Dimethylbut-2-ynedioate mediated esterification of acids via sp3 C-N bond cleavage of benzylic tertiary amines

Article abstract of DOI:10.1016/j.tet.2012.08.024

A straightforward synthetic transformation of tertiary amines to the esterification of equimolar amounts of acids was demonstrated in this manuscript. The present protocol can be regarded as a straightforward synthetic transformation of tertiary amines to the esterification of equimolar amounts of acid. Moreover, the reaction is fundamentally new chemistry for the sp ³ C-N bond cleavage coupled with esterification. The esterification reaction conditions are very mild and functional group-tolerated, such as hydrosilanes, alcohols, phenol, and amino acids. A mechanism is proposed in which the tertiary amine reacts with dimethyl but-2-ynedioate to form zwitterionic salt, and then the zwitterionic intermediate subsequently accept hydrogen to assist the nucleophilic attack of oxygen atom of carboxyl group at the benzyl group of tertiary amine, while a separate reaction pathway leads to esterification.

Full text of DOI:10.1016/j.tet.2012.08.024

Tetrahedron 68 (2012) 8916e8923
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Dimethylbut-2-ynedioate mediated esterification of acids via sp3 CeN bond
cleavage of benzylic tertiary amines
,
,
,
a
Hao Shen a y, Xing Lu a y, Ke-Zhi Jiang a, Ke-Fang Yang a, Yixin Lu c, Zhan-Jiang Zheng a , Guo-Qiao Lai ,
*
Li-Wen Xu a
,b,
*
a Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 310012, PR China
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China
c Department of Chemistry and Medicinal Chemistry Program, Life Sciences Institute, National University of Singapore, 3 Science Drive 3, Republic of Singapore 117543
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 June 2012
Received in revised form 18 July 2012
Accepted 10 August 2012
Available online 16 August 2012
A straightforward synthetic transformation of tertiary amines to the esterification of equimolar amounts
of acids was demonstrated in this manuscript. The present protocol can be regarded as a straightforward
synthetic transformation of tertiary amines to the esterification of equimolar amounts of acid. Moreover,
the reaction is fundamentally new chemistry for the sp3 CeN bond cleavage coupled with esterification.
The esterification reaction conditions are very mild and functional group-tolerated, such as hydrosilanes,
alcohols, phenol, and amino acids. A mechanism is proposed in which the tertiary amine reacts with
dimethyl but-2-ynedioate to form zwitterionic salt, and then the zwitterionic intermediate subsequently
accept hydrogen to assist the nucleophilic attack of oxygen atom of carboxyl group at the benzyl group of
tertiary amine, while a separate reaction pathway leads to esterification.
Keywords:
Esterification
CeN cleavage
Acid
Tertiary amine
Silanes
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
carbonenitrogen bond had a long history and the past years have
seen significant research attention focused on breaking of carbon
The nitrogen-containing compounds, such as amines, amides,
enamines, and imines, are valuable and commercially important
bulk chemicals, and of great importance for organic chemistry and
medicinal chemistry. Thus in the preparation and transformation of
nitrogen-containing compounds, the making and breaking of sp3
carbonenitrogen bond in the construction of functional molecules
are important step in the synthesis of pharmaceutical candidates,
fine chemicals, and polymers.1,2 However, tertiary amines have
never been applied directly as a reactive substrate or building block
to the preparation of esters via CeN bond cleavage, except as a base
to promote the esterification of acids with alcohols. Carbon-
enitrogen bonds are generally quite stable to strong acid, base,
metal salts, and most of synthetic reagents including oxidants and
reductants. Therefore, the synthetic application of the breaking or
cleavage of carbonenitrogen bond to form new carbonecarbon or
carboneheteroatom bond is one of the challenging topics in or-
ganic synthesis. While the breaking of carbonenitrogen bonds in
organic synthesis are almost entirely explored, catalytic breaking of
nitrogen bonds to form new compounds.3
For example, in 1980s, it has been shown that the carbone
nitrogen bonds of porphyrin are susceptible to cleavage by
4
Ru3(CO)12
.
Recent work have also shown that transition metal
complexes,3e,5 Brønsted acid,6 and Lewis acid,7 were able to facili-
tate the breaking of carbonenitrogen bond and make amino or
amide groups to serve as leaving groups toward a range of nucle-
ophiles. However, a key limitation of these protocols is the re-
quirement for harsh reaction conditions, such as high temperature,
stronger base, and waste-rich, and the need to use stoichiometric or
greater amount of catalysts in some cases. In addition, except
transition metal-catalyzed reduction, there are few approaches
reported for the breaking of sp3 CeN bond in tertiary amines that
are valuable bases and very stable moieties in organic trans-
formation.8 Thus, although many organic transformations via sp3
CeN bond cleavage have been widely encountered and in-
vestigated, developing simple and practical protocols for utilization
of tertiary amines in organic synthesis based on the chemistry of
selective breaking of sp3 CeN bond is exceedingly difficult because
they are tolerant under strong acid and basic conditions. Herein, we
reported the esterification of acids with tertiary amines, including
hydrosilane-modified amines. A mechanism is also proposed in the
esterification and side aza-Michael reaction. To the best of our
* Corresponding authors. Fax: þ86 571 28865135; e-mail addresses: liwenxu@
hznu.edu.cn, licpxulw@yahoo.com (L.-W. Xu).
y
These authors contributed equally to this work.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.024

H. Shen et al. / Tetrahedron 68 (2012) 8916e8923
8917
R2
N
knowledge, the direct esterification of acids with tertiary amines
O
R
?
but not alcohols and quaternary ammonium salt has never been
R1
R1
COOH
R3
reported in the past.9
R
O
This work
Organic esters represent an important family of useful in-
termediates widely employed in the synthesis of fine chemicals,
agricultural chemicals, and polymers, such as drugs, plasticizers,
perfumes, cosmetics, food preservatives, solvents, polyester, poly-
carbonates, and chiral auxiliaries.10 It is one of the most commonly
encountered functionality in organic chemistry. In the past, nu-
merous methods have been used widely in the synthesis of bi-
ologically active molecules involved the esterification.11 In general,
classical esterification reactions have been described with numer-
ous chemical methods based on the dehydration of acids and al-
cohols.12 However, the inherent fault connected to this classic
approach results from the reversibility of the reaction or the
equilibration of the condensation reaction, which makes it neces-
sary to use an excess of one of the reagents in the presence of
promoters, such as stoichiometric strong bases, acids, phosphine
(Mitsunobu reaction), or Lewis acid catalysts (Scheme 1, up).10e13 In
this context, recent advances have focused on methods able to
develop catalytic, group-tolerant, environmentally benign, and
mild reaction conditions.14 It should be noted that several research
groups have recently reported the catalytic oxidative esterification
of aldehydes by transition metal catalysts and N-heterocyclic car-
bine (Scheme 1, down).11e15 However, there were few methods
reached high atom efficiency. In particular, the direct condensation
between carboxylic acids and alcohols or other precursors of al-
cohols with a 1:1 stoichiometry without catalyst is a challenge. It
was suggested that the development of fundamentally new and
mild esterification procedure of carboxylic acids with the equi-
molar amounts of additional reagents was highly desirable in or-
ganic transformation (Scheme 2).
Scheme 2. Novel esterification based on sp3 CeN bond cleavage.
2. Results and discussion
Initially, during our exploration of novel reaction based on the
chemistry of inactivated sp3 CeN bond cleavage and utilization
of (4-bromophenyl)-N,N-dimethylmethanamine (1a, Scheme of
Table 1), interestingly, we found the three-component reaction of
1a, dimethyl but-2-ynedioate (2a), and 4-chlorobenzoic acid (3a),
resulted in moderate yield of ester (4a, 50% yield) and aza-Michael
adduct (dimethyl 2-(dimethylamino)maleate) (A-4a, 45% yield) in
N,N-dimethylformamide (DMF) at room temperature overnight
(14 h). These unexpected products, aminofumarate and esters, are
synthetically useful building blocks or intermediates in organic
synthesis.1e6,16 It is inconceivable that the tertiary amine could act
as a substitute of alcohols. From a standpoint point of practical
transformation of functional group, equally molecular ratio (1:1:1)
of three reactants is practical for esterification reaction. Thus fol-
lowing the initial finding of a novel esterification reaction, we
studied the solvent effects on the enhancement of conversion.
