prepared (standard)
solution of Bu3SnH in hexane or benzene in a pyrex tube. A crystal
of AIBN was added. After de-gassing through freeze-thaw cycles,
the tube was sealed and the sample emersed in an oil-bath at
the required temperature. For temperatures below 50◦, reactions
were initiated by irradiation with a 200 W mercury lamp. Product
analyses were performed by gas chromatography and products
were identified by comparison with authentic standards prepared
as described below, or by direct isolation from the reaction mixture
using preparative GC. All kinetic experiments were performed in
triplicate. Under these conditions, eqn (1) (Scheme 2) reduces to:
Ethyl 2-bromohept-6-enoate, prepared in identical fashion to 9
from 15 and N-bromosuccinimide, was reacted with excess sodium
methoxide to afford the acid (17) after acidic workup. Further
treatment with thionyl chloride followed by 3-hydroxy-4-methyl-
(3H)-thiazole-2-thione afforded 10 in low yield (Scheme 4).
Thionocarbonate 11 was prepared according to Scheme 5
in which ethyl trifluoroacetate was reacted with 4-
pentenylmagnesium bromide to afford the alcohol 18. This
transformation requires two-equivalents of the Grignard
reagent; the first equivalent adds to the ester to afford the
trifluoromethylketone which is then further reduced with the
second equivalent of reagent. The reduction of trifluoromethyl
ketones by Grignard reagents is well documented.27 Further
treatment with phenylchlorothionocarbonate afforded the
required precursor 11 in moderate yield.
[5 - H]
kc
=
(2)
[4b - H] kH [Bu3SnH]
Similar equations apply for each cyclization reaction in this
study.
Application of eqn (2) to the data collected from the experiments
described above, together with known values for kH,28–30 afforded
the rate and associated Arrhenius data listed in Table 1.ꢀ
Bromides 13 and 14 were prepared by reacting ethylene glycol
with sodium hydride followed by either (Z)- or (E)-1-bromo-2-
hexene (Scheme 6). Alcohols 19 were obtained in 75% yield after
separation from byproduct 20 by MPLC; presumably 20 arises by
an SN2¢ process. While the E isomer was isolated in excellent purity,
the Z isomer was contaminated with approximately 20% of the E
isomer, however this did not present a problem during the kinetic
study.¶ Further treatment of 19 with phosphorus tribromide under
standard conditions afforded the required bromides (13, 14) in low
yield after flash chromatography.
The final precursor (12) was prepared from 2-hydroxy-
tetrahydropyran following treatment with n-butyltriphenylpho-
sphorane under Wittig conditions to give (Z)-5-nonen-1-ol (21).
Oxidation to the corresponding aldehyde followed by treatment
with n-butylmagnesium bromide afforded the alcohol 22 in
moderate yield. Conversion to the corresponding thionocarbonate
was achieved in analogous fashion to the preparation of 11
(Scheme 7).
As radical 24 is known to undergo reversible cyclization,32
ring-closure of 1a was also expected to be reversible; indeed this
was confirmed by dilution experiments which showed increased
formation of the thermodynamically more stable trans product 3a
at lower Bu3SnH concentrations. Therefore, for the ring-closure of
1a, we chose to examine the application of rate eqn (3) for reversible
ring closure as illustrated for 24 in Scheme 8. Eqn (3) integrates to
eqn (4) under pseudo first-order and to eqn (5) under second-order
conditions.‡ Assuming that the first two terms in the Taylor series
expansion dominate, eqn (5) can be expanded to eqn (6), which
together with eqn (4) is capable of providing cyclization (kc) as
well as hydrogen transfer (kH) rate constants through application
¶ Product ratios for 14 obtained from reactions using the 80 : 20 ratio of
14 : 13 were corrected using the data obtained using pure 13.
ꢀ Previously published data for 1a and 1b, the tert-butyl substituted system
23,23 and the diester 2431 are included for completeness.
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were employed in each of these studies (benzene vs. THF) and this
may account for the observed discrepancies, in particular in the
observed 2a/2b ratios.
In the case of 1a, differences are once again noted; the most
significant being in the Arrhenius functions. We speculate that,
perhaps, the experiments leading to entry 2 were affected by trace
amount of benzeneselenol, possibly through minor decomposition
of the phenylseleno precursor used in that study;28 benzeneselenol
contaminants are known to interfere with radical kinetics.33
It was not possible to produce reliable Arrhenius data for
radicals 4 as the bromides 13, 14 appeared to initiate before the
reaction solution had reached the desired temperature; this was
partially overcome by addition of the precursor to a preheated
solution of Bu3SnH in hexane, however, scatter in the data at higher
temperatures nevertheless meant that the room temperature data
were the most robust.
Identification of Products
As mentioned above, products resulting from kinetic experiments
were identified either by GC comparison with synthesized authen-
tic standards, or through direct isolation from reaction mixtures
using preparative GC. Indeed, 5-H, and 25-H32 were isolated
reaction products.
The remaining product standards were prepared according to
Scheme 9. Ester 1a-H was prepared by the treatment of diester
15 with sodium chloride in DMSO at elevated temperatures as
described by Schmidt and Ingold,34 while a 95 : 5 mixture of
3a-H : 2a-H was prepared from cyclohexane following literature
precident.35
Scheme 8
of known values for k¢H ; kH values for ester-substituted radicals
were unknown at the time this work was carried out.
