Tunable Synthesis of α-Amino Boronic Esters from Available Aldehydes and Amines through Sequential One-Pot Dehydration and Copper-Catalyzed Borylacylation

Article abstract of DOI:10.1021/acs.joc.9b02887

Copper-catalyzed multicomponent borylacylation of imines with acid chlorides and bis(pinacolato)diboron was developed for the preparation of synthetically useful and pharmacologically relevant α-amino boronic acid derivatives. Starting from a range of acid chlorides and imines with aryl, heteroaryl, and alkyl substituents, most of these ligand-free reactions proceeded smoothly at room temperature in moderate to good yields. Furthermore, a facile and convenient one-pot, multistep access to the direct synthesis of α-amino boronic acid derivatives from available aldehydes and amines was also developed.

Full text of DOI:10.1021/acs.joc.9b02887

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Note
Tunable synthesis of #-amino boronic esters from
available aldehydes and amines through sequential one-
pot dehydration and copper-catalyzed borylacylation
Qi Xia, Hua-Rong Chang, Juan Li, Jiayi Wang, Yanqing Peng, and Gonghua Song
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02887 • Publication Date (Web): 30 Dec 2019
Downloaded from pubs.acs.org on December 31, 2019
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Tunable synthesis of α-amino boronic esters from available
aldehydes and amines through sequential one-pot dehydration
and copper-catalyzed borylacylation
9
Qi Xia, Hua-Rong Chang, Juan Li, Jia-Yi Wang, Yan-Qing Peng and Gong-Hua Song *
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Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China
University of Science and Technology, Shanghai, 200237, P. R. China.
ABSTRACT:
multicomponent
Copper-catalyzed
borylacylation of
R1
NH2
O
R1
H
O
cat. CuCl/base
R1
N
R3
N
imines with acid chlorides and
bis(pinacolato)diboron was developed
for the preparation of synthetically useful
and pharmacologically relevant α-amino
boronic acid derivatives. Starting from a
R3
R2
Cl
B2pin2
O
R2 Bpin
toluene, r.t.
R2
H
Up to 88% yield
37 examples
range of acid chlorides and imines with aryl, heteroaryl, and alkyl substituents, most of these ligand-free
reactions proceeded smoothly at room temperature in moderate to good yields. Furthermore, a facile and
convenient one-pot, multi-step access to the direct synthesis of α-amino boronic acid derivatives from
available aldehydes and amines was also developed.
In the last few decades, organoboronic acids and their derivatives have been widely applied in synthetic
organic chemistry,1, 2 carbohydrate recognition,3 transmembrane transport4 and separation of glycoproteins.
They can also be used as pharmacologically active agents in some cases such as a unique class of enzyme
inhibitors due to their substantial selectivity in the formation of reversible covalent bonds with the targeted
enzymes.5, 6 Important biomedical applications have been established for the compounds containing an α-
amino boronic acids group. For instance, Bortezomib,7 Ixazomib,8 Dutoglitin,9 Talabostat10 and
Delanzomib11 (Fig 1), have been evaluated and optimized as the second-generation protease inhibitors in
the clinical trials. Additionally, many other bioactivities such as anticancer, antiviral, and antibacterial
properties have also been found for α-amino boronic acid compounds.12 With such success, the enormous
potential of α-amino boronic acids attracts more and more attention to their preparation method.13 However,
the difficulty in the isolation of α-amino boronic acids constitutes a major synthetic challenge since the
formation of a three-membered ring adduct between the boron and nitrogen atoms can induce the C-B bond
cleavage.14 For this reason, efficient routes for the synthesis of functionalized α-amino boronic acids and
esters are still quite limited. Only a few protocols including the addition of α-amino organometallic
compounds to boron-containing electrophiles,15 the addition of nucleophilic boron reagents to imines,16 the
hydroboration of enamides17 and the C(sp3)-H borylation reaction18, etc., have been reported.
