A Mild and Chemoselective Hydrosilylation of α-Keto Amides by Using a Cs2CO3/PMHS/2-MeTHF System

Article abstract of DOI:10.1002/ejoc.201700374

A Cs₂CO₃-catalyzed hydrosilylation reaction of α-keto amides that proceeds through the in situ formation of MeSiH₃ has been developed by using inexpensive polymethylhydrosiloxane in 2-methyltetrahydrofuran (2-MeTHF) as the solvent. A wide range of aryl and alkyl α-keto amides, prepared from anilines and alkylamines, were subjected to the hydrosilylation conditions to afford α-hydroxy amides in moderate to excellent yields. This transition-metal-free protocol was applied to a chemoselective hydrosilylation, in which reduction occurred at the carbonyl of the α-keto amide functionality over that of the simple ketone, and further extended to a gram-scale protocol.

Full text of DOI:10.1002/ejoc.201700374

A Journal of
Accepted Article
Title: A Mild and Chemoselective Hydrosilylation of ꢀ-Keto Amides
using Cs2CO3/PMHS/2-MeTHF System
Authors: Govindharaj Kumar, Alagesan Muthukumar, and
Govindasamy Sekar
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700374
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10.1002/ejoc.201700374
European Journal of Organic Chemistry
FULL PAPER
A Mild and Chemoselective Hydrosilylation of -Keto Amides
using Cs2CO3/PMHS/2-MeTHF System
Govindharaj Kumar, Alagesan Muthukumar, and Govindasamy Sekar*[a]
Abstract: A Cs2CO3-catalyzed hydrosilylation of -keto amides
through in situ formation of MeSiH3 from inexpensive
polymethylhydrosiloxane in 2-MeTHF as solvent is developed. A
wide range of aryl and alkyl -keto amides derived from anilines and
alkyl amines are subjected to hydrosilylation to afford -hydroxy
amides in moderate to excellent yields. This transition metal-free
protocol can be applied to chemoselective hydrosilylation where the
reduction undergoes only to the keto functionality of -keto amides
in the presence of simple ketones and further extended to a gram-
scale reaction.
using Ph2SiH2.[11] However, use of expensive Ph2SiH2 usually
results in high molecular weight silanol based by-products which
may cause separation issues.
Very recently, we have developed a mild K3PO4-catalyzed
chemoselective reduction of -keto amides to highly important
-hydroxy amides or mandelamides[12] using cheap, shelf-stable,
water soluble and eco-friendly polymethylhydrosiloxane (PMHS)
as the hydride source.[13] But the transformation is associated
with few shortcomings like reduced or failed reactivity of aliphatic
amine derived -keto amides and limited substrate scope for the
chemoselective hydrosilylation of -keto amides bearing isolated
ketones. Hence, finding of a better catalytic system to overcome
the limitations is needed. Similar to phosphate bases, carbonate
bases are mild basic, commercially available and known for their
catalytic activities in organic transformations.[14] Thus we
planned to explore our research in the carbonate-catalyzed
hydrosilylation.
Introduction
Reduction of carbon-hetero atom multiple bonds is always of
crucial importance in synthetic organic chemistry which involves
several applications in both academic and industrial research.[1]
Although various transition metal-catalyzed reduction reactions
are found to be known so far,[2] the current research endeavours
are involved in development of alternative catalytic systems
which are free from transition metals to avoid contamination of
such metal impurities in pharmaceutically related products.[3]
Traditionally, boron and aluminium based reducing agents are
being used as hydride source for the reduction of carbonyl
functionalities. However, the use of these reagents is associated
with certain drawbacks like need of inert and low temperature
conditions, sensitivity to air as well as moisture, tedious workup
procedures and chemoselective issues etc.[4]
As part of our interest in reduction chemistry,[15] we herein
report a Cs2CO3-catalyzed chemoselective hydrosilylation of -
keto amides using PMHS. This methodology depicts selective
hydrosilylation of keto functionality of -keto amides in presence
of amide and simple ketone functionalities (Scheme 1).
Hydrosilanes have become alternative to the traditional
reagents for the reduction of functionalities such as carbonyl,
nitro, imine and alkyne due to their air stability, economic and
environmentally benign properties.[5] In this context, metal-free
hydrosilylation of carbonyl groups has received importance
among chemists in recent years. The metal-free hydrosilylation
can be classified into two major categories such as acid- and
base-catalyzed hydrosilylation reactions.[6] Among them, base-
catalyzed hydrosilylation of carbonyls is the topic of our interest.
Recently, KOtBu,[7] NaOH/KOH[8] and TBAF[9] have been
presented as active catalysts for hydrosilylation of ketones,
esters, amides and imides. In addition, Cui and co-workers have
reported Cs2CO3 as an efficient catalyst for hydrosilylation of
amides using PhSiH3.[10] Later, the same group has explored
chemoselective hydrosilylation of aldehydes as well as ketones
Scheme 1. Cs2CO3-catalyzed chemoselective hydrosilylation of -keto amide.
Results and Discussion
The optimization study was carried out with 0.5 mmol of simple
-keto anilide 1a as the model substrate which was derived from
phenylglyoxalic acid and aniline. The results of the optimization
studies have been depicted in Table 1. Initially, the activity of
alkali metal carbonates has been tested. When 1a was treated
with 2.0 equiv. of PMHS and 10 mol% of Cs2CO3 as the catalyst
in toluene at 60 oC, it gave the chemoselectively reduced -
hydroxy amide 2a in 55% yield and the global reduction product
3a in 40% yield, respectively (entry 1). When the reaction was
brought to ambient temperature,
a better selectivity was
[a]
G. Kumar, A. Muthukumar, Dr. G. Sekar*, Department of Chemistry,
Indian Institute of Technology Madras, Chennai-600036, India
E-mail: gsekar@iitm.ac.in
observed as the reaction gave 83% of 2a and 8% of 3a in 12 h
(entry 2). Then the amount of catalyst was reduced to 5 mol%
and it rendered exclusively 92% of 2a in 16 h (entry 3). The
results with other hydrosilanes such as Et3SiH, (EtO)3SiH,
Cl(CH3)2SiH and Cl2(CH3)SiH were not productive. Then, the
Homepage: http://chem.iitm.ac.in/faculty/sekar/
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201700374
European Journal of Organic Chemistry
FULL PAPER
role of solvent for this chemoselective hydrosilylation reaction
was examined. When polar aprotic solvents like 1,4-dioxane and
THF were used as solvents for 24 h, similar results were found
(entries 4 and 5). The chlorinated solvents DCM and 1,2-DCE
gave the corresponding product in 64% and 75% yields,
respectively (entries 6 and 7).
the transformation (entry 15). From the optimization studies, it is
understood that only Cs2CO3 and K2CO3 are capable to show
activity than rest of the carbonate bases which indicate the size
of the cations associated with carbonate play a vital role in
determining the reaction rate. This observation is in accordance
with Fajan’s rule i.e., when the size of cation increases, the ionic
character of the salt increases. Among the ions of alkali and
alkaline earth metals, Cs+ has the largest ionic radius and
weakest polarizing field.[17] Thus Cs2CO3 exists in ionic form
which may assist the carbonate ion freely available to interact
with hydrosilanes. Considering the yield of product and reaction
time, Cs2CO3 was chosen as the catalyst for this transformation.
