Absolute rate constants for hydrogen atom transfer from tertiary amides to the cumyloxyl radical: Evaluating the role of stereoelectronic effects

Article abstract of DOI:10.1021/jo5013459

A time-resolved kinetic study of the hydrogen atom transfer (HAT) reactions from a series of alkanamides to the cumyloxyl radical (CumO^?) was carried out. With N,N-dialkylformamides HAT preferentially occurs from the formyl C-H bond, while in N-formylpyrrolidine HAT mostly occurs from the ring α-C-H bonds. With the acetamides and the alkanamides almost exclusive HAT from the C-H bonds that are α to nitrogen was observed. The results obtained show that alignment between the C-H bond being broken and the amide π-system can lead to significant increases in the HAT rate constant (k _H). This finding points toward the important role of stereoelectronic effects on the HAT reactivity and selectivity. The highest k_H values were measured for the reactions of CumO^? with N-acylpyrrolidines. These substrates have ring α-C-H bonds that are held in a conformation that is optimally aligned with the amide π-system, thus allowing for the relatively facile HAT reaction. The lowest k_H value was measured for the reaction of N,N-diisobutylacetamide, wherein the steric bulk associated with the N-isobutyl groups increases the energy barrier required to reach the most suitable conformation for HAT. The experimental results are well supported by the computed BDEs for the C-H bonds of the most representative substrates.

Full text of DOI:10.1021/jo5013459

Article
pubs.acs.org/joc
Absolute Rate Constants for Hydrogen Atom Transfer from Tertiary
Amides to the Cumyloxyl Radical: Evaluating the Role of
Stereoelectronic Effects
Michela Salamone, Michela Milan, Gino A. DiLabio, and Massimo Bietti*,†
†
†
‡,§
†
Dipartimento di Scienze e Tecnologie Chimiche, Universita
̀
“Tor Vergata”, Via della Ricerca Scientifica 1, I-00133 Rome, Italy
National Institute for Nanotechnology, National Research Council of Canada, 11421 Saskatchewan Drive, Edmonton, Alberta,
Canada T6G 2M9
‡
§
Department of Chemistry, University of British Columbia, Okanagan, 3333 University Way, Kelowna, British Columbia, Canada V1
V 1 V7
*
S Supporting Information
ABSTRACT: A time-resolved kinetic study of the hydrogen atom transfer (HAT)
•
reactions from a series of alkanamides to the cumyloxyl radical (CumO ) was carried
out. With N,N-dialkylformamides HAT preferentially occurs from the formyl C−H
bond, while in N-formylpyrrolidine HAT mostly occurs from the ring α-C−H bonds.
With the acetamides and the alkanamides almost exclusive HAT from the C−H bonds
that are α to nitrogen was observed. The results obtained show that alignment between
the C−H bond being broken and the amide π-system can lead to significant increases in
the HAT rate constant (k ). This finding points toward the important role of
H
stereoelectronic effects on the HAT reactivity and selectivity. The highest k values
H
•
were measured for the reactions of CumO with N-acylpyrrolidines. These substrates
have ring α-C−H bonds that are held in a conformation that is optimally aligned with the amide π-system, thus allowing for the
relatively facile HAT reaction. The lowest k value was measured for the reaction of N,N-diisobutylacetamide, wherein the steric
H
bulk associated with the N-isobutyl groups increases the energy barrier required to reach the most suitable conformation for
HAT. The experimental results are well supported by the computed BDEs for the C−H bonds of the most representative
substrates.
INTRODUCTION
Scheme 1
■
Hydrogen atom transfer (HAT) reactions to reactive oxygen-
centered radicals such as alkoxyls have attracted considerable
interest, and several aspects of these reactions have been
1
−8
studied in detail.
Among these studies, the role of structural
and medium effects on the HAT reactivity of alkoxyl radicals
9
−14
15−19
toward amines,
carbons
phenols,
has been examined. However, limited information
is presently available on the reactivity of alkoxyl radicals toward
and ethers and hydro-
2
0−27
In this study, information on the HAT selectivity was also
•
provided, showing in particular that HAT to CumO occurs
2
8
amides, despite the great importance of this class of
compounds. Amides are widely used as solvents for a variety
of purposes and are often taken as simple models for peptide
bonds in proteins and polypeptides. Moreover, HAT reactions
from amides to alkoxyl radicals are currently being employed in
an increasing number of synthetically useful C−H functional-
from both the formyl and N-methyl C−H bonds of DMF
(Scheme 1), with the formyl being the preferred abstraction
•
site. The reaction of CumO with DMA results in preferential
HAT from the N-methyl groups, with HAT from the acetyl
group occurring as a minor pathway.
Another aspect of interest is the possible role of stereo-
electronic effects in HAT reactions from amides. Stereo-
electronic effects have been studied in detail for HAT from the
α-C−H bonds of amines and ethers to alkoxyl radi-
29−40
ization procedures.
