Transition Metal-Free Aroylation of Diarylmethanes with N-Bn-N-Boc Arylamides and N-Acylpyrroles

Article abstract of DOI:10.1002/adsc.202000622

In the last 20 years, efficient transition metal catalysts for the α-arylation of enolates have been introduced. Despite the popularity and utility of these reactions, there remains room for improvement (reduced costs, elimination of transition metals and specialized ligands). Herein is reported a general, scalable and green method for aroylation of simple diarylmethane pronucleophiles through direct acyl C?N cleavage of N-Bn?N-Boc arylamides and N-acylpyrroles under transition metal-free conditions. Importantly, a 1 : 1 ratio of the amide to the pronucleophile is employed. Unlike use of Weinreb amides, this method avoids preformed organometallics (organolithium and Grignard reagents) and does not employ cryogenic temperatures, which are difficult and costly to achieve on scale. The operationally simple protocol provides straightforward access to a variety of sterically and electronically diverse 1,2,2-triarylethanones, a group of compounds with high-value in medicinal chemistry. (Figure presented.).

Full text of DOI:10.1002/adsc.202000622

Title: Transition Metal-Free Aroylation of Diarylmethanes with N-Bn-N-
Boc Arylamides and N-Acylpyrroles
Authors: Patrick J. Walsh, Jie Li, Fan Yang, Dong Zou, Huan Wang,
Yichen Zhao, Liyi Zhao, Linlin Li, and Shuguang Chen
This manuscript has been accepted after peer review and appears as an
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000622
Link to VoR: https://doi.org/10.1002/adsc.202000622

10.1002/adsc.202000622
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Transition Metal-Free Aroylation of Diarylmethanes with N-
Bn-N-Boc Arylamides and N-acylpyrroles
a
a
Fan Yang,⁺ Dong Zou,⁺ Shuguang Chen,b Huan Wang,a Yichen Zhao,a Liyi Zhao,a
Linlin Li,a Jie Li,a* and Patrick J. Walshb*
a
Department of Pharmacy, School of Medicine, Zhejiang University City College, No. 48, Huzhou Road, Hangzhou
310015, P. R. China
Email: lijie@zucc.edu.cn
b
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street,
Philadelphia, Pennsylvania 19104-6323, USA
Email: pwalsh@sas.upenn.edu
⁺
These authors contributed equally to this work
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######.((Please
delete if not appropriate))
Abstract. In the last 20 years, efficient transition metal
catalysts for the α-arylation of enolates have been introduced.
Despite the popularity and utility of these reactions, there
remains room for improvement (reduced costs, elimination of
transition metals and specialized ligands). Herein is reported
a general, scalable and green method for aroylation of simple
diarylmethane pronucleophiles through direct acyl C–N
cleavage of N-Bn-N-Boc arylamides and N-acylpyrroles
under transition metal-free conditions. Importantly, a 1 : 1
ratio of the amide to the pronucleophile is employed. Unlike
use of Weinreb amides, this method avoids preformed
organometallics (organolithium and Grignard reagents) and
does not employ cryogenic temperatures, which are
difficult and costly to achieve on scale. The operationally
simple protocol provides straightforward access to a variety
of sterically and electronically diverse 1,2,2-
triarylethanones, a group of compounds with high-value in
medicinal chemistry.
Keywords: transition metal-free; aroylation; amide, enolate
diarylmethane
and Zhang (Fe-catalyzed C–H functionalization).[7]
Despite the importance of metal-catalyzed α-arylation
reactions, there remains room for improvement. These
include avoidance of precious metals (that ultimately
generate metal waste) and the use of expensive ligands.
Towards these objectives, Grimaud, Ciofini, Ollevier,
Introduction
α-Aryl carbonyl compounds, such as 1,2-diaryl- and
1,2,2-triarylethanones, have attracted considerable
attention as important synthetic targets due to their
presence in natural products[1] and bioactive molecules. Taillefer and co-workers developed a transition metal-
[2]
In addition, these structural motifs have been used
as chemical intermediates in the production of
marketed drugs, such as Tamoxifen, Daidzein,
Oxcarbazepine, and Droloxifene.[3] The most popular
route for the synthesis of these privileged carbonyl
compounds largely relies on palladium-catalyzed α-
arylation of ketone enolates,[4] which was pioneered
simultaneously by Buchwald, Hartwig, and Miura in
1997 (Fig. 1A, i).[5] Subsequently, several other α-
arylations with different metals (Fig. 1A. ii-iv) were
developed for the synthesis of 1,2,2-triarylethanones
by the groups of Taillefer (Cu-catalyzed with Ar-I),[3b]
Itami (Ni-catalyzed with carbonates and carbamates),[6]
free method for the α-arylation of enolizable aryl
ketones with aryl iodides via a free radical process (Fig.
