N-Heterocyclic Carbene-Catalyzed Radical Relay Enabling Vicinal Alkylacylation of Alkenes

Article abstract of DOI:10.1021/jacs.9b07194

The N-heterocyclic carbene-catalyzed radical relay enables the vicinal alkylacylation of styrenes, acrylates and acrylonitrile using aldehydes and tertiary alkyl carboxylic acid-derived redox-active esters. This protocol introduces tertiary alkyl groups and acyl groups to C-C double bonds with complete regioselectivity to produce functionalized ketone derivatives. The radical relay mechanism involves single electron transfer from the enolate form of a Breslow intermediate and radical addition of the resultant alkyl radical to the alkene followed by radical-radical coupling.

Full text of DOI:10.1021/jacs.9b07194

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Communication
N-Heterocyclic Carbene-Catalyzed Radical
Relay Enabling Vicinal Alkylacylation of Alkenes
Takuya Ishii, Kenji Ota, Kazunori Nagao, and Hirohisa Ohmiya
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b07194 • Publication Date (Web): 26 Aug 2019
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N-Heterocyclic Carbene-Catalyzed Radical Relay Enabling Vicinal
Alkylacylation of Alkenes
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Takuya Ishii, Kenji Ota, Kazunori Nagao*, and Hirohisa Ohmiya*
Division of Pharmaceutical Sciences, Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanaza-
wa 920-1192, Japan
Supporting Information Placeholder
an alkene such as styrene (1.3 × 105 s–1) or acrylate (1.1 × 106 s–
ABSTRACT: The N-heterocyclic carbene-catalyzed radi-
cal relay enables the vicinal alkylacylation of styrenes,
acrylates and acrylonitrile using aldehydes and tertiary al-
1).8 Thus, the radical addition/radical–radical coupling pathway as
shown in Figure 1B would be kinetically feasible.
Herein, we report an unprecedented radical relay by organoca-
kyl carboxylic acid-derived redox-active esters. This proto-
talysis, reminiscent of that by transition-metal catalysis or photo-
col introduces tertiary alkyl groups and acyl groups to C–C
redox catalysis. The NHC catalysis allows for vicinal alkylacyla-
double bonds with complete regioselectivity to produce
tion of styrenes, acylates and acrylonitriles using aldehydes and
functionalized ketone derivatives. The radical relay mecha-
tertiary alkyl carboxylic acid-derived redox-active esters.9 This
nism involves single electron transfer from the enolate
protocol could introduce tertiary alkyl groups and acyl groups into
form of a Breslow intermediate and radical addition of the
resultant alkyl radical to the alkene followed by radical–
radical coupling.
C–C double bonds with complete regioselectivity to produce
functionalized ketone derivatives. Notably, the protocol does not
require metals, additional reagents (oxidant, reductant) or light.
A. Transition metal-catalyzed vicinal alkylcarbofunctionalization
Vicinal dicarbofunctionalization of widely available alkenes,
which results in simultaneous formation of two C–C bonds, is an
attractive and efficient method for the synthesis of complex car-
bon frameworks.1 This method relies heavily on the use of transi-
tion-metal catalysts. However, transition-metal-catalyzed vicinal
alkylcarbofunctionalization of alkenes, installing a sp3-alkyl group
and another carbon group into the substrate, is challenging be-
cause in situ generated alkyl metal intermediates can undergo
potential side reactions such as β-H elimination and isomerization.
