Aryl formate as bifunctional reagent: Applications in palladium-catalyzed carbonylative coupling reactions using in situ generated CO

Article abstract of DOI:10.1002/anie.201311198

After decades of development, carbonylation reactions have become one of the most powerful tools in modern organic synthesis. However, the requirement of CO gas limits the applications of such reactions. Reported herein is a versatile and practical protocol for carbonylative reactions which rely on the cooperation of phenyl formate and nonaflate, and the generation of CO in situ. This protocol has a high functional-group tolerance and could be applied in carbonylations with C, N, and, O nucleophiles. The corresponding amides, alkynones, furanones, and aryl benzoates were synthesized in good yields. Transformers: A versatile and practical protocol for carbonylation reactions involve the cooperation of phenyl formate and nonaflate with generation of CO in situ. This protocol has a high functional-group tolerance and could be applied in carbonylative couplings with C, N, and O nucleophiles. The corresponding amides, alkynones, furanones, and aryl benzoates were synthesized in good yield.

Full text of DOI:10.1002/anie.201311198

Angewandte
Chemie
DOI: 10.1002/anie.201311198
Cross-Coupling
Aryl Formate as Bifunctional Reagent: Applications in Palladium-
Catalyzed Carbonylative Coupling Reactions Using In Situ Generated
CO**
Haoquan Li, Helfried Neumann, Matthias Beller,* and Xiao-Feng Wu*
Abstract: After decades of development, carbonylation reac-
tions have become one of the most powerful tools in modern
organic synthesis. However, the requirement of CO gas limits
the applications of such reactions. Reported herein is a versatile
and practical protocol for carbonylative reactions which rely
on the cooperation of phenyl formate and nonaflate, and the
generation of CO in situ. This protocol has a high functional-
group tolerance and could be applied in carbonylations with C,
N, and, O nucleophiles. The corresponding amides, alkynones,
furanones, and aryl benzoates were synthesized in good yields.
E
ver since the pioneering work of Heck and Schoenberg in
1974, palladium-catalyzed carbonylative transformations of
aryl halides have undergone impressive developments.[1] It
has now constituted one of the most efficient and widely used
methodologies for constructing carbonyl-containing com-
pounds, such as aldehydes, amides, esters, etc.[2] However,
the high toxicity, and odorless and flammable character of CO
gas means that transformations using CO gas must be
operated with special care. Usually, autoclaves and well-
ventilated fume hoods, equipped with special CO detectors
and alarms, are required for these reactions, and has actually
hindered the applications of such reactions.
Scheme 1. Comparison of the prior work to the current work.
Given the disadvantages of using gaseous CO “CO-free”
carbonylation reactions have attracted a lot of attention over
the last three decades.[2b,3] To generate CO and consume CO
in a closed system, a two-chamber technique was recently
developed by Skrydstrup and co-workers. By using this
technique, 9-methylfluorene-9-carbonyl chloride (COgen)
was developed to generate CO gas with the assistance of
a palladium catalyst (Scheme 1). And it was also reported to
be suitable for 13C-isotope labeling.[4] Notably, formic acid was
also developed to generate CO through a dehydration
reaction in sulfuric acid at elevated temperatures (Morgan
reaction).[4b] In contrast, the in situ generation of CO from
metal carbonyl complexes was proven to be compatible with
a number of carbonylation reactions, both for one-pot
transformations and the two-chamber technique.[5] Remark-
ably, alkyl formate was developed for the alkoxycarbonyla-
tion of olefins and aryl halides as well. Compared to alkyl
formate, aryl formate was reported to generate CO in the
presence of base under much milder reaction conditions.[6]
The groups of Manabe[7] and Tsuji[8] independently reported
the esterification of aryl halides using aryl formates. Also, the
synthesis of amides, alkyl esters, amides, and thioesters can be
achieved by a two-step process using 2,4,6-trichlorophenyl
formate[7c] as a reactive intermediate. However, because of
the fact that phenol could also acts as a strong nucleophile in
the reaction, the choice of direct carbonylative coupling
partners, such as amines, alkynes, alkenes, was limited.