To begin with the scope of this protocol, initially, a set of -
keto anilides were subjected to hydrosilylation under the
optimized reaction conditions and the results are shown in Table
2. Substrates with electron-releasing groups, like 4-methyl and
2,6-dimethyl containing -keto anilides reacted smoothly to give
the corresponding -hydroxy anilides 2b and 2c in 85% and
72% yields, respectively. When 4-methoxy phenyl tethered to
the keto part of -keto anilide was treated under the standard
reaction conditions, it gave 90% of the corresponding product 2d
in 8 h. The mild electron-acceptor halo substituted -keto
anilides were converted to the corresponding -hydroxy anilides
2e-2g in moderate to excellent yields.
Table 1. Optimization of reaction conditions.[a]
Yield[b] (%)
Temp.
(oC)
Time
(h)
Entry
MxCO3 (mol%)
Solvent
2a
55
83
92
80
80
64
75
93
nd
88
nd
nd
nd
nd
nd
3a
40
8
1
Cs2CO3 (10)
Cs2CO3 (10)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Na2CO3 (5)
K2CO3 (5)
Li2CO3 (5)
CaCO3 (5)
SrCO3 (5)
BaCO3 (5)
None
Toluene
Toluene
Toluene
1,4-Dioxane
THF
60
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
10
12
16
24
24
30
24
6
2
3
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd[c]
4
5
6
DCM
Table 2. Scope of -keto anilides.[a],[b]
7
1,2-DCE
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
8
9
48
36
48
48
48
48
48
10
11
12
13
14
15
[a] Reaction conditions: 0.5 mmol of 1a in 2.0 mL of solvent.
[b] Isolated yield.
[c] In the absence of catalyst.
nd = not detected.
Interestingly, when the greener solvent 2-MeTHF (2-
methyltetrahydrofuran)[16] was used, a drastic improvement in
reactivity was observed. This resulted in 93% of the selective
reduction product in 6 h (entry 8). Next, other carbonate bases
were screened as catalyst for this reduction process (entries 9-
11). In the case of K2CO3, the reaction was slow and yielded
88% of 2a in 36 h (entry 10). However, the reactions with
Na2CO3 and Li2CO3 failed to proceed even after 48 h (entries 9
and 11). Further, the ability of alkaline earth metal carbonates
like CaCO3, SrCO3 and BaCO3 to activate Si-H bond of PMHS
was studied (entries 12-14). The formation of -hydroxy amide
was observed in none of the cases. A failure of reaction in the
absence of catalyst indicates the essence of catalyst to effect
[a] Reaction conditions: 0.5 mmol of 1 in 2.0 mL of 2-MeTHF.
[b] Isolated yield.
[c] 4.0 equiv. of PMHS was used.
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10.1002/ejoc.201700374
European Journal of Organic Chemistry
FULL PAPER
Table 4. Scope of chemoselective hydrosilylation of -keto amide.[a],[b]
When the strong electron-acceptors bearing -keto anilides
were subjected for reduction, they resulted in corresponding
products 2h-2l in 70-84% yields. It is important to mention that
the functional groups like nitro, amido, cyano and halo which are
prone to reduction were well tolerated. 1-Amino naphthalene
derived -keto amide rendered 85% of the respective -hydroxy
amide 2m in 9 h. When the di--keto amide prepared from 4-
(aminomethyl)aniline was treated for hydrosilylation, 70% of di-
-hydroxy amide 2n was isolated in 22 h. Interestingly, 2-
oxobutanoic acid derived aliphatic -keto amides bearing
enolizable protons were successfully converted in this base-
catalyzed hydrosilylation protocol to the respective -hydroxy
amides 2o and 2p in 76% and 73% yields, respectively.
From our previous report,[13] it is evident that the alkyl amine
derived -keto amides are less reactive than aniline derived -
keto amides. So, our focus was shifted towards the reactivity of
-keto amides that were prepared from alkyl amines and their
derivatives (Table 3). To our delight, the reactions worked well
under the standard reaction conditions. Cyclopropyl group
containing -keto amide resulted in the respective product 5a in
73% yield. Similarly, cyclohexyl group bearing -keto amide also
gave the corresponding product 5b in 72% yield. n-Butyl amine
and allyl amine containing -keto amides yielded 75% of 5c in
16 h and 76% of 5d without affecting the double bond in 16 h.
Likewise, 4-methoxy and 2-chloro benzylamines derived -keto
amides were also successfully reduced to the corresponding
mandelamides 5e and 5f in 78% and 80% yields, respectively.
[a] Reaction conditions: 0.5 mmol of 6 in 2.0 mL of 2-MeTHF.
[b] Isolated yield.
The efficiency of chemoselective hydrosilylation was tested
on a gram-scale reaction. For this purpose, 5.24 mmol of the -
keto amide 6c was subjected to reduction using 0.26 mmol of
Cs2CO3 and 10.48 mmol of PMHS in 20 mL of 2-MeTHF at
ambient temperature for 28 h (Scheme 2). The reaction gave
80% of the selectively reduced product 7c without perturbing the
acetyl group and the solvent 2-MeTHF was recovered after
workup with no major loss. It is noteworthy that an improvement
in the yield and similar selectivity were observed in this reaction
in comparison with the small-scale reaction (Table 4, 7c).
Table 3. Scope of -keto amides derived from alkyl amines.[a],[b]
Scheme 2. Gram-scale chemoselective hydrosilylation.