Cl
N
O
O
H
H
COOH
COOH
N
N
O
N
N
B(OH)2
N
B
H
H
O
Cl
O
O
Ph
O
Bortezomib (Velcade R
)
Ixazomib citrate (Ninlaro R
)
O
O
H
B(OH)2
B(OH)2
N
H
N
N
N
Ph
N
N
B(OH)2
O
H
HN
NH2
O
HO
Delanzomib
Talabostat
Dutoglipin
Fig 1. Represent bioactive compound bearing an α-amino boronic acid structure.
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Scheme 1. Approaches to synthesize α-amino boronic esters.
4
5
(a) Addition of bis(pinacolato)diboron to imines
6
7
8
PG
PG
H
B2pin2, L*/Cu(I)
MOR
HN
Ar
N
PG: protecting group
Bpin
Ar
9
(b) One-pot aminoboration of aldehydes
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TMS
Piv
O
N
B2pin2, L*/Pt(0)
then PivCl
LiHMDS
HN
Ar
H
Ar
H
R
Bpin
This work:
bis(pinacolato)diboron
(c)
Cu(I)-catalyzed borylacylation of imine with acid chlorides and
O
O
R1
H
O
R3
Cl
R1
NH2
R1
N
R3
N
H
R2
R2
then B2pin2, Base/Cu(I)
R2
Bpin
Among those methods, the transition-metal-catalyzed addition of bis(pinacolato)diboron to imines might
be the most efficient and straightforward approach.19 Ellman,20 Fernańdez,21 Lin,22 and Liao23 have provided
different catalysts and ligands systems for the synthesis of simple α-amino boronate esters (Scheme 1a).
However, these approaches suffer from some drawbacks such as high catalyst loading, complex and
expensive ligands, harsh conditions, long reaction times and narrow substrate scope due to the adoption of
only N-protected imine as the starting material. Morken and Hong provided a protocol of converting
aldehydes into N-acyl α-amino boronic esters or peptide derivatives catalyzed by an asymmetric platinum
(0) phosphonate (Scheme 1b).24 This transformation included the Pt-catalyzed diboration of in situ-
generated silyl imines with B2Pin2, followed by the direct acylation of the diboration adducts to provide N-
acyl α-amino boronic esters. However, this protocol required not only expensive Pt catalysts and complex
ligand, but also tedious reaction setup and long reaction time. Therefore, a simple and effective method for
the preparation of functionalized α-amino boronate esters with diverse substituents on the nitrogen atom has
remained an elusive goal. As our continuous efforts on the development of efficient boration strategy with
bis(pinacolato)diboro,25 we reported herein a copper-catalyzed multicomponent borylacylation of imines
with acid chlorides and bis(pinacolato)diboron in a one-pot two-step reaction. Furthermore, the widely
available aldehydes and amines were directly converted to α-amino boronic esters through sequential one-
pot dehydration and borylacylation under mild conditions with broad substrate scopes (Scheme 1c).
The borylacylation of imines with acid chlorides and B2pin2 was studied firstly. By employing the copper-
catalyzed borylacylation of N-benzyltolylaldimine (1a), benzoyl chloride (2a) and B2pin2 as the model
reaction, a variety of reaction conditions was investigated (Table 1). In the initial experiments, the target
product 3a was only obtained in 5% (Table 1, entry 1). It was found then that the choice of the base is crucial
for the success of the reaction. For example, when K2CO3 or tBuOK was added to the reaction mixture, the
desired α-amino boronic esters 3a was obtained in low yields (Table 1, entries 2 and 3). A large amount of
aldehyde was detected in the reaction products, indicating that the decomposition of imine 1a occurred. To
our delight, the target product 3a was obtained in 25% and 70% yields, respectively, with tBuONa or tBuOLi
as the base (Table 1, entries 4 and 5). Only trace of 3a was detected when Et3N was used (Table 1, entry 6).