1A, v).[8] Kürti and co-workers also developed a
transition metal-free arylation of ketones using nitro
aromatics as the aryl electrophiles (Fig. 1A, vi).[9] In
addition to α-arylations, other methods to prepare
1,2,2-triarylethanones are known.[10]
The present synthesis of 1,2,2-triarylethanones was
inspired by the work of Szostak and co-workers, who
demonstrated the transamidation of activated and
unactivated amides with non-nucleophilic amines
under transition metal-free conditions (Fig. 1B).[11a,b]
We were curious if related activated amides (with
1
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10.1002/adsc.202000622
Advanced Synthesis & Catalysis
decreased amidic resonance[11c]) could be employed
with different classes of nucleophiles. In particular, we
have built a program around reversible in situ
deprotonation of weakly acidic pro-nucleophiles.
Among these, the in situ deprotonation of toluene
derivatives for metal catalyzed arylations,[12]
aminobenzylation of aldehydes,[13] and a new indole
synthesis from 2-fluoro toluenes are notable.[14] For the
current study, we became interested in the use of
amides as electrophiles with in situ generated
conditions where the pro-nucleophiles are reversibly
deprotonated by KN(SiMe3)2 (Fig. 1D). The
advantages to this synthesis of 1,2,2-triarylethan-1-
ones over enolate arylation is that expensive transition
metals and ligands, along with their accompanying
waste, can be avoided.
organometallic
reagents
to
afford
1,2,2-
triarylethanones.
Traditionally, the conversion of amides to ketones
relies on the use of Weinreb amides (Fig. 1C),[15]
which have been applied with great effect in the
coupling of elaborate fragments in complex natural
product synthesis. Typically, Weinreb amides are
subjected to addition of preformed organometallic
nucleophiles, such as organolithiums, Grignard
reagents or hydride sources. Weinreb amides largely
solved the problem of over addition of the
organometallic reagent to the newly formed ketone or
aldehyde. Despite their overwhelming success,
Weinreb amides do have limitations, including
decreased reactivity of the amide C=O carbonyl
toward electrophiles, requiring the use of strongly
nucleophilic organometallic reagents with reduced
functional group tolerance, and side reactions that take
place at the N(Me)OMe unit.[16] A significant
improvement over use of traditional Weinreb amide
chemistry would be use of air and moisture stable pro-
nucleophiles that could be readily converted to
nucleophiles under experimentally convenient
conditions. Less well-known approaches to conversion
of amides to ketones, such as Wolfe’s use of 2-methyl
pyridine based nucleophiles with N,N-dimethyl
amides[17]
or
Katritzky’s
use
of
N-
Fig. 1 Reactions of carbonyl compounds. A. Methods for -
arylation of enolates catalyzed by transition metals and in
the absence of transition metal catalysts. B. Transamidation
reactions. C. Weinreb’s ketone synthesis. D. Synthesis of
acylbenzotriazoles[18] have some advantages, because
they use pro-nucleophiles. These approaches, however,
are typically performed with the strong base LDA at
temperatures that are costly and challenging to access
on scale (below –70 oC).
1,2,2-triarylethanones
conditions (this work).
under
transition
metal-free
Given that amides are common place in chemical
synthesis, biology, and drug discovery,[19] extension of
the Weinreb ketone synthesis beyond the confines of
the Weinreb amide could, in principle, significantly
broaden the potential of this strategy. Furthermore, by
diversifying the amides that are effective substrates in
Weinreb-type ketone syntheses, it may be possible to
engender chemoselectivity among amide coupling
partners with amides bearing different N-substituents.
Herein we present the results of our efforts to
identify amides that participate in the ketone synthesis
under conditions with in situ generation of the
organometallic nucleophile. We have discovered that
both N-Bn-N-Boc arylamides and N-acylpyrroles react
with diarylmethane-based pro-nucleophiles under
Results and Discussion
Reaction optimization. In our prior investigations, we
studied the use of diphenylmethane and related
pronucleophiles in palladium[20] and nickel[21]
catalyzed cross-coupling processes with aryl halides.