To shed light on the mechanism of the reaction, a 1:1
mixture of Cs2CO3 and PMHS was stirred in CDCl3 at room
temperature for 2 h. The resultant reaction mixture was analyzed
by 1H-NMR spectroscopy (Figure 1). The peak corresponding to
Si-H in Figure 1A disappeared and a new quartet was observed
at 3.52 ppm in Figure 1B. Also the appearance of new quartet at
0.18 ppm perhaps indicates the formation of MeSiH3 during the
course of the reaction.[19] This result is in consistent with the
experiment reported by Nikonov et al. who demonstrated that
when more basic KOtBu, KOH and TBAF were treated with
PMHS, a quick formation of MeSiH3 was observed via siloxane-
silane rearrangement that acted as the reducing agent. But the
formation of MeSiH3 was observed with weaker acetate catalyst
only at 70 oC.[7b] Since Cs2CO3 is a moderate base and the
hydrosilylation of -keto amides worked well at ambient
temperature, there could be a possibility for the formation of
MeSiH3 from the interaction of carbonate ion with PMHS. In
addition, removal of the volatile compounds from the
Cs2CO3/PMHS/2-MeTHF mixture prior to the addition of 1a
resulted in no hydrosilylation.
[a] Reaction conditions: 0.5 mmol of 4 in 2.0 mL of 2-MeTHF.
[b] Isolated yield.
Next, the scope of chemoselective hydrosilylation of -keto
amides bearing two similar functional groups was studied. That
is, when acetyl or aroyl substituted -keto amides were treated,
the keto group of -keto amides should undergo hydrosilylation
to give corresponding mandelamides without affecting the
simple ketones. Acetyl group attached to ortho, meta and para
positions of anilide ring was well tolerated and resulted in
corresponding acetyl -hydroxy amides 7a-7c in good yields. 4-
Benzoyl substituted -keto amide was also converted to 7d in
66% yield. Notably, in the case of aliphatic -keto amide system
bearing ethyl and methyl keto groups, the reduction took place
only at ethyl ketone to give the corresponding -hydroxy amide
7e in 65% yield.
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10.1002/ejoc.201700374
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Based on the experimental evidences,
a
plausible
mechanism is proposed in Scheme 4. Initially, the dibasic
carbonate ion A might interact with PMHS B to give the silicone
gel (MeSi(O-)3)n C and MeSiH3 D. Further interaction of A with D
would give the pentavalent silicate species E. Interaction of E
with N-H functionality of -keto amide F would give the
hexavalent species G which is nucleophilic in nature[20] and
might undergo simultaneous hydride transfer to the activated
ketone and carbonate A expulsion for next catalytic cycle to give
silyl ether I. Hydrolysis of I might result in -hydroxy amide J.
Alternatively, the reaction might undergo via the deprotonation of
secondary N-H of -keto amide to give an amidate which might
further coordinate with methylsilane to form a silicate species.
Then the hydride transfer might take place through an
intramolecular fashion to give -hydroxy amide.
Figure 1. 1H-NMR spectra of PMHS (A) and PMHS and Cs2CO3 (B) in CDCl3
(500 MHz).
In order to isolate the silyl ether intermediate, a reaction was
carried out by purging the MeSiH3 gas which was generated
from one compartment by the reaction of PMHS with Cs2CO3
(1:1 ratio) in dry 2-MeTHF to another compartment containing -
keto amide 1a and 5 mol% of Cs2CO3 in dry 2-MeTHF with the
aid of continuous nitrogen gas flow. However, isolation of the
silyl ether intermediate was unsuccessful as the reaction
rendered 86% of -hydroxy amide 2a as the sole product. This
might be due to the unstability of silyl ether of -hydroxy amide
in the reaction medium and as a result, a rapid Si-O bond
cleavage might have taken place.
To confirm this observation, the silyl ether
8 was
synthesized[13] and subjected to the optimized reaction
conditions (Scheme 3, eq. 1). The reaction resulted in the
formation of -hydroxy amide 2a in 68% yield. This experiment
confirms that the silyl ether of -hydroxy amide undergoes a
rapid hydrolysis during the course of the reaction. Furthermore,
to know the reactivity of tertiary -keto amide, N-methyl--keto
amide 9 was treated under the standard reaction conditions
(Scheme 3, eq. 2). The reaction failed to give the corresponding
-hydroxy amide even after 24 h. This depicts the importance of
free amide N-H functionality for the progress of the reaction by
the chelation between amide N-H and silane and thereby it may
enhance the reactivity of -keto amide. This could be the
possible reason for the selective reduction -keto amide than
the rest of the functional groups.
Scheme 4. Plausible reaction pathway for carbonate-catalyzed hydrosilylation
of -keto amide.
Conclusions
In conclusion,
a
mild and efficient Cs2CO3-catalyzed
hydrosilylation of -keto amides to highly important
mandelamides has been developed using PMHS in 2-MeTHF.
A study on various carbonate catalysts revealed the importance
of the size of cations associated with the carbonate anion. Both
aromatic and aliphatic ketones of -keto amides prepared from
aliphatic as well as aromatic amines were successfully
underwent hydrosilylation and rendered the -hydroxy amides in
moderate to excellent yields. Site-selective reduction of -keto
amides and extension to a gram-scale reaction are important
features of this protocol. Use of transition metal-free catalyst,
inexpensive PMHS and recoverable green solvent 2-MeTHF
make this transformation an eco-friendly process. The
mechanistic study involves the formation of MeSiH3 from the
interaction of Cs2CO3 with PMHS which was detected in 1H-NMR
spectroscopy.
Scheme 3. Control experiments.
Experimental Section
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10.1002/ejoc.201700374
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General Considerations
resulting residue was purified by silica gel column chromatography
(eluent: hexanes-ethyl acetate, 80:20) to result pure N-(4-acetylphenyl)-
2-hydroxy-2-phenylacetamide 7c in 80% yield.