In order to validate our assumptions, we chose to first apply
eqns 4 and 6 to the diethyl 1,1-dicarboxy-5-hexenyl radical 24.
To that end, chloride 16 was reacted under the (pseudo first-
order) reaction conditions described above, as well as under second
order conditions.‡ The cyclization data obtained in this manner
are included in Table 1 and, gratifyingly, are in good agreement
with those obtained by Roberts several years later using kinetic
EPR techniques.31 These experiments also provided approximate
kH data for the trapping of 24 by Bu3SnH; kH ~ 9 ¥ 105 M-1s-1 at
25◦ in benzene.** To the best or our knowledge, kH data for 24
have not been reported previously.
Our data for 24 have greater uncertainties than those reported
by Roberts mainly because application of eqn (5) requires extrap-
olation of the data to the intercept of eqn (4) where [Bu3SnH]
vanishes.
It is interesting to note that the 6-endo product, diethyl
cyclohexanedicarboxylate was only observed (~ 5%) at stannane
concentrations of 0.01 M or below, consistent with reversible 5-exo
ring-closure.32
When these techniques were applied to radical 1a, and the
kc/kH data obtained were combined with hydrogen transfer rate
constants (kH) reported by Newcomb30 some ten years after this
work was carried out, the kinetic data provided in Table 1 (entry
1) were obtained.
Interestingly, radical 1b proved to ring-close in an irreversible
fashion under our reaction conditions; once again application of
kH values provided by Newcomb29 afforded the data in entry 3
of Table 1. While our data are very similar to those reported by
Newcomb for 1b (entry 4),25 it is notable that different solvents
Scheme 9 Reagents and conditions: (a) Acetyl chloride, AlCl3, 23%; (b)
NaOBr, 86%; (c) SOCl2 (d) EtOH. 36% over two steps; (e) SF4; (f) LiAlH4,
97%; (g) NaH, MeI; (h) NaH, EtI, 23%; (i) n-Butyltriphenylphosphonium
bromide, NaH, DMSO, 29% (j) H2, Pd-C; 98%.
Ether 1b-H was prepared from commercially available 5-hexen-
1-ol, while an 80 : 20 mixture of 3b-H : was obtained from
2-methylcyclohexanone by reduction with lithium aluminium
hydride followed by Williamson etherification.36
A 95 : 5 mixture of trifluoromethylcyclopentanes 3c-H : 2c-H
was prepared from the 95 : 5 mixture of acids 26 by treatment
with sulfur tetrafluoride, while the remaining peak in the gas
chromatogram obtained after the reaction of 1c was assigned to
** log kH ~ 7.4–2.0/q
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Table 2 Relative rate data for the 5-exo cyclizations of some substituted
The alkyl-substituted systems (entries 8, 9) ring-close with
rate constants lower than the “parent”, consistent with possible
steric factors, while entries 10 and 11 demonstrate that excessive
stabilization of the radical also retards ring-closure.
Values of 4 ¥ 106 s-1 for kc for each of the (E)- and (Z)-3-oxa-
5-nonenyl radicals 4 are to be compared with data for the parent
3-oxahexen-1-yl radical which ring-closes with a rate constant of
9.3 ¥ 106 s-1 at 25◦ in cyclopropane.21,39 The data also suggest that
the geometry of the double bond has little effect on ring-closure
rate constants for hexenyl-type radicals.
5-hexenyl radicals in different solvents
[cis/trans]
Entry
Radical
benzene or hexane
DMEa
1-propanol
1
2
3
4
1b
1c
6
0.95
1.13
0.57
3.1
0.93
1.86
0.57
4.4
0.94
1.70
0.57
5.9
23c
Inspection of Table 2 reveals interesting trends associated with
the effect of solvent polarity on ring-closure. In two of the four
systems investigated, the cis/trans ratio is generally observed to
increase as the solvent polarity is increased, however two systems
show no difference in this ratio as the solvent is changed. While
these results are intriguing, we are not in a position to provide an
explanation for these observations at present.
b
kc/kH
benzene or hexane
DMEa
1-propanol
5
6
7
8
1b
1c
6
0.398
0.160
0.136
0.078
0.347
0.216
0.112
0.062
0.278
0.293
0.094
0.039
23c
Table 2 also reveals interesting trends in kc/kH as solvent
polarity is changed. Entries 5, 7 and 8 show that for radicals
with electron donating or alkyl groups, kc/kH generally decreases
as the solvent polarity is increased, while the (withdrawing)
trifluoromethyl-substituted system (entry 6) shows a clear opposite
trend. Indeed kc/kH approximately doubles for radical 1c in
moving from hydrocarbon to propanol, while it halves for 23.
These observations are very likely to be the result of a delicate
interplay between energy and entropy terms operating in both
hydrogen-transfer as well as cyclization reactions.
For example, if we consider alkyl radicals to be nucleophilic,
then the transition state for hydrogen transfer from tin to carbon
is likely to be polarized as depicted in 28. Polar solvents will
stabilize 28 over non-polar solvents leading to an increase in kH
and, consquently, a decrease in kc/kH.
a 1,2-Dimethoxyethane. b kc = kcis + ktrans c Ref. 23.