The radical relay strategy has been known to overcome such prob-
lems.2,3 This process involves single electron transfer (SET) from
an organometal intermediate (R1–TMA) to an alkyl electrophile
and radical addition of the resultant alkyl radical to an alkene
followed by radical recombination (Figure 1A). Recently, a visi-
ble light-mediated catalyzed radical relay has been introduced as a
new approach for the vicinal alkylcarbofunctionalization of al-
kenes.4
TM
R1
or
M
R3
R5 R4
R1
R3
R5 R4
X
+
+
R2
R2
R1 X / reductant
metal-catalyzed radical relay
R3
R5 R4
R2
R3
RX
R1 TMA
R1 TMB
– X–
R5 R4
R2
recombination
radical addition
SET
B. NHC-catalyzed vicinal alkylacylation of alkenes (this work)
O
NHC
O
O
O
R3
R5 R4
R3
R5 R4
redox-active ester
+
N
+
R2
R1
O
R1
H
R2
O
Earlier, we developed the N-heterocyclic carbene (NHC)-based
radical catalysis that enabled the decarboxylative coupling of aryl
aldehydes and tertiary alkyl carboxylic acid-derived redox active
esters.5,6 The reaction pathway involves SET from the enolate
form of a Breslow intermediate, derived from the aldehyde, NHC
and a base, to a redox ester followed by recombination of the
resultant radical pair to form a carbon–carbon bond. This finding
prompted us to consider whether such NHC catalysis could
enable the vicinal alkylcarbofunctionalization of alkenes through
a radical relay mechanism involving SET from the enolate form
and radical addition of the resultant alkyl radical to an alkene
followed by radical–radical coupling (Figure 1B). Based on the
NHC-catalyzed radical ring-closing experiment in our previous
study,5 we estimated that the rate of radical–radical coupling be-
tween the Breslow-derived ketyl radical and a tertiary alkyl radi-
cal was equal to that of 5-exo-radical cyclization (1.1 × 105 s–1).7
This process is slower than addition of a tertiary alkyl radical to
organocatalyzed radical relay
O–
O–
Ar
R2
R3
R3
R5 R4
RCONHPI
S
R1
S
R1
+
R5 R4
– CO2
– Nphth
R2
N
N
Ar
radical addition
k = 1.3 × 105 s-1
radical–radical coupling
SET
enolate form of
Breslow int.
k = 1.1 × 105 s-1
Figure 1. Radical relay strategies for vicinal alkylcarbofunctionalization
of alkenes
Upon exploring the various reaction parameters based on our
earlier investigations on the NHC-catalyzed decarboxylative cou-
pling of aryl aldehydes and alkyl carboxylic acid-derived redox
active esters,5 we found that the reaction using benzaldehyde (1a)
(0.2 mmol), styrene (2a) (0.4 mmol) and N-(acyloxy)phthalimide
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3a (0.3 mmol) occurred in the presence of catalytic amounts of
Page 2 of 6
aryl aldehydes were subjected to the reaction (Table 2, top). Nei-
ther electron-rich nor electron-deficient functional groups in the
aromatic ring affected the reactivity (4baa–4faa). The reaction
was compatible with halogen substituents, which can be utilized
for further derivatizations (4gaa–4iaa). Although a substituent at
the meta position of benzaldehyde was tolerated (4jaa), o-
substituted aryl aldehyde completely inhibited the reaction (data
not shown). Electron-rich and electron-deficient heteroaromatic
rings such as pyridine, thiophene and benzofuran participated in
the reaction (4kaa–mlaa). 2-Naphthaldehyde was a suitable sub-
strate (4naa). The use of aliphatic aldehyde as a coupling partner
resulted in no product formation (data not shown).
1
2
3
4
5
6
7
8
the N-2,6-diisopropylphenyl-substituted six-membered ring fused
thiazolium salt N16,10 (5 mol %) as the NHC precursor and
Cs2CO3 (10 mol %) in DMSO at 80 °C to afford the three-
component alkylacylation product (4aaa) in 84% yield (Table 1,
entry 1). The acyl and tertiary alkyl moieties were introduced at
the a and b carbons of styrene, respectively, with complete regi-
oselectivity. A small amount of the expected side product, 5aa
derived from the NHC-catalyzed two-component coupling of 1a
and 3a, was observed.
9
The steric and electronic natures of the NHC catalyst had
marked influence on the reactivity (Table 1, entries 2–5). Using
N2 possessing a 7-membered backbone, which exhibited high
performance in the previously reported two-component coupling,5
resulted in a decrease in the product yield of 4aaa (entry 2). N3
having a 5-membered backbone did not show substrate conver-
sion (entry 3). The use of a dimethyl backbone instead of the cy-
clohexane backbone in N1 diminished the product yield (entry 4).
Changing the substituent on the nitrogen in NHC to a smaller
mesityl group caused a significant decrease in the reactivity (entry
5). Other NHCs having triazolium, imidazolium or oxazolium
structures were ineffective (data not shown).
