2-Methyltetrahydrofuran (2-MeTHF): A Green Solvent for Pd?NHC-Catalyzed Amide and Ester Suzuki-Miyaura Cross-Coupling by N?C/O?C Cleavage

Article abstract of DOI:10.1002/adsc.201901188

The palladium-NHC-catalyzed (NHC=N-heterocyclic carbene) Suzuki-Miyaura cross-coupling of amides and esters via highly chemoselective N?C(O) and O?C(O) cleavage with aryl boronic acids using green, sustainable and eco-friendly 2-methyltetrahydrofuran (2-MeTHF) is reported. A variety of amides and aryl esters were coupled with aryl boronic acids in high to excellent yields. This method employs commercially-available, air- and moisture-stable Pd(II) ?NHC precatalysts. Crucially, the use of 2-MeTHF leads to the highest TON reported to date in amide N?C(O) bond cross-coupling. This operationally-simple protocol was utilized in the synthesis a bioactive ketone intermediate, emphasizing the potential of 2-MeTHF as a green solvent in unconventional amide bond disconnection. Given the tremendous importance of amide bond cross-coupling strategies and the drive to maintain full sustainability in cross-coupling processes, we expect that the synthetic method will be of broad interest.

Full text of DOI:10.1002/adsc.201901188

Title: 2-Methyltetrahydrofuran (2-MeTHF): A Green Solvent for Pd–
NHC-Catalyzed Amide and Ester Suzuki–Miyaura Cross-
Coupling by N–C/O–C Cleavage
Authors: Peng Lei, Yun Ling, Jie An, Steven Nolan, and Michal
Szostak
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901188
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Advanced Synthesis & Catalysis
10.1002/adsc.201901188
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
2
-Methyltetrahydrofuran (2-MeTHF): A Green Solvent for Pd–
NHC-Catalyzed Amide and Ester Suzuki–Miyaura Cross-
Coupling by N–C/O–C Cleavage
Peng Lei,*,a,b,c Yun Ling, Jie An, Steven P. Nolan, and Michal Szostak*
b
b
d
,c
a
College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China
b
Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, United States
Fax: (+1)-973-353-1264; phone: (+1)-973-353-5329; e-mail: michal.szostak@rutgers.edu
Department of Chemistry and Center for Sustainable Chemistry, Ghent University, Krijgslaan 281, 9000 Ghent,
Belgium
c
d
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. The palladium-NHC-catalyzed (NHC = N- traditionally inert amide or ester bonds are converted
heterocyclic carbene) Suzuki–Miyaura cross-coupling of into acyl-metal intermediates using catalytic
amides and esters via highly chemoselective N–C(O) and protocols
with
significantly
improved
[
13]
O–C(O) cleavage with aryl boronic acids using green, chemoselectivity and atom economy.
sustainable and eco-friendly 2-methyltetrahydrofuran (2-
MeTHF) is reported. A variety of amides and aryl esters
were coupled with aryl boronic acids in high to excellent
yields. This method employs commercially-available, air-
and moisture-stable Pd(II)–NHC precatalysts. Crucially,
the use of 2-MeTHF leads to the highest TON reported to
date in amide N–C(O) bond cross-coupling. This
operationally-simple protocol was utilized in the synthesis
a bioactive ketone intermediate, emphasizing the potential
of 2-MeTHF as a green solvent in unconventional amide
bond disconnection. Given the tremendous importance of
amide bond cross-coupling strategies and the drive to
maintain full sustainability in cross-coupling processes, we
expect that the synthetic method will be of broad interest.
Meanwhile, in recent years, much attention has
focused on cross-coupling reactions in
environmentally friendly media. Remarkably,
organic solvents constitute up to 90% of the non-
aqueous waste generated in pharmaceutical industry,
and the major waste stream in academic
laboratories.
amide bond cross-coupling technologies, it is
surprising that catalytic methods using green solvents
are to date unknown.
In 2017, our laboratory introduced the use of
Pd(II)–NHC precatalysts for amide N–C bond cross-
[14,15]
[16]
Given the tremendous potential of
[4a]
coupling. This catalytic system proved to be the
most reactive in cross-coupling of amides reported to
[3a]
date. To improve sustainability and green profile of
amide bond cross-coupling, herein, we report the first
method to perform palladium-catalyzed Suzuki–
Miyaura cross-coupling of amides and esters via
highly chemoselective N–C(O) and O–C(O) cleavage
Keywords: 2-MeTHF; Suzuki–Miyaura; cross-coupling;
C–N activation; C–O activation; Pd-NHCs
using green, sustainable and eco-friendly 2-
Introduction
[17,18]
methyltetrahydrofuran (2-MeTHF)
(Figure 1).