.
be 1c-H after it was removed from the reaction mixture by the
addition of excess bromine.
Alkenes 4a-H and 4b-H were prepared from commercially
available (Z)- or (E)-2-hexen-1-ol after treatment with sodium
hydride followed by iodoethane.
Hydrocarbon 6-H was prepared by the reaction of
nonanal with n-butylenetriphenylphorphorane, while an 91 : 9
mixture of cis- and trans-1,2-dibutylcyclopentane was pre-
pared from 2-butylcyclohexanone37 by the action of n-
butylenetriphenylphorphorane and subsequent hydrogenation
(H2/Pd-C) of the resultant alkene 27.
Solvent Effect Studies
We were interested in what effect, if any, solvent plays in
the cyclization chemistry of substituted hexenyl radicals. As a
consequence, we published solvent-effect data for 23 showing that
the stereoselectivity of the cyclized product was sensitive to solvent
polarity.23 We now report solvent effect data for other radicals in
this study. Table 2 lists the cis/trans ratios observed for radicals 1b,
1c, 6 and 23 at 25◦ in non-polar (benzene or hexane), intermediate
polarity (DME) and polar (1-propanol) solvents, together with
relative rate constant data (kc/kH).
On the other hand, in the case of 1c, the trifluoromethyl sub-
stituent is likely to destabilize transition state 28; the consqeuence
of this would be a reduced dependence of kH on solvent polarity.
Assuming Beckwith–Houk transition states for the cyclization of
1c,21,22 the CF3 group will lead to polarized transition states 29 for
cyclization leading to an increase in kc as well as the cis/trans ratio,
as cis-29 is likely to have a greater dipole moment than trans-29.
It is clear that further examples of solvent-dependent values of
kc/kH are needed before a definitive conclusion can be drawn,
however, our data urge the use of caution when combining
Arrhenius or kinetic data that have been determined in different
solvents.
Discussion
The data listed in Table 1 provide interesting insight into the
effect of substitution on the rate constants for hexenyl radical
ring-closures. Firstly, electron-withdrawing groups (entries 1, 2, 5)
appear to increase the rate of cyclization relative to the methoxy-
substituted system; kcis + ktrans values of 2 ¥ 105 s-1 are observed for
the cyclization 1a and 1c, while 1b (entries 3, 4) ring-closes with
a (combined) rate constant of 1.6 ¥ 104 s-1 at 25◦. These values
are to be compare◦d with reported data for the 5-hexenyl radical
(2.3 ¥ 105 s-1 at 25 )21,24 and the “1-methyl-5-hexenyl radical” (1,
R = Me) (1.5 ¥ 104 s-1 at 25◦).21,38 Arrhenius data suggest that these
rate constants are mosly affected by changes in activation energy
for ring-closure, and that the effects are observed for both modes
(cis/trans) of cyclization.
Conclusions
Rate constant data and Arrhenius parameters have been deter-
mined for a series of substituted hexenyl radicals of differing
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electronic and steric demand. Electron-withdrawing groups di-
rectly attached to the radical centre slightly accelerate 5-exo ring-
closure, while donating groups would appear to retard the rate of
cyclization. Steric factors, es expected, slow the cyclization process,
which also appears to be largely unaffected by the geometry (E/Z)
of the alkene.
Interestingly, the nature of the solvent would appear to have a
significant influence on this chemistry with the cis/trans stereose-
lectivity sometimes improved as the solvent polarity is increased.
Except for the system containing the CF3 (electron-withdrawing
group) which displays an increase in kc/kH, a general decrease in
the kc/kH ratio as solvent polarity is noted; for most systems these
changes have been speculated to arise mainly from changes in kH
in the various solvents employed.
(t, J = 8 Hz, 6H); IR (neat): 1765, 1740, 1640 cm-1; (Found: C,
47.0; H, 6.5. C12H19BrO4 requires C, 46.9; H, 6.3%).
Ethyl 2-chlorohept-6-enoate (9). Diethyl 1-chlorohex-5-en-1,1-
dicarboxylate (16) (2.5 g, 9.52 mmol) was added to a stirred
solution of sodium hydroxide (2.0 g, 50 mmol) in ethanol (60 mL)
and the mixture heated under reflux for 4 h, then cooled.
The precipitate was collected and dissolved in aqueous sodium
bicarbonate (20 mL) and the solution washed with ether (4¥),
the combined extracts dried (MgSO4) and the solvent removed
to yield the crude diacid which was heated neat at 130–140 ◦C
until the evolution of carbon dioxide had ceased. The residue
was dissolved in thionyl chloride (30 mL) and the mixture heated
under reflux until the evolution of gas had ceased (~1 h). The
excess thionyl chloride was removed in vacuo, ethanol (40 mL)
added and solution heated to reflux for 10 min. After cooling the
solvent was removed in vacuo to give a brown oil that was distilled
(Ku¨gelro◦hr) to give the title ester as a colourless oil (1.26 g, 69%).