In order to obtain information on the role of structural
effects on these reactions, we recently carried out a detailed
time-resolved kinetic study in acetonitrile solution on the
reactions of alkoxyl radicals with N,N-dimethylformamide
12−14,25−27,42
cals.
These studies reveal that the reaction is
most rapid when the α-C−H bond being broken is eclipsed
with the heteroatom lone pair. This eclipsing allows for the
41
(
DMF) and N,N-dimethylacetamide (DMA). This work led
to a description of the reactions of the cumyloxyl radical
•
•
(
PhC(CH ) O , CumO ) with DMF and DMA in terms of the
Received: June 17, 2014
Published: July 10, 2014
3
2
direct HAT mechanism shown in Scheme 1 for DMF.
©
2014 American Chemical Society
7179
dx.doi.org/10.1021/jo5013459 | J. Org. Chem. 2014, 79, 7179−7184

The Journal of Organic Chemistry
Article
optimal orbital overlap required to impart the greatest amount
of stabilization through the delocalization of the developing
excess spin on the carbon center from which the hydrogen
atom is transferred. The time-resolved kinetic studies therefore
provide quantitative information on the role played by
stereoelectronic effects in these reactions. Despite this fact,
limited information is available on the role of stereoelectronic
effects on HAT from amides to alkoxyl radicals; to the best of
our knowledge, there is only one kinetic study that deals with
The results of these studies were rationalized on the basis of
the favorable alignment between the ring C−H bonds and the
47
nitrogen lone pair orbital and clearly show that in the
reactions of amides stereoelectronic effects can strongly
influence both the HAT reactivity and selectivity.
Within this framework, we have extended our recent time-
resolved kinetic study in acetonitrile solution on the reactions
•
of CumO with DMF and DMA to the reactions of this radical
with a wide variety of tertiary amides, namely N,N-
diethylformamide (DEF), N,N-diethylacetamide (DEA), N,N-
diisobutylacetamide (DIA), N-formylpyrrolidine (FPRD), N-
acetylpyrrolidine (APRD), N-acetylpiperidine (APPD), N-(2,2-
dimethylpropanoyl)pyrrolidine (PvPRD), N,N-dimethylpropa-
namide (DMP), N,N,2-trimethylpropanamide (TrMP),
N,N,2,2-tetramethylpropanamide (TMP), and N,N,3,3-tetrame-
thylbutanamide (TMB), whose structures are displayed in
Chart 1, with the goal of uncovering the role of substrate
structure and of stereoelectronic effects on these reactions.
43
such effects, and it involves an aminoxyl radical (see below).
The operation of stereoelectronic effects has been proposed in
order to account for the peculiar inter- and intramolecular
selectivities observed in HAT reactions from amides and
lactams to a variety of hydrogen-abstracting species. For
example, in product studies of the reactions of 1-methyl-2-
4
4
pyrrolidone and other lactams with the tert-butoxyl radical,
45
the ethyl radical, and photoexcited tetrabutylammonium
decatungstate, preferential formation of products derived
4
6
from HAT from the ring C−H bonds adjacent to nitrogen
(
Scheme 2, a) as compared to the exocyclic methyl C−H
RESULTS
■
•
CumO was generated by 266 nm laser flash photolysis (LFP)
of nitrogen-saturated acetonitrile solutions (T = 25 °C)
containing dicumyl peroxide, as described in eq 1.
Scheme 2
In acetonitrile solution, CumO• is characterized by an
absorption band in the visible region of the spectrum centered
bonds (Scheme 2, b) was observed, as quantified by the
product ratios derived from the two competitive pathways that
are between 6 and 13.
48−50
at 485 nm,
and its main decay pathway is represented by
24,49
C−CH β scission.
In a kinetic study of the reactions of the benzotriazole-N-oxyl
3
43
•
Time-resolved kinetic studies of the reactions of CumO
radical (BTNO) with acetamides, significantly higher rate
with the amides shown in Chart 1 were carried out by LFP
constants for HAT (k ) from the benzylic C−H bonds α to
H
•
following the decay of the CumO visible absorption band as a
nitrogen were measured for N-acetyltetrahydroisoquinoline in
comparison to N-benzylacetamide (Scheme 3).
function of the amide concentration. The observed rate
constants (k ) gave excellent linear relationships when plotted
obs
against substrate concentration, and the second-order rate
Scheme 3
•
constants for HAT from the amides to CumO (k ) were
H
obtained from the slope of these plots. As an example, Figure 1
•
shows the kobs vs [substrate] plots for the reactions of CumO
with APRD (filled circles) and DIA (open circles) for
measurements carried out in acetonitrile at T = 25 °C.
•
Additional plots for HAT from the other amides to CumO
are displayed in the Supporting Information (Figures S1−S9).