Considering the reduced environmental impact of 2-
MeTHF and the fact that this solvent is obtained from
renewable resources, the combination of biorelevant
amide cross-coupling with sustainable 2-MeTHF
offers an attractive protocol for industrial and
academic applications. It should be further noted that
this protocol is compatible with the [Pd(IPr)(1-t-Bu-
The central importance of the amide functional group
in chemistry and biology[
1,2]
has spurred the
development of an arsenal of catalytic methods for
functionalization of amides by transition-metal-
[3–8]
catalyzed N–C(O) cleavage.
It is estimated that
more than 75% of drug candidates feature an amide
bond, with more than two-third of new FDA drug
approvals containing an amide, thus presenting
[4h]
ind)Cl] precatalyst.
In a broader context, this Update reports the first
example of N–C(O) and O–C(O) cross-coupling in
green solvents, and demonstrates the generality of
these reactions with respect to both coupling partners.
This protocol using favorable green 2-MeTHF could
be readily performed on a preparative gram scale at
low catalyst loading. Important features of our study
unique opportunites in the modification of
pharmaceuticals.[
9,10]
The ground-state-destabilization
manifold of amides has been further translated into
the activation of esters via initial insertion into the O–
C(O) bond.[
11,12]
The cross-coupling products of these
technologies yield chemicals that are highly attractive
in academic and industrial sectors because
1
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Advanced Synthesis & Catalysis
10.1002/adsc.201901188
include: (1) The developed method employs
commercially-available, air- and moisture-stable
Pd(II)–NHC precatalysts;[
19,20]
(2) the high solubility
of the base in 2-MeTHF leads to the highest TON
reported to date for amide N–C(O) bond cross-
coupling; (3) this operationally-simple protocol
allows for the cross-coupling of a variety of amides
and aryl esters with aryl boronic acids in high to
excellent yields, including one-pot activation/cross-
coupling of secondary amides; (4) the method was
utilized in the synthesis a bioactive ketone
intermediate, emphasizing the potential of 2-MeTHF
as a green solvent for unconventional amide bond
disconnection.
Figure 2. Structures of Pd(II)-NHC Precatalysts for
Suzuki–Miyaura Cross-Coupling in Ecofriendly 2-MeTHF.
Equation 1. Effect of Precatalysts on the Suzuki–Miyaura
[
a]
Cross-Coupling of Amides in Ecofriendly 2-MeTHF.
[a]Conditions: amide (1.0 equiv), Ar-B(OH)
Pd-NHC (3 mol%), K CO (3.0 equiv), H O (5 equiv), 2-
MeTHF (0.25 M), 23 °C, 15 h.
(1.2 equiv),
2
2
3
2
the reaction could be carried our with other
commercially-available Pd(II)–NHC precatalysts (Pd-
[
23]
[24]
PEPPSI-IPr, 95%; Pd(IPr)(1-t-Bu-ind)Cl, 92%)
(
Figure 2), highlighting the potential of 2-MeTHF as
a general solvent for amide bond cross-coupling. It
also should be noted that the amount of waste is an
important consideration in evaluating sustainability in
addition to the toxicity of solvents and reagents
Figure 1. (a) Activation of Amides and Esters. (b)
Sustainable 2-MeTHF in Suzuki–Miyaura Cross-Coupling
of Amides and Esters.
[18c]
used.
eq 1, 1a, [Pd(IPr)(cin)Cl], 3 mol%, 2-MeTHF, RT),
8% yield is obtained using 1.2 equiv of K CO ,
We note that under the standard conditions
(
Results and Discussion
9
2
3
consistent with facile transmetallation under these
conditions.