Bp ~100 C/0.2 mmHg; 1H NMR d 5.4–6.1 (m, 1H), 4.7–5.2 (m,
2H), 3.9–4.4 (m, 3H), 1.0–2.4 (m, 6H), 1.25 (t, J = 7 Hz, 3H);
IR (neat): 1745, 1640 cm-1. (Found: C, 56.8; H, 8.1. C9H15ClO4
requires C, 56.6; H, 7.9%).
Experimental
Unless otherwise stated, all starting materials and reagents were
purchased from Aldrich and were used without further purifica-
tion. Bu3SnH was prepared as previously described40 and distilled
before use.
Ethyl 2-bromohept-6-enoate was prepared in identical fashion to
9 using diethyl 1-bromohex-5-en-1,1-dicarboxylate and isolated
as a◦ colourless oil after distillation (350 mg, 16%).%). Bp
Medium performance liquid chromatography (MPLC) was
performed using a Merck LiChroprep Si 60 (40–63 mm) column
fitted with a Waters R-403 differential refractometer detector.
Analytical GC experiments were performed on various capillary
columns purchased from SGE as detailed in the ESI‡ using a
Varian 6000 or Hewlett-Packard 3390A gas chromatograph fitted
with an HP 3390A integrator. Preparative GC was performed
using either a 20% SE-30 on Chromosorb W (80–100 mesh) or 3%
OV-17 on GC-Q (80–100 mesh) column.
1
~90 C/1.0 mmHg; H NMR d 5.6–6.1 (m, 1H), 4.9 –5.2 (m,
2H), 4.1–4.4 (m, 3H), 1.0–2.3 (m, 6H), 1.29 (t, J = 7 Hz, 3H); IR
(neat): 1740, 1640 cm-1; MS (CI) m/z (relative intensity) 166/168
(35), 155 (25). HRMS calcd. for C9H15BrO2 [M - Br]+ 155.1072,
found 155.1072.
2-Methoxyhept-6-enoic acid (17). Ethyl 2-bromohept-6-
enoate (300 mg, 1.28 mmol) was added to a solution of sodium
methoxide in methanol (prepared by adding dry methanol (10 mL)
to sodium hydroxide (180 mg, 7.5 mmol) with vigorous stirring)
and the mixture heated under reflux for 20 h. After cooling, the
resultant solution was poured into 10% hydrochloric acid (50 mL)
and the mixture extracted with ether (3¥). The combined extracts
were washed with brine, dried (MgSO4) and the solvent removed
in vacuo. The residue was distilled (Ku¨gelroh◦r) to give the title
acid as a colourless oil (185 mg, 91%). Bp ~80 C/0.4 mmHg; 1H
NMR d 10.3 (s, br, 1H), 5.7 –5.9 (m, 1H), 4.9–5.1 (m, 2H), 3.7–3.8
(m, 1H), 3.43 (2, 3H), 2.0–2.1 (m, 2H), 1.7–1.8 (m, 2H), 1.5–1.6
(m, 2H); 13C NMR d 178.1, 138.0, 114.9, 80.0, 58.2, 33.2, 31.9,
24.2; IR (neat): 3080 (br), 1720, 1640 cm-1. (Found: C, 60.7; H,
9.0. C9H15ClO4 requires C, 60.7; H, 8.9%).
Remaining instrumentation and general experimental methods
(etc.) are provided in full in previous publications.41
Experimental details for the preparation or isolation of product
standards are provided as part of the ESI.‡
Diethyl 1-chlorohex-5-en-1,1-dicarboxylate (16). Diethyl hex-
5-en-1,1-dicarboxylate26 (15) (3.0 g, 13.2 mmol) was added to
a suspension of sodium hydride (360 mg, 15.0 mmol) in DMF
(50 mL) and the mixture stirred under nitrogen until the evolution
of hydrogen has ceased (~20 min). N-Chlorosuccinimide (1.73 g,
12.9 mmol) was added and the mixture stirred for 45 min, after
which it was poured into water (250 mL), extracted with ether (3¥),
the combined extracts dried (MgSO4) and the solvent removed in
vacuo to give a brown oil. Excess DMF was removed by filtration
through a short silica column, eluted with dichloromethane. The
solvent was removed in vacuo and the residue distilled (Ku¨gelrohr)
to give the title ester as a colourless oil (2.8 g, 81%). Bp ~100
◦C/0.1 mmHg; 1H NMR d 5.4–6.1 (m, 1H), 4.7–5.3 (m, 2H), 4.23
(q, J = 8 Hz, 2H), 1.0–2.5 (m, 6H), 1.30 (t, J = 8 Hz, 6H); IR (neat):
1765, 1745, 1640 cm-1; MS (CI) m/z (relative intensity) 263/265
(74), 39 (100). (Found: C, 54.9; H, 7.3. C12H19ClO4 requires C,
54.9; H, 7.3%).
3-(2-Methoxyhept-6-enoyl)-4-methyl-(3H)-thiazole-2-thione
(10). 3-Hydroxy-4-methyl-(3H)-thiazole-2-thione (140 mg, 950
mmol), 2-methoxyhept-6-enoyl chloride (prepared from 2-
methoxyhept-6-enoic acid (17) (140 mg, 886 mmol) and thionyl
chloride (3 mL)), pyridine (100 mL) and 4-dimethylaminopyridine
(4 mg) were stirred in ether (5 mL) for 20 min. The precipitate was
filtered off and the solvent removed in vacuo. The residual green
oil was separated by flash chromatography (dichloromethane) to
afford the title thiohydroxamic ester as a pale oil (60 mg, 24%).