The target product was obtained in 30% yield with DBU (Table 1, entry 7). Subsequently, a series of
transition metal salts were used to evaluate their catalytic capability. The target product 3a could be detected
only in the presence of copper salts, and Cu(II) salts gave a little worse results than Cu(I) salts (Table 1,
entry 8-11). The best yield of 3a was achieved by using CuCl as the catalyst. Nickel, iron and zinc salts did
not show any catalytic activity (Table 1, entry 12-14). The effects of solvents on the reaction were also
examined. THF, 1, 4-dioxane and diethyl ether gave the target product 3a in lower yields than toluene (Table
1, entries 15-17). Only trace of 3a was detected in polar solvents such as CH3CN, DMSO and DMF (Table
1, entry 18-20). Finally, the catalyst loading was optimized. Either decreasing or increasing the catalyst
loading from 1.0 mol% would result in a decline in the yield of 3a (Table 1, entry 21-22). To investigate
the potential of this transformation in asymmetry borylacylation, several commercially available chiral
ligands have been adopted. However, the enantioselectivity of the products was unfortunately low (less than
3% ee).
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Table 1. Optimization of reaction conditions.
4
5
6
7
8
O
B
O
N
copper catalyst (1 mol%)
N
Cl
H
B2pin2 (1.5 equiv.)
base (2.0 equiv.)
solvent (3 mL), r.t., 30 min
O
O
1a
2a
(0.6 mmol)
(0.5 mmol)
3a
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Entry
Copper cat.
CuBr
Base
Solvent
Yield (%)a
1
2
Cs2CO3
K2CO3
tBuOK
tBuONa
tBuOLi
Et3N
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
5
trace
8
CuBr
3
CuBr
4
CuBr
25
5
CuBr
70
6
CuBr
trace
30
7
CuBr
DBU
8
CuBr2
CH3COOCu
CuI
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
tBuOLi
51
9
63
10
11
12
13
14
15
16
17
18
19
20
21c
22d
68
76 (72) b
CuCl
NiCl2
FeCl3
ZnCl2
CuCl
-
-
-
23
CuCl
1,4-dioxane
Et2O
38
CuCl
29
CuCl
CH3CN
DMSO
DMF
trace
trace
trace
48
CuCl
CuCl
CuCl
toluene
toluene
CuCl
73
Reaction conditions: (1) imine (0.5 mmol), acid chloride (0.6 mmol) in solvent (3.0 mL), r.t., 2 min. (2) catalyst (0.005 mmol), B2pin2 (0.75
mmol) and bases (1.0 mmol) were added, r.t., 30 min under N2. a GC yield (dodecane as an internal standard). b Isolated yield is given in
parenthesis. c The amount of catalyst was 0.0025 mmol. d The amount of catalyst was 0.0075 mmol.
With the optimal reaction conditions in hand, a variety of imines were adopted to investigate the scope
and limitation of the transformation (Table 2). It seems that both electron-donating and electron-
withdrawing groups attached to the phenyl ring of the C-aryl-substituted imines were compatible under the
standard reaction conditions. An array of functional groups at the p- and m-position such as p-CH3, p-OCH3,
p-SCH3, p-F, p-Cl, p-Br, p-CF3, p-CO2Me and m-Br groups were well-tolerated, affording 3a-i in good
yields of 65-85%. Meanwhile, the desired product 3j and 3k with the phenyl ring bearing a group at the
ortho-position were formed in moderate yields, indicating that the steric effect has slight influence on the
reaction. Imines derived from 2-naphthaldehyde and heteroaryl aldehyde also reacted smoothly to form 3l
and 3m in satisfying yields. Therefore, the reaction is tolerant of various C-aryl-substituted imines.
Unfortunately, the imine derived from trimethylacetaldehyde and n-butylamine provided the corresponding
product 3w in a low yield of 8%. In addition, different N-substituted imines were also investigated. The use
of N-alkyl-substituted imines afforded 3n-q in good yields of 69-82%. Considering the widely biological
activities of peptide boronic acid derivatives, several different amino acids have been adopted for this
transformation. Unfortunately, only the imine derived from glycine methyl ester could react smoothly.
When other amino acid esters such as alanine methyl ester and phenylalanine methyl ester were involved,
the pre-prepared imines were decomposed under the optimal reaction conditions. Even by performing the
reaction in an ice bath to weaken the reaction condition, the decomposition of imines still happened.