Amide bond cross-coupling provides new
opportunities to elaborate the stable amide linkage
into valuable chemicals.[1–3] 2-MeTHF has been
regarded as a very attractive solvent for orga-
nometallic reactions.[ Unlike THF, 2-MeTHF is
produced from bioresources, furfural or levulinic acid,
which is indispensable in decreasing waste generation
With optimal conditions in hand, the scope of
the amide bond cross-coupling in 2-MeTHF was next
evaluated. The conditons using 3.0 equiv of base
17]
[4a]
were selected for comparison purposes. As shown
in Schemes 1-3, a variety of boronic acids and amides
can be deployed in this sustainable cross-coupling
protocol. As revealed in Scheme 1, these mild
conditions are compatible with electronically-diverse
boronic acids, including electron-neutral (3a, 3c),
electron-donating (3d) and deactivating electron-
withdrawing groups (3e, 3f). Steric-hindrance is well-
tolerated (3b). The functional group tolerance
towards an alkyl ester should be noted (3e) as this
substrate would be problematic in the addition of
[18]
in chemical and pharmaceutical sectors.
More
importantly, inorganic bases are more soluble in 2-
MeTHF than in THF,[17a,b] which leads to high
efficiency in select organometallic processes. Water
[21]
helps to activate the Pd–NHC catalyst system.
We focused our efforts on the Suzuki–Miyaura
cross-coupling of N-Boc activated secondary
[8]
amides (Ar = Ph, R = Ph, RE = 9.7 kcal/mol; RE =
resonance energy; Winkler-Dunitz parameters: =
[25]
hard organometallic reagents to Weinreb amides.
1
8.8°; 
The optimized
Pd(IPr)(cin)Cl] (3 mol%) (cin = cinnamyl) in the
presence of K CO (3 equiv) in 2-MeTHF under
exceedingly mild room temperature conditions.
Interestingly, a base screen revealed K CO to be
superior to KOH, K PO and KF under these
N
= 18.9°) using various Pd-NHC precatalysts.
As shown in Scheme 2, this method was found to be
effective with diverse amides, including sterically-
hindered (3b‘), electronically-deactivated (3d‘),
containing electrophilic functional groups (3e‘) as
well as those containing fluorinated moieties (3f‘,3g)
and heterocycles (3h) that constitute common motifs
process
(eq
1)
employs
[22]
[
2
3
2
3
3
4
[26]
in pharmaceutical chemistry.
conditions. Importantly, the cross-coupling could be
carried out efficiently using only a slight excess of
boronic acid (1.2 equiv). Finally, we established that
To test the limits of this cross-coupling process
using sustainable 2-MeTHF, we systematically
2
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Advanced Synthesis & Catalysis
10.1002/adsc.201901188
Scheme 1. Scope of the Suzuki–Miyaura Cross-Coupling
of Amides in Ecofriendly 2-MeTHF: Amides.
Scheme 4. Scope of the Suzuki–Miyaura Cross-Coupling
of Esters in Ecofriendly 2-MeTHF.
[a,b]
[a,b]
[a]Conditions: Amide (1.0 equiv), Ar-B(OH)
Pd] (3 mol%), K CO (3.0 equiv), H O (5.0 equiv), 2-
MeTHF (0.25 M), 23 °C, 15 h. Isolated yields. Ar-
B(OH) (2.0 equiv).
(1.2 equiv),
[a]Conditions: Ester (1.0 equiv), Ar-B(OH)
[Pd] (3 mol%), KOH (3.0 equiv), H O (5.0 equiv), 2-
MeTHF (0.25 M), 23 °C, 15 h. Isolated yields.
2
2
(2.0 equiv),
[
2
3
2
2
[
b]
[c]
[b]
2
examined
cross-coupling
of
electronically-
nucleophile
Scheme 2. Scope of the Suzuki–Miyaura Cross-Coupling
of Amides in Ecofriendly 2-MeTHF: Boronic Acids.
matched/mismatched
electrophile/
[a,b]
couples (Scheme 3). It is now established that the
rate- determining step in amide cross-coupling
involves transmetallation,
substitution of the amide affects amidic resonance.
[
21]
while electronic-
[8]
We found that all combinations (3i, 3j, 3j‘, 3k) gave
the ketone products in excellent 95-98% yields,
attesting to the generality of this sustainable catalytic
protocol. Note that this includes the challenging
combination of cross-coupling of electronically-
deactivated amide with electronically-deactivated
[11b,4h]
boronic acid (3j).
We also found that the
notoriously difficult bis-ortho-methyl substituted
biaryl ketone (3l) could be prepared in excellent yield.
Furthermore, the cross-coupling of an alkyl amide
(
3m) can be carried out, demonstrating that this
[a]Conditions: Amide (1.0 equiv), Ar-B(OH)
system catalyzes the reaction of aliphatic amides. It is
worthwhile to note that the use of various N-alkyl-N-
Boc derivatives is typically feasible using Pd(II) –
NHCs due to similar amidic resonance of the amide
2
(1.2 equiv),
[
Pd] (3 mol%), K
MeTHF (0.25 M), 23 °C, 15 h. Isolated yields. Ar-
B(OH) (2.0 equiv).