Solvent screening showed dichloromethane (DCM) and tetrahy-
drofuran (THF) to be the most suitable solvent, allowing for
a smooth reaction to give corresponding ester in good yields
overnight (for example, 74% and 71% isolated yield of ester 1a was
obtained, respectively, in DCM and THF, see Table 1). In addition,
optimizing studies demonstrate the importance of the combination
of dimethyl but-2-ynedioate (2a) and 4-chlorobenzoic acid (3a) for
the happening of sp3 CeN bond cleavage in (4-bromophenyl)-N,N-
dimethylmethanamine (1a).
O
Table 1
Me
Optimization of reaction conditions in the esterification: screening of solventsa
R1
O
Br
Br
O
O
X= OH
heat
R2
N
N
N
O
O
OMe
R1
classic procedure
O
R2OH
Cl
R
1a
R1
O
X= OH
R1COX
O
Catalyst-free
acid, base,
M(OR)n
4a
or Lewis acid atalyst
X = OH, Cl,
O
COOMe
M = B, n = 3
M = Si, n = 4
solvent, 14 h
Cl
+
O
RY
COOMe
X = OH
R
R1
O
COOH
O
R'
O
Y= Br,
I, etc
N
R1
COOMe
R
COOMe
X= OH
R-N2
O
2a
3a
CH2N2
R1
R
A-4a
O
Entry
Solvent
Yield of esterb (%)
Me/R
O
O
1
2
3
4
5
CH3CN
DMF
DMSO
MeOH
CHCl3
13
50
18
20
33
39
30
71
40
44
O
R
R'
6
7
8
9
Hexanes
Et2O
THF
1,4-Dioxane
Toluene
N-heterocyclic
carbene
R'CH2Br
O
O
O
R'CH2OH
Pd, Au, etc
R'CH2Br
H
10
R
R
O
R'
R
O
R'
a
N-heterocyclic
carbene
Reaction conditions: 4-chlorobenzoic acid (1 mmol), (4-bromophenyl)-N,N-
dimethylmethanamine (1 mmol), dimethyl but-2-ynedioate (1 mmol), in corre-
sponding solvent (5 mL), at room temperature for 14 h.
O2
O
Crossed-Tishchenko
reaction
b
Isolated yields.
R'
H
O
With a working protocol in place, the generality of this three-
component reaction of tertiary amines, acids, and 2a, was next
exemplified. Utilizing the optimized conditions delineated in
Table 1, this protocol allows the incorporation of both electron-
R
O
R'
Scheme 1. Synthetic routes to esters.

8918
H. Shen et al. / Tetrahedron 68 (2012) 8916e8923
withdrawing and -donating substituents within aromatic rings of
acids, as well as substitution of tertiary amines, giving the desired
esters and aza-Michael adducts in good yields (up to 95% yield) in
all cases (Tables 2 and 3). As shown in Table 2, a range of aromatic
and alkyl acids, including N-protected amino acids, were converted
into the corresponding esters, which were isolated in moderate to
excellent yields (50e95% yield). The reaction tolerated a series of
aromatic and alkyl acids that containing nitro-, bromide, chloride,
methyl, also behaved well in this transformation (Table 2). In ad-
dition, it should be noted that N-cbz or Boc protected amino acids
were also proceeded nicely to provide the corresponding amino
esters in promising yields (entries 10e13), which are synthetically
useful building blocks for the preparation of peptides and potential
pharmaceuticals, amino compounds.
These promising results prompted us to further demonstrate the
generality of this procedure, as shown in Scheme 3, the combina-
tional use of different acids and tertiary amines was proved to be
useful protocol to various esters and dimethyl 2-aminofumarates
simultaneously. Due to the mildness of the reaction conditions,
this reaction would be ideal alternative etherification and amina-
tion to traditional methods. In addition, with the same reaction
time (14 h), it was concluded that these substrates showed slight
differences in reactivity.
R2
N
R
O
R1
R1
2a
R3
R
COOH
O
DCM, RT, 14 h
1
3
5
TMS
TMS
Ph
Ph
O
O
O
Ph
Table 2
O
Scope of the etherification: variation of the acid componenta
O
O
O
Br
O
R2 = R3 = Et
5a: 64% yield
R2 = R3 = Me
5b: 76% yield
R2 = R3 = Et
R2, R3 = -(CH2)4-
5d: 62% yield
Br
5c: 62% yield
Br
2a
N
O2N
R
O
R
COOH
NO2
I
DCM, RT, 14 h
Br
Ph
O
O
O
O
O
1a
O
O
R2 = R3 = Et
3
O
4
O
R2 = R3 = Et
R2, R3 = -(CH2)4-
R2, R3 = -(CH2)4-
5e: 80% yield
5f: 94% yield
Yieldb (%)
5g: 94% yield
5h: 40% yield
Entry R-COOH
O
O
O
1
2
3
4
5
6
7
8
R¼Ph
4a: 73(95)c
4b: 75
4c: 74
O
O
Br
Br
R¼4-Fe2-MePh
R¼p-ClePh
R¼o-MePh
R¼m-IePh
R¼o-NO2Ph
R¼o-BrePh
R¼p-NO2Ph
Stearic acid
N
Boc
O
O
O
R2 = R3 = Me
5j: 85% yield
Ph
TMS
Br
4d: 63
I
R2, R3 = -(CH2)4-
5l: 64% yield
4e: 66(93)c
4f: 53
R2 = R3 = Me
5i: 72% yield
R2 = R3 = Me
5k: 86% yield
4g: 45(85)c
4h: 50(87)c
4i: 55
Scheme 3. Further scope of the esterification reaction: variation of the tertiary amine
and acid component.
9
10
11
12
13
N-Boc-
L
-proline
-phenylalanine
-phenylalanine
4j: 62
4k: 63
4l: 58
N-Cbz-
L
Next, we applied the optimized conditions to other reactive
tertiary amines. Despite there are numerous approaches to esters
from acids, aldehydes, or alcohols, it is still a challenge to improve
known methods and develop new procedures that will allow the
use of equimolar amounts of sensitive substrates. The present es-
terification method with tertiary amines and acids would provide
a very mild reaction conditions that allow the use of sensitive
substrates. Therefore we turned the attention to the esterification
transformation of unstable tertiary amines containing SieH func-
tional group.
N-Boc-
L
N-Cbz-(S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 4m: 57
a
Reaction conditions: acid (0.5 mmol), (4-bromophenyl)-N,N-dimethyl- meth-
anamine (0.5 mmol), dimethyl but-2-ynedioate (0.5 mmol), DCM 2.5 mL, at room
temperature for 14 h.
b
Isolated yields.
c
The yield in parentheses was isolated after the reaction was carried out for 24 h.