Nevertheless, the N-phenyl-substituted imines gave the desired products 3r and 3s in relatively lower yields.
However, when an electron-donating group was attached either to the C-substituted phenyl ring (3t and 3u)
or to the N-substituted phenyl ring (3v) of imines, the yields of the target products were improved.
We then explored the scope of this copper-catalyzed borylacylation of imines with a variety of
commercially available acid chlorides to afford the corresponding α-amino boronic esters (Table 3). Both
electron-donating and -withdrawing groups on the para-positions of the aryl ring of acid chlorides were
tolerated, affording the corresponding desired product 4a-e in good yields. With a phenyl ring bearing a Br
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group at the meta- or ortho-position, the desired products 4f and 4g were formed in lower yields, indicating
that the reactivity of an acid chloride was slightly influenced by the steric hindrance. Alkyl acid chlorides
such as acetyl chloride and 3-methylcrotonoyl chloride could also be involved in the transformation and
give the products 4h and 4i in 69% and 70% yields, respectively. In case of heterocyclic acid chlorides,
corresponding products 4j and 4k were obtained in good yields.
Table 2. Preparation of α-amino boronic esters from various imines. a, b, c
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R1
H
O
O
CuCl (1 mol%)
R1
N
N
Cl
R2
tBuOLi (2.0 equiv.)
B2pin2 (1.5 equiv.)
toluene, r.t.
R2 Bpin
1
2a
3
O
B
O
B
O
N
O
N
N
N
O
O
B
B
O
O
O
O
O
O
SCH3
OCH3
3a
3a'
3b
: 15 min, 72%
O
: 15 min, 70%
O
: 15 min, 75%
3c
: 15 min, 72%
O
O
N
N
N
N
B
O
B
O
B
B
O
O
O
O
O
O
CF3
F
Cl
Br
3g
: 30 min, 65%
3e
: 15 min, 78%
O
3f
: 15 min, 80%
O
3d
: 15 min, 79%
O
O
N
N
N
N
Cl
Br
Br
B
O
B
O
B
B
O
O
O
O
O
O
COOMe
Cl
3k
: 60 min, 55%
3j
: 15 min, 52%
O
3h
3i
: 45 min, 85%
: 45 min, 71%
O
O
O
B
N
N
N
N
S
B
O
B
B
O
O
O
O
O
O
O
3m
3n
3n'
: 30 min, 56%
: 15 min, 82%
: 15 min, 78%
O
3l
: 30 min, 88%
O
O
H3CO
O
COOMe
N
N
N
N
OCH3
B
B
O
O
B
O
B
O
O
O
O
O
3o
3o'
3p
: 30 min, 81%
O
: 30 min, 75%
O
: 30 min, 70%
O
3q
: 15 min, 73%
O
N
N
N
N
COOMe
B
B
B
O
O
O
B
O
O
O
O
O
Cl
3q'
3r
3s
: 15 min, 69%
O
: 30 min, 38%
: 30 min, 26%
O
3t
: 30 min, 60%
OCH3
O
N
N
N
B
O
B
O
B
O
O
O
O
OCH3
c
3u
: 45 min, 68%
3w
: 30 min, 8%
3v
: 30 min, 73%
a Reaction conditions: (1) imines (0.5 mmol), acid chlorides (0.6 mmol) in toluene (3.0 mL), r.t., 2min. (2) CuCl (0.005 mmol), B2pin2 (0.75
mmol) and tBuOLi (1.0 mmol) were added, r.t., 30 min under N2. b Isolated yield. c GC yield.
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Table 3. Preparation of α-amino boronic esters from various acid chlorides. a, b
4
5
O
N
6
7
8
9
O
R3
N
CuCl (1 mol%)
H
R3 Cl
tBuOLi (2.0 equiv.)
B2pin2 (1.5 equiv.)
toluene, r.t.