Chart 1
7
180
dx.doi.org/10.1021/jo5013459 | J. Org. Chem. 2014, 79, 7179−7184

The Journal of Organic Chemistry
Article
53
approach, as described previously5. In some cases, the CBS-
4
QB3 composite ab initio approach was also used. Calculations
were generally performed using the Gaussian-09 program
55
package. In some cases, the Gaussian-03 package was used.
The calculated BDEs for the different C−H bonds of these
substrates are displayed in Table 2, together with the previously
41
calculated values for DMF and DMA.
Table 2. Calculated Bond Dissociation Enthalpies (BDEs)
−1
for the C−H Bonds of Tertiary Amides (kcal mol )
CBS-
QB3
a
molecule
bond
B3P86
b
HCON(CH3)2 (DMF)
H−CO
94.7
93.6
93.8
94.3
91.5
92.3
93.9
90.1
90.5
99.3
91.8
93.9
98.8
91.0
93.0
98.8
89.6
91.0
98.8
91.5
93.6
95.0
94.7
94.8
α-C−H (trans)
α-C−H (cis)
H−CO
α-C−H (trans)
α-C−H (cis)
H−CO
HCON(CH CH ) (DEF)
2
3 2
Figure 1. Plots of the observed rate constant (kobs) against [substrate]
•
for the reactions of the cumyloxyl radical (CumO ) with N-
acetylpyrrolidine (APRD, filled circles) and N,N-diisobutylacetamide
HCON(CH
)
2
4
(FPRD)
(
DIA, open circles), measured in nitrogen-saturated MeCN solution at
α-C−H (trans)
α-C−H (cis)
•
T = 25 °C by following the decay of CumO at 490 nm. From the
linear regression analysis the following values are obtained: CumO +
APRD, intercept 7.24 × 10 s , k = 9.24 × 10 M s , r = 0.9965;
CumO + DIA, intercept 7.21 × 10 s , k = 3.12 × 10 M s , r =
0
•
b
2
CH CON(CH ) (DMA)
H−CH CO
99.6
92.5
94.1
3
3
2
5
−1
6
−1 −1
2
H
α-C−H (trans)
α-C−H (cis)
•
5
−1
5
−1 −1
2
H
.9915.
CH CON(CH CH ) (DEA)
H−CH CO
3
2
3
2
2
α-C−H (trans)
α-C−H (cis)
All of the kinetic data thus obtained are collected in Table 1.
Also included in this table are the kH values measured
CH CON(CH ) (APRD)
H−CH CO
3
2
4
2
•
41
previously for the reactions of CumO with DMF and DMA.
α-C−H (trans)
α-C−H (cis)
In order to provide a better understanding of the HAT
•
selectivity observed in the reactions of CumO with the tertiary
CH CON[CH CH(CH ) ] (DIA)
H−CH CO
99.1
93.0
94.8
3
2
3
2
2
amides displayed in Chart 1 (see below), we calculated the
bond dissociation enthalpies (BDEs) for the C−H bonds of
DEF, FPRD, DEA, DIA, and APRD. The BDEs were computed
α-C−H (trans)
α-C−H (cis)
a
5
1,52
cis and trans refer to the stereochemical relationship between the
using the B3P86
/6-311G(2d,2p) density functional theory
carbonyl group and an N-alkyl group (in DMF, DEF, DMA, DE,A and
DIA) or an α-CH moiety of the pyrrolidine ring (in FPRD and
APRD). Reference 41.
2
b
Table 1. Second-Order Rate Constants (k ) for the
Reactions of the Cumyloxyl Radical (CumO ) with Tertiary
H
•
Amides
k /M− s−1
1
a
H
DISCUSSION
■
Formamides
Acetamides
With the formamide series as a starting point, identical rate
constants were measured for DMF and DEF, and a 4-fold
b
(1.24 ± 0.02) × 106
(1.25 ± 0.02) × 10
(4.93 ± 0.02) × 106
DMF
DEF
6
increase in k was observed on going from these two amides to
H
FPRD
N-formylpyrrolidine (FPRD). In the acetamide and alkanamide
series, ∼2- and 4-fold decreases in k were observed on going
from DMA to DEA and DIA, respectively, whereas very small
H
b
(1.24 ± 0.03) × 106
DMA
DEA
5
(6.64 ± 0.07) × 10
increases in k were observed on going from DMA to DMP,
H
5
DIA
(3.14 ± 0.02) × 10
TrMP, TMP, and TMB (i.e., by replacing the acetyl methyl
group of DMA with ethyl, isopropyl, tert-butyl, and neopentyl
groups, respectively). Within the last two series, significant
6
APRD
APPD
(9.0 ± 0.2) × 10
(3.17 ± 0.02) × 106
Alkanamides
increases in k were observed on going from the acyclic amides
H
DMP
TrMP
TMP
(1.55 ± 0.05) × 106
(1.69 ± 0.08) × 106
to the N-acylpyrrolidines and piperidines (APRD, PvPRD, and
APPD), with an increase in k that approaches a factor of 30
6
H
(1.41 ± 0.06) × 10
(1.6 ± 0.1) × 10
5
−1 −1
when the least reactive amide (DIA, k = 3.14 × 10 M s ) is
6
H
TMB
6
compared with the most reactive one (APRD, k = 9.0 × 10
H
PvPRD
(5.17 ± 0.02) × 106
−1 −1
M
s ).