Hydroxy groups are very useful functional groups and
they are frequently converted into sulfonates, such as
trifluorosulfonate (OTf), and subjected to a variety of addi-
tional transformations because of their leaving ability.[9] More
recently, nonafluorobutanesulfonyl fluoride (NfF), has
become a more attractive sulfonylating reagent because of
its stability, reactivity, and availability.[10] Actually, it is now
produced on the industrial scale by anodic fluorination of
a cyclic sulfolene precursor.[11] In 2012, our group reported the
palladium carbonylative synthesis of esters and amides
starting from the in situ generated nonaflate under low
pressure of carbon monoxide (1 bar).[12] With our continuous
interest in developing carbonylation reactions, our initial idea
[*] H. Li, Dr. H. Neumann, Prof. Dr. M. Beller, Dr. X.-F. Wu
Leibniz-Institut fꢀr Katalyse an der Universitꢁt Rostock e.V.
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
E-mail: matthias.beller@catalysis.de
xiao-feng.wu@catalysis.de
[**] We thank the state of Mecklenburg-Vorpommern and the Bundes-
ministerium fꢀr Bildung und Forschung (BMBF) for financial
support. We also thank the analytic department in LIKAT for analytic
support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201311198.
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Table 1: Carbonylative synthesis of amides.[a,b]
was to transform the in situ generated phenol into the aryl
nonaflate, which could further act as a pseudohalide. The
in situ generated CO accompanied by a nucleophile, thus
furnishes carbonylation reactions without the need for
external CO (Scheme 1).
We started our investigations using the following reaction
conditions: aniline (0.5 mmol, 1 equiv), phenyl formate
(0.5 mmol, 1 equiv), FNf (0.5 mmol, 1 equiv), with 2 mol%
of Pd(OAc)2, 6 mol% of BuPAd2, and with 3 equivalents of
Et3N as a base in MeCN at 808C for 24 hours. Surprisingly,
22% of benzanilide was observed and phenyl benzoate and
phenylnonaflate were observed as by products. Subsequently,
we tested various ligands (dppe, dppp, dppb, PPh3, etc.) and
bases, and also varied the amounts of phenyl formate and
nonafluorosulfonyl fluoride used (see the Supporting Infor-
mation). We identified the optimized reaction conditions to
be include dppp (3 mol%) as the ligand, Pd(OAc)2 (2 mol%)
as the catalyst, with 1.5 equivalents of phenyl formate and
2 equivalents of FNf, which acts as the pseudohalide and as
well as the CO source, and the desired benzanilide was
formed in 93% yield in the presence of 1 equivalent of
aniline.
With the best reaction conditions, different anilines were
subjected to the reaction (Table 1). Anilines bearing electron-
donating groups, such as anisidine and toluidine, resulted in
excellent yields (90% and 96%, respectively). Also, many
anilines bearing electron-withdrawing groups, such as the
cyano, carboxylate group, chloro, and fluoro group, gave good
yields of the corresponding amides (81–88%). Even the
trifluoromethyl group, which is a strong electron-withdrawing
group, led to moderate yield of the desired amide upon
isolation (65%). Additionally, to learn about the steric effect
of aniline derivatives, ortho-toluidine was tested, and
although the conversion was lower, 75% of the product was
obtained upon isolation. Naphthyl amine was then tested and
moderate yield was obtained (64%). More interestingly, the
reaction works well with a heteroaromatic amine such as 2-
aminopyrazine, and good yield was obtained (71%). Notably,
in the case of 3-amino-2-chloropyridine, the corresponding
amide was isolated in 55% yield and the chloro substituent on
the pyridine ring remained intact, even though it is considered
to be highly reactive under palladium catalysis. However, the
use of aliphatic amines such as morpholine and octylamine
was not successful and afforded only the formylation product
of the corresponding amines. Moreover, to learn about the
electronic effects as well as the steric effect of the phenyl
formate on this reaction, different formates were tested in
addition. Although ortho-methoxy-substituted phenyl for-
mate gave lower yield (50%), the other aryl formates showed
good reactivity towards the corresponding benzanilides.
1,3-Ynones moieties are known as versatile substrates for
natural product synthesis.[13] With this in mind, it would be
interesting to synthesize these molecules under CO-free
conditions. During the course of our reaction optimization
(see Table S2 in the Supporting Information), we found that
when the scale of the reaction was increased to 1 mmol,
a higher pressure of generated CO was necessary to facilitate
the reaction. After optimization [Pd(OAc)2 (5 mol%), dppf
(7.5 mol%), Et3N (5 equiv), phenyl formate (2 equiv), NfF
[a] Reaction conditions: Aniline (0.5 mmol), phenyl formate
(0.75 mmol), C4F9SO2F (2 equiv), Pd(OAc)2 (2 mol%), dppp (3 mol%),
Et3N (3 equiv), CH3CN (2 mL) in a 12 mL sealed vial, 808C, 16 h.