Table 3
Further scope of the esterification reaction: variation of the tertiary amine
Silanes containing SieH, such as Et3SiH, (EtO)3SiH, PhMeSiH2,
and other hydrosilanes, were synthetically useful reagents in
hydrosilylation and hydrogenation,17 in which the great majority is
easy to handle, inexpensive, and convenient. In general, hydro-
silanes were prepared from chlorosilanes with LiAlH4,18 and the
functionalization of hydrosilanes without destroying the SieH is
not an easy task because hydrosilanes are both easily oxidized and
reactivated compounds in the presence of Brønsted acids, Lewis
acids, and transition metal complexes (Cu, Pd, Ir, Ni, etc.).19 To the
best of our knowledge, there are no reports on the esterification of
functional silanes containing hydrosilane moieties. Herein, we hy-
pothesized that the incorporation of ester groups access to new
potential and various hydrosilanes for next transformation and
hydrosilylation.
component
R2
N
Cl
R1
2a
R1
O
Cl
COOH
R3
DCM, RT, 14 h
O
1
3a
4
Entry
R1
R2
R3
Yielda (%)
1
2
3
4
5
6
7
8
9
o-BrPh
m-BrPh
o-TMSPh
m-TMSPh
p-TMSPh
Ph
Et
Et
Me
Me
Me
d
Et
Et
Me
Me
Me
4n: 84
4o: 81
4p: 95
4q: 75
4r: 76
4s: 92
4s: 93
4t: 90
4t: 91
e(CH2)4e
e(CH2)5e
e(CH2)5e
e(CH2)4e
Ph
d
b
-Naphthaline
-Naphthaline
d
b
d
The optimized reaction conditions as above were then applied
to the esterification of silicon-containing tertiary amines (6a). In
this regard, synthesis of various hydrosilanes (7aep) containing
both SieH and ester moieties was carried out on the basis of above
findings. The investigation of the scope of the acids revealed that
variation of the substituent of aromatic acids could be tolerated and
generally good isolated yields. Especially for the substrates con-
taining phenol moiety (7d and 7p), it could be tolerated under the
esterification conditions, which would be very useful for the che-
moselective esterification in the presence of different functional
a
Isolated yields.
Accordingly, various substrates of tertiary amines that contain-
ing aromatic and alkyl groups, were resulted in esters with 59e91%
yields and various aza-Michael adducts (A-4aed, see
Supplementary data), dimethyl 2-aminofumarates, in 51e91% iso-
lated yields (Table 3). The reaction conversion depend on the time,
therefore it should be noted that all the reactions could give more
excellent yields with extended reaction times.

H. Shen et al. / Tetrahedron 68 (2012) 8916e8923
8919
groups. As can be seen, the presence of a free SieH group did not
diminish the efficiency of the click CeN cleavage and esterification
(Scheme 4). This result is very important since these hydrosilanes
are difficult to be obtained from lithiation and silylation of ester-
containing bromides directly.
Scheme 6. Firstly, 1H NMR was used to probe the possible species
present after mixing the acid (4-chlorobenzoic acid) with dimethyl
but-2-ynedioate, acid with tertiary amine ((4-bromophenyl)-N,N-
dimethylmethanamine), and dimethyl but-2-ynedioate with ter-
tiary amine in CDCl3. The spectra observed for these mixtures are
quite different (also see Supplementary data, p 19e21). There is no
additional information for the mixture of acid with tertiary amine
or dimethyl but-2-ynedioate, however, it is interestingly that the
mixing of tertiary amine with dimethyl but-2-ynedioate leads to
appearance of many unidentified peaks, in which there are some
complex and split signals between 2.0 and 5.0 ppm. It could be
concluded that the zwitterionic intermediate (I) was formed in this
case. Moreover, in the spectrum of the reaction mixtures of acid,
amine, and dimethyl but-2-ynedioate, the proton of acid signal
changed dramatically from 11.861 to 9.058 ppm and then dis-
appeared during the reaction procedure, which showed the for-
mation of transition state (II) because of the featured chemical shift
of the acidic proton signal (Fig. 1). These information and data
supported the formation of zwitterionic intermediate (I) and sub-
sequential dehydrogenation reaction of acid. This transition state
(II) may lead to facile intermolecular CeO bond-forming, OeH and
CeN cleavage. Therefore, these valuable experimental data and
information clearly support the mechanistic procedure via the
zwitterionic salt (I) as shown in Scheme 6, in which the tertiary
amine reacts with dimethyl but-2-ynedioate to form zwitterionic
salt (I), and then the zwitterionic intermediate subsequently accept
hydrogen to assist the nucleophilic attack of oxygen atom of car-
boxyl group at the benzyl group of tertiary amine, while a separate
reaction pathway leads to esterification and side aza-Michael
reaction.
H
Si
H
Si
2a
n-BuLi
Me2SiHCl
Br
RCOOH(3)
O
N
DCM, RT, 14 h
N
O
R
6a: o-position
6b: m-position
6a: p-position
7
I
Br
O
Me
OH
O
O
O
O
O
O
O
H
Si
H
Si
H
Si
H
Si
7a: 58% yield
Si
7c: 57% yield
Si
7d: 62% yield
Si
7b: 64% yield
Si
H
H
H
H
I
I
O
O
Cl
O
O
O
O
O
O
7e: 66% yield
7g: 70% yield
7f: 65% yield
7h: 58% yield
O
O
Si
H
Si
H
O
O
Br
Me
O
F
O
Si
H
Si
H
O
O
7j: 64% yield
O
7i: 62% yield
7k: 58% yield
7l: 56% yield
O
O
O
O
O
O
O
F
Me
OH
Me
Me
Br
Si
H
Si
H
Si
H
Si
H
7m: 71% yield
7o: 58% yield
7p: 58% yield
7n: 58% yield
Scheme 4. Synthesis of esters of hydrosilane derivatives containing SieH via sp3 CeN
bond cleavage.
The possible competitive reaction with tertiary amine 1a in the
presence of alcohol (phenylmethanol) and phenol proceeded suc-
cessfully to obtain the only desired product 4a (Scheme 5), and the
yield was not decreased in comparison to that of previous reaction.
Both this result and above findings appear to suggest again that the
esterification reaction conditions are very mild and functional group-
tolerated, such as hydrosilanes, alcohols, phenol, and amino acids.
N
OH
COOH
OH
Br
2a
O
DCM, RT, 14 h
O
Br
4a: 75% yield
1a
1:1:1
Scheme 5. Competitive esterification reaction of acid with amine, phenol and alcohol.
On the basis of experimental results, NMR analysis (Fig. 1 and
see Supplementary data), ESI-MS (see Supplementary data), and
kinetic analysis (Fig. 2), we assume the reaction to proceed more
possibly by the intermolecular SN2 substitution illustrated in
Fig. 1. 1H NMR (400 MHz, CDCl3) of the reaction mixture of 1a, 2a, and 3a every about
20 min (from up to down: 10 min, 30 min, 50 min, 70 min, 100 min).

8920
H. Shen et al. / Tetrahedron 68 (2012) 8916e8923
aromatic tertiary amines are different, in which methyl aliphatic
amine could lead to promising yield of the desired ester 8a in low
yield via CeN cleavage but aromatic amines resulted in no reaction.
These results showed that CeN cleavage is possible through the
rearrangement of the zwitterionic intermediate, and the steric and
electronic effects on nitrogen atom play crucial role for the CeN
cleavage and rearrangement.
COOCH2CH3
COOMe
+
DMAD
DCM, 42h
N
N
Cl
8b: 7%
Cl
8a: 53%
DMAD
8a: 27%
DCM, 42h
O
O
DMAD
N
8a: 39%
DCM, 42h
COOH
Cl
Cl
8c: 14%
N
DMAD
DCM, 42h
no reaction, only starting material
N
DMAD
no reaction
DCM, 42h
DMAD
DCM, 42h
N
no reaction
Fig. 2. Kinetic studies on the reaction-system shown below (k(H/D)¼1.1): (A) The re-
action of PhCOOD (3), DMAD (2), 1-(4-bromophenyl)-N,N-dimethylmethanamine (1),
and DCM as solvent. (B) The reaction of PhCOOH (3), DMAD (2), 1-(4-bromophenyl)-
N,N-dimethylmethanamine (1), and DCM as solvent.
Scheme 7. Esterification of acid with aliphatic and aromatic tertiary amines at room
temperature.
3. Conclusions
In summary, we have found a highly convenient esterification
via breaking of CeN bond of tertiary amines to result in useful es-
ters. In addition, we have developed a novel and practical method
for the synthesis of functional esters that containing SieH group.