In these reactions, the weakly acidic C(sp3)−H bonds
of diarylmethanes and toluene derivatives (pKa 25~43
in DMSO)[22] were reversibly deprotonated under
basic reaction conditions [usually with silylamides:
MN(SiMe3)2, M = Li, Na, K and in some cases with
additives[23]]. The resulting carbanions then acted as
nucleophiles toward the transition metals, undergoing
2
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10.1002/adsc.202000622
Advanced Synthesis & Catalysis
transmetallation. In the present investigations, under
transition metal-free conditions, amides are used as the
electrophiles with the goal of generating 1,2,2-
triarylethanones.
phenyl group of 4-benzylpyridine (4-OMe, 4-F, 4-tBu,
4-Me, 2-Me, and 1-naphthyl) afforded the desired
ketones (3ab, 3ac, 3ad, 3ae, 3af, 3ag) in 68–82% yield.
It is noteworthy that sterically-hindered substrates
bearing a 2-tolyl or 1-naphthyl reacted with similar
efficiency as less hindered substrates. In the case of
3ab, LiN(SiMe3)2 was superior to KN(SiMe3)2 while
NaN(SiMe3)2 outperformed KN(SiMe3)2 with 3ac and
3ae. The reason for the observed reactivity is not clear
at this point.
In addition to 4-benzyl pyridines, less acidic
diarylmethane analogues were successfully employed.
Both the parent diphenylmethane (2h, pKa 32 in
DMSO) and 3-benzylpyridine (2i, pKa 30.1 in DMSO)
proved to be suitable substrates, with desired products
isolated in 68 (3ah) and 82% (3ai) yield, respectively.
Furans bearing benzyl groups at the 2- (2j, 2k) or 3-
position (2l) were also examined. The isomeric
substrates all underwent the base-mediated
transformation to give the product in 60–68% yield
(3aj, 3ak, 3al). Furthermore, 2-benzyl benzofuran 2m
was successfully benzoylated to afford 3am in 65%
yield. Under the conditions outline here, both N-Bn-N-
Boc acetamide and N-Bn-N-Boc pivalamide did not
provide the desired products. Overall, a variety of
1,1,2-triaryl ethanones were readily assembled in good
yields without the assistance of transition metal
catalysts and using equal amounts of both coupling
partners.
We initiated our studies with N-Bn-N-Boc
benzamide 1a and 4-benzylpyridine 2a. The pro-
nucleophile, 4-benzylpyridine 2a, was chosen because
the pKa in DMSO is 26.7, facilitating deprotonation.
Additionally, pyridines are among the most prevalent
heterocycles in medicinal chemistry, increasing the
value of the products.[24] Five different bases were
tested in DME [LiN(SiMe3)2, NaN(SiMe3)2,
KN(SiMe3)2, NaOtBu, and KOtBu] at 80 °C for 12 h
(Table 1, entries 1–5). The silyl amide bases yielded
the desired product (32–86%), with KN(SiMe3)2 the
most promising. In contrast, both NaOtBu and KOtBu
failed to afford the product (Table 1, entries 4–5).
Solvents [dioxane, toluene, THF, and CPME
(cyclopentyl methyl ether), Table 1, entries 6–9] were
next examined, but the reaction in DME outperformed
the other solvents by ≥30%. Lowering the temperature
was next examined, but only 32% yield was observed
at 60 °C, and no desired product was detected at 40 °C
(Table 1, entries 10–11). We note that benzamides
with N-Me-N-Boc and NBoc2 gave lower yields than
N-Bn-N-Boc benzamide. Based on these reactions, the
optimized reaction conditions employ equal amounts
of the amide and 4-benzylpyridine with 3 equiv
KN(SiMe3)2 at 80 °C for 12 h in DME (Table 1, entry
3).
Table 2. Scope of diarylmethane derivativesa,b
Table 1. Reaction Optimization Studiesa
entry
base
solvent
temp. (o C)
Yieldb (%)
1
2
3
4
5
6
7
8
LiN(SiMe3)2
NaN(SiMe3)2
KN(SiMe3)2
NaOtBu
DME
DME
DME
DME
80
80
80
80
80
80
80
80
80
60
40
54
32
86
0
KOtBu
DME
0
KN(SiMe3)2
KN(SiMe3)2
KN(SiMe3)2
KN(SiMe3)2
KN(SiMe3)2
KN(SiMe3)2
dioxane
toluene
THF
CPME
DME
trace
trace
56
52
32
0
9
10
11
DME
aReactions were conducted with 1a (0.1 mmol), 2a (0.1 mmol),
and base (0.6 mmol) with solvent (1 mL) for 12 h. bIsolated yields.