All the carbonate salts and hydrosilanes were purchased from Sigma–
Aldrich, Alfa Aesar and Spectrochem Pvt. Ltd. 2-MeTHF was purchased
from Alfa Aesar. Thin-layer chromatography (TLC) was performed using
Merck silica gel 60 F254 pre-coated plates (0.25 mm) and visualized by
UV fluorescence quenching. Silica gel for column chromatography (100–
200 mesh) was purchased from Avra Synthesis Pvt. Ltd. 1H and 13C
2-Hydroxy-N,2-diphenylacetamide 2a: Yield 93%; colorless solid; mp =
148-150 oC (Lit.[15e] mp = 150-151 oC); Rf = 0.32 (hexanes:ethyl acetate
(8:2); IR (KBr) ν = 3428, 3298, 3248, 3298, 3240,1655, 1555, 1497, 1236,
907, 782 cm-1; 1H NMR (500 MHz, DMSO-d6) δ = 5.10 (d, J = 4.5 Hz,
1H ), 6.43 (d, J = 5.0 Hz, 1H), 7.04 (t, J = 7.5 Hz, 1H), 7.25-7.31 (m, 3H),
7.32-7.38 (m, 2H), 7.51 (d, J = 7.5 Hz, 2H), 7.69 (d, J = 7.5 Hz, 2H), 9.91
(s, 1H); 13C NMR (125 MHz, DMSO-d6) δ = 74.0, 119.7, 123.5, 126.6,
127.6, 128.1, 128.6, 138.5, 140.9, 171.2; HRMS (ESI) calcd for
C14H13NO2Na [M+Na]+ 250.0844; found 250.0859.
1
NMR spectra were recorded on a Bruker 400 or 500 MHz instrument. H
NMR spectra are reported relative to residual CHCl3 (δ = 7.26 ppm) or
DMSO-d6 (δ= 2.50 ppm). 13C NMR are reported relative to CHCl3 (δ =
77.16 ppm) or DMSO-d6 (δ = 39.52 ppm). FTIR spectra were recorded
on a JASCO spectrometer and are reported in frequency of absorption
(cm-1). High resolution mass spectra (HR-MS) were recorded on Q-Tof
Micro mass spectrometer.
2-Hydroxy-2-phenyl-N-(p-tolyl)acetamide 2b: Yield 85%; colorless
solid; mp
= =
165-167 oC (Lit.[13] mp 167-168 oC); Rf = 0.43
General Experimental Procedure for Synthesis of -Keto Amides
(hexanes:ethyl acetate (7:3); IR (KBr) ν = 3284, 3196, 1672, 1542, 1415,
1
1357, 1183, 961, 767, 698 cm-1; H NMR (500 MHz, DMSO-d6) δ = 2.24
(s, 1H), 5.08 (d, J = 5.0 Hz, 1H), 6.40 (d, J = 5.0 Hz, 1H), 7.09 (d, J = 8.5
Hz, 2H), 7.26-7.33 (m, 1H), 7.35-7.37 (m, 2H), 7.49-7.53 (m, 2H), 7.55-
7.60 (m, 2H), 9.82 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ = 20.4, 74.0,
119.7, 126.6, 127.6, 128.1, 129.0, 132.4, 136.0, 140.9, 170.9; HRMS
(ESI) calcd for C15H15NO2Na [M+Na]+ 264.1000; found 264.0985.
To a stirred mixture of benzoylformic acid (2.0 mmol) and Et3N (4.0
mmol) in CH2Cl2 (10 mL) at 0 C, thionyl chloride (4.0 mmol) was added
o
dropwise under a nitrogen atmosphere. The stirring was continued for 20
min and then a suspension of the corresponding amine (2.0 mmol) in
CH2Cl2 (10 mL) was added slowly to the reaction mixture at 0 oC under a
nitrogen atmosphere. The stirring was continued at room temperature
and the completion of reaction was monitored by TLC. The organic layer
was washed with water and with saturated NaHCO3 solution for two
times, respectively or until the effervescence stopped. Finally, the organic
layer was washed with water, dried over Na2SO4 and evaporated under
reduced pressure. The solid residue was purified by silica gel column
chromatography.
N-(2,6-Dimethylphenyl)-2-hydroxy-2-phenylacetamide 2c: Yield 72%;
colorless solid; mp = 140-142 oC (Lit.[13] mp = 140-141 oC); Rf = 0.48
(hexanes:ethyl acetate (7:3); IR (KBr) ν = 3386, 3313, 1668, 1522, 1046,
751, 695 cm-1; 1H NMR (400 MHz, DMSO-d6) δ = 2.01 (s, 6H), 5.11 (d, J
= 4.4 Hz, 1H), 6.35 (d, J = 4.4 Hz, 1H), 6.98-7.10 (m, 3H), 7.26-7.32 (m,
1H), 7.34-7.40 (m, 2H), 7.55 (d, J = 7.2 Hz, 2H), 9.39 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ = 17.9, 74.0, 126.4, 126.6, 127.5, 127.6, 128.0,
134.8, 135.4, 141.4, 170.9; HRMS (ESI) calcd for C16H17NO2Na [M+Na]+
278.1157; found 278.1129.
General
Experimental
Procedure
for
Cs2CO3-catalyzed
Chemoselective hydrosilylation of -Keto Amides
2-Hydroxy-2-(4-methoxyphenyl)-N-phenylacetamide 2d: Yield 90%;
colorless solid; mp = 93-95 oC (Lit.[15e] mp = 94-95 oC); Rf = 0.34
(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3330, 2967, 1655, 1506, 1260,
1124, 1046, 909, 769 cm-1; 1H NMR (400 MHz, DMSO-d6) δ = 3.73 (s,
3H), 5.03 (d, J = 4.0 Hz, 1H), 6.31 (d, J = 4.4 Hz, 1H), 6.91 (d, J = 8.0 Hz,
2H), 7.04 (t, J = 6.8 Hz, 1H), 7.28 (t, J = 7.2 Hz, 2H), 7.42 (d, J = 8.0 Hz,
2H), 7.69 (d, J = 7.2 Hz, 2H), 9.86 (s, 1H); 13C NMR (100 MHz, DMSO-
d6) δ = 55.1, 73.6, 113.5, 119.6, 123.5, 127.8, 128.6, 133.0, 138.6, 158.3,
171.4.
To an oven-dried reaction tube equipped with a magnetic bar, -keto
amide (0.5 mmol) and Cs2CO3 (0.05 mmol) were weighed and 2.0 mL of
2-MeTHF was added. Then, 1.0 mmol of PMHS was slowly added to the
reaction mixture. The reaction tube was closed with a glass stopper and
the resulting reaction mixture was stirred vigorously at room temperature.
The progress of the reaction was monitored by TLC. After complete
consumption of starting material, 10 mL of 5% aqueous NaOH solution
was added to the reaction and the resulting mixture was stirred for 10
min. The reaction mixture was extracted with ethyl acetate (2×10 mL).
The combined organic layers were washed with brine, dried over
anhydrous MgSO4, filtered off and the solvent was removed under
reduced pressure. The resulting residue was purified by silica gel column
chromatography (eluent= hexanes:ethyl acetate, 80:20) to obtain pure a-
hydroxyamide.