Bpin
R
1n
1n'
: R = CH3
: R = H
2
R
4
10
11
12
13
14
15
16
17
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19
20
21
22
23
24
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46
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49
50
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59
60
O
N
O
O
B
O
N
N
N
Cl
F3C
Br
F
B
O
B
O
O
B
O
O
O
O
O
4d
: 15 min, 70%
O
4b
: 15 min, 82%
O
4a
4c
: 15 min, 85%
: 15 min, 78%
O
O
Br
Br
N
N
N
N
H3CO
B
B
B
O
O
B
O
O
O
O
O
O
4e
4f
4g
: 15 min, 78%
O
: 30 min, 62%
O
: 30 min, 34%
O
4h
: 15 min, 69%
N
O
B
O
N
N
S
O
B
B
O
O
O
O
4j
: 15 min, 85%
4i
: 15 min, 70%
4k
: 15 min, 88%
a Reaction conditions: (1) imines (0.5 mmol), acid chlorides (0.6 mmol) in toluene (3.0 mL), r.t., 2min. (2) CuCl (0.005 mmol), B2pin2 (0.75
mmol) and tBuOLi (1.0 mmol) were added, r.t., 30 min under N2. b Isolated yield.
Encouraged by the success in the borylacylation of imines, we next sought to directly convert aldehydes
to α-amino boronic esters. As showed in Table 4, this one-pot multi-step process starting from aldehydes
could provide a highly effective strategy for the preparation of a variety of α-amino boronic esters.
Table 4. Direct conversion of aldehydes to α-amino boronic esters. a, b
O
O
a)
R2
R2
H
R2
R3 Cl
NH2
R3
O
N
N
6
2a
H
B
O
MgSO4
toluene, r.t.
b) B2pin2
CuCl, tBuOLi
toluene, r.t.
R1
O
3
1a
5
R1
R1
not isolated
O
B
O
N
O
B
O
B
N
N
N
S
O
B
O
O
O
O
O
O
O
3o
: 82%
3n
: 85%
N
3a
3m
: 52%
: 76%
O
O
O
O
N
N
N
COOMe
S
O
B
O
B
B
O
B
O
O
O
O
O
3q
4h
: 64%
: 72%
3t
4k
: 86%
: 58%
a Reaction conditions: (1) aldehydes (0.5 mmol), amines (0.5 mmol), MgSO4 (1.0 mmol) in toluene (2 mL), r.t., 10 min. (2) acid chlorides
(0.6 mmol) dissolved in toluene (1.0 mL) was added, r.t., 2min. (3) CuCl (0.005 mmol), B2pin2 (0.75 mmol) and tBuOLi (1.0 mmol) were
added, r.t., 30 min under N2. b Isolated yield.
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Scheme 2. Control experiments.
4
5
6
7
8
9
O
O
N
(1)
no B2pin2
N
Cl
H
H
CuCl, tBuOLi
toluene, r.t.
tBuO
1a
2a
7a
68%
(2)
N
2a
no
starting material
remains
10
11
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13
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32
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34
35
36
37
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41
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43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
B2pin2 (1.2 equiv.)
standard conditions
1a
O
(3)
(4)
N
no Base
starting material
decomposed
Cl
H
CuCl
B2pin2 (1.2 equiv.)
toluene, r.t.
2a
1a
O
O
N
CuCl, tBuOLi
N
tBuO
7a
B2pin2 (1.2 equiv.)
toluene, r.t.
Bpin
3a
In order to understand the mechanism of the borylacylation of imines and the pathway of by-product
formation, various control experiments were carried out. By-product 7a was formed in a yield of 68% when
B2pin2 was removed from the reaction system (Scheme 2, eq 1). It means that the tBuOLi can also react
with imine in the absence of B2pin2. Almost all of the starting materials remained unchanged without the
presence of benzoyl chloride under the standard conditions (Scheme 2, eq 2). This indicated that B2pin2
could not directly react with the imine. Furthermore, when tBuOLi was excluded from the reaction mixture,
the starting material imine was gradually decomposed to corresponding aldehyde and amine (Scheme 2, eq
3). Eventually, the isolated by-product 7a was treated with B2pin2 under standard conditions, and no target
product was detected (Scheme 2, eq 4). It was thus affirmed that 7a is not an intermediate of the reaction,
but one of the by-products.
