Palladium-catalyzed decarboxylative acylation of O-phenyl carbamates with α-oxocarboxylic acids at room temperature

Article abstract of DOI:10.1002/adsc.201200993

A palladium-catalyzed oxidative acylation of O-phenyl carbamates with α-oxocarboxylic acids via selective aromatic C-H bond activation is described. This protocol represents the first ortho-acylation of phenol derivatives, and a catalytic amount of triflic acid additive is crucial for this transformation. Copyright

Full text of DOI:10.1002/adsc.201200993

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DOI: 10.1002/adsc.201200993
Palladium-Catalyzed Decarboxylative Acylation of O-Phenyl
Carbamates with a-Oxocarboxylic Acids at Room Temperature
Satyasheel Sharma,+a Aejin Kim,+a Eonjeong Park,a Jihye Park,a Minyoung Kim,a
Jong Hwan Kwak,a,* Sang Hwi Lee,a Young Hoon Jung,a and In Su Kima,*
a
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
Fax : (+82)-31-292-8800; e-mail: jhkwak@skku.edu or insukim@skku.edu
+
These authors contributed equally.
Received: November 11, 2012; Published online: February 22, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200993.
Abstract: A palladium-catalyzed oxidative acylation
of O-phenyl carbamates with a-oxocarboxylic acids
via selective aromatic C H bond activation is de-
scribed. This protocol represents the first ortho-acy-
lation of phenol derivatives, and a catalytic amount
of triflic acid additive is crucial for this transforma-
tion.
tives is highly desired to minimize synthetic steps and
to avoid waste formation.
À
Transition metal-catalyzed oxidative acylation of ar-
omatic compounds with various directing groups,[11]
e.g., arylpyridines,[12] oxime,[13] acetanilides,[14] and
indole,[15] with aldehydes or alcohols were described.
À
However, decarboxylative C H bond acylations using
a-oxocarboxylic acids as acyl anion equivalents were
relatively unexplored. Gooßen first reported the Pd-
catalyzed decarboxylative cross-coupling reaction of
aryl bromides with a-oxocarboxylate salts as acyl
sources to provide unsymmetrical diaryl ketones.[16]
Later, Ge described elegant studies on Pd-catalyzed
decarboxylative ortho-acylation of acetanilides and
À
À
Keywords: acylation; C H activation; a-oxocarbox-
ylic acids; palladium; O-phenyl carbamates
Transition metal-catalyzed cross-coupling reactions phenylpyridines with a-oxocarboxylic acids via C H
with aryl metal reagents and aryl halides are one of bond activation.[17] Guo and Duan demonstrated de-
the most reliable tools for the synthesis of natural carboxylative acylation of cyclic enamides with a-oxo-
products and medically relevant molecules.[1] Recent- carboxylic acids to afford b-acylenamides via a cyclic
ly, transition metal-catalyzed decarboxylative cross- vinylpalladated intermediate.[18] Recently, we reported
coupling reactions using arylcarboxylic acids or aryl- a Pd-catalyzed decarboxylative acylation of O-methyl-
carboxylates as aryl surrogates have emerged as pow- ketoximes with a-keto acids.[19]
À
erful alternatives[2] since these methods avoid the for-
Catalytic C H bond functionalization of O-phenyl
mation of toxic metal wastes generated from stoichio- carbamates is a promising synthetic strategy for sub-
metric organometallic reagents, thus providing new stituted phenol derivatives.[20] Inspired by our recent
protocols for Mirozoki–Heck type reactions,[3] oxida- studies on transition metal-catalyzed oxidative acyla-
tive arylation,[4] redox-neutral biaryl synthesis,[5] and tion of benzamides[21] with aldehydes, we herein pres-
allylation.[6]
ent the palladium-catalyzed oxidative ortho-acylation
The ortho-acylphenols are important structural of O-phenyl carbamates with a-oxocarboxylic acids
motifs in natural products,[7] and are known to be im- via C H bond activation (Scheme 1).