1H NMR d 6.28 (s, 1H), 5.7–5.9 (m, 1H), 4.9–5.1 (m, 2H), 4.1–4.3
(m, 1H), 3.55 (d, J = 4 Hz, 3H), 2.17 (s, 2H), 1.9–2.2 (m, 4H),
1.6–1.8 (m, 2H); 13C NMR d 168.3, 137.8, 136.6, 115.1, 106.7,
79.1, 58.9, 33.1, 32.3, 24.3, 13.3; MS m/z (relative intensity) 288
Diethyl 1-bromohex-5-en-1,1-dicarboxylate was prepared in
identical fashion to 16 using diethyl hex-5-en-1,1-dicarboxylate26
(15) (3.0 g, 13.2 mmol) and N-bromosuccinimide (2.30 g,
12.9 mmol). The title compound was isolated as a colourless oil
after distillation. Bp ~100 ◦C/0.1 mmHg; 1H NMR d 5.4–6.1 (m,
1H), 4.7–5.3 (m, 2H), 4.23 (q, J = 8 Hz, 2H), 1.0–2.5 (m, 6H), 1.30
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Org. Biomol. Chem., 2011, 9, 1736–1743 | 1741
©

(1), 261 (48), 214 (10), 132 (100). HRMS calcd. for C12H17NO3S2
[M + H]+ 288.0728, found 288.0728.
(m, 2H), 0.90 (t, J = 7.3 Hz, 3H); 13C NMR d 133.7 (Z), 134.9 (E),
126.0 (Z), 126.2 (E), 71.4 (Z), 71.9 (E), 66.7 (Z), 71.2 (E), 61.6,
29.6 (Z), 34.4 (E), 22.6 (Z), 22.3 (E), 13.7; IR (neat): 3420 (br),
1660 cm-1.
1,1,1-Trifluorohept-6-en-2-ol (18). Ethyl trifluoroacetate
(2.0 g, 14.1 mmol) in dry ether (5 mL) was added dropwise to
an ice-cooled, stirred solution of 4-pentenylmagnesium bromide
(prepared from magnesium (800 mg, 33 mmol), 5-bromopent-1-
ene (4.47 g, 30 mmol) in dry ether (10 mL)). The mixture was
heated at reflux for 1 h, then poured into 10% hydrochloric acid
(100 mL) and extracted with ether (3¥). The combined extracts
were washed with water (2¥), dried (MgSO4) and the solvent
removed in vacuo. The residue was distilled to give the title alcohol
(E)-1-Bromo-2-(2-hexen-1-oxy)ethane (13). Phosphorus tri-
bromide (220 mg, 820 mmol) was added to a solution of (E)-
2-(2-hexen-1-oxy)ethanol (E-19) (300 mg, 2.08 mmol) in ether
(10 mL). Pyridine (160 mL) was added and the mixture stirred
at r.t. overnight. The mixture was poured into 10% hydrochloric
acid (20 mL), extracted with pentane (2¥), the combined extracts
washed with satd. sodium bicarbonate, brine, dried (MgSO4) and
the solvent removed in vacuo. The brown residue was separated by
flash chromatography (40% pentane in dichloromethane) to give
◦
1
as a colourless oil (1.3 g, 56%). Bp = 145–147 C; H NMR d
5.4–6.2 (m, 1H), 4.7–5.2 (m, 2H), 3.6–4.2 (m, 1H), 2.36 (s, br,
1H), 1.3–2.3 (m, 6H); MS m/z (relative intensity) 168 (0.2), 150
(31), 54 (100). HRMS calcd. for C7H11F3O [M]+ 168.0762, found
168.0761.
1
the title compound as a colourless oil (65 mg, 38%). H NMR d
5.49–5.72 (m, 2H), 3.79–4.01 (m, 2H), 3.70–3.76 (m, 2H), 3.43–
3.49 (m, 2H), 1.97–2.10 (m, 2H), 1.34–1.49 (m, 2H), 0.91 (t, J =
7.3 Hz, 3H); 13C NMR d 135.5, 125.9, 71.9, 69.6, 34.3, 30.4, 22.2,
13.7; IR (neat): 1660 cm-1; MS m/z (relative intensity) 206/208
(2), 163/165 (63), 107/109 (100). HRMS calcd. for C8H1579BrO
[M]+ 206.0306, found 206.0299.
(Z)-1-Bromo-2-(2-hexen-1-oxy)ethane (14) was prepared in
identical fashion to 13 using (Z)-2-(2-hexen-1-oxy)ethanol (Z-19)
and isolated as a colourless oil (64 mg, 37%). 1H NMR d 5.49–5.71
(m, 2H), 4.09–4.12 (m, 1.6H), 3.79–4.01 (m, 0.4H), 3.68–3.77 (m,
2H), 3.44–3.49 (m, 2H), 1.95–2.13 (m, 2H), 1.32–1.50 (m, 2H),
0.91 (t, J = 7.3 Hz, 3H); 13C NMR d 134.1 (Z), 135.3 (E), 125.6
(Z), 125.9 (E), 69.8 (Z), 71.9 (E), 66.6 (Z), 69.6 (E), 29.6 (Z), 34.3
(E), 22.6 (Z), 22.2 (E), 13.7. HRMS calcd. for C8H1579BrO [M]+
206.0306, found 206.0295.