[b] Yields of isolated products. dppp=l,3-bis(diphenylphosphanyl)pro-
pane.
(2.5 equiv), phenylacetylene (1 equiv, 1 mmol) at 808C for
16 h] good yield of the desired alkynone was obtained (81%;
Table 2). The the scope of this transformation was then
investigated, and moderate to good yields were obtained with
different substituted phenylacetylenes and aryl formats under
identical reaction conditions (54–88%).
Furanones represent an important family of organic
compounds in natural products and bioactive derivatives.
Our previous work has shown that by using a carbonylative
reaction, furanones can be synthesized under palladium-
catalyzed coupling reactions.[14] Surprisingly, when prop-2-yn-
1-ylbenzene (6) was subjected to the reaction conditions, the
furanone 7a was obtained selectively with a moderate yield
(76%; Scheme 2). Other phenyl formates, such as para-
fluorophenyl formate and even the sterically hindered ortho-
methoxy phenyl formate, were tested without further opti-
mization and gave the desired furanones in 67–71% yields
upon isolation. This reaction represents the first carbonylative
synthesis of furanones in a CO-free manner.
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Table 2: Carbonylative synthesis of alkynone without external CO.[a,b]
Scheme 3. Palladium-catalyzed synthesis of symmetrical phenyl ben-
zoate derivatives without external CO. Reaction conditions: Phenyl
formate (1 mmol), C4F9SO2F (0.5 equiv), Pd(OAc)2 (1 mol%), Xant-
phos (1.5 mol%), Et3N (1.5 equiv), CH3CN (2 mL) in a 12 mL sealed
vial, 808C, 16 h. Yields are those of the isolated products. Xant-
phos=9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene.
produced by our procedure as well. Phenyl 4-methoxyben-
zoate was isolated in 83% yield from phenyl formate and p-
methoxyphenol in a one-pot manner without further optimi-
zation (Scheme 4).
With respect to the reaction mechanism, as shown in
Scheme 5, the aryl formate decomposes to generate one
molecule of CO and phenol which will further react with
perfluorobutanesulfonyl fluoride to generate aryl nonaflate
(ArONf). Palladium acetate is reduced to Pd0 and starts the
catalytic cycle.[15] Subsequently, nonaflate will act as a pseu-
dohalide and undergo oxidative addition with Pd0. After the
[a] Reaction conditions: Phenylacetylene (1 mmol), phenyl formate
(2 mmol), C4F9SO2F (2.5 equiv), Pd(OAc)2 (5 mol%), dppf (7.5 mol%),
Et3N (5 equiv), CH3CN (5 mL) in a 12 mL sealed vial, 808C, 16 h.
[b] Yields of isolated products. dppf=1,1’-bis(diphenylphosphino)ferro-
cene.
Scheme 4. Palladium-catalyzed synthesis of unsymmetrical phenyl ben-
zoates without external CO. Reaction conditions: p-methoxyphenol
(0.5 mmol, 1 equiv), phenylformate (0.75 mmol), C4F9SO2F (1.5 equiv),
Pd(OAc)2 (2 mol%), Xantphos (3 mol%), Et3N (3 equiv), CH3CN
(2 mL) in a 12 mL sealed vial, 808C, 16 h. Yields are those of isolated
products.
Scheme 2. Palladium-catalyzed carbonylative synthesis of furanone
without external CO.
Based on our previous experience with the alkoxycarbo-
nylation of phenols to give esters using in situ formed aryl
nonaflates with 1 bar of external CO gas, we further extended
our methodology to ester synthesis in the absence of external
CO gas and using phenyl formate as the only substrate
(Scheme 3). By using Pd(OAc)2 (1 mol%), Xantphos
(1.5 mol%), NfF (0.5 equiv), and phenyl formate (1 equiv)
in acetonitrile at 808C, phenyl benzoate was produced in 87%
yield. With other phenyl formates (p-F, p-OMe, and o-OMe),
yields from 64 to 90% were obtained.
Notably, in addition to the above-mentioned symmetrical
aryl benzoates, unsymmetrical phenyl benzoates can be
Scheme 5. Proposed reaction mechanism.
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Keywords: carbon monoxide · carbonylation · cross-coupling ·
homogeneous catalysis · palladium
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