The present protocol can be regard as a novel and straightforward
synthetic transformation for the esterification of acid with amines
but not alcohols. It is a straightforward synthetic transformation of
tertiary amines to the esterification of equimolar amounts of acids
in view of the following advantages, such as no excess of one of the
reagents, no catalysts, and no additional toxic coupling reagent or
drying agent was used in the esterification. It is also a facile route to
two different products that are synthetically useful compounds.
And the tertiary amine could work as protecting group before the
molecule was introduced a new group, such as hydrosilane. In ad-
dition, the esterification reaction conditions are very mild and
functional group-tolerated, such as hydrosilanes, phenol, and
amino acids. Moreover, the reaction is fundamentally new chem-
istry for the sp3 CeN bond cleavage coupled with esterification.
Although further research is required to establish the possible
mechanism, without the slightest doubt, experiments along these
lines as well as extensions of the methodology to the synthesis of
functional esters, and polyesters are predictable.
MeOOC
COOMe
N
O
O
R
N
COOMe
COOMe
N
MeOOC
COOMe
R
I
O H
COOMe
COOMe
O
O
R
OH
N
II
Scheme 6. Proposed mechanism of esterification of acid with tertiary amine.
Following the hypothesis of the formation of the stable zwit-
terionic intermediate (I) in the absence of acid, we started an in-
vestigation with the determination of KIE effect. Certainly the
useful result in Fig. 2 is the obvious KIE effect (k(H/D)¼1.1) pre-
dicted for substitution of COOD for COOH in acid, which reasonably
supported that motion and hydrogenation of the acid to zwitter-
ionic intermediate (I) played an important role in the cleavage of
carbonenitrogen and oxygenehydrogen bond.
At the last, to support the possible mechanism of esterification,
we performed the esterification reaction using different aliphatic
and aromatic tertiary amines instead of benzylic tertiary amines.
Aliphatic and aromatic tertiary amines were known as stable Lewis
base and difficult to be substrates in organic transformation. As
shown in Scheme 7, notably, the reactivities of various aliphatic and
4. Experimental section
4.1. General
All reagents and solvents were used directly without purifica-
tion. Flash column chromatography was performed over silica
(200e300 mesh). Infrared (IR) spectra were recorded on Brucker IR

H. Shen et al. / Tetrahedron 68 (2012) 8916e8923
8921
spectrometer (TENSOR27), nmax in cmꢀ1
.
1H NMR and 13C NMR
1433, 1373, 1287, 1249, 1163, 1130, 1106, 1043, 1029, 940, 886, 838,
744, 644, 597, 555 cmꢀ1; HRMS (ESI) [MþNa]þ calculated for
[C16H17BrNaO2Si]þ: 371.0073, found: 371.0080.
spectra were recorded at 400 and 100 MHz, respectively, on Ad-
vance (Brucker) 400 MHz Nuclear Magnetic Resonance Spectrom-
eter, and were referenced to the internal solvent signals. Thin layer
chromatography was performed using silica gel; F254 TLC plates and
visualized with ultraviolet light. EI and CI mass spectra were per-
formed on a Trace DSQ GC/MS spectrometer. Data are reported in
the form of (m/z). The products were confirmed by GCeMS &
HRMS, and usual spectral methods (1H NMR, 13C NMR). Chemical
shifts are reported in parts per million using tetramethylsilane
(TMS) in the solvent of CDCl3 as the internal standard (1H NMR:
TMS at 0.00 ppm, CDCl3 at 7.26 ppm; 13C NMR: CDCl3 at 77.0 ppm,
DMSO at 39.43). Data are reported as follows: chemical shift,
multiplicity (s¼singlet, d¼doublet, q¼quartet, br¼broad,
m¼multiplet), and coupling constants (hertz), integration. The ESI-
MS analysis of the samples was operated on an LCQ advantage mass
spectrometer (ThermoFisher Company, USA), equipped with an ESI
ion source in the positive ionization mode, with data acquisition
using the Xcalibur software (Version 1.4).
4.2.4. 2-(Dimethylsilyl)benzyl 2-hydroxy-3-methylbenzoate (7d). 1H
NMR (400 MHz, CDCl3):
7.29e7.47 (m, 5H), 6.70e6.74 (m, 1H), 5.46 (s, 2H), 2.26 (s, 3H),
0.46 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
¼11.0 (s, 1H), 7.58e7.66 (m, 2H),
d
¼170.3, 160.2, 140.1,
138.2, 136.5, 134.3, 130.0, 129.1, 127.8, 127.5, 126.6, 118.4, 111.6,
66.8, 15.7, 2.2, ꢀ3.1; IR (film): nmax¼3175, 3059, 3013, 2957, 2922,
2182, 1726, 1672, 1615, 1595, 1463, 1385, 1326, 1287, 1249, 1170,
1148, 1083, 1038, 962, 887, 835, 794, 755, 704, 648, 568 cmꢀ1
;
HRMS (ESI) [MþNa]þ calculated for [C17H20NaO3Si]þ: 323.1074,
found: 323.1080.
4.2.5. 3-(Dimethylsilyl)benzyl benzoate (7e). 1H NMR (400 MHz,
CDCl3):
d
¼8.08e8.10 (m, 2H), 7.38e7.61 (m, 7H), 5.38 (s, 2H),
4.43e4.47 (m, 1H), 0.36e0.37 (m, 6H); 13C NMR (100 MHz, CDCl3):
d
¼166.5, 138.1, 135.4, 134.0, 133.9, 133.0, 130.2, 129.7 (2C), 129.2,
128.4 (2C), 128.2, 66.9, ꢀ3.8 (2C); IR (film): nmax¼3089, 3061, 2959,
2900, 2851, 2118, 1790, 1717, 1601, 1585, 1451, 1414, 1369, 1263, 1715,
1097, 1069, 882, 829, 796, 762, 709, 627, 536 cmꢀ1; HRMS (ESI)
[MþNa]þ calculated for [C16H18NaO2Si]þ: 293.0968, found:
293.0964.
4.2. General procedure for the esterification of acids with
tertiary amines via CeN cleavage
At room temperature, organic carbonyl acid
0.5 mmol) was added into a reaction tube equipped with a small
magnet. Then a solution of tertiary amine (R1CH2-NR2R3,
3 (R-COOH,
1
4.2.6. 3-(Dimethylsilyl)benzyl 4-chlorobenzoate (7f). 1H NMR
0.5 mmol) in DCM (2.5 mL) was added dropwise in 2 min. After the
mixture was stirred at room temperature for a few minutes, 1 equiv
of dimethyl acetylenedicarboxylate (DMAD, 2) was added. The re-
action was stirred overnight at room temperature, and then mon-
itored by TLC with silica gel coated plates. After being stirred for
14 h, the solvent was removed and the residue was purified by
a flash column chromatography with silica gel with ethyl acetate/
hexane (1:25e30) as eluent to give the desired products 4, 5, and 7.