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The range of tertiary alkyl carboxylic acid derived redox esters
is shown in Table 2, middle. The use of pivalic acid or 2-methyl-
2-phenylpropanoic acid gave high product yields (4aab and
4aac). Various tertiary carboxylic acids bearing a ring system
engaged in the alkylacylation. For example, 3-, 5- or 6-membered
rings were tolerated (4aad–4aaf). Adamantyl and bicy-
clo[2,2,2]octyl groups were introduced efficiently (4aag and
4aah). Benzoate and THP groups remained untouched under the
reaction conditions (4aai and 4aaj). The reaction using a-oxy or
a-amino carboxylic acids occurred to afford the corresponding
ketones (4aak–4aam). This reaction could be applied to the late-
stage functionalization of pharmaceutical drugs such as bezafi-
brate and gemfibrozil with excellent yields (4aan and 4aao). Un-
fortunately, primary and secondary redox active esters were not
compatible in this reaction (data not shown).
The choice of base was also critical for this reaction (Table 1,
entries 6–8). As shown above, cesium carbonate was found to be
best. The reaction proceeded less effectively when cesium car-
bonate was replaced with potassium carbonate (entry 6). The use
of strong organic bases such as DBU and TMG showed low reac-
tion efficiencies (entries 7 and 8).
Table 2, bottom summarizes the results of the reactions of vari-
ous alkenes under the NHC catalyst system.11 Functional groups
such as methoxy, benzyl ether, bromo and acetal substituents were
tolerated in the aromatic ring of the vinyl arenes (4aca–4afa).
Naphthyl and thiophene-substituted alkene substrates were also
suitable (4aga and 4aha). Notably, Michael acceptors such as
acylate and acrylonitrile participated in the reaction (4aia and
4aja). The acyl and tertiary alkyl groups were delivered to the a
and b carbons of the acylate and acrylonitrile with complete regi-
oselectivity.
Table 1. Screening of catalysts and bases for reaction of 1a, 2a and 3aa
O
Ph
Ph
4aaa
NBoc
O
N1 (5 mol %)
Cs2CO3 (10 mol %)
O
O
+
+
Ph
N
O
Ph
H
O
DMSO
80 ˚C, 4 h
O
NBoc
Ph
1a
2a
3a
NBoc
5aa
O
entry
Change from standard conditions
Yield
of Yield of
O
A.
R3
R5 R4
4aaa (%)b
5aa (%)b
R1
R1
S
H
1
2
3
4
5
6
7
8
none
84 (84)
76
13
15
0
R2
1
N
Ar
4
N2 instead of N1
N3 instead of N1
N4 instead of N1
N5 instead of N1
K2CO3 instead of Cs2CO3
DBU instead of Cs2CO3
TMG instead of Cs2CO3
OH
0
S
R1
52
16
3
O–
N
Ar
11
S
NHC-catalyzed
radical relay
R1
R3
R5 R4
A
+
74
17
14
9
N
Cs+X–
R2
Ar
55
C
E
–
X = CsCO3
,
PhthN–
HX
47
O– Cs+
S
R1
N
R2
enolate form of
Breslow intermediate
Ar
– PhthNCs
– CO2
O
1 or 3
Me
Me
R
4 R3
Me
+
iPr
iPr
B
iPr
+
+
+
O
D
S
N
S
N
S
N
S
N
Me
–
–
–
ClO4
R2
–
ClO4
N
ClO4
ClO4
Me
iPr
iPr
iPr
O
R2
N1
N2 (n = 3)
N3 (n = 1)
N4
N5
O
R
4 R3
2
3
a Reaction was carried out with 1a (0.2 mmol), 2a (0.4 mmol), 3a (0.3
mmol), NHC (0.01 mmol), and Cs2CO3 (0.02 mmol) in DMSO (0.4 mL)
B.
O
O
NHC (10 mol %)
Cs2CO3 (20 mol %)
at 80 °C for 4 h. 1H NMR yield based on 1a. DMSO = dimethylsulfox-
b
O
O
O
+
ide. DBU
tetramethylguanidine.
=
1,8-diazabicyclo[5.4.0]-7-undecene. TMG
=
1,1,3,3-
N
Ph
Ph
H
DMSO, 80 ˚C, 4 h
O
1a
3b
(1.5 equiv.)