O-Phenyl-O-(1,1,1-trifluorohept-6-en-2-yl)thionocarbonate (11).
1,1,1-Trifluorohept-6-en-2-ol (18) (500 mg, 2.98 mmol) was dis-
solved in dichloromethane (15 mL) and pyridine (940 mg) added.
The reaction vessel was flushed with argon, phenylchloroth-
ionocarbonate (570 mg, 3.30 mmol) added, and the mixture
stirred at r.t. under argon overnight. The mixture was poured
into water (100 mL) and extracted with ethyl acetate (2¥). The
combined extracts were washed with 10% hydrochloric acid (4¥),
satd. sodium bicarbonate, brine, dried (MgSO4) and the solvent
removed in vacuo. The residue was separated by MPLC (40% ethyl
acetate: hexane) to give the title compound as a yellow oil (610 mg,
1
67%). H NMR d 6.9–7.6 (m, 5H), 5.4–6.2 (m, 2H), 4.8–5.2 (m,
2H), 1.2–2.4 (m, 6H); 13C NMR d 194.7, 153.6, 137.4, 126.9, 129.7,
121.7, 115.7, 123.6 (q, JCF = 183 Hz), 78.9 (q, JCF = 32 Hz), 33.3,
27.3, 23.6; MS m/z (relative intensity) 305 (100), 223 (9), 211 (8),
195 (8), 110 (38), 94 (95). HRMS calcd. for C14H15F3O2S [M + H]+
305.0823, found 305.0822.
(Z)-9-Tridecen-5-ol (22). (Z)-5-Nonen-1-ol42 (500 mg,
3.51 mmol), pyridinium dichromate (2.71 g, 7.2 mmol) and
˚
finely divided 4 A molecular sieves (2.4 g) were stirred in
dichloromethane (18 mL) for 3 h. The solution was filtered
through a short silica column eluted with dichloromethane. The
filtrate was collected and the solvent removed in vacuo to give crude
(Z)-5-nonenal. The crude aldehyde was added dropwise to an
ice-cooled solution of n-butylmagnesium bromide (prepared from
magnesium (80 mg, 3.23 mmol) and 1-bromobutane (390 mg,
2.85 mmol) in dry ether (5 mL)). The resultant solution was
heated under reflux for 1 h, then poured into 10% hydrochloric
acid (50 mL) and extracted with ether (3¥). The combined extracts
were dried (MgSO4) and the solvent removed in vacuo. The residue
was separated by MPLC (20% ethyl acetate in dichloromethane)
and further purified by Ku¨gelrohr distillation to give the title
alcohol as a colourless oil (260 mg, 92%). Bp ~ 120 ◦C/1.5 mmHg;
1H NMR d 5.33–5.39 (m, 2H), 3.48–3.62 (m, 1H), 1.94–2.10 (m,
(E)-2-(2-Hexen-1-oxy)ethanol (E-19). Dry ethane-1,2,-diol
(16 mL) was added to sodium hydride (454 mg, 19 mmol) with
vigorous stirring with the reaction vessel cooled in an ice bath.
When the evolution of hydrogen had ceased, (E)-1-bromo-2-
hexene (3.0 g, 18.0 mmol) was added and the solution stirred
at 100 ◦C overnight. After cooling, the residual ethane-1,2-diol
was removed by filtration through a short silica column eluted
with ethyl acetate. Removal of the solvent in vacuo afforded
a brown oil that was separated by MPLC (1 : 1 ethyl acetate–
dichloromethane). The third fraction proved to contain the title
compound which was further distilled to afford the product as a
◦
colourless oil (2.0 g, 75%). Bp ~ 130 C/40 mmHg (Ku¨gelrohr);
1H NMR d 5.48–5.78 (m, 2H), 3.97 (d, J = 5.9 Hz, 2H), 3.69–3.74
(m, 2H), 3.52 (t, J = 7.5 Hz, 2H), 3.21 (s, br, 1H), 1.97–2.08 (m,
2H), 1.32–1.46 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H); 13C NMR d
134.9, 126.2, 71.9, 71.2, 61.6, 34.4, 22.3, 13.7; IR (neat): 3420 (br),
1670 cm-1. (Found: C, 66.5; H, 11.0. C8H16O2 requires C, 66.6; H,
11.2%).
4H), 1.84 (s, br, 1H), 1.31–1.54 (m, 12H), 0.86–0.93 (m, 6H); 13
C
NMR d 130.1, 129.7, 71.9, 37.3, 37.1, 29.4, 27.9, 27.3, 25.8, 22.9,
22.8, 14.1, 13.8; IR (neat): 3340 (br), 1650 cm-1. HRMS calcd. for
C20H30O2S [M+H]+ 335.2045, found 335.2046.