Most of compounds are known and confirmed by NMR, ESI-MS, IR
(see Supplementary data). For hydrosilane-containing esters
(7aep):
(400 MHz, CDCl3):
1H), 7.47e7.49 (m, 1H), 7.40e7.44 (m, 3H), 5.38 (s, 2H), 4.46e4.50
(m, 1H), 0.38e0.39 (m, 6H); 13C NMR (100 MHz, CDCl3):
139.5, 138.1, 135.2, 134.1, 134.0, 131.1 (2C), 129.3, 128.8 (2C), 128.6,
128.2, 67.1, ꢀ3.8 (2C); IR (film): nmax¼3049, 2958, 2899, 2121, 1723,
1595, 1488, 1415, 1371, 1269, 1172, 1114, 1015, 888, 849, 759, 734,
525 cmꢀ1; HRMS (ESI) [MþNa]þ calculated for [C16H17ClNaO2Si]þ:
327.0579, found: 327.0590.
d
¼8.01e8.04 (m, 2H), 7.62 (s, 1H), 7.55e7.56 (m,
d¼165.6,
4.2.7. 3-(Dimethylsilyl)benzyl
(400 MHz, CDCl3):
2-iodobenzoate (7g). 1H NMR
¼7.98e8.00 (m, 1H), 7.81e7.83 (m, 1H), 7.65 (s,
d
1H), 7.49e7.55 (m, 2H), 7.37e7.42 (m, 2H), 7.13e7.17 (m,1H), 5.39 (s,
4.2.1. 2-(Dimethylsilyl)benzyl-2-iodobenzoate
(400 MHz, CDCl3):
(7a). 1H
NMR
2H), 4.44e4.48 (m, 1H), 0.37e0.38 (m, 6H); 13C NMR (100 MHz,
d
¼8.00 (d, J¼8.0 Hz, 1H), 7.81 (dd, J1¼1.6 Hz,
CDCl3):
d
¼166.4, 141.4, 138.1, 135.1, 134.9, 134.2, 134.1, 132.7, 131.1,
J2¼8 Hz, 1H), 7.51e7.59 (m, 2H), 7.34e7.44 (m, 3H), 7.12e7.17 (m,
129.5, 128.2, 127.9, 94.2, 67.6, ꢀ3.7 (2C); IR (film): nmax¼3050, 3020,
1H), 5.48 (s, 2H), 4.61e4.64 (m, 1H), 0.37e0.38 (m, 6H); 13C NMR
2957, 2850, 2118, 1729, 1583, 1562, 1464, 1430, 1369, 1287, 1249,
(100 MHz, CDCl3):
d
¼166.2, 141.2, 140.6, 137.3, 135.0, 134.8, 132.7,
1121, 1198, 1043, 1016, 956, 887, 832, 792, 762, 739, 650, 545 cmꢀ1
;
131.0, 129.7, 129.3, 127.9 (2C), 94.3, 67.5, ꢀ3.1 (2C); IR (film):
nmax¼3058, 3008, 2958, 2853, 2125, 1728, 1583, 1563, 1464, 1431,
1373, 1286, 1249, 1130, 1098, 1044, 940, 885, 741, 639, 597,
551 cmꢀ1; HRMS (ESI) [MþNa]þ calculated for [C16H17INaO2Si]þ:
418.9935, found: 418.9939.
HRMS (ESI) [MþNa]þ calculated for [C16H17INaO2Si]þ: 418.9935,
found: 418.9944.
4.2.8. 3-(Dimethylsilyl)benzyl 3-iodobenzoate (7h). 1H NMR
(400 MHz, CDCl3):
d
¼8.42 (s, 1H), 8.05 (d, J¼8.0 Hz, 1H), 7.88 (d,
J¼7.6 Hz, 1H), 7.62 (s, 1H), 7.54e7.56 (m, 1H), 7.40e7.49 (m, 2H),
4.2.2. 2-(Dimethylsilyl)benzyl benzoate (7b). 1H NMR (400 MHz,
7.16e7.20 (t, J¼8.0 Hz, 1H), 5.37 (s, 2H), 4.45e4.49 (m, 1H),
CDCl3):
5.49 (s, 2H), 4.63e4.67 (m, 1H), 0.40e0.41 (m, 6H); 13C NMR
(100 MHz, CDCl3):
d
¼8.08e8.10 (m, 2H), 7.52e7.62 (m, 3H), 7.36e7.46 (m, 4H),
0.38e0.39 (m, 6H); 13C NMR (100 MHz, CDCl3):
d
¼165.0, 141.9,
138.6, 138.2, 135.1, 134.2, 134.0, 132.1, 130.1, 129.4, 128.9, 128.2,
93.9, 67.3, ꢀ3.7 (2C); IR (film): nmax¼3061, 3020, 2957, 2899,
2119, 1720, 1566, 1470, 1417, 1370, 1255, 1170, 1118, 1080, 959,
921, 886, 833, 794, 744, 673, 647, 627, 539 cmꢀ1; HRMS (ESI)
[MþNa]þ calculated for [C16H17INaO2Si]þ: 418.9935, found:
418.9946.
d
¼166.4, 141.1, 137.2, 135.0, 133.1, 130.2, 129.8
(2C), 129.7, 129.2, 128.4 (2C), 127.8, 66.9, ꢀ3.1 (2C); IR (film):
nmax¼3060, 3009, 2959, 2902, 2127, 1789, 1720, 1601, 1585, 1452,
1441, 1375, 1314, 1270, 1209, 1176, 1109, 1069, 1026, 943, 886, 838,
794, 757, 711, 646 cmꢀ1; HRMS (ESI) [MþNa]þ calculated for
[C16H18NaO2Si]þ: 293.0968, found: 293.0965.
4.2.9. 3-(Dimethylsilyl)benzyl 2-bromobenzoate (7i). 1H NMR
4.2.3. 2-(Dimethylsilyl)benzyl 2-bromobenzoate (7c). 1H NMR
(400 MHz, CDCl3):
d
¼7.81e7.83 (m, 1H), 7.65e7.68 (m, 2H),
(400 MHz, CDCl3):
d
¼7.80e7.82 (m, 1H), 7.65e7.68 (m, 1H), 7.58 (d,
7.49e7.56 (m, 2H), 7.37e7.43 (m, 1H), 7.30e7.36 (m, 2H), 5.40 (s,
J¼7.2 Hz, 1H), 7.53 (d, J¼7.6 Hz, 1H), 7.41e7.45 (m, 1H), 7.30e7.38
2H), 4.45e4.49 (m, 1H), 0.37e0.38 (m, 6H); 13C NMR (100 MHz,
(m, 3H), 5.49 (s, 2H), 4.61e4.65 (m, 1H), 0.38e0.39 (m, 6H); 13C
CDCl3):
d
¼166.0, 138.1, 134.9, 134.4, 134.2, 134.1, 132.7, 132.2, 131.5,
NMR (100 MHz, CDCl3):
132.0, 131.4, 129.7, 129.2, 127.9, 127.2, 121.9, 67.4, ꢀ3.1 (2C); IR
(film): nmax¼3058, 3008, 2958, 2901, 2126, 1732, 1590, 1566, 1469,
d
¼165.9, 140.6, 137.2, 135.0, 134.4, 132.6,
129.4, 128.2, 127.2, 121.8, 67.6, ꢀ3.7 (2C); IR (film): nmax¼3051, 3022,
2958, 2851, 2119, 1732, 1590, 1567, 1470, 1433, 1369, 1290, 1249,
1163, 1119, 1043, 1029, 956, 888, 832, 762, 745, 698, 645, 603,

8922
H. Shen et al. / Tetrahedron 68 (2012) 8916e8923
551 cmꢀ1; HRMS (ESI) [MþNa]þ calculated for [C16H17BrNaO2Si]þ:
7.42e7.51 (m, 3H), 7.28e7.30 (m, 2H), 5.40 (s, 2H), 4.48e4.52 (m,
1H), 2.67 (s, 3H), 0.40e0.41 (m, 6H); 13C NMR (100 MHz, CDCl3):
371.0073, found: 371.0061.
d
¼167.3, 140.4, 137.5, 137.2, 134.4 (2C), 132.1, 131.8, 130.8, 129.4,
4.2.10. 3-(Dimethylsilyl)benzyl 4-fluoro-2-methylbenzoate (7j). 1H
127.6 (2C), 125.8, 66.4, 21.9, ꢀ3.7 (2C); IR (film): nmax¼3072, 3021,
NMR (400 MHz, CDCl3):
7.30e7.55 (m, 3H), 6.90e6.96 (m, 2H), 5.35 (s, 2H), 4.45e4.48 (m,
d
¼7.99e8.03 (m, 1H), 7.62 (s, 1H),
2959, 2930, 2118, 1721, 1603, 1576, 1457, 1291, 1250, 1110, 1076, 880,
837, 765, 737 cmꢀ1
;
HRMS (ESI) [MþNa]þ calculated for
1H), 2.64 (s, 3H), 0.38e0.39 (m, 6H); 13C NMR (100 MHz, CDCl3):
[C17H20NaO2Si]þ: 307.1125, found: 307.1122.
d
¼166.4, 163.4, 144.1, 138.1, 135.4, 134.0 (2C), 133.4, 129.2, 128.2,
125.6, 118.6, 112.9, 66.8, 22.1, ꢀ3.8 (2C); IR (film): nmax¼3087, 3049,
Acknowledgements
2960, 2900, 2120, 1786, 1722, 1609, 1587, 1495, 1413, 1368, 1307,
1251, 1120, 1074, 1012, 954, 889, 774, 734, 689, 601, 521 cmꢀ1
;
Financial support by the National Natural Science Foundation of
China (NSFC, No. 20973051 and 21173064), Program for Excellent
Young Teachers in Hangzhou Normal University (HNUEYT, JTAS
2011-01-014), Zhejiang Provincial Natural Science Foundation of
China (Q12B020037), and Qianjiang talent project of Zhejiang
Province of China (No. 2010R0017) are appreciated.