5ab
N1 22%
N2 56%
The generality of the NHC-catalyzed three-component alkylac-
ylation was evaluated by exploring different substrates. Various
Scheme 1. Mechanistic considerations
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= –0.95 ~ –0.97 V vs. SCE in MeCN).12 Subsequently, the single
1
2
3
4
5
6
electron transfer event between the enolate B and 3 provides a
ketyl radical (C) and an alkyl radical (D), respectively. After addi-
tion of the resultant tertiary alkyl radical D to alkene 2 forming
secondary radical E, the radical–radical coupling between C and
E followed by elimination releases the alkylacylation product 4
and regenerates NHC for the next catalytic cycle.13
We proposed the NHC-catalyzed radical relay mechanism for
the vicinal alkylacylation of alkene 2 using aldehyde 1 and redox
ester 3 as depicted in Scheme 1A. The initial reaction between 1
and NHC forms a neutral Breslow intermediate (A). Next, depro-
tonation of the enol OH in A by cesium carbonate generates the
high reducing enolate form of the Breslow intermediate (B) (E0
ox
7
8
Table 2. Substrate scopea,b
9
O
O
N1 (5 mol %)
Cs2CO3 (10 mol %)
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11
12
13
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15
16
17
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60
O
iPr
O
R3
R5 R4
+
R3
R1
+
N
+
S
N
R2
O
R1
DMSO, 80 ˚C, 4 h
H
R2
–
R5 R4
ClO4
O
O
iPr
N1
1
2
3
4
Scope of Aldehydes
O
O
O
Ph
4daa, 87%
NBoc
Ph
NBoc
Ph
NBoc
Ph
NBoc
NBoc
MeS
MeO
O
CF3O
MeO
Me
4baa, 85%
4caa, 90%
4eaa, 80%
O
O
O
O
Ph
Ph
NBoc
Ph
NBoc
Ph
NBoc
Ph
NBoc
CF3
Cl
F
Br
4faa, 65%
4haa, 87%
4gaa, 79%
4iaa, 79%
4jaa, 83%
O
O
O
O
Ph
NBoc
O
Ph
4maa, 44%
NBoc
S
Ph
NBoc
Ph
NBoc
N
4kaa, 88%
4laa, 86%
4naa, 82%
Scope of Redox-Active Esters
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
O
Ph
Ph
Ph
O
Ph
Ph
Ph
Ph
4aab, 75%
4aac, 58%
4aad, 40%
4aae, 45%
4aaf, 86%
O
O
O
OAc
Ph
Ph
Ph
OBz
Ph
OTHP
Ph
Ph
Ph
Ph
Ph
Ph
CO2Me
4aag, 71%c
4aah, 67%
4aak, 73%
4aai, 78%
4aaj, 79%
O
O
O
O
Ph
O
O
NMeBoc
Ph
Ph
Ph
N
H
Ph
O
Ph
Boc
N
Ph
Ph
Cl
4aal, 92%d
4aam, 85%
4aan, 98%
4aao, 74%e
Scope of Alkenes
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
NBoc
NBoc
NBoc
NBoc
NBoc
O
O
Me
Me
Br
OMe
OBn
4aea, 99%e
4afa, 83%
4aca, 81%
4ada, 83%
4aba, 81%
O
O
S
Ph
O
O
NBoc
Ph
Ph
MeO
Ph
NBoc
NBoc
CN
NBoc
O
OMe
4aga, 94%
4aja, 60%
4aha, 59%
4aia, 53%
a Reaction was carried out with aldehyde 1 (0.2 mmol), alkene 2 (0.4 mmol), redox-active ester 3 (0.3 mmol), N1 (0.01 mmol), and Cs2CO3 (0.02 mmol) in
DMSO (0.4 mL) at 80 °C for 4 h. b A small amount of two-component coupling product 5 was observed. c N1 (0.02 mmol) and Cs2CO3 (0.04 mmol) were
used. d Diastereomeric ratio is 1:1. e Isolated as the corresponding alcohol (see Supporting Information).