Substrate scope. The substrate scope of 4-
benzylpyridine derivatives was explored with N-Bn-
N-Boc benzamide 1a. As shown in Table 2, substrates
bearing electronically-diverse substituents on the
3
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10.1002/adsc.202000622
Advanced Synthesis & Catalysis
aReaction conditions: N-Bn-N-Boc benzamide (0.2 mmol),
diarylmethane (0.2 mmol), KN(SiMe3)2 0.6 mmol, DME
b
c
(0.2 M), 80 oC, 12 h. Isolated yields. Reaction conducted
in tetrahydrofuran (THF). d6 mmol of LiN(SiMe3)2. e6 mmol
of NaN(SiMe3)2.
Next, we examined the substrate scope of amides in
benzoylation of 4-benzylpyridine (2a). Beyond the
parent reaction to give 3aa with the benzamide (1a),
various arylamides bearing different substituents on
the aryl group gave the expected products in moderate
to good yields (62–86%, Table 3). 2-Naphthylamide
and biphenyl-4-amide furnished 3ba and 3ca in 78%
and 75% yield, respectively. Benzamides possessing
alkyl groups (4-tBu, 4-Me, and 3-Me) gave products
3da, 3ea, and 3fa in 75–80% yield. Substrates bearing
electron-donating groups (4-NMe2, 4–OMe, 2-OMe)
underwent addition in 62–68% yield to give the
expected products (3ga, 3ha, 3ka). Benzamides
supporting halides (4-F and 4-Cl) provided ketone
products in 80–82% yield (3ia and 3ja). These
substrates are primed for further functionalization
through cross-coupling strategies. Additionally,
heterocyclic furylamide and thienylamide also
participated in this protocol, affording the product 3la–
3ma in 70 and 63% yields, respectively. As outlined
in Table 3, some substrates performed better with
LiN(SiMe3)2 (3ca, 3ha, 3la) while others (3ga, 3ai,
3ja) gave better yields with NaN(SiMe3)2. This
observation is surprising, because it is dependent on
the amide electrophile. Overall, a wide range of 1,2,2-
triaryl ethanones can be prepared by aroylation of
simple diarylmethane derivatives with N-Bn-N-Boc
arylamides.
aReaction conditions: N-Bn-N-Boc amide (0.2 mmol), 4-
benzylpyridine (0.2 mmol), KN(SiMe3)2 0.6 mmol, DME
(0.2 M), 80 oC, 12 h. bIsolated yield. cReaction conducted in
cyclopentyl methyl ether (CPME). d6 mmol of LiN(SiMe3)2.
e6 mmol of NaN(SiMe3)2.
The success of Weinreb amides for the synthesis of
ketones and aldehydes is attributed to the stability of
the tetrahedral intermediates formed upon addition of
strong nucleophiles to the carbonyl groups of these
substrates (Figure 1C).[15] Another class of amides that
form stable tetrahedral intermediates is N-
acylpyrroles.[25] An advantage of N-acylpyrroles is that
the lone pair is delocalized into the pyrrole and less
available for delocalization into the carbonyl group.
As a result, the carbonyl group is significantly more
electrophilic than Weinreb amides and also more
reactive than amides in general. The reactivity of N-
acylpyrroles is on par with that of ketones.[26] Another
advantage of N-acylpyrroles, also stemming from the
delocalization of the N-lone pair, is that the pyrrole
does not readily bind to metals, reducing its ability to
act as a leaving group. Thus, stable tetrahedral
intermediates can be isolated.[25g] Of relevance to this
work, examples using N-acylpyrroles for the synthesis
of ketones are known, but usually require
inconveniently low temperatures[27] (–48 to –78 oC) to
insure the tetrahedral intermediate does not break
down, allowing a second addition to take place.[27b]
These additions often furnish the pyrrolylcarbinol
product.