HRMS (ESI) [MþNa]þ calculated for [C17H19FNaO2Si]þ: 325.1031,
found: 325.1041.
4.2.11. 4-(Dimethylsilyl)benzyl 2-iodobenzoate (7k). 1H NMR
(400 MHz, CDCl3):
1H), 5.38 (s, 2H), 4.46 (s, 1H), 0.36 (s, 6H); 13C NMR (100 MHz,
CDCl3):
d
¼7.83e8.00 (m, 2H), 7.39e7.58 (m, 5H), 7.15 (s,
d
¼166.3, 141.4, 137.9, 136.5, 134.9, 134.4 (2C), 132.8, 131.1,
Supplementary data
128.7, 127.9 (2C), 94.3, 67.3, ꢀ3.7 (2C); IR (film): nmax¼3070, 3019,
2957, 2900, 2854, 2118, 1729, 1583, 1562, 1464, 1429, 1397, 1372,
1287, 1249, 1133, 1108, 1044, 1016, 880, 836, 765, 741 cmꢀ1; HRMS
(ESI) [MþNa]þ calculated for [C16H17INaO2Si]þ: 418.9935, found:
418.9950.
Supplementary data of general remarks and the procedure of
the esterification reaction, NMR data diagrams for all the ester
products 4e7 associated with this article. These data include MOL
files and InChikeys of the most important compounds described in
this article. Supplementary data related to this article can be found
at http://dx.doi.org/10.1016/j.tet.2012.08.024.
4.2.12. 4-(Dimethylsilyl)benzyl acetate (7l). 1H NMR (400 MHz,
CDCl3):
4.42e4.46 (m, 1H), 2.11 (s, 3H), 0.35e0.36 (m, 6H); 13C NMR
(100 MHz, CDCl3):
¼170.9, 137.7, 136.9, 134.3 (2C), 127.7 (2C), 66.3,
21.0, ꢀ3.8 (2C); IR (film): nmax¼3073, 3020, 2959, 2119, 1740, 1604,
d¼7.55e7.57 (m, 2H), 7.36e7.37 (m, 2H), 5.12 (s, 2H),
d
References and notes
1436, 1378, 1362, 1227, 1110, 1030, 968, 882, 838, 765, 530 cmꢀ1
;
1. Selected reviews for carbonenitrogen bond formation: (a) Magriotis, P. A. An-
gew. Chem., Int. Ed. 2001, 40, 4377e4379; (b) Xu, L. W.; Xia, C. G. Eur. J. Org. Chem.
2005, 633e639; (c) Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz, U. Adv.
Synth. Catal. 2006, 348, 23e39; (d) Hartwig, J. F. Nature 2008, 455, 314e322; (e)
HRMS (ESI) [MþNa]þ calculated for [C11H16NaO2Si]þ: 231.0812,
found: 231.0810.
€
Harwig, J. F. Acc. Chem. Res. 2008, 41, 1534e1544; (f) Muller, T. E.; Hultzsch, K. C.;
4.2.13. 4-(Dimethylsilyl)benzyl 2-bromobenzoate (7m). 1H NMR
Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795e3892; (g) Surry, D. S.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6338e6361; (h) Weiner, B.;
Szymanski, W.; Janssen, D. B.; Minnaard, A. J.; Feringa, B. L. Chem. Soc. Rev. 2010,
39, 1656e1691.
2. Selected recent examples for carbonenitrogen bond breaking: (a) Katritzky, A.
R.; Yao, J.; Bao, W.; Qi, M.; Steel, P. J. J. Org. Chem. 1999, 64, 346e350; (b) Shen,
H.; Xie, Z. J. Organomet. Chem. 2009, 694, 1652e1657; (c) Shen, H.; Wang, Y.; Xie,
Z. Org. Lett. 2011, 13, 4562e4565; (d) Jin, Y. H.; Fang, F.; Zhang, X.; Liu, Q. Z.;
Wang, H. B.; Tian, S. K. J. Org. Chem. 2011, 76, 4163e4167.
(400 MHz, CDCl3):
d
¼7.83 (s, 1H). 7.34e7.66 (m, 7H), 5.40 (s, 2H),
4.47 (s, 1H), 0.37 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
¼165.9, 137.8,
136.5, 134.5, 134.4 (2C), 132.7, 132.0, 131.5, 127.8 (2C), 127.2, 121.9,
67.3, ꢀ3.7 (2C); IR (film): nmax¼3071, 3019, 2958, 2900, 2118, 1915,
1732, 1650, 1590, 1567, 1460, 1433, 1372, 1298,1248, 1107, 1044,
1030, 943, 830, 836, 765, 744, 670, 645, 559 cmꢀ1; HRMS (ESI)
[MþNa]þ calculated for [C16H17BrNaO2Si]þ: 371.0073, found:
371.0064.
3. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.;
Wiley: New York, NY, 1999; (b) Kaminskaia, N. V.; Spingler, B.; Lippard, S. J. J.
Am. Chem. Soc. 2001, 123, 6555e6573; (c) Lin, B. L.; Clough, C. R.; Hillhouse, G. L.
J. Am. Chem. Soc. 2002, 124, 2890e2891; (d) Moore, I. F.; Kluger, R. J. Am. Chem.
Soc. 2002, 124, 1669e1673; (e) Lei, Y.; Wrobleski, A. D.; Golden, J. E.; Powell, D.
4.2.14. 4-(Dimethylsilyl)benzyl 4-fluoro-2-methylbenzoate (7n). 1H
ꢀ
R.; Aube, J. J. Am. Chem. Soc. 2005, 127, 4552e4553; (f) Klima, R. F.; Jadhav, A. V.;
NMR (400 MHz, CDCl3):
d
¼8.00e8.04 (m, 1H), 7.59e7.61 (m, 2H),
Singh, P. N. D.; Chang, M.; Vanos, C.; Sankaranarayanan, J.; Vu, M.; Ibrahim, N.;
7.45e7.47 (m, 2H), 6.90e6.96 (m, 2H), 5.35 (s, 2H), 4.45e4.49 (m,
ꢀ
Ross, E.; McCloskey, S.; Murthy, R. S.; Krause, J. A.; Ault, B. S.; Gudmundsdottir,
1H), 2.64 (s, 3H), 0.37e0.38 (m, 6H); 13C NMR (100 MHz, CDCl3):
A. D. J. Org. Chem. 2007, 72, 6372e6381; (g) Alizadeh, A.; Sabahnoo, H.; Zohreh,
N.; Noaparast, Z.; Zhu, L. G. Synlett 2011, 2495e2498; (h) Muranaka, K.;
Ichikawa, S.; Matsuda, A. J. Org. Chem. 2011, 76, 9278e9293.
4. (a) Chan, Y. W.; Renner, M. W.; Balch, A. L. Organometallics 1983, 2, 1888e1889;
(b) Chan, Y. W.; Wood, F. E.; Renner, M. W.; Hope, H.; Balch, A. L. J. Am. Chem.