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Page 4 of 6
Component Coupling Reaction of Alkyl Halides, 1,3-Dienes, and Trime-
To gain insight into the effect of the NHC catalyst, we
conducted two-component couplings between aldehyde 1a and
redox ester 3b using six- and seven-membered ring fused
thiazolium salts N1 and N2 (Scheme 1B). The six-membered N1
was less effective than the seven-membered N2 in terms of
product yield of 5ab. This might be due to the slow radical–
radical coupling of the N1-derived ketyl radical and the tertiary
alkyl radical. This is consistent with the experimental
observations that N1 has higher chemoselectivity than N2
(4aaa/5aa) in the three-component coupling (see Table 1, entries
1 and 2).14
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cene-Catalyzed Regioselective Alkylation of Styrenes with Grignard Re-
agents Using b-Bromoethyl Ethers, Thioethers, or Amines. Terao, J.;
Kato, Y.; Kambe, N. Chem. Asian J. 2008, 3, 1472. (c) Wang, F.; Wang,
D.; Mu, X.; Chen, P.; Liu, G. Copper-Catalyzed Intermolecular Trifluo-
romethylarylation of Alkenes: Mutual Activation of Arylboronic Acid
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Tandem Difluoroalkylation-Arylation of Enamides Catalyzed by Nickel.
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Z.; Nevado, C. Nickel-Catalyzed Reductive Dicarbofunctionalization of
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Shrestha, B.; Thapa, S.; Khanal, N.; Basnet, P.; Lebrun, R. W.; Giri, R.
Ni-Catalyzed Regioselective Alkylarylation of Vinylarenes via C-
(sp3)−C(sp3)/C(sp3)−C(sp2) Bond Formation and Mechanistic Studies. J.
Am. Chem. Soc. 2018, 140, 9801. (g) Zhang, K. F.; Bian, K. J.; Li, C.;
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1
2
3
4
5
6
7
8
9
In summary, we demonstrated the NHC organocatalyzed
vicinal alkylacylation of styrenes, acylates and acrylonitrile using
simple aldehydes and tertiary alkyl carboxylic acid-derived redox-
active esters to produce functionalized ketone derivatives. The
reaction proceeds through a radical relay mechanism, in which the
NHC organocatalyst precisely controls SET, radical addition and
radical–radical coupling. Our NHC-based radical catalysis pre-
sents a new platform for C–C bond formation in organic synthesis.
Studies on the asymmetric version of this alkylacylation (see
Supporting Information) and mechanistic investigations aided by
theoretical calculations are currently ongoing in our laboratory.
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(3) For transition-metal catalyzed intermolecular alkylcarbofunctionalization of
alkenes through non-radical relay mechanism, see: (a) Zhang, L.; Lov-
inger, G. J.; Edelstein, E. K.; Szymaniak, A. A.; Chierchia, M. P.;
Morken, J. P. Catalytic Conjunctive Cross-Coupling Enabled by Metal-
Induced Metallate Rearrangement. Science 2016, 351, 70. (b) Lovinger,
G. J.; Morken, J. P. Ni-Catalyzed Enantioselective Conjunctive Coupling
with C(sp3) Electrophiles: A Radical-Ionic Mechanistic Dichotomy. J.
Am. Chem. Soc. 2017, 139, 17293. (c) Derosa, J.; Tran, V. T.; Boulous, M.
N.; Chen, J. S.; Engle, K. M. Nickel-Catalyzed β,γ-
Dicarbofunctionalization of Alkenyl Carbonyl Compounds via Conjunc-
tive Cross-Coupling. J. Am. Chem. Soc. 2017, 139, 10657. (d) Derosa, J.;
van der Puyl, V. A.; Tran, V. T.; Liu, M.; Engle, K. Directed Nickel-
Catalyzed 1,2-Dialkylation of Alkenyl Carbonyl Compounds. Chem. Sci.
2018, 9, 5278.
ASSOCIATED CONTENT
Supporting Information. Experimental details and characteriza-
tion data for all new compounds (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
(4) For selected papers on visible light-mediated alkylcarbofunctionalization of
alkenes though radical relay mechanism, see: (a) Klauck, F. J. R.; Yoon,
H.; James, M. J.; Lautens, M.; Glorius, F. Visible-Light-Mediated Deam-
inative Three-Component Dicarbofunctionalization of Styrenes with Ben-
zylic Radicals. ACS Catal. 2019, 9, 236. (b) Liu, J.; Li, W.; Xie, J.; Zhu,
C. Photoredox 1,2-Dicarbofunctionalization of Unactivated Al-
kenes via Tandem Radical Difluoroalkylation and Alkynyl Migration. Org.