N-(2-Bromophenyl)-2-hydroxy-2-phenylacetamide 2e: Yield 93%;
colorless solid; mp = 78-80 oC; Rf = 0.30 (hexanes:ethyl acetate (8:2); IR
1
(KBr) ν = 3288, 3047, 1658, 1546, 1405, 1268, 1064, 767, 622 cm-1; H
NMR (500 MHz, DMSO-d6) δ = 5.17 (d, J = 3.5 Hz, 1H), 7.00 (t, J = 4.5
Hz, 1H), 7.05-7.11 (m, 1H), 7.28-7.33 (m, 1H), 7.34-7.41 (m, 3H), 7.50
(d, J = 7.0 Hz, 2H), 7.64-7.71 (m, 1H), 8.07-8.12 (m, 1H), 9.64 (s, 1H);
13C NMR (125 MHz, DMSO-d6) δ = 73.7, 114.4, 122.2, 125.9, 126.7,
127.9, 128.3, 128.5 132.6, 135.4, 140.4, 170.9; HRMS (ESI) calcd for
C14H12BrNO2Na [M+Na]+ 327.9949; found 327.9967.
Experimental Procedure for the Gram-Scale Synthesis of N-(4-
Acetylphenyl)-2-hydroxy-2-phenylacetamide 7c
To an oven-dried 50 mL round-bottom flask equipped with a magnetic
bar, 1.40 g of N-(4-acetylphenyl)-2-oxo-2-phenylacetamide 6c (5.24
mmol) and 84 mg of Cs2CO3 (0.26 mmol) were weighed and 20 mL of 2-
MeTHF was added. Then, 0.6 mL (10.48 mmol) of PMHS was slowly
added to the reaction mixture. The container was closed with a glass
stopper and allowed for vigorous stirring at room temperature for 28 h.
After complete consumption of starting material, 25 mL of 5% aqueous
NaOH solution was added to the reaction and the resulting mixture was
stirred for 10 min. The organic layer was withdrawn, dried over
anhydrous MgSO4, filtered off and the solvent was removed under
reduced pressure. The solvent was recovered without major loss. The
N-(3-Chlorophenyl)-2-hydroxy-2-phenylacetamide 2f: Yield 61%;
colorless solid; mp = 166-168 oC; Rf = 0.23 (hexanes:ethyl acetate (8:2);
IR (KBr) ν = 3393, 3298, 3062, 1648, 1529, 1460, 1246, 1031, 887, 764
cm-1; 1H NMR (500 MHz, DMSO-d6) δ = 5.11 (d, J = 4.5 Hz, 1H), 6.51 (d,
J = 4.5 Hz, 1H), 7.09-7.12 (m, 1H), 7.26-7.30 (m, 1H), 7.31-7.33 (m, 1H),
7.34-7.38 (m, 2H), 7.51 (d, J = 7.5 Hz, 2H), 7.63-7.67 (m, 1H), 10.14 (s,
1H); 13C NMR (125 MHz, DMSO-d6) δ = 74.1, 118.2, 119.2, 123.2, 126.6,
127.7, 128.1, 130.3, 132.9, 140.0, 140.6, 171.7; HRMS (ESI) calcd for
C14H12NO2ClNa [M+Na]+ 284.0454; found 284.0477.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700374
European Journal of Organic Chemistry
FULL PAPER
N-(4-Chlorophenyl)-2-hydroxy-2-phenylacetamide 2g: Yield 89%;
colorless solid; mp = 162-164 oC (Lit.[13] mp = 159-160 oC); Rf = 0.25
(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3285, 2905, 1623, 1519, 1245,
(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3388, 3326, 1667, 1599, 1529,
1
1271, 1116, 832, 594 cm-1; H NMR (400 MHz, DMSO-d6) δ = 5.28 (d, J
= 4.4 Hz, 1H), 6.57 (d, J = 4.4 Hz, 1H), 7.29-7.36 (m, 1H), 7.40 (t, J = 7.2
Hz, 2H), 7.45-7.56 (m, 3H), 7.57-7.66 (m, 3H), 7.78 (d, J = 8.0 Hz, 1H),
7.84-7.98 (m, 2H), 10.07 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ = 74.0,
121.7, 122.2, 125.6, 126.0, 126.1, 126.7, 127.7, 127.9, 128.2, 133.0,
133.7, 141.0, 171.7.
1
1059, 822, 699, cm-1; H NMR (500 MHz, DMSO-d6) δ = 5.09 (d, J = 4.5
Hz, 1H), 6.49 (d, J = 4.5 Hz, 1H), 7.26-7.31 (m, 1H), 7.32-7.34 (m, 2H),
7.35-7.38 (m, 2H), 7.50 (d, J = 7.5 Hz, 2H), 7.75 (d, J = 9.0 Hz, 2H),
10.10 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ = 74.1, 121.3, 126.6,
127.1, 127.7, 128.2, 128.5, 137.6, 140.7, 171.4; HRMS (ESI) calcd for
C14H12NO2ClNa [M+Na]+ 284.0454; found 284.0481.
2-Hydroxy-N-(4-(2-hydroxy-2-phenylacetamido)benzyl)-2-
phenylacetamide 2n: Yield 80%; colorless solid; mp = 189-191 oC
(Lit.[13] mp = 191-192 oC); Rf = 0.24 (hexanes:ethyl acetate (8:2); IR (KBr)
ν = 3269, 3077, 1629, 1536, 1058, 850, 727, 519 cm-1; 1H NMR (400
MHz, DMSO-d6) δ = 4.10-4.30 (m, 2H), 4.95 (d, J = 4.8 Hz, 1H), 5.08 (d,
J = 4.8 Hz, 1H), 6.18 (d, J = 4.8 Hz, 1H), 6.42 (d, J = 4.4 Hz, 1H), 7.11 (d,
J = 8.4 Hz, 2H), 7.23-7.29 (m, 2H), 7.30-7.32 (m, 2H), 7.33-7.38 (m, 3H),
7.39-7.44 (m, 2H), 7.47-7.53 (m, 2H), 7.55-7.61 (m, 2H), 8.48 (t, J = 6.0
Hz, 1H), 9.87 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ = 41.3, 73.6, 74.0,
119.5, 126.6, 127.4, 127.6, 127.9, 128.1, 134.7, 137.1, 140.9, 141.3,
171.0, 172.2; HRMS (ESI) calcd for C23H22N2O4Na [M+Na]+ 413.1477;
found 413.1471.