a
Our previous findings on the selectivity of the reaction
between CumO and DMA, combined with the observation
Measured in N -saturated acetonitrile solution at T = 25 °C
2
•
41
employing 266 nm LFP: [dicumyl peroxide] = 10 mM. k values were
determined from the slope of the kobs vs [substrate] plots, where in
turn kobs values were measured following the decay of the CumO
visible absorption band at 490 nm. Average of at least two
H
that the C−H bonds of tert-butyl groups display an extremely
56
•
low reactivity toward alkoxyl radicals, indicate that HAT from
•
TMP to CumO occurs almost exclusively from the N-methyl
b
determinations. Reference 41.
groups. Accordingly, the very similar k values measured for
H
7
181
dx.doi.org/10.1021/jo5013459 | J. Org. Chem. 2014, 79, 7179−7184

The Journal of Organic Chemistry
Article
DMA, DMP, TrMP, TMP, and TMB point toward the N-
methyl groups of these substrates as the preferred sites for
HAT.
increased BDEs are found on going from APRD to DEA and
DMA. A similar explanation can be put forward to explain the
increase in k observed on going from DMA, DEA, and DIA to
H
On the basis of these observations, and of the calculated
BDEs for DMA, DEA, and DIA which indicate that the C−H
bonds adjacent to the carbonyl group are at least 5 kcal mol−
stronger than the α-C−H bonds of the N-alkyl groups, it can be
APPD, where, however, the ∼3-fold decrease in k observed on
H
going from APRD to APPD reasonably reflects the role of the
chairlike conformation of the piperidine ring in APPD where, in
comparison to APRD, optimal overlap with the amide π-system
can be achieved only for the two axial α-C−H bonds.
1
concluded that also the k values measured for the reactions of
H
•
CumO with DEA and DIA mostly reflect HAT from the latter
As pointed out in our previous study on the reaction of
•
41
bonds. On the basis of this observation, the decrease in kH
measured on going from DMA to DEA and DIA, despite the
corresponding decrease in the N-alkyl α-C−H BDE and the
different numbers of abstractable hydrogen atoms (6 for DMA
and 4 for DEA and DIA, respectively), points toward the
operation of stereoelectronic effects. The observed decrease in
kH can be accounted for by the increase in steric bulk associated
with the replacement of the N-methyl groups in DMA with
ethyl and isobutyl groups that reduces the accessibility of the
CumO with DMA in acetonitrile solution, HAT preferen-
tially occurs from the N-methyl group that is in a trans
relationship to the carbonyl group. This result is in line with the
2.1 kcal mol− lower BDE value calculated for the α-C−H
bonds of the trans N-methyl group in comparison to those of
the group in the cis arrangement. The similar differences in the
BDEs for the trans and cis α-C−H bonds of DEA, DIA, and the
1
−1
N-methylene groups of APRD (between 1.4 and 2.1 kcal mol ;
see Table 2) suggest that also HAT involving these substrates
preferentially occurs from the C−H bonds of the methylene
group that is in a trans relationship to the carbonyl group.
•
abstractable hydrogen atoms to CumO . The bulkier groups
will also have associated with them larger rotational barriers
separating the molecules from the most suitable conformation
for HAT, where optimal overlap between the α-C−H bond and
the amide π-system can be achieved.
Along this line, the ca. 2-fold decrease in k measured on going
H
from APRD to PvPRD can be explained on the basis of steric
effects, where the presence of the bulky tert-butyl group limits
•
The up to 30-fold increase in k observed on going from
the accessibility to CumO of the α-C−H bonds of the trans N-
H
DMA, DEA, and DIA to APRD and from TMP to PvPRD can
be explained using similar arguments on the basis of orbital
overlap. In APRD and PvPRD, the four pyrrolidine α-C−H
bonds are held in a conformation that allows for weakening of
these bonds through the overlap of the C−H antibonding
orbital with the delocalized amide π-system. This conformation
similarly allows for favorable overlap between the developing p
orbital nominally containing the unpaired electron and the
amide π-system. These orbital interactions, which are illustrated
in Figure 2, provide a significant kinetic advantage for HAT in
comparison to the corresponding acyclic N,N-dialkylamides,
where similar orbital overlaps are not maintained by a rigid
molecular structure. The calculated α-C−H BDEs (Table 2)
support the role of orbital overlap in these systems, where
methylene group.