(Z)-O-Phenyl-O-(9-tridecen-5-yl)thionocarbonate (12) was pre-
pared in identical fashion to 11 using (Z)-9-tridecen-5-ol (22)
(120 mg, 610 mmol) and phenylchlorothionocarbonate (123 mg,
710 mmol) and was isolated as a pale oil after flash chromatography
(20% dichloromethane in hexane) (150 mg, 74%). 1H NMR d 7.06–
7.42 (m, 5H), 5.28–5.49 (m, 3H), 1.99–2.14 (m, 4H), 1.31–1.80 (m,
12H), 0.86–0.94 (m, 6H); 13C NMR d 194.9, 153.5, 130.4, 129.2,
129.4, 126.3, 122.1, 85.5, 33.2, 33.1, 29.4, 27.3, 27.0, 25.2, 22.9,
(Z)-2-(2-Hexen-1-oxy)ethanol (Z-19) was prepared in identical
fashion to E-19 and isolated as a colourless oil (2.0 g, 75%) con-
taining 20% of the (E)-isomer (E-19) by 13C NMR spectroscopy.
◦
1
Bp ~ 130 C/40 mmHg (Ku¨gelrohr); H NMR d 5.45–5.80 (m,
2H), 4.05–4.10 (m, 1.6H), 3.95–4.00 (m, 0.4H), 3.65–3.80 (m, 2H),
3.45–3.60 (m, 2H), 3.05 (s, br, 1H), 1.95–2.10 (m, 2H), 1.30–1.50
1742 | Org. Biomol. Chem., 2011, 9, 1736–1743
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The Royal Society of Chemistry 2011
©

22.6, 14.0, 13.8; MS (CI) m/z (relative intensity) 355 (5), 248 (2),
231 (100), 198 (58). (Found: C, 78.7; H, 13.3. C8H16O2 requires C,
78.7; H, 13.2%).
4 M. Berthelot, La Synthe`se Chimique, Algave, Paris, 1887.
5 A. Wurtz, Justus Liebigs Ann. Chim., 1855, 96, 364.
6 D. H. Hey and W. A. Waters, Chem. Rev., 1937, 21, 169.
7 M. S. Karasch, E. T. Margolis and F. R. Mayo, J. Org. Chem., 1937, 2,
393.
Kinetic experiments. The sample, prepared as described below,
was thermolysed (T > 50 ◦C) or photolysed (T < 50 ◦C) at
constant temperature for times indicated in the ESI.‡ Thermolysis
was achieved by immersing the sample in a constant temperature
oil bath, while photolysis was achieved by irradiating the sample
with a 250 W mercury lamp at a distance of 20 cm while immersed
in a constant temperature water bath (or liquid ammonia bath
for temperatures of -33 ◦C). The sample mixtures were directly
analysed by gas chromatography (GC) using capillary columns
as detailed in the ESI.‡ Product identification was achieved by
direct GC comparison with standards prepared or isolated as de-
scribed in the ESI.‡ Suitable hydrocarbon internal standards were
incorporated into some reactions for the purpose of determining
product concentrations.
8 F. R. Mayo, F. M. Lewis and C. Walling, Discuss. Faraday Soc., 1947,
2, 285.
9 See: C. Walling, Free Radicals in Solution, Wiley, New York, 1957 and
refs. cited therein.
10 A. L. J. Beckwith and K. U. Ingold in Rearrangements in Ground and
Excited States, P. deMayo, ed., Academic Press, New York, 1980 and
refs. cited therein.
11 M. Julia, Acc. Chem. Res., 1971, 4, 386 and refs. cited therein.
12 For examples see: D. H. R. Barton and S. W. McCombie, J. Chem.
Soc., Perkin Trans. 1, 1975, 1574; D. H. R. Barton, D. Crich and W.
Motherwell, Tetrahedron, 1985, 41, 3901; D. H. R. Barton, D. Crich,
A. L
o¨bberding and S. Z. Zard, Tetrahedron, 1986, 42, 2329.
13 J.-M. Surzur in Reactive Intermediates, R. A. Abromovitch, ed., Plenum
Press, New York, 1982 and refs. cited therein.
14 A. G. Davies, Organotin Chemistry, Wiley-VCH, Weinheim, 1997 and
refs. cited therein.
15 For example see: H. Fischer, J. Am. Chem. Soc., 1986, 108, 3925.
16 For example of Giese Reaction see: B. Giese, Angew. Chem., Int. Ed.
Engl., 1985, 24, 553.
17 For example see: D. P. Curran and D. M. Rakiewicz, Tetrahedron, 1985,
41, 3943.
18 For example see: M. Newcomb, Tetrahedron, 1993, 49, 1151.
19 A. L. J. Beckwith, Tetrahedron, 1981, 37, 3073.
20 A comprehensive list of references for this period is impossible to
provide. See: B. Giese, Radicals in Organic Synthesis: Formation of
Carbon–Carbon Bonds, Pergamon Press, Oxford, 1986 and refs. cited
therein.
21 A. L. J. Beckwith and C. H. Schiesser, Tetrahedron, 1985, 41, 3925.
22 D. C. Spellmeyer and K. N. Houk, J. Org. Chem., 1987, 52, 959.
23 A. L. J. Beckwith, M. D. Cliff and C. H. Schiesser, Tetrahedron, 1992,
48, 4641 see also: J. C. Tripp, C. H. Schiesser and D. P. Curran, J. Am.