2-Hydroxy-2-phenyl-N-(4-(trifluoromethyl)phenyl)acetamide 2h: Yield
70%; colorless solid; mp = 178-180 oC (Lit.[13] mp = 175-176 oC); Rf =
0.22 (hexanes:ethyl acetate (8:2); IR (KBr) ν = 3322, 3166, 2697, 1649,
1541, 1273, 1122, 911, 770, cm-1; 1H NMR (500 MHz, DMSO-d6) δ =
5.14 (d, J = 4.5 Hz, 1H), 6.53 (d, J = 4.5 Hz, 1H), 7.26-7.32 (m, 1H),
7.33-7.39 (m, 2H), 7.46-7.54 (m, 2H), 7.65 (d, J = 8.5 Hz, 2H), 7.94 (d, J
= 8.5 Hz, 2H), 10.31 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ = 74.1,
119.7, 123.2, 123.3, 123.5, 123.7, 124.0, 125.4, 125.8, 125.9, 126.6,
127.8, 128.2, 140.5, 142.2, 171.9; HRMS (ESI) calcd for C15H12F3NO2Na
[M+Na]+ 318.0718; found 318.0735.
2-Hydroxy-N-(3-nitrophenyl)-2-phenylacetamide 2i: Yield 84%;
colorless solid; mp = 144-146 oC (Lit.[13] mp = 142-143 oC); Rf = 0.23
(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3288, 2956, 1628, 1542, 1058,
754, 695, cm-1; 1H NMR (500 MHz, DMSO-d6) δ = 5.15 (d, J = 4.5 Hz,
1H), 6.59 (d, J = 4.5 Hz, 1H), 7.27-7.33 (m, 1H), 7.34-7.40 (m, 2H), 7.50-
7.55 (m, 2H), 7.59 (t, J = 8.0 Hz, 1H), 7.91 (dd, J1 = 8.0 Hz, J2 = 1.5 Hz,
1H), 8.12 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 1H), 8.77 (s, 1H), 10.50 (s, 1H);
13C NMR (125 MHz, DMSO-d6) δ = 74.2, 113.9, 118.1, 125.9, 126.6,
127.8, 128.2, 130.1, 139.8, 140.5, 147.9, 172.2; HRMS (ESI) calcd for
C14H12N2O4 [M+Na]+ 295.0695; found 295.0679.
2-Hydroxy-N-phenylbutanamide 2o: Yield 80%; colorless solid; mp =
129-131 oC (Lit.[9d] mp = 129-130 oC); Rf = 0.19 (hexanes:ethyl acetate
(8:2); IR (KBr) ν = 3394, 3296, 2967, 1647, 1528, 1440, 1117, 757 cm-1;
1H NMR (500 MHz, DMSO-d6) δ = 0.91 (t, J = 7.0, 3H), 1.55-1.66 (m, 1H),
1.68-1.79 (m, 1H) 3.93-4.10 (m, 1H), 5.67 (d, J = 5.0 Hz, 1H), 7.04 (t, J =
7.5 Hz, 1H), 7.29 (t, J = 7.5 Hz, 2H), 7.70 (d, J = 8.0, 2H), 9.60 (s, 1H);
13C NMR (125 MHz, DMSO-d6) δ = 9.5, 27.4, 72.6, 119.6, 123.3, 128.6,
138.6, 172.9; HRMS (ESI) calcd for C10H13NO2Na [M+Na]+ 202.0844;
found 202.0825.
N-(2,6-Dimethylphenyl)-2-hydroxybutanamide
2p:
Yield
80%;
o
4-(2-Hydroxy-2-phenylacetamido)benzamide 2j: Yield 70%; colorless
solid; mp
colorless solid; mp = 104-106 C; Rf = 0.26 (hexanes:ethyl acetate (8:2);
IR (KBr) ν = 3332, 2968, 2925, 1660, 1503, 1127, 772, 589 cm-1; 1H
NMR (500 MHz, DMSO-d6) δ = 0.96 (t, J =7.5 Hz, 3H), 1.60-1.71 (m, 1H),
1.72-1.83 (m, 1H), 2.13 (s, 6H), 3.99-4.10 (m, 2H), 5.58 (d, J = 5.0 Hz,
1H), 7.04-7.13 (m, 3H), 9.07 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ =
9.4, 18.1, 27.6, 72.4, 126.2, 127.5, 135.0, 135.2, 172.5; HRMS (ESI)
calcd for C12H17NO2Na [M+Na]+ 230.1157; found 230.1169.
= =
158-160 oC (Lit.[13] mp 161-162 oC); Rf = 0.20
(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3295, 3236, 2918, 1656, 1594,
1405, 1276, 1076, 850, 743 cm-1; 1H NMR (400 MHz, DMSO-d6) δ = 5.12
(d, J = 4.5 Hz, 1H), 6.50 (d, J = 4.5 Hz, 1H), 7.21-7.32 (m, 2H), 7.33-7.41
(m, 2H), 7.52 (d, J = 6.8 Hz, 2H), 7.73-7.90 (m, 5H), 10.14 (s, 1H); 13C
NMR (100 MHz, DMSO-d6) δ = 74.0, 118.8, 126.5, 127.6, 128.1, 128.2,
129.1, 140.6, 141.1, 167.3, 171.5; HRMS (ESI) calcd for C15H14N2O3Na
[M+Na]+ 293.0920; found 293.0909.
N-Cyclopropyl-2-hydroxy-2-phenylacetamide 5a: Yield 80%; colorless
solid; mp = 118-120 oC; Rf = 0.20 (hexanes:ethyl acetate (8:2); IR (KBr) ν
= 3299, 3220, 1658, 1570, 1533, 1349, 1068, 694, 680 cm-1; 1H NMR
(500 MHz, DMSO-d6) δ = 0.44-0.52 (m, 2H), 0.55-0.62 (m, 2H), 2.61-2.69
(m, 1H), 4.86 (d, J = 5.0 Hz, 1H), 6.05 (d, J = 5.0 Hz, 1H), 7.23-7.28 (m,
1H), 7.31-7.34 (m, 2H), 7.37-7.41 (m, 2H), 7.97 (s, 1H); 13C NMR (125
MHz, DMSO-d6) δ = 5.6, 22.3, 73.5, 126.5, 127.3, 127.9, 141.3, 173.2;
HRMS (ESI) calcd for C11H12NO2Na [M+Na]+ 214.0844; found 214.0866.