Soc. 1984, 106, 3380e3381; (c) Balch, A. L.; Chan, Y. W.; Olmstead, M. M.;
Renner, M. W.; Wood, F. E. J. Am. Chem. Soc. 1988, 110, 3897e3902.
d
¼166.3,163.5,144.2,137.7,137.0,134.4 (2C),133.5,127.6 (2C),125.5,
118.6, 112.9, 66.5, 22.1, ꢀ3.8 (2C); IR (film): nmax¼3073, 3020, 2959,
2932, 2120, 1723, 1609, 1586, 1495, 1449, 1371, 1306, 1251, 1121,
1077, 1012, 955, 881, 836, 773, 705, 601, 532 cmꢀ1; HRMS (ESI)
[MþNa]þ calculated for [C17H19FNaO2Si]þ: 325.1031, found:
325.1045.
5. (a) Jones, W. D. Organometallics 1986, 5, 1823e1829; (b) Calafat, A. M.; Marzilli,
L. G. Inorg. Chem. 1993, 32, 2906e2911; (c) Yamamoto, Y.; Seta, J.; Murooka, H.;
ꢀ
Han, X. H. Inorg. Chem. Commun. 2003, 6, 202e205; (d) Ardura, D.; Lopez, R.;
Sordo, T. L. J. Org. Chem. 2006, 71, 7315e7321.
4.2.15. 4-(Dimethylsilyl)benzyl 2-hydroxy-3-methylbenzoate
6. Selected examples for Brønsted acid catalysts, see: (a) Chung, K. H.; Kim, J. N.;
Ryu, E. K. Tetrahedron Lett. 1994, 35, 2913e2914; (b) Seong, M. R.; Lee, H. J.; Kim,
J. N. Tetrahedron Lett. 1998, 39, 6219e6222; (c) Lee, H. J.; Seong, M. R.; Kim, J. N.
Tetrahedron Lett. 1998, 39, 6223e6226; (d) Liu, C.-R.; Li, M.-B.; Cheng, D.-J.;
Yang, C.-F.; Tian, S.-K. Org. Lett. 2009, 11, 2543e2545; (e) He, Q.-L.; Sun, F.-L.;
Zheng, X.-J.; You, S.-L. Synlett 2009, 1111e1114; (f) Yang, B.-L.; Tian, S.-K. Chem.
Commun. 2010, 6180e6182.
(7o). 1H NMR (400 MHz, CDCl3):
d
¼11.01 (s, 1H), 7.33e7.76 (m,
6H), 6.78e6.79 (m, 1H), 5.39 (s, 2H), 4.45e4.46 (m, 1H), 2.28 (s, 3H),
0.37 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
¼170.4, 160.2, 138.0,
136.6, 136.4, 134.4 (2C), 127.6 (2C), 127.5, 126.7, 118.5, 111.7, 66.8,
15.7, ꢀ3.8 (2C); IR (film): nmax¼3179, 3020, 2958, 2923, 2120, 1730,
1671, 1615, 1463, 1433, 1383, 1327, 1289, 1249, 1110, 1084, 1011, 881,
835, 757, 624, 572 cmꢀ1; HRMS (ESI) [MþNa]þ calculated for
[C17H20NaO3Si]þ: 323.1074, found: 323.1089.
7. Selected examples for Lewis acid catalysts, see: (a) Stamm, H.; Onistschenko, A.;
ꢀ
Buchholz, B.; Mall, T. J. Org. Chem. 1989, 54, 193e199; (b) Esquivias, J.; Gomez-
ꢀ
Arrayas, R.; Carretero, J. C. Angew. Chem., Int. Ed. 2006, 45, 629e633; (c) Alonso,
ꢀ
ꢀ
I.; Esquivias, J.; Gomez-Arrayas, R.; Carretero, J. C. J. Org. Chem. 2008, 73,
6401e6404; (d) Lee, K. Y.; Lee, H. S.; Kim, H. S.; Kim, J. N. Bull. Korean Chem. Soc.
2008, 29, 1441e1442; (e) Liu, C.-R.; Li, M.-B.; Yang, C.-F.; Tian, S.-K. Chem.dEur. J.
2009,15, 793e797; (f) Liu, C.-R.; Yang, F.-L.; Jin, Y.-Z.; Ma, X.-T.; Cheng, D.-J.; Li, N.;
Tian, S.-K. Org. Lett. 2010, 12, 3832e3835; (g) Jiang, Z.-Y.; Zhang, C.-H.; Gu, F. -L.;
4.2.16. 4-(Dimethylsilyl)benzyl 2-methylbenzoate (7p). 1H NMR
(400 MHz, CDCl3):
d¼8.01e8.03 (m, 1H), 7.62e7.63 (m, 2H),

H. Shen et al. / Tetrahedron 68 (2012) 8916e8923
8923
Yang, K.-F.; Lai, G.-Q.; Xu, L.-W.; Xia, C.-G. Synlett 2010,1251e1254; (h) Yang, C. F.;
Wang, J. Y.; Tian, S. K. Chem. Commun. 2011, 8343e8345.
2005, 70, 8625e8627; (d) Zhu, L.; Zhu, Y.; Meng, X.; Hao, J.; Li, Q.; Wei, Y.; Lin, Y.
Chem.dEur. J. 2008, 14, 10923e10927; (e) Ansell, R. J.; Barrett, S. A.; Meegan, J.
E.; Warriner, S. L. Chem.dEur. J. 2007, 13, 4654e4664; (f) Sanchez, A.; Pedroso,
ꢀ
8. (a) Smith, P. A. S.; Loeppky, R. N. J. Am. Chem. Soc. 1967, 89, 1147e1157; (b)
Mariella, R. P.; Brown, K. H. Can. J. Chem. 1973, 51, 2177e2179; (c) Goodrow, M.;
Musker, W. K. J. Org. Chem. 1983, 48, 3332e3333; (d) Alhambra, C.; Castro, J.;
E.; Grandas, A. Eur. J. Org. Chem. 2010, 2600e2606; (g) Heller, S. T.; Sarpong, R.
Org. Lett. 2010, 12, 4572e4575; (h) Shiina, I.; Nakata, K.; Ono, K.; Onda, Y.;
Itagaki, M. J. Am. Chem. Soc. 2010, 132, 11629e11641; (i) Leng, Y.; Wang, J.; Zhu,
D.; Ren, X.; Ge, H.; Shen, L. Angew. Chem., Int. Ed. 2009, 48, 168e171; (j) Saka-
kura, A.; Kawajiri, K.; Ohkubo, T.; Kosugi, Y.; Ishihara, K. J. Am. Chem. Soc. 2007,
129, 14775e14779; (k) Ishihara, K.; Nakagawa, S.; Sakakura, A. J. Am. Chem. Soc.
2005, 127, 4168e4169; (l) Furrow, M. E.; Myers, A. G. J. Am. Chem. Soc. 2004, 126,
12222e12223; (m) Dhakshinamoorthy, A.; Sharmila, A.; Pitchumani, K. Chem.
dEur. J. 2010, 16, 1128e1132; (n) Vuluga, D.; Legros, J.; Crousse, B.; Bonnet-
Delpon, D. Chem.dEur. J. 2010, 16, 1776e1779.
ꢀ
ꢀ
Chiara, J. L.; Fernandez, E.; Fernandez-Mayoralas, A.; Fiandor, J. M.; García-
Ochoa, S.; Martín-Ortega, M. Tetrahedron Lett. 2001, 42, 6675e6678; (e) Dong,
Z.; Scammels, P. J. J. Org. Chem. 2007, 72, 9881e9885; (f) Aschwanden, P.;
Stephenson, C. R.; Carreira, E. M. Org. Lett. 2006, 8, 2437e2440; (g) Couturier, M.;
Tucker, J. L.; Andresen, B. M.; Dube, P.; Negri, J. T. Org. Lett. 2001, 3, 465e467;
ꢀ
(h) Concellon, J. M.; Rodríguez-Solla, H.; Del Amo, V.; Díaz, P. J. Org. Chem. 2010,
75, 2407e2410; (i) Behloul, C.; Guijarro, D.; Yus, M. Synthesis 2004, 1274e1280;
(j) Sato, M.; Gunji, Y.; Ikeno, T.; Yamada, T. Synthesis 2004, 1434e1438.