As mentioned previously, HAT from DMF to CumO occurs
•
from both the formyl and N-methyl C−H bonds (see Scheme
41
1), with the formyl being the preferred abstraction site. When
the decrease in k observed on going from DMA to DEA,
H
which largely reflects HAT from the α-C−H bonds of the N-
alkyl groups, is taken into account, a similar decrease in
reactivity should also be observed for HAT from the α-C−H
bonds of the N-alkyl groups on going from DMF to DEF. The
•
almost identical k
with DMF and DEF (k
values measured for the reactions of CumO
H
6
6
−1 −1
= 1.24 × 10 and 1.25 × 10 M s ,
H
respectively) are indicative of an increase in the rate constant
for HAT from the formyl C−H bond on going from DMF to
DEF. This behavior is consistent with the electrophilic
7
character of alkoxyl radicals and with the electron-releasing
character of the dialkylamino group that increases on going
5
7,58
from DMF to DEF
effects in these reactions.
and points toward the role of polar
The increase in k observed on going from DMF and DEF
H
to FPRD can be explained by the operation of stereoelectronic
effects, where orbital overlaps between the four pyrrolidine α-
C−H bonds and the amide π-system analogous to those
illustrated in Figure 2 make HAT from these bonds the
preferred reaction pathway. This is again consistent with the
calculated α-C−H BDEs (Table 2) that are between 1 and 3
kcal mol− lower than those measured for the α-C−H bonds of
the N-alkyl groups of DMF and DEF.
1
Calculations were also performed to assess the magnitude of
the barrier heights associated with HAT from the α-C−H
•
bonds of DEA, DIA, and APRD to CumO . Transition states
5
9
Figure 2. Selected natural orbitals for N-acetylpyrrolidine (APRD)
a, b) and the associated carbon centered radical (c, d). For the sake of
were verified through the vibration frequency analysis, which
showed in all cases a single imaginary mode that connects
reactants to products. Gas-phase free-energy barriers with
(
clarity, the orbitals shown in a and c represent the nitrogen p-type
orbital that is part of the delocalized amide bond. The obital shown in
b represents an APRD C−H antibonding orbital, and the orbital in d
represents the carbon p-type orbital of the radical. The relative phases
of the orbitals are shown with different colors. The interactions
between the N and C centers within the molecular and radical species
can be understood by envisioning the overlap of the orbitals in a and b
and the orbitals in c and d.
respect to infinitely separated reactants were computed to be
1
1
2.6 and 15.0 kcal mol− for DEA and DIA, respectively.
Despite being too high in consideration of the measured rate
constants, these results support the notion that steric repulsion
plays a relatively larger role in the reaction involving DIA. The
gas-phase free energy barrier for the reaction involving APRD is
7
182
dx.doi.org/10.1021/jo5013459 | J. Org. Chem. 2014, 79, 7179−7184

The Journal of Organic Chemistry
Article
−
1
instead 7.6 kcal mol , which is consistent with the favorable
alignment of the α-C−H from which the hydrogen atom is
being transferred with the amide bond π-orbital, thus
supporting the important role played by stereoelectronic effects
in these reactions.
the calculations. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail for M.B.: bietti@uniroma2.it.
In conclusion, detailed information on the role of structural
effects on HAT reactions from tertiary amides to CumO has
•
Notes
been provided by means of time-resolved kinetic and
computational studies. The results show that optimal orbital
overlap between the C−H antibonds in the molecule and p-
type orbitals in the corresponding carbon-centered radicals that
are α to nitrogen and the amide π-system determines a
significant kinetic advantage for HAT. Accordingly, the highest
kH values have been measured for HAT from N-acylpyrroli-
dines, substrates for which the pyrrolidine α-C−H bonds are
held in a conformation that allows optimal overlap between
these bonds and the delocalized amide π-system, whereas, in
the acetamide series, a decrease in kH with increasing
substitution at the α-carbon has been observed. These results
provide a quantitative evaluation of the role played by
stereoelectronic effects in these reactions, showing moreover
that these effects can influence both the HAT reactivity and
selectivity. The implications of these findings and the possible
exploitation of the observed effects in synthetically useful
procedures are currently under investigation in our laboratory.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the Ministero dell’Istruzione dell’Uni-
versita
̀
e della Ricerca (MIUR), project 2010PFLRJR (PRIN
2010-2011), is gratefully acknowledged. We thank Prof.
Lorenzo Stella for the use of LFP equipment. We are grateful
to Westgrid for access to computational resources.
REFERENCES
■
(
1) Halliwell, B.; Gutteridge, J. M. C. Free Radicals in Biology and
Medicine, 4th ed.; Oxford University Press: Oxford, U.K., 2007.