Table 3. Scope of amidesa,b
Based on the reactivity of N-acylpyrroles, we
decided to examine the aroylation of diarylmethanes
4
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10.1002/adsc.202000622
Advanced Synthesis & Catalysis
with these substrates to expand the generality of our
method. We were pleased to find that aroylation could
be successfully extended to encompass N-acylpyrroles
under conditions similar to those used in the reactions
described earlier (see the Supporting Information for
reaction optimization). Examination of the scope
indicated that a broad range of diarylmethanes and N-
acylpyrroles were viable substrates in this
transformation (Table 4). Using 4-benzylpyridine with
a variety of substituents on the benzyl group (4-OMe,
4-F, 4-tBu, 4-Me, 2-Me, 3ab–3af) provided products
in 80–84% yields. It is interesting that the sterically
demanding 2-tolyl derivative did not exhibit
diminished reactivity. Less acidic 3-benzylpyridine
was also a fine substrate, furnishing the product in
84% yield. Pronucleophiles 2- and 3-benzyl furans
also participated in the reaction (65–75% yield). 2-
Benzyl benzofuran proved to be a very good substrate,
providing the product in 86% yield.
The N-acylpyrroles could also be varied, as
demonstrated with a series of reactions using 4-
benzylpyridine as the pronucleophile. Aryl N-
acylpyrroles bearing aryls with 2-naphthyl, or phenyl
groups substituted with 4-Ph, 4-Me, 3-Me, 4-NMe2, 4-
OMe, 4-F, and 4-Cl reacted to furnish the products in
72–85% yield. Only the more sterically hindered 2-
methoxy phenyl N-acylpyrrole proved to be a
challenging substrate, furnishing the product in 40%
yield. However, the yield was improved when 6 equiv
of 18-crown-6 was added, generating the product in
72% yield. The 2-furanyl and 2-thiofuranyl N-
acylpyrroles were also good substrates, providing the
products in 65 and 72% yield. To illustrate the
practicality of our method, we conducted the reaction
of 4-benzylpyridine (2a) with N-benzoylpyrrole (4a)
on a 4 mmol scale. The aroylation product 3aa was
isolated in 82% yield. Like the previous reactions of
N-Bn-N-Boc amides, reactions with N-acylpyrroles
were performed with only one equiv of the
pronucleophile.
aReaction conditions:
N-Acylpyrrole (0.2 mmol),
diarylmethane (0.2 mmol), NaN(SiMe3)2 (0.3 mmol), THF
o
(0.1 M), 80 C, 12 h. bIsolated yields. cReaction performed
on 4 mmol scale. dThe reactions were executed in 1,4-
dioxane. e6 mmol of 18-crown-6.
Mechanistic Experiments. We next wanted to
understand the reason that the addition reactions
give high selectivity for mono-addition products.
With the N-acylpyrroles, we envisioned that the
deprotonated pronucleophile derived from 2a
would add to the N-acylpyrrole to form a
tetrahedral intermediate (Scheme 1). From here,
two possibilities were considered. The first was
that the tetrahedral intermediate formed upon
addition of the nucleophile to the N-acylpyrroles
was stable, as was observed by others.[25g] We
viewed this possibility as less likely, because the
We next employed the N-acylpyrrole derived from
cinnamic acid. We were pleased to find that the
product 5na could be generated under the standard
conditions in 68% yield. For aliphatic acid derivatives,
we employed the N-acylpyrrole prepared from
cyclopropane carboxylic acid. This substrate reacted
to give 5oa in 73% yield.
Table 4. Transition metal-free aroylation of heteroaryl aryl
methanes with N-acylpyrrolesa,b
o
reaction was conducted at 80 C. The second
possibility was that the tetrahedral intermediate
underwent collapse to afford the ketone 3aa. The
ketone 3aa could undergo a second addition of the
deprotonated pronucleophile, however, this
product was not observed. Alternatively, the
5
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10.1002/adsc.202000622
Advanced Synthesis & Catalysis
ketone could be deprotonated by the excess indicated that the major components were the
NaN(SiMe3)2 to generate an enolate that would be same. Among other resonances (see Supporting
inert to further reaction with the deprotonated
pronucleophile.
Information for details), both the deprotonated
ketone and the reaction mixture in the J Young
tube contained resonances at 174.6 ppm. A
resonance at this location is not characteristic of a
ketone, but instead is in the expected range for an
O-C=C oxygen-bound enolate carbon (which in
related systems appear at 165–175 ppm).[28] These
results indicate that the enolate is the product of
the reaction, which undergoes protonation on
workup with water to generate the observed
ketones.