Scheme 3. Possible reaction mechanism.
O
Cl
t
Bpin
BuO
R3
O
Cl
R1
2
R3
N
R1 NH2
R1
H
tBuOLi
Bpin
Cu
R2
N
H
10
R2
9
B2pin2
O
1
R2
H
tBuOLi
CuCl
Cu Bpin
tBuO
H
R1
H
R1
N
Cl
O
N
R2
O
R2
O
R3
R1
O
R3
R3
N
R1
R3
N
R2
Bpin
R2
OtBu
3
7
Based on the control experimental results and referred to literatures, a plausible reaction mechanism for
this reaction is proposed (Scheme 3). Initially, a Cu-Bpin intermediate 10 is generated by the reaction of
CuCl with B2pin2 assisted by the tBuOLi. At the same time, the imine, either as a starting material or the
intermediate product derived from dehydration of an aldehyde with an amine, quickly reacts with acid
chloride to form the N-acyliminium salt 9. The Cu-Bpin is then regioselectively added to the C=N of 9 to
give the desired product 3 and regenerate the copper catalyst to complete the catalytic cycle. On the other
hand, the by-product 7 is formed by the nucleophilic attack of tBuOLi on 9. While an imine is not a viable
electrophile in cross coupling reactions, the presence of the acid chloride creates a highly reactive N-
acyliminium salt which is readily involved in the transmetalation with B2Pin2 and generates corresponding
α-amino boronate esters.26
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CONCLUSION
In summary, we have developed an efficient, versatile, and simple copper-catalyzed borylacylation of
imines with acid chlorides and bis(pinacolato)diboron. A more straightforward one-pot multi-step protocol
for the synthesis of α-amino boronic esters starting from aldehydes and amines was also successfully
performed. The dehydration of aldehydes and amines offers access to imines that readily undergo ligand-
free Cu-catalyzed borylacylation to provide the desired α-amino boronic esters in good yields. The mild
reaction conditions, broad substrate scopes and easy availability of starting materials make this strategy a
valuable tool for generating highly substituted α-amino boronic esters, which are of considerable interest as
potential biologically active compounds.
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EXPERIMENTAL SECTION
General information. All the reactions of using toluene as solvent were carried out in moisture free
environment. Chemicals, solvents were procured from commercial sources and all solvents were dried by
standard methods. Melting points were recorded on an EZ-melt MPA120 (Stanford Research Systems, Inc.,
USA) and are uncorrected. The preparative thin-layer chromatography plates used were HSGF 254 plates
(thickness of coating: 0.4-0.5 mm, 20 cm × 20 cm, Huanghai® from Yantai, Shandong province, China).
The 1H NMR and 13C{1H} NMR spectra were recorded on a Bruker AM-400 spectrometer (400 MHz and
100 MHz, respectively) using TMS as internal standard. CDCl3 was used as the NMR solvent for α-amino
boronic esters in most cases. Chemical shifts were recorded in parts per million (d) relative to CDCl3 at 7.26
1
for H NMR and 77.23 for 13C{1H} NMR. Gas chromatography-mass spectrometry (GC-MS) was
performed on Agilent 7890A/5975C. Gas chromatograms were recorded on Agilent 7890A. The starting
material imines were synthesized from amines and aldehydes in the presence of MgSO4, and characterized
by GC-MS according to the literature.27
General procedure for preparation of α-amino boronic esters. A mixture of the CuCl (0.50
mg, 0.005 mmol, 1.00 mol %), bis(pinacolato)diboron (189.7 mg, 0.75 mmol, 1.50 equiv.), and tBuOLi (80
mg, 1 mmol, 2.00 equiv.) was placed in a 10-mL microwave tube with a magnetic stirring bar. After being
sealed with a cap, the reaction tube was filled with N2.In another vial, toluene (3.00 mL) was added followed
by the imines (0.50 mmol, 1 equiv.) and the acid chlorides (0.60 mmol, 1.20 equiv.) were added dropwise.