Chem. Front. 2018, 5, 797 (c) Guo, L.; Tu, H.-Y.; Zhu, S.; Chu, L. Selec-
tive, Intermolecular Alkylarylation of Alkenes via Photoredox/Nickel
Dual Catalysis. Org. Lett. 2019, 21, 4771. (d) Overman, L. E.; Weires, N.
A.; Slutskyy, Y. Facile Preparation of Spirolactones by an Alkoxycar-
bonyl Radical Cyclization Cross-Coupling Cascade. Angew. Chem., Int.
Ed. 2019, 58, 8561. (e) Cuadros, S.; Horwitz, M. A.; Schweitzer-Chaput,
B.; Melchiorre, P. A Visible-Light Mediated Three-Component Radical
Process Using Dithiocarbamate Anion Catalysis. Chem. Sci. 2019, 10,
5484. (f) Lv, X.-L.; Wang, C.; Wang, Q.-L.; Shu, W. Rapid Synthesis of
γ-Arylated Carbonyls Enabled by the Merge of Copper- and Photocatalyt-
ic Radical Relay Alkylarylation of Alkenes. Org. Lett., 2019, 21, 56. (g)
García-Domínguez, A.; Mondal, R.; Nevado, C. Dual Photoredox/Nickel-
Catalyzed Three Component Carbofuncationalization of Alkenes. Angew.
Chem. Int. Ed. 2019, 58, DOI:10.1002/anie.201906692.
(5) (a) Ishii, T.; Kakeno, Y.; Nagao, K.; Ohmiya, H. N-Heterocyclic Carbene-
Catalyzed Decarboxylative Alkylation of Aldehydes. J. Am. Chem. Soc.
2019, 141, 3854. See also: (b) Song, R.; Chi, Y. R. N-Heterocyclic Car-
bene Catalyzed Radical Coupling of Aldehydes with Redox-Active Esters.
Angew. Chem. Int. Ed. 2019, 58, 8628.
(6) For our NHC-based catalysis, see: (a) Yasuda, S.; Ishii, T.; Takemoto, S.;
Haruki, H.; Ohmiya, H. Synergistic N-Heterocyclic Carbene/Palladium-
Catalyzed Reactions of Aldehyde Acyl Anions with either Diarylmethyl
or Allylic Carbonates. Angew. Chem. Int. Ed. 2018, 57, 2938. (b) Haruki,
H.; Yasuda, S.; Nagao, K.; Ohmiya, H. Dehydrative Allylation between
Aldehydes and Allylic Alcohols through Synergistic N-Heterocyclic Car-
bene/Palladium Catalysis. Chem. Eur. J. 2019, 25, 724. (c) Takemoto, S.;
Ishii, T.; Yasuda, S.; Ohmiya, H. Synergistic N-Heterocyclic Car-
bene/Palladium-Catalyzed Allylation of Aldehydes with Allylic Car-
bonates. Bull. Chem. Soc. Jpn. 2019, 92, 937.
Kazunori Nagao: nkazunori@p.kanazawa-u.ac.jp
Hirohisa Ohmiya: ohmiya@p.kanazawa-u.ac.jp
ORCID
Kazunori Nagao: 0000-0003-3141-5279
Hirohisa Ohmiya: 0000-0002-1374-1137
ACKNOWLEDGMENT
This work was supported by JSPS KAKENHI Grant Number
JP18H01971 to Scientific Research (B), JSPS KAKENHI Grant
Number JP17H06449 (Hybrid Catalysis), and Kanazawa Univer-
sity SAKIGAKE project 2018 (to H.O.).
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Vicinal C-Functionalization of Alkenes. Pd/Light-Induced Multicompo-
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(11) The reaction of 1,2-disubstituted alkenes such as chalcone or methyl
cinnamate did not proceed at all due to the slow rate of the radical addi-
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(13) The further addition of benzyl radical E to alkene 2 was not detected. This
would be due to the slower rate of addition of benzyl radical to styrene
(1.1 × 103 s–1, see ref 8) than that of radical–radical coupling between C
and E (1.1 × 105 s–1) (see Scheme 1A).
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(14) Further information on the effect of NHC catalyst is available in Support-
ing Information.
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