Scheme 1. Possible reaction pathways.
To explore these key features of the reaction
mechanism, experiments were conducted. When
the reaction between 4-benzyl pyridine (2a) and N-
acylpyrrole 4a with NaN(SiMe3)2 (3 equiv) was
performed under the standard conditions, but
worked up with D2O, the crude reaction product
and contained 94% deuterium at the
-carbon
(3aa-d1, Scheme 2A). This is the product expected
if the enolate were generated under the reaction
conditions. We next desired to explore the
possibility of enolate formation by directly
examining the reaction products before workup.
Thus, the reaction between 4-benzyl pyridine (2a
)
and N-acylpyrrole 4a with NaN(SiMe3)2 (3 equiv)
was performed in a degassed and sealed J Young
NMR tube in THF-d8 (Scheme 2B) The sealed
Scheme 2. A. Deuterium quenching studies and B. Analysis
of the reaction mixture in THF-d8 before workup.
o
tube was heated for 12 h at 80 C in an oil bath
before cooling to room temperature and analysis Conclusion
1
by NMR spectroscopy. The H NMR spectrum of
We have developed a transition metal-free and
this reaction solution consisted of a mixture of
compounds, including sodium pyrrol-1-ide [which
was verified by independent synthesis from
pyrrole and NaN(SiMe3)2, see Supporting
Information for details]. To determine if the
enolate was also present in the reaction mixture,
the independently synthesized ketone (3aa) was
treated with NaN(SiMe3)2 (3 equiv) in THF-d8 at
room temperature (Scheme 2C). Analysis of the 1H
NMR of this solution indicated the majority of the
resonances were identical to the reaction mixture
when the reaction was conducted in the J Young
NMR tube (Scheme 2b), suggesting that the
product before workup was an E/Z mixture of the
enolates. Examination of the 13C{1H} NMR
spectrum of the ketone treated with NaN(SiMe3)2
and comparison with the 13C{1H} NMR of the
reaction mixture in the J Young NMR tube
operationally-simple method for aroylation of
diarylmethanes with N-Bn-N-Boc arylamides and N-
acylpyrroles to afford
a
variety of 1,2,2-
triarylethanone derivatives. 1,2,2-Triarylethanones
belong to a class of privileged carbonyl compounds
with various applications and biological activities. The
scope of the aroylation is broad with high functional
group compatibility and enables rapid incorporation of
heteroaryl groups. In most cases, the reagents used are
commercially available and inexpensive. Mechanistic
studies indicate the product of the reaction before
workup is the enolate, explaining why a second
addition does not take place. This approach is
complementary to popular palladium catalyzed α-
arylations, and more economical. The novelty and
advantages are: 1) the use of air stable pronucleophiles
and amide electrophiles, 2) in situ reversible
deprotonation to reveal reactive nucleophiles, and 3)
6
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10.1002/adsc.202000622
Advanced Synthesis & Catalysis
Acknowledgements
the avoidance of transition metals. An important
feature of this method is it circumvents the use of
preformed air- and moisture-sensitive organometallic
reagents. Given the significant role of amides in
modern chemistry, we envision that this process will
be of interest in chemical sciences and medicinal
chemistry.
LJ thanks National Natural Science Foundation of China
(31670357) and Hangzhou Science and Technology Information
Institute of China (20150633B45). PJW thanks the US National
Science Foundation (CHE-1902509).
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atmosphere. A solution of 4-benzylpyridine (33.8 mg, 0.2
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followed by addition of the solvent. The reaction mixture
was stirred for 12 h at 80 °C. After cooling to room
temperature, the reaction mixture was quenched with three
drops of H2O, passed through a short pad of silica gel and
eluted with ethyl acetate (1 mL × 3). The combined organic
solution was concentrated under reduced pressure. The
crude material was loaded onto a silica gel column and
purified by flash chromatography.
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8
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Advanced Synthesis & Catalysis
FULL PAPER
Transition metal-free aroylation of diarylmethanes
with N-Bn-N-Boc arylamides and N-acylpyrroles
Adv. Synth. Catal. Year, Volume, Page – Page
Fan Yang,‡a Dong Zou,‡a Shuguang Chen,b Huan
Wang,a Yichen Zhao,a Liyi Zhao,a Linlin Li,a Jie
Li,a* and Patrick J. Walshb*
9
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