(2) (a) Salamone, M.; Giammarioli, I.; Bietti, M. Chem. Sci. 2013, 4,
3
255−3262. (b) Salamone, M.; Mangiacapra, L.; DiLabio, G. A.; Bietti,
M. J. Am. Chem. Soc. 2013, 135, 415−423. (c) Salamone, M.;
Giammarioli, I.; Bietti, M. J. Org. Chem. 2011, 76, 4645−4651.
(3) Kawashima, T.; Ohkubo, K.; Fukuzumi, S. J. Phys. Chem. B 2010,
1
14, 675−680.
EXPERIMENTAL SECTION
(4) Cosa, G.; Scaiano, J. C. Org. Biomol. Chem. 2008, 6, 4609−4614.
■
(
(
5) Litwinienko, G.; Ingold, K. U. Acc. Chem. Res. 2007, 40, 222−230.
Materials. Spectroscopic grade acetonitrile was used in the kinetic
experiments. Dicumyl peroxide was of the highest commercial quality
available and was used as received. N,N-Diethylformamide (DEF), N-
formylpyrrolidine (FPRD), N,N-diethylacetamide (DEA), N,N-dime-
thylpropanamide (DMP), and N,N,2-trimethylpropanamide (TrMP)
were of the highest commercial quality available and were used as
6) Orlando, J. J.; Tyndall, G. S.; Wallington, T. J. Chem. Rev. 2003,
1
(
(
(
03, 4657−4689.
7) Roberts, B. P. Chem. Soc. Rev. 1999, 28, 25−35.
8) Weber, M.; Fischer, H. J. Am. Chem. Soc. 1999, 121, 7381−7388.
9) Bietti, M.; Salamone, M. Org. Lett. 2010, 12, 3654−3657.
6
0
(10) Suleman, N. K.; Flores, J.; Tanko, J. M.; Isin, E. M.; Castagnoli,
received. N,N-Diisobutylacetamide (DIA), N-acetylpyrrolidine
61
61
N., Jr. Bioorg. Med. Chem. 2008, 16, 8557−8562.
(11) Lalevee, J.; Graff, B.; Allonas, X.; Fouassier, J. P. J. Phys. Chem. A
́
(
APRD), N-acetylpiperidine (APPD), N,N,2,2-tetramethylpropa-
62 63
namide (TMP), N,N,3,3-tetramethylbutanamide (TMB), and N-
64
2007, 111, 6991−6998.
12) Finn, M.; Friedline, R.; Suleman, N. K.; Wohl, C. J.; Tanko, J.
M. J. Am. Chem. Soc. 2004, 126, 7578−7584.
13) Pischel, U.; Nau, W. M. J. Am. Chem. Soc. 2001, 123, 9727−
737.
14) Griller, D.; Howard, J. A.; Marriott, P. R.; Scaiano, J. C. J. Am.
Chem. Soc. 1981, 103, 619−623.
15) Bietti, M.; Salamone, M.; DiLabio, G. A.; Jockusch, S.; Turro, N.
J. J. Org. Chem. 2012, 77, 1267−1272.
16) Correia, C. F.; Borges dos Santos, R. M.; Estac
P.; Costa Cabral, B. J.; Martinho Simoes, J. A. ChemPhysChem 2004, 5,
217−1221.
17) Snelgrove, D. W.; Lusztyk, J.; Banks, J. T.; Mulder, P.; Ingold, K.
U. J. Am. Chem. Soc. 2001, 123, 469−477.
18) MacFaul, P. A.; Ingold, K. U.; Lusztyk, J. J. Org. Chem. 1996, 61,
316−1321.
19) Das, P. K.; Encinas, M. V.; Steenken, S.; Scaiano, J. C. J. Am.
Chem. Soc. 1981, 103, 4162−4166.
20) Bietti, M.; Martella, R.; Salamone, M. Org. Lett. 2011, 13, 6110−
113.
(
2,2-dimethylpropanoyl)pyrrolidine (PvPRD) were synthesized by
(
reaction of the pertinent acyl chloride (acetyl chloride, 2,2-
dimethylpropanoyl chloride, or 3,3-dimethylbutanoyl chloride) with
a 2-fold excess of the secondary amine (pyrrolidine, piperidine,
diisobutylamide, and dimethylamine). In all cases the product was
purified by flash chromatography (silica gel, eluent dichloromethane or
(
9
(
1
dichloromethane/methanol 50/1) and identified by H NMR
(
(
Supporting Information, Figures S10−S15).