N-(2-Cyanophenyl)-2-hydroxy-2-phenylacetamide 2k: Yield 80%;
colorless solid; mp = 130-132 oC; Rf = 0.26 (hexanes:ethyl acetate (8:2);
IR (KBr) ν = 3394, 3311, 2234, 1688, 1521, 1446, 1297, 918, 771 cm-1;
1H NMR (400 MHz, DMSO-d6) δ = 5.19 (d, J = 2.0 Hz, 1H), 6.81 (d, J =
2.8 Hz, 1H), 7.20-7.34 (m, 2H), 7.35-7.40 (m, 2H), 7.52 (d, J = 7.6 Hz,
2H), 7.67 (t, J = 7.6 Hz, 1H), 7.78-7.88 (m, 2H), 10.09 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ = 73.6, 105.7, 116.5, 123.7, 125.3, 126.8, 127.8,
128.2, 133.0, 133.9, 139.8, 140.4, 171.4; HRMS (ESI) calcd for
C15H13N2O2 [M+H]+ 253.0977; found 253.0981.
N-Cyclohexyl-2-hydroxy-2-phenylacetamide 5b: Yield 80%; colorless
solid; mp = 98-100 oC; Rf = 0.22 (hexanes:ethyl acetate (8:2); IR (KBr) ν =
3340, 3263, 2933, 2666, 1642, 1542, 1450, 1060, 702 cm-1; 1H NMR
(500 MHz, DMSO-d6) δ = 1.05-1.16 (m, 1H), 1.18-1.30 (m, 4H), 1.49-1.58
(m, 1H), 1.59-1.72 (m, 4H), 3.46-3.57 (m, 1H), 4.87 (d, J = 5.0 Hz, 1H),
6.08 (d, J = 5.0 Hz, 1H), 7.23-7.28 (m, 1H), 7.29-7.34 (m, 2H), 7.37-7.41
(m, 2H), 7.70 (d, J = 8.5, 1H); 13C NMR (125 MHz, DMSO-d6) δ = 24.7,
25.1, 32.2, 32.3, 47.2, 73.4, 126.5, 127.3, 127.9, 141.5, 171.0; HRMS
(ESI) calcd for C14H19NO2Na [M+Na]+ 256.1313; found 256.1330.
N-(4-Cyanophenyl)-2-hydroxy-2-phenylacetamide 2l: Yield 80%;
colorless solid; mp = 130-132 (Lit.[15e] mp = 131-132 oC); Rf = 0.28
(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3408, 2327, 1655, 1570, 1523,
1
1426, 1277, 748, 717 cm-1; H NMR (400 MHz, DMSO-d6) δ = 5.15 (d, J
= 4.4 Hz, 1H), 6.55 (d, J = 4.4 Hz, 1H), 7.27-7.40 (m, 3H) 7.51 (d, J = 7.2
Hz, 2H), 7.75 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H), 10.36 (s, 1H);
13C NMR (100 MHz, DMSO-d6) δ = 74.1, 105.3, 119.0, 119.8, 126.6,
127.8, 128.2, 133.1, 140.4, 142.8, 172.1.
N-Allyl-2-hydroxy-2-phenylacetamide 5c: Yield 80%; colorless solid;
mp = 74-78 oC; Rf = 0.18 (hexanes:ethyl acetate (7:3); IR (KBr) ν = 3408,
2327, 1655, 1570, 1523, 1426, 1277, 748, 717 cm-1; 1H NMR (400 MHz,
CDCl3) δ = 3.75 (d, J = 3.6 Hz, 1H), 3.87 (tt, J1 = 6.0 Hz, J2 = 1.2 Hz, 2H),
2-Hydroxy-N-(naphthalen-1-yl)-2-phenylacetamide 2m: Yield 80%;
colorless solid; mp = 115-117 oC (Lit.[13] mp = 113-114 oC); Rf = 0.25
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700374
European Journal of Organic Chemistry
FULL PAPER
5.03 (d, J = 3.2 Hz, 1H), 5.04-5.09 (m, 1H), 5.09-5.12 (m, 1H), 5.72-5.84
(m, 1H), 6.04 (s, 1H), 7.25-7.42 (m, 5H); 13C NMR (100 MHz, CDCl3) δ =
41.9, 74.3, 116.6, 127.0, 128.8, 129.0, 133.7, 139.5, 172.2; HRMS (ESI)
calcd for C11H13NO2Na [M+Na]+ 214.0844; found 214.0866.
1067, 754, 693 cm-1; 1H NMR (500 MHz, DMSO-d6) δ = 2.51 (s, 3H)
(merge with DMSO-d6), 5.14 (d, J = 4.0 Hz, 1H), 6.52 (d, J = 4.5 Hz, 1H),
7.27-7.32 (m, 1H), 7.33-7.39 (m, 2H), 7.52 (d, J = 8.0 Hz, 2H), 7.86 (d, J
= 8.5 Hz, 2H), 7.91 (d, J = 8.5 Hz, 1H), 10.26 (s, 1H); 13C NMR (125 MHz,
DMSO-d6) δ = 26.5, 74.1, 119.0, 126.6, 127.8, 128.2, 129.3, 132.0, 140.5,
142.9, 171.9, 196.6.
N-Butyl-2-hydroxy-2-phenylacetamide 5d: Yield 80%; colorless solid;
mp = 70-72 oC; Rf = 0.18 (hexanes:ethyl acetate (8:2); IR (KBr) ν = 3334,
3263, 1659, 1563, 1410, 1061, 728, 619 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ = 0.84 (t, J = 7.2 Hz, 3H), 1.17-1.29 (m, 2H), 1.33-1.44 ( m,
2H), 3.07 (q, J = 6.8 Hz, 2H), 4.88 (d, J = 3.2 Hz, 1H), 6.09 (d, J = 4.4 Hz,
1H), 7.22-7.28 (m, 1H), 7.29-7.35 (m, 1H), 7.37-7.43 (m, 2H) 7.93 (t, J =
5.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ = 13.7, 19.5, 31.3, 37.9,
73.5, 126.5, 127.3, 127.9 141.5, 171.9; HRMS (ESI) calcd for
C12H17NO2Na [M+Na]+ 230.1157; found 230.1168.