Chem. Soc., 2005, 127, 5518.
24 A. L. J. Beckwith and G. Moad, J. Chem. Soc., Chem. Commun., 1974,
472; A. L. J. Beckwith, V. W. Bowry and C. H. Schiesser, Tetrahedron,
1991, 47, 121; D. Dakternieks, D. J. Henry and C. H. Schiesser, J. Phys.
Org. Chem., 1999, 12, 233.
25 M. Newcomb, M. A. Filipkowski and C. C. Johnson, Tetrahedron Lett.,
1995, 36, 3643.
Standard Method A. Standard solutions of Bu3SnH in the
required solvent were prepared to concentrations detailed in the
ESI.‡ A pyrex tube was charged with the required solution (100
mL), the required radical precursor 9–14, 16 (~ 10 mol%) and a
crystal of AIBN added. The solution was frozen in liquid nitrogen
and the tube sealed under vacuum. After the solution had thawed,
the tube was heated or irradiated at the required temperature and
then analysed as described.
Standard Method B. Standard solutions were prepared as
described in Method A. A vial fitted with a septum inlet was
charged with the required solution (100 mL) and a crystal of AIBN
added. Deoxygenation was achieved by passing a slow stream of
nitrogen through the solution for 1–2 min. The vial was immersed
in the required constant temperature bath for 5 min. The required
radical precursor 13 or 14 was injected. After 5–10 min. the sample
was removed and analysed as described.
26 R. G. Salomon, D. J. Coughlin, S. Ghosh and M. G. Zagorski, J. Am.
Chem. Soc., 1982, 104, 998.
Standard Method C. Bu3SnH (1.0 equiv.) and the required
radical precursor 9 or 16 (1.05 equiv) were dissolved in benzene and
made up to concentrations as described in the ESI.‡ A pyrex tube
was charged with the required solution (200 mL) and a few crystals
of AIBN added. The solution was frozen in liquid nitrogen under
vacuum, thawed and then refrozen. The tube was sealed under vac-
uum, thawed, heated or irradiated and then analysed as described.
27 K. N. Campbell, J. O. Knobloch and K. B. Campbell, J. Am. Chem.
Soc., 1950, 72, 4380.
28 C. Chatgilialoglu, K. U. Ingold and J. C. Scaiano, J. Am. Chem. Soc.,
1981, 103, 7739.
29 C. C. Johnson, J. H. Horner, C. Tronche and M. Newcomb, J. Am.
Chem. Soc., 1995, 117, 1684.
30 M. Newcomb, J. H. Horner, M. A. Filipkowski, C Ha and S.-U. Park,
J. Am. Chem. Soc., 1995, 117, 3674.
31 V. Diart and B. P. Roberts, J. Chem. Soc., Perkin Trans. 2, 1992, 1761.
32 M. Julia and M. Maumy, Bull. Soc. Chim. Fr., 1969, 2415.
33 D. Crich, G. Daniel, K. Venkataramanan and P. Mitesh, Acc. Chem.
Res., 2007, 40, 453.
Acknowledgements
34 P. Schmidt and K. U. Ingold, J. Am. Chem. Soc., 1978, 100, 2493.
35 C. D. Nenitzescu and C. N. Ionescu, Justus Liebigs Ann. Chem., 1931,
491, 189.
36 H. C. Brown and V. Varma, J. Am. Chem. Soc., 1966, 88, 2871; M.-H.
Rei, J. Org. Chem., 1978, 43, 2173.
This work would not have been possible without the generous
support of the Australian National University. CHS acknowledges
the award of a Commonwealth Scholarship during the period
of this work. We also thank the Australian Research Council
through the Centres of Excellence Scheme for providing generous
funding to support free radical research in Australia in the post-
Renaissance period.
37 A. Ijima, H. Mizuno and K. Takahashi, Chem. Pharm. Bull., 1972, 20,
197.
38 A. L. J. Beckwith, I. A. Blair and G. Phillipou, Tetrahedron Lett., 1974,
15, 2251.
39 A. L. J. Beckwith and S. A. Glover, Aust. J. Chem., 1987, 40,
157.
40 G. J. M. Van der Kerk, J. G. Noltes and J. G. A. Luijten, J. Appl. Chem.,
References
1957, 366.
41 A. L. J. Beckwith, D. M. O’Shea and S. W. Westwood, J. Am. Chem.
Soc., 1988, 110, 2565; A. L. J. Beckwith, V. W. Bowry and G. Moad,
J. Org. Chem., 1988, 53, 1632.
42 G. Ohloff, C. Vial, F. Naef and M. Pawlak, Helv. Chim. Acta, 1977, 60,
1161.
1 F. O. Rice and K. K. Rice, The Aliphatic Free Radicals, Johns Hopkins
Press, Baltimore, 1935 and refs. cited therein.
2 M. Gomberg, J. Am. Chem. Soc., 1900, 22, 757.
3 See forewords in: P. Renaud and M. P. Sibi, Radicals in Organic
Synthesis Vols. 1 and 2, Wiley-VCH, Weinheim, 2001.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 1736–1743 | 1743
©