Laser Flash Photolysis Studies. LFP experiments were carried
(
́
io, S. G.; Telo, J.
out with a laser kinetic spectrometer using the fourth harmonic (266
nm) of a Q-switched Nd:YAG laser, delivering 8 ns pulses. The laser
energy was adjusted to ≤10 mJ/pulse by the use of the appropriate
filter. A 3.5 mL Suprasil quartz cell (10 mm × 10 mm) was used in all
experiments. Nitrogen-saturated acetonitrile solutions of dicumyl
peroxide (10 mM) were employed. All of the experiments were
carried out at T = 25 ± 0.5 °C with magnetic stirring. The observed
rate constants (kobs) were obtained by averaging three to five
individual values and were reproducible to within 5%.
̃
1
(
(
1
(
(
6
Second-order rate constants for the reactions of the cumyloxyl
radical with the amides were obtained from the slopes of the kobs
(
21) Koner, A. L.; Pischel, U.; Nau, W. M. Org. Lett. 2007, 9, 2899−
(
measured following the decay of the cumyloxyl radical visible
absorption band at 490 nm) vs [amide] plots. Fresh solutions were
used for every amide concentration. Correlation coefficients were in all
cases >0.99. The rate constants displayed in Table 1 are the average of
at least two independent experiments, typical errors being ≤10%.
2902.
(22) Camara, S.; Gilbert, B. C.; Meier, R. J.; van Duin, M.;
Whitwood, A. C. Org. Biomol. Chem. 2003, 1, 1181−1190.
(23) MacFaul, P. A.; Arends, I. W. C. E.; Ingold, K. U.; Wayner, D. D.
M. J. Chem. Soc., Perkin Trans. 2 1997, 135−145.
(24) Avila, D. V.; Brown, C. E.; Ingold, K. U.; Lusztyk, J. J. Am. Chem.
ASSOCIATED CONTENT
Supporting Information
■
Soc. 1993, 115, 466−470.
*
S
(
25) Malatesta, V.; Scaiano, J. C. J. Org. Chem. 1982, 47, 1455−1459.
Figures and tables giving plots of k vs substrate concentration
(26) Beckwith, A. L. J.; Easton, C. J. J. Am. Chem. Soc. 1981, 103,
obs
•
1
for the reactions of CumO , H NMR spectra, and details of
615−619.
7
183
dx.doi.org/10.1021/jo5013459 | J. Org. Chem. 2014, 79, 7179−7184

The Journal of Organic Chemistry
Article
(
6
(
27) Malatesta, V.; Ingold, K. U. J. Am. Chem. Soc. 1981, 103, 609−
14.
28) Chatgilialoglu, C.; Lunazzi, L.; Macciantelli, D.; Placucci, G. J.
Am. Chem. Soc. 1984, 106, 5252−5256.
29) Wang, R.; Liu, H.; Yue, L.; Zhang, X.-K.; Tan, Q.-Y.; Pan, R.-L.
Tetrahedron Lett. 2014, 55, 2233−2237.
30) Sun, M.; Zhang, T.; Bao, W. Tetrahedron Lett. 2014, 55, 893−
96.
31) (a) Sathish Kumar, G.; Arun Kumar, R.; Santhosh Kumar, P.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,
N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
(
̈
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.;
(
8
(
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09,
Revision D.01; Gaussian, Inc., Wallingford, CT, 2009.
4
−1
(56) As an example, the rate constant k
= 3.9 × 10 M s−1 has
H
Veera Reddy, N.; Vijaya Kumar, K.; Lakshmi Kantam, M.; Prabhakar,
S.; Rajender Reddy, K. Chem. Commun. 2013, 49, 6686−6688.
b) Santhosh Kumar, P.; Sathish Kumar, G.; Arun Kumar, R.; Veera
Reddy, N.; Rajender Reddy, K. Eur. J. Org. Chem. 2013, 1218−1222.
(
been measured for HAT from tert-butylbenzene to the tert-butoxyl
8
radical.
(
(57) An increase in Lewis basicity is observed on going from DMF to
DEF, as measured by Gutmann’s donor numbers (DN), defined as the
32) (a) Li, D.; Liu, J.; Zhao, Q.; Wang, L. Chem. Commun. 2013, 49,
negative ΔH values for 1:1 adduct formation between SbCl
5
and
3
2
640−3642. (b) Zhang, X.; Wang, M.; Zhang, Y.; Wang, L. RSC Adv.
donor solvents in the noncoordinating solvent 1,2-dichloroethane. DN
−1
58
=
26.6 and 30.9 kcal mol for DMF and DEF, respectively.
58) Reichardt, C.; Welton, T. Solvents and Solvent Effects in Organic
Chemistry, 4th ed.; Wiley-VCH: Weinheim, Germany, 2010.
013, 3, 1311−1316. (c) He, T.; Li, H.; Li, P.; Wang, L. Chem.
(
Commun. 2011, 47, 8946−8948.
(
4
(
1
33) Wang, H.; Guo, L.-N.; Duan, X.-H. Org. Biomol. Chem. 2013, 11,
573−4576.