N-(4-Benzoylphenyl)-2-hydroxy-2-phenylacetamide 7d: Yield 66%;
colorless solid; mp = 134-136 oC; Rf = 0.25 (hexanes:ethyl acetate (8:2);
IR (KBr) ν = 3315, 3163, 1650, 1544, 1488, 1396, 1059, 694, 493 cm-1;
1H NMR (500 MHz, DMSO-d6) δ = 5.17 (d, J = 4.0 Hz, 1H), 6.52 (d, J =
4.5 Hz, 1H), 7.27-7.32 (m, 1H), 7.34-7.40 (m, 2H), 7.50-7.58 (m, 4H),
7.62-7.67 (m, 1H), 7.68-7.75 (m, 4H), 7.91 (d, J = 8.0 Hz, 2H), 10.32 (s,
1H); 13C NMR (125 MHz, DMSO-d6) δ = 74.1, 119.0, 126.6, 127.7, 128.2,
128.5, 129.4, 130.9, 131.7, 132.3, 137.5, 140.6, 142.7, 171.9, 194.6;
HRMS (ESI) calcd for C21H17NO3Na [M+Na]+ 354.1106; found 354.1131.
2-Hydroxy-N-(4-methoxybenzyl)-2-phenylacetamide 5e: Yield 80%;
colorless solid; mp = 139-141 oC (Lit.[13] mp = 141-142 oC); Rf = 0.22
(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3356, 3256, 1655, 1662, 1289,
1061, 729, 601 cm-1; 1H NMR (400 MHz, DMSO-d6) δ = 3.71 (s, 3H),
4.16-4.23 (m, 2H), 4.94 (d, J = 4.4 Hz, 1H) 6.17 (d, J = 4.4 Hz, 1H) 6.83
(d, J = 8.0 Hz, 2H) 7.13 (d, J = 8.4 Hz, 2H), 7.23-7.28 (m, 1H), 7.29-7.35
(m, 2H) 7.41 (d, J = 7.2 Hz, 2H), 8.44 (t, J = 5.2 Hz, 1H); 13C NMR (100
MHz, DMSO-d6) δ = 41.2, 55.0, 73.5, 113.6, 126.6, 127.4, 127.9, 128.5,
131.6, 141.4, 158.1, 172.0; HRMS (ESI) calcd for C16H17NO3Na [M+Na]+
294.1108; found 294.1085.
N-(4-Acetylphenyl)-2-hydroxybutanamide 7e: Yield 65%; colorless
solid; mp = 80-82 oC; Rf = 0.24 (hexanes:ethyl acetate (8:2); IR (KBr) ν =
3347, 3266, 1656, 1533, 1188, 1057, 696, 500 cm-1; 1H NMR (500 MHz,
DMSO-d6) δ = 0.92 (t, J = 7.5 Hz 3H), 1.55-1.65 (m, 1H), 1.69-1.79 (m,
1H), 2.52 (s, 3H), 3.97-4.02 (m, 1H), 7.85-7.89 (m, 2H), 7.90-7.94 (m,
2H), 9.98 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ = 9.5, 26.5, 27.3,
72.7, 118.9, 129.3, 131.8, 143.0, 173.6, 196.6. HRMS (ESI) calcd for
C16H15NO3Na [M+Na]+ 244.0950; found 244.0961.
N-(2-Chlorobenzyl)-2-hydroxy-2-phenylacetamide 5f: Yield 80%;
colorless solid; mp = 123-125 oC (Lit.[13] mp = 124-125 oC); Rf =
0.20(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3293, 3214, 1653, 1595,
1410, 1308, 1070, 768, 689 cm-1; 1H NMR (400 MHz, DMSO-d6) δ =
4.32-4.35 (m, 2H), 5.02 (d, J = 4.5 Hz, 1H), 6.29 (d, J = 4.5 Hz, 1H),
7.16-7.20 (m, 1H), 7.23-7.27 (m, 2H), 7.28-7.31 (m, 1H), 7.32-7.37 (m,
2H), 7.39-7.43 (m, 1H), 7.44-7.48 (m, 2H), 8.55 (s, 1H); 13C NMR (100
MHz, DMSO-d6) δ = 73.6, 126.5, 127.0, 127.4, 128.2, 128.4, 129.0,
131.8, 136.4, 141.2, 172.5; HRMS (ESI) calcd for C15H14NO2ClNa
[M+Na]+ 298.0611; found 298.0612.
Acknowledgements
We thank DST (project no.: SB/S1/OC-72/2013) for financial
support. GK thanks UGC, New Delhi and ALM thanks CSIR,
New Delhi for Senior Research Fellowship. We also thank the
Department of Chemistry, IIT Madras for instrumental facilities.
Keywords: Cesium carbonate • Metal-free• Chemoselectivity•
Hydrosilylation • Green solvent
N-(2-Acetylphenyl)-2-hydroxy-2-phenylacetamide 7a: Yield 54%;
colorless solid; mp = 112-114 oC (Lit.[15e] mp = 118-119 oC); Rf = 0.26
(hexanes:ethyl acetate (8:2); IR (KBr) ν = 3294, 3205, 2922, 1658, 1528,
1452, 1105, 749, 614, cm-1; 1H NMR (500 MHz, DMSO-d6) δ = 2.67 (s,
3H), 5.10 (d, J = 4.0 Hz, 1H), 6.80 (d, J = 3.5 Hz, 1H), 7.20 (t, J = 7.5 Hz,
1H), 7.26-7.32 (m, 1H), 7.35 (t, J = 7.0 Hz, 2H), 7.47 (d, J = 7.5 Hz, 2H),
7.59 (d, J = 7.5 Hz, 1H), 8.09 (d, J = 7.5 Hz, 1H), 8.61 (d, J = 8.5 Hz, 1H),
12.43 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ = 28.8, 74.1, 119.6,
122.7, 122.8, 126.5, 127.7, 128.2, 132.4, 134.5, 139.2, 140.6, 172.3,
202.4; HRMS (ESI) calcd for C16H15NO3Na [M+Na]+ 292.0950; found
292.0933.
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FULL PAPER
Chemoselective Hydrosilylation
Govindharaj Kumar, Alagesan
Muthukumar, Dr. G. Sekar*
Page No. – Page No.
A Mild and Chemoselective
Hydrosilylation of -Keto Amides
using Cs2CO3/PMHS/2-MeTHF System
A Cs2CO3-catalyzed chemoselective hydrosilylation of -keto amides to highly important mandelamides is developed using
PMHS as hydride source in eco-friendly green solvent 2-MeTHF. The mechanistic study reveals the formation of MeSiH3
from the base-catalyzed degradation of PMHS that can be the active species for hydrosilylation.
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