À
portant synthetic intermediates in organic synthesis.[8]
Our initial study started from the coupling of
Friedel–Crafts acylation[9] and anionic Fries rear- phenyl dimethylcarbamate (1a) with phenylglyoxylic
rangement[10] are common methods for the prepara- acid (2a), according to the reaction conditions used in
tion of ortho-acylphenols. However, these methods the coupling of acetanilides with a-oxocarboxylic
present intrinsic drawbacks including the use of haz- acids[17a] (Table 1, entry 1). However, the combination
ardous Lewis acids, the deficiency of regioselectivity, of PdACTHNUGTRNEUNG(TFA)2 and (NH4)2S2O8 in diglyme solvent did
and the prefunctionalization of coupling partners. not promote the coupling of 1a and 2a. After exten-
Therefore, the development of truly catalytic alterna- sive examination for optimal reaction conditions, we
found the use of a catalytic amount of triflic acid
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Satyasheel Sharma et al.
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from PdACHTUNGTRNEUNG
(OAc)2 and TfOH.[20d] In this paper, the tri-
flate anion can tune the electrophilicity of the Pd(II)
center and improve the the insertion of Pd(II) into
À
the aromatic C H bonds of phenol esters. Screening
of solvents showed that DCE was the most effective
solvent in this coupling reaction (Table 1, entries 4–6).
Further study revealed that TfOH is unique in its
ability to facilitate high levels of conversion (Table 1,
entries 7 and 8). Other oxidants such as K2S2O8, Ag2O
and AgCO3 under otherwise identical conditions were
far less effective (Table 1, entries 9–11). Logically, it
was thought that the ratio of 3a and 3aa can be con-
trolled by the amounts of a-oxocarboxylic acid and
oxidant (Table 1, entries 12 and 13). Indeed, upon use
of 1.5 equiv. of (NH4)2S2O8 under otherwise identical
Scheme 1. Pd-catalyzed oxidative acylation of O-phenyl car-
bamates with a-oxocarboxylic acids.
(TfOH) additive in DCE solvent is very crucial for conditions, the formation of monoacylated product 3a
this transformation, producing monoacylated product was found to improve substantially (12:1) in good
3a and bisacylated product 3aa in 75% combined yield (68%). Also, the combination of 1.5 equiv. of 2a
yield with a 3:1 ratio, as shown in entries 2 and 3.
and 1.2 equiv. of (NH4)2S2O8 provided a significantly
Fu and Liu reported the isolation and X-ray analy- increased formation of 3a (>20:1) in moderate yield
sis of the O-phenyl carbamate palladacycle generated (58%). However, a reduction (1.2 equiv.) in the load-
Table 1. Selected optimization of reaction conditions.[a]
Entry
Oxidant (equiv.)
Additive (mol%)
TfOH (20)
Solvent
Yield [%][b] (3a:3aa)[c]
1[d]
2
3
4
5
6
7
8
9
10
11
12
13[e]
14[f]
15[g]
A
N
ACHTUNGTRENNUNG
N
R
E
T
R
diglyme
DCE
DCE
diglyme
THF
DMF
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
N.R.
75 (3:1)
N.R.
N.R.
trace
8
N.R.
trace
26 (5:1)
N.R.
TfOH (20)
TfOH (20)
TfOH (20)
AcOH (50)
TFA (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
K2S2O8 (2)
Ag2O (2)
Ag2CO3 (2)
T
ACHTUNGTRENNUNG
N.R.
68 (12:1)
58 (>20:1)
46 (15:1)
41 (1:1)
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
[a]
Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), PdACHTUNTRGNEU(GN OAc)2 (5 mol%), oxidant (quantity noted), additive (quantity
noted), solvent (2 mL) at room temperature for 20 h in pressure tubes.
[b]
[c]
[d]
[e]
[f]
Combined isolated yields of 3a and 3aa.
Ratio of 3a and 3aa was determined by crude H NMR analysis.
1
PdACHTUNGTRENNUNG(TFA)2 (5 mol%).
2a (0.45 mmol, 1.5 equiv.).
2a (0.36 mmol, 1.2 equiv.).
2a (0.9 mmol, 3 equiv.).
[g]
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Palladium-Catalyzed Decarboxylative Acylation of O-Phenyl Carbamates
Table 2. Scope of O-phenyl carbamates.[a]
[a]
Reaction conditions: 1a–j (0.3 mmol), 2a (0.6 mmol), Pd
(NH4)2S2O8 (0.45 mmol), TfOH (20 mol%), DCE (2 mL) in pressure tubes.
Yield isolated by column chromatography.
ACHTUNGRTEN(NUNG OAc)2 (5 mol%),
[b]
[c]
1
Ratio of monoacylated and bisacylated products determined by crude H NMR anal-
ysis.
408C.