2 3 2
CO (3.0 equiv), H O (5.0 equiv), 2-
[
b]
[c]
2
[3a]
bond. Activated alkanecarboxamides are limited to
primary and secondary alkanecarboxamides.
Scheme 3. Scope of the Suzuki–Miyaura Cross-Coupling
of Amides in Ecofriendly 2-MeTHF: Further Examples.
[a,b]
We then turned our attention to the cross-
coupling of aryl esters. Electronic-destabilization of
the O–C(O) bond in aryl esters enables synthetically
appealing catalytic cross-coupling by C–O acyl
[3a,4h,11]
cleavage.
Interestingly, we found that 2-
MeTHF is suitable for the selective Suzuki–Miyaura
cross-coupling of phenolic esters. In this case, the
inexpensive KOH was found to be the preferred base.
As shown in Scheme 4, these conditions are
compatible with the cross-coupling of sterically- and
electronically-varied ester/boronic acid combinations,
affording ketone products in good to excellent yields
using [Pd(IPr)(cin)Cl] as catalyst. The exquisite
chemoselectivity for the cross-coupling of an aryl
ester in the presence of its alkyl counterpart is
noteworthy (3e‘).
[a]Conditions: Amide (1.0 equiv), Ar-B(OH)
Pd] (3 mol%), K CO (3.0 equiv), H O (5.0 equiv), 2-
MeTHF (0.25 M), 23 °C, 15 h. Isolated yields.
(2.0 equiv),
2
Pleasingly, the optimized conditions allow for
the cross-coupling of diverse amides, including N,N-
[
2
3
2
[
b]
Boc amides (Scheme 5, entry 1) that are readily
2
3
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Advanced Synthesis & Catalysis
10.1002/adsc.201901188
Scheme 5. Scope of Amides in the Suzuki–Miyaura Cross-
common acyclic amides (N-R/Boc, N-R/Ts, N-Boc )
are compatible with the cross-coupling protocol in
ecofriendly 2-MeTHF.
2
Coupling in Ecofriendly 2-MeTHF.[
a,b]
To further demonstrate the generality of this
sustainable cross-coupling, we applied this method to
the synthesis of a bioactive ketone intermediate in the
[27]
commercial preparation of Flumorph, a promising
new generation pesticide (Scheme 6). As shown, the
high cross-coupling efficiency at room temperature
emphasizes the potential of 2-MeTHF as a green
solvent in unconventional amide bond disconnection.
Pleasingly, the cross-coupling of amide (1a)
proceeded on a gram scale in 98% yield using only
[a]Conditions: amide (1.0 equiv), Ar-B(OH)
(2.0 equiv),
2 3 2
Pd] (3 mol%), K CO (3.0 equiv), H O (5.0 equiv), 2-
2
0
.10 mol% of the air-stable [Pd(IPr)(cin)Cl] catalyst,
[
demonstrating the scalability of this new cross-
coupling protocol (Scheme 7).
MeTHF (0.25 M), 23 °C, 15 h.. b]Isolated yields.
[
Furthermore, one-pot activation/cross-coupling
is feasible as illustrated by the reaction of N-Ph-
benzamide (Scheme 8). The use of [Pd(IPr)(1-t-Bu-
Scheme 6. Synthesis of Flumorph Intermediate by the
Amide Suzuki–Miyaura Cross-Coupling in 2-MeTHF.
[23]
ind)Cl]
gave slightly better reactivity in this
instance. The one-pot activation/cross-coupling
establishes facile and sustainable generation of metal-
acyl moieties from secondary amides.
Finally, encouraged by the high cross-coupling
reactivity observed in 2-MeTHF, we explored
reactions using lower catalytic loadings. We found
that the cross-coupling of amide (1a) is feasible at 50
ppm [Pd] loading (TON = 12,000, 60 °C, 2-MeTHF,
Scheme 7. Scale-up at Low Catalyst Loading in 2-MeTHF.
2
.0 M) (Scheme 9). It is clear that the high turnover is
possible through the improved solubility of K CO
1.2 equiv) in 2-MeTHF that enables more
2
3
(
[17]
concentrated solutions. This represents the highest
TON reported to date in amide cross-coupling, and
shows the advantage of using environmentally-
friendly 2-MeTHF over THF (TON <2,000).