34) Li, X.; Li, B.; You, J.; Lan, J. Org. Biomol. Chem. 2013, 11, 1925−
928.
(
59) Reed, A. E.; Weinhold, F. J. Chem. Phys. 1985, 83, 1736−1740.
(60) Reis, A. K. C. A.; Rittner, R. Spectrochim. Acta, Part A 2007, 66,
6
(
81−685.
61) Vokkaliga, S.; Jeong, J.; LaCourse, W. R.; Kalivretenos, A.
Tetrahedron Lett. 2011, 52, 2722−2724.
62) Clayden, J.; Watson, D. W.; Chambers, M. Tetrahedron 2005,
1, 3195−3203.
63) Pine, S. H.; Catto, B. A.; Yamagishi, F. G. J. Org. Chem. 1970,
5, 3663−3666.
64) Rao, Y.; Li, X.; Danishefsky, S. J. J. Am. Chem. Soc. 2009, 131,
2924−12926.
(
(
35) Ding, S.; Jiao, N. Angew. Chem., Int. Ed. 2012, 51, 9226−9237.
36) Yan, Y.; Zhang, Y.; Feng, C.; Zha, Z.; Wang, Z. Angew. Chem.,
(
6
(
3
(
1
Int. Ed. 2012, 51, 8077−8081.
(
(
37) Xia, Q.; Chen, W. J. Org. Chem. 2012, 77, 9366−9373.
38) Mai, W.-P.; Wang, H.-H.; Li, Z.-C.; Yuan, J.-W.; Xiao, Y.-M.;
Yang, L.-R.; Mao, P.; Qu, L.-B. Chem. Commun. 2012, 48, 10117−
0119.
39) Lao, Z.-Q.; Zhong, W.-H.; Lou, Q.-H.; Li, Z.-J.; Meng, X.-B. Org.
Biomol. Chem. 2012, 10, 7869−7871.
40) Barve, B. D.; Wu, Y.-C.; El-Shazly, M.; Chuang, D.-W.; Chung,
1
(
(
Y.-M.; Tsai, Y.-H.; Wu, S.-F.; Korinek, M.; Du, Y.-C.; Hsieh, C.-T.;
Wang, J.-J.; Chang, F.-R. Eur. J. Org. Chem. 2012, 6760−6766.
(
41) Salamone, M.; Milan, M.; DiLabio, G. A.; Bietti, M. J. Org.
Chem. 2013, 78, 5909−5917.
42) Salamone, M.; Martella, R.; Bietti, M. J. Org. Chem. 2012, 77,
556−8561.
43) Coniglio, A.; Galli, C.; Gentili, P.; Vadala,
009, 7, 155−160.
44) Iley, J.; Tolando, R.; Costantino, L. J. Chem. Soc., Perkin Trans. 2
001, 1299−1305.
45) Yoshimitsu, T.; Arano, Y.; Nagaoka, H. J. Am. Chem. Soc. 2005,
27, 11610−11611.
46) Angioni, S.; Ravelli, D.; Emma, D.; Dondi, D.; Fagnoni, M.;
Albini, A. Adv. Synth. Catal. 2008, 350, 2209−2214.
47) Formally, overlap of the C−H bond is with the amide π-system
rather than the nitrogen lone pair.
48) Avila, D. V.; Ingold, K. U.; Di Nardo, A. A.; Zerbetto, F.;
Zgierski, M. Z.; Lusztyk, J. J. Am. Chem. Soc. 1995, 117, 2711−2718.
49) Baciocchi, E.; Bietti, M.; Salamone, M.; Steenken, S. J. Org.
Chem. 2002, 67, 2266−2270.
50) Konya, K. G.; Paul, T.; Lin, S.; Lusztyk, J.; Ingold, K. U. J. Am.
(
8
(
̀
R. Org. Biomol. Chem.
2
(
2
(
1
(
(
(
(
(
Chem. Soc. 2000, 122, 7518−7527.
(
(
(
51) Becke, A. D. J. Chem. Phys. 1993, 98, 5648−5652.
52) Perdew, J. P. Phys. Rev. B 1986, 33, 8822−8824.
53) Johnson, E. R.; Clarkin, O. J.; DiLabio, G. A. J. Phys. Chem. A
2
(
003, 107, 9953−9963.
54) (a) Montgomery, J. A., Jr.; Frisch, M. J.; Ochterski, J. W.;
Petersson, G. A. J. Chem. Phys. 2000, 112, 6532−6542. (b) Mont-
gomery, J. A., Jr.; Frisch, M. J.; Ochterski, J. W.; Petersson, G. A. J.
Chem. Phys. 1999, 110, 2822−2827.
(
55) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
7
184
dx.doi.org/10.1021/jo5013459 | J. Org. Chem. 2014, 79, 7179−7184