[d]
ing of 2a with 1.5 equiv. of (NH4)2S2O8 was found to tion of meta-substituted O-phenyl carbamates 1h and
decrease the generation of acylated products 3a and 1i preferentially occurred at the more sterically acces-
3aa, albeit resulting in a high level of monoselectivity sible position to afford the corresponding product 3h
(15:1), as shown in entry 14. In contrast, by increasing and 3i as a single regioisomer. These data suggest that
the amounts of 2a and (NH4)2S2O8, the formation of steric effects of the substrate strongly interfere with
3a and 3aa was significantly decreased (Table 1, the formation of the cyclopalladated intermediate or
entry 15).
the proximity of a-oxocarboxylic acid 2a into the cy-
To evaluate the substrate scope of this process, clopalladated intermediate. However, fluoro-substitut-
a range of O-phenyl carbamates was subjected under ed O-phenyl carbamate 1j at the meta-position deliv-
the optimal reaction conditions (Table 2). The cou- ered a separable mixture of monoacylated and bisacy-
pling of phenylglyoxylic acid (2a) and symmetrical O- lated compounds in 54% combined yield with a low
phenyl carbamates 1b–1d with an electron-donating level of monoselectivity (2:1) under the current cata-
group (OMe) and halogen groups (F and Cl) at the lyst system.
para-position were found to be favored in the acyla-
To further explore the substrate scope and limita-
tion reaction to afford the corresponding products tions, a range of a-oxocarboxylic acids was screened
3b–3d with excellent levels of monoselectivities (> under optimal reaction conditions, as shown in
20:1), whereas substrates with electron-withdrawing Table 3. Electron-rich and electron-deficient phenyl-
groups (e.g., NO2 and CO2Et) at the para-position glyoxylic acids 2b–2f substituted at either the para- or
failed to deliver the acylation products under our op- meta-positions proved to be good substrates for this
timal reaction conditions. The ortho-substituted O- transformation, affording the corresponding products
phenyl carbamates 1e–1g were also found to be fa- 4b–4f. The halogen moieties on phenylglyoxylic acids
vored in this catalyst system. In addition, the acyla- 2g–2j were all tolerated under these reaction condi-
Adv. Synth. Catal. 2013, 355, 667 – 672
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Table 3. Scope of a-oxocarboxylic acids.[a]
[a]
[b]
Reaction conditions: 1d (0.3 mmol), 2b–l (0.6 mmol), PdACTHNUGTRNEUNG(OAc)2 (5 mol%), (NH4)2S2O8
(0.45 mmol), TfOH (20 mol%), DCE (2 mL) in pressure tubes.
Yield of product isolated by column chromatography.
tions. Notably, the chloro and bromo groups offer ver- hancing the rate of electrophilic metalation.[23] Thus
satile synthetic functionality for further manipulations the palladacycle I can react with 2a to afford the in-
using other cross-coupling reactions. In addition, 2- termediate II, which can undergo decarboxylation fol-
(naphthalen-2-yl)-2-oxoacetic acid (2k) and 2-oxo-2-
(thiophen-2-yl)acetic acid (2l) were also found to be
favored in the reaction to afford the desired products
4k and 4l with a slightly decreased reactivity.
Further investigations for the monoacylation and
bisacylation reactions of biscarbamate analogues were
conducted (Scheme 2). As expected, biscarbamate 5a
was converted to the monoacylated product 6a in
50% yield under optimal reaction conditions. Also, bi-
phenyl compound 5b containing two carbamate di-
recting groups provided exclusively bisacylated prod-
uct 6b in 61% yield using two times of the reaction
conditions used for monoacylation.
The postulated mechanism is outlined in Scheme 3.
First, a coordination of the O atom of 1a to Pd(II)
and the subsequent directed cyclopalladation provides
a 6-membered palladacycle I.[22] At this stage, OTf
anion may remarkably improve the electrophilicity of
the Pd center, in comparison with acetate anion, en- analogues.
Scheme 2. Monoacylation and bisacylation of biscarbamate
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Palladium-Catalyzed Decarboxylative Acylation of O-Phenyl Carbamates
with EtOAc (10 mL ꢁ 3). The combined organic layer was
dried over Mg2SO4 and concentrated under vacuum. The
residue was purified by silica gel column chromatography
(n-hexanes/EtOAc=10:1) to afford 3; yield: 60.2 mg (66%).
Acknowledgements
This work was supported by National Research Foundation
of Korea (No. 2010-0002465) funded by the Ministry of Edu-
cation, Science and Technology.
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2
À
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