Scheme 8. One-Pot N-Activation/Amide Cross-Coupling
in 2-MeTHF.
Conclusions
In summary, this Update reports the first method to
perform cross-coupling of unconventional amide and
ester electrophiles in green solvents. We have
demonstrated the utility of green, sustainable and
renewable 2-methyltetrahydrofuran as an attractive
solvent for the palladium-NHC-catalyzed Suzuki–
Miyaura cross-coupling of amides and esters. This
Scheme 9. Determination of TON in 2-MeTHF.
operationally-convenient
method
employs
commercially-available, air- and moisture-stable
Pd(II)-NHC precatalysts, and is compatible with a
wide range of amides and boronic acid components.
The potential of these cross-couplings has been
demonstrated in large-scale synthesis, one-pot
prepared from unactivated primary amides as well as
N-Ar/Ts sulfonamides (entry 2) and N-alkyl/Boc
carbamates (entry 3). Thus, this green protocol allows
one to take advantage of different amide bond
activation/cross-coupling and the synthesis
a
bioactive ketone intermediate. More broadly, the use
of 2-methyltetrahydrofuran creates two opportunities
in amide bond cross-coupling: (1) it enables the use
of ecofriendly, sustainable processes for the catalytic
generation of metal-acyl moieties, and, (2) it takes
advantage of the beneficial physico-chemical
properties of 2-MeTHF, enabling highly efficient
cross-coupling. Considering the importance of amide
bond cross-coupling strategies and clear advantages
gained from using sustainable solvents in cross-
[3,8]
precursors and activation mechanisms.
It should
be noted that the acyl-cross-coupling manifold is
fundamentally different from decarbonylative cross-
coupling amides. In general, the acyl cross-coupling
is at present at much more evolved stage of
development than decarbonylative cross-couplings.
Our results establish that the most useful examples of
N-acyclic amides that could be prepared directly from
4
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Advanced Synthesis & Catalysis
10.1002/adsc.201901188
coupling protocols, we expect that the method will
find broad application in organic synthesis.
2011, 5, 22-54; d) L. Brunton, B. Chabner, B.
Knollman,
Goodman
and
Gilman’s
The
Pharmacological Basis of Therapeutics, MacGraw-Hill,
New York, 2010.
Experimental Section
[
3] For reviews on N–C functionalization, see: a) S. Shi, S.
P. Nolan, M. Szostak, Acc. Chem. Res. 2018, 51, 2589-
General 4Ibn] formation. General methods have been
published.[
2
599; b) C. Liu, M. Szostak, Org. Biomol. Chem. 2018,
6, 7998-8010; c) D. Kaiser, A. Bauer, M. Lemmerer,
1
General Procedure for the Suzuki-Miyaura Cross-
Coupling of Amides in EcoFriendly 2-MeTHF. An
oven-dried vial equipped with a stir bar was charged with
an amide substrate (neat, 1.0 equiv), potassium carbonate
N. Maulide, Chem Soc. Rev. 2018, 47, 7899-7925; d) R.
Takise, K. Muto, J. Yamaguchi, Chem. Soc. Rev. 2017,
4
6, 5864-5888; e) C. Liu, M. Szostak, Chem. Eur. J.
(
[
typically, 3.0 equiv), boronic acid (typically, 1.2 equiv),
Pd(IPr)(cin)Cl] (Neolyst CX31, typically, 3 mol%),
2017, 23, 7157-7173; f) G. Meng, M. Szostak, Eur. J.
Org. Chem. 2018, 20-21, 2352-2365.
placed under a positive pressure of argon, and subjected to
three evacuation/backfilling cycles under high vacuum. 2-
MeTHF (typically, 0.25 M) and water (typically, 5.0 equiv)
were added with vigorous stirring at room temperature and
the reaction mixture was stirred for the indicated time.
After the indicated time, the reaction mixture was diluted
[4] For representative acyl coupling, see: a) P. Lei, G.
Meng, M. Szostak, ACS Catal. 2017, 7, 1960-1965; b)
G. Meng, M. Szostak, Org. Lett. 2015, 17, 4364-4367;
c) G. Meng, S. Shi, M. Szostak, ACS Catal. 2016, 6,
with EtOAc (10 mL), filtered, and concentrated. The
7
335-7339; d) P. Lei, G. Meng, Y. Ling, J. An, M.