9. (a) Gruntz, U.; Katritzky, A. R.; Kenney, D. H.; Rezends, M. C.; Sheikh, H. J. Chem.
Soc., Chem. Commun. 1977, 701e701; (b) Katritzky, A. R.; Gruntz, U.; Kenney, D.
H.; Rezende, M. C.; Sheikh, H. J. Chem. Soc., Perkin Trans. 1 1979, 430e432.
10. (a) Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, U.K, 1991; Vol. 6, p 309; (b) Comprehensive Organic Group Trans-
formation; Katritzky, A. R., Meth-Kohn, O., Rees, C. W., Eds.; Pergamon: Oxford,
U.K, 1995; Vol. 5, p 182; (c) Larock, R. C. Comprehensive Organic Transformation;
Wiley-VCH: New York, London, 1999; (d) Khanbabaee, K.; Großer, M. Eur. J. Org.
Chem. 2003, 2128e2131; (e) Yamamoto, N.; Ohmori, Y.; Sakakibara, T.; Sasaki,
K.; Juneja, L. R.; Kajihara, Y. Angew. Chem., Int. Ed. 2003, 42, 2537e2540; (f) Va,
P.; Roush, W. R. Org. Lett. 2007, 9, 307e310.
11. Recent examples: (a) Xu, B.; Liu, X.; Haubrich, J.; Madix, R. J.; Friend, C. M.
Angew. Chem., Int. Ed. 2009, 48, 4206e4209; (b) Hashimi, A. S. K.; Lothschutz, C.;
Ackermann, M.; Doepp, R.; Anantharaman, S.; Marchetti, B.; Bertagnolli, H.;
Rominger, F. Chem.dEur. J. 2010, 16, 8012e8019; (c) De Sarkar, S.; Grimme, S.;
Studer, A. J. Am. Chem. Soc. 2010, 132, 1190e1191; (d) Maiji, B.; Vedachalan, S.;
Ge, X.; Cai, S.; Liu, X. W. J. Org. Chem. 2011, 76, 3016e3023; (e) Iwahana, S.; Iida,
H.; Yashima, E. Chem.dEur. J. 2011, 17, 8009e8013; (f) Xin, Y. C.; Shi, S. H.; Xie,
D. D.; Hui, X. P.; Xu, P. F. Eur. J. Org. Chem. 2011, 6527e6531; (g) Yasukawa, T.;
Miyamura, H.; Kobayashi, S. Chem.dAsian J. 2011, 6, 621e627; (h) Tejel, C.;
Ciriano, M. A.; Passarelli, V. Chem.dEur. J. 2011, 17, 91e95.
15. Selected examples: (a) Dugger, R. W.; Ragan, J. A.; Ripin, D. H. B. Org. Process Res.
Dev. 2005, 9, 253e258; (b) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T.
Org. Biomol. Chem. 2006, 4, 2337e2347; (c) Ekoue,-Kovi, K.; Wolf, C. Chem.dEur.
J. 2008, 14, 6302e6315; (d) Wu, X. F.; Darcelli, C. Eur. J. Org. Chem. 2009,
1144e1147; (e) Uno, T.; Inokuma, T.; Takemoto, Y. Chem. Commun. 2012,
1901e1903; (f) Luo, F.; Pan, C.; Cheng, J. Synlett 2012, 357e366.
16. About aminofumarate 5: (a) Wang, F. S.; Zhang, D.; Kong, C.; Qing, Y.
Tetrahedron Lett. 2011, 52, 3295e3297; (b) Attanasi, O. A.; Berretta, S.;
De Crescentini, L.; Favi, G.; Giorgi, G.; Mantellini, F.; Nicolini, S. Adv. Synth.
Catal. 2011, 353, 595e605; (c) Seki, H.; Georg, G. I. J. Am. Chem. Soc. 2010, 132,
15512e15513.
ꢀ
17. Selected recent reviews: (a) Díez-Gonzalez, S.; Nolan, S. P. Acc. Chem. Res. 2008,
41, 349e358; (b) Marciniec, B. In Hydrosilylation: a Comprehensive Review on
Recent Advances; Springer Science: Netherlands, 2009; (c) Addis, D.; Das, S.;
Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2011, 50, 6004e6011.
18. (a) Benkese, R. A. r.; Foster, D. J. J. Am. Chem. Soc. 1952, 74, 5314e5317; (b)
Kobayashi, K.; Kato, T.; Masuda, S. Chem. Lett. 1987, 101e104; (c) Carilla, J.; Fajarí,
ꢀ
L.; Julia, L.; Riera, J.; Loveras, J.; Verdaguer, N.; Fita, I. J. Organomet. Chem. 1992,
423, 163e171; (d) Kobayashi, K.; Kato, T.; Unno, M.; Masuda, S. Bull. Chem. Soc.
Jpn. 1997, 70, 1393e1401; (e) Jankowski, P.; Schaumann, E.; Wicha, J.; Zarecki,
A.; Adiwidjaja, G.; Asztemborska, M. Chem. Commun. 2000, 1029e1030; (f)
Trzoss, M.; Shao, J.; Bienz, S. Tetrahedron: Asymmetry 2004, 15, 1501e1505; (g)
Rendler, S.; Auer, G.; Keller, M.; Oestreich, M. Adv. Synth. Catal. 2006, 348,
1171e1182; (h) Igawa, K.; Kokan, N.; Tomooka, K. Angew. Chem., Int. Ed. 2010, 49,
728e731.
12. (a) Otera, J. Angew. Chem., Int. Ed. 2001, 40, 2044e2045; (b) Otera, J. Esterifi-
cation; Wiely-VCH: Weinheim, 2003; (c) Tidwell, T. T. Angew. Chem., Int. Ed.
2005, 44, 6812e6814; (d) Dzik, W. I.; Gooßen, L. J. Angew. Chem., Int. Ed. 2011,
50, 11047e11049.
13. (a) McNulty, J.; Capretta, A.; Laritchev, V.; Dyck, J.; Robertson, A. J. Angew. Chem.,
Int. Ed. 2003, 42, 4051e4054; (b) Houston, T. A.; Wilkinson, B. L.; Blanchfield, J.
T. Org. Lett. 2004, 6, 679e681; (c) Gopinath, P.; Nilaya, S.; Muraleedharan, K. M.
Org. Lett. 2011, 13, 1932e1935.
19. Recent reviews and examples: (a) Widenhoefer, R. A. Acc. Chem. Res. 2002,
35, 905e913; (b) Chatgilialoglu, C. Chem.dEur. J. 2008, 14, 2310e2320;
(c) Bracegirdle, S.; Anderson, E. A. Chem. Soc. Rev. 2010, 39, 4114e4129;
(d) Inagaki, T.; Phong, L. T.; Furuta, A.; Ito, J-i.; Nishiyama, H. Chem.dEur. J. 2010,
16, 3090e3096; (e) Chen, X. H.; Deng, Y.; Jiang, K.; Lai, G. Q.; Ni, Y.; Yang,
K. F.; Jiang, J. X.; Xu, L. W. Eur. J. Org. Chem. 2011, 1736e1742; (f) Xu, L. W.;
Li, L.; Lai, G. Q.; Jiang, J. X. Chem. Soc. Rev. 2011, 40, 1777e1790.
ꢀ
14. Recent examples: (a) Morcillo, S. P.; De Cienfuegos, L. A.; Mota, A. J.; Justicia, J.;
Robles, R. J. Org. Chem. 2011, 76, 2277e2281; (b) Luo, F.; Pan, C.; Qian, P.; Cheng,
J. J. Org. Chem. 2010, 75, 5379e5381; (c) Chen, C. T.; Munot, Y. S. J. Org. Chem.