1
sample was analyzed by H NMR (CDCl
3
, 500 MHz) and
Szostak, J. Org. Chem. 2017, 82, 6638-6646; e) L. Hie,
N. F. F. Nathel, T. K. Shah, E. L. Baker, X. Hong, Y. F.
Yang, P. Liu, K. N. Houk, N. K. Garg, Nature 2015,
GC-MS to obtain conversion, selectivity and yield using
internal standard and comparison with authentic samples.
Purification by chromatography on silica gel
(
EtOAc/hexanes) afforded the title product.
5
24, 79-83; f) J. Amani, R. Alam, S. Badir, G. A.
Molander, Org. Lett. 2017, 19, 2426-2429; g) S. Ni, W.
Zhang, H. Mei, J. Han, Y. Pan, Org. Lett. 2017, 19,
Representative Procedure for the Suzuki-Miyaura
Cross-Coupling of Amides in EcoFriendly 2-MeTHF
2
536-2539; h) P. Lei, G. Meng, S. Shi, Y. Ling, J. An,
(
1.0 g scale). An oven-dried vial equipped with a stir bar
was charged with tert-butyl benzoyl(phenyl)carbamate
3.36 mmol, 1.00 g, 1.0 equiv), potassium carbonate (10.10
mmol, 1.395 g, 3.0 equiv), p-tolylboronic acid (6.73 mmol,
.915 g, 2.0 equiv), [Pd(IPr)(cin)Cl] (0.10 mol%, 2.2 mg),
R. Szostak, M. Szostak, Chem. Sci. 2017, 8, 6525-6530,
and references cited therein.
(
0
[
5] For representative decarbonylative coupling, see: a) G.
Meng, M. Szostak, Angew. Chem. Int. Ed. 2015, 54,
14518-14522; b) S. Shi, G. Meng, M. Szostak, Angew.
Chem. Int. Ed. 2016, 55, 6959-6963; c) G. Meng, M.
Szostak, Org. Lett. 2016, 18, 796-799; d) H. Yue, L.
Guo, H. H. Liao, Y. Cai, C. Zhu, M. Rueping, Angew.
Chem. Int. Ed. 2017, 56, 4282-4285; e) H. Yue, L. Guo,
S. C. Lee, X. Liu, Angew. Chem. Int. Ed. 2017, 56,
placed under a positive pressure of argon, and subjected to
three evacuation/backfilling cycles under high vacuum. 2-
MeTHF (1.0 M) and water (16.80 mmol, 0.303 g, 5.0
equiv) were added with vigorous stirring at room
temperature and the reaction mixture wasstirred for 15 h at
room temperature. After the indicated time, the reaction
mixture was diluted with EtOAc (20 mL), filtered, and
1
concentrated. The sample was analyzed by H NMR
(
3
CDCl , 500 MHz) and GC-MS to obtain conversion,
selectivity and yield using internal standard and
comparison with authentic samples. Purification by
chromatography on silica gel (EtOAc/hexanes) afforded
the title product; 98% (0.647 g).
3
3
972-3976; f) S. Shi, M. Szostak, Org. Lett. 2017, 19,
095-3098; g) P. X. Zhou, S. Shi, J. Wang, Y. Zhang,
C. Li, C. Ge, Org. Chem. Front. 2019, 6, 1942-1947,
and references cited therein.
Acknowledgements
[6] For a biomimetic esterification by N–C activation, see:
C. C. D. Wybon, C. Mensch, K. Hollanders, C. Gadals,
W. A. Herrebout, S. Ballet, B. U. W. Maes, ACS Catal.
Rutgers University and the NSF (CAREER CHE-1650766) are
gratefully acknowledged for support. The Bruker 500 MHz
spectrometer was supported by the NSF-MRI grant (CHE-
2
018, 8, 203-218.
1
2
229030). P.L. thanks the China Scholarship Council (No.
01606350069).
[
[
7] For a chromium-catalyzed N–C activation, see: C.
Chen, P. Liu, M. Luo, X. Zeng, ACS Catal. 2018, 8,
5
864-5868.
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UPDATE
2
-Methyltetrahydrofuran (2-MeTHF): A Green
Solvent for Pd–NHC-Catalyzed Amide and Ester
Suzuki–Miyaura Cross-Coupling by N–C/O–C
Cleavage
Adv. Synth. Catal. Year, Volume, Page – Page
Peng Lei,* Yun Ling, Jie An, Steven P. Nolan,
Michal Szostak*
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