Subsequently, the mixture in the vial was syringed into the front nitrogen protected microwave tube. At last,
the reaction was allowed to stir at ambient temperature (25 ℃) for 15 to 30 minutes. The resulting mixture
was filtered through a pad of celite and the mixture was extracted with diethyl ether (3 × 10 mL). The
combined organic phase was dried by the use of MgSO4 and then concentrated in vacuo. Crude material
was purified by silica gel column chromatography using acetate and petroleum ether as the eluent to obtain
the desired product. The products were further characterized by HRMS (EI), 1H NMR and 13C{1H} NMR.
General procedure for preparation of product 3a on a 5 mmol scale. A mixture of the CuCl
(5.0 mg, 0.05 mmol, 1.00 mol %), bis(pinacolato)diboron (1.90 g, 7.5 mmol, 1.50 equiv.), and tBuOLi (800
mg, 10 mmol, 2.00 equiv.) was placed in a 100 ml round bottom flask with a magnetic stirring bar. The
flask was sealed with a rubber septum and filled with N2. In another 100 ml round bottom flask, toluene
(30.0 mL) was added followed by the imine 1a (876 mg, 5.0 mmol, 1 equiv.) and the benzoyl chloride (843
mg, 6.0 mmol, 1.20 equiv.) were added dropwise at 0 ℃. Subsequently, the mixture in the 100 ml round
bottom flask was syringed into the front nitrogen protected round bottom flask. At last, the reaction was
allowed to stir at ambient temperature (25 ℃) for 1h. The resulting mixture was filtered through a pad of
celite and the mixture was extracted with diethyl ether (3 × 30 mL). The combined organic phase was dried
by the use of MgSO4 and then concentrated in vacuo. Crude material was purified by silica gel column
chromatography using acetate and petroleum ether as the eluent to obtain the desired product as white solid
(1.42 g, 70% yield). The products were further characterized by HRMS (EI), 1H NMR and 13C{1H} NMR.
General procedure for directly converting aldehydes to α-amino boronic esters. A mixture
of the CuCl (0.50 mg, 0.005 mmol, 1.00 mol %), bis(pinacolato)diboron (189.7 mg, 0.75 mmol, 1.50 equiv.),
and tBuOLi (80 mg, 1 mmol, 2.00 equiv.) was placed in a 10-mL microwave tube with a magnetic stirring
bar. After being sealed with a cap, the reaction tube was filled with N2. In another vial, a mixture of
aldehydes (0.5 mmol), amines (0.5 mmol), MgSO4 (0.120 g, 1.0 mmol) and dry toluene (2.0 mL) was
irradiated at ambient temperature (25 ℃) for 10 min. Then the acid chlorides (0.60 mmol, 1.20 equiv.) were
added dropwise in the mixture. Subsequently, the mixture in the vial was syringed into the front nitrogen
protected microwave tube. At last, the reaction was allowed to stir at ambient temperature (25 ℃) for 15 to
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30 minutes. The resulting mixture was filtered through a pad of celite and the mixture was extracted with
diethyl ether (3 × 10 mL). The combined organic phase was dried by the use of MgSO4 and then
concentrated in vacuo. Crude material was purified by silica gel column chromatography using acetate and
petroleum ether as the eluent to obtain the desired product. The products were further characterized by
HRMS (EI), 1H NMR and 13C{1H} NMR.
N-butyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)benzamide
(3a).
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Eluent:
petroleum ether/ethyl acetate (3:1). White solid; yield 72% (293mg); m.p. 169.5-170.6 ℃. H NMR (400
MHz, CDCl3) δ 7.67 – 7.60 (m, 2H), 7.58 – 7.53 (m, 1H), 7.49 (t, J = 7.4 Hz, 2H), 7.14 – 7.07 (m, 4H), 3.87
(s, 1H), 3.52 (ddd, J = 13.8, 9.4, 6.9 Hz, 1H), 3.08 (ddd, J = 14.0, 9.5, 4.7 Hz, 1H), 2.34 (s, 3H), 1.53 (dtd,
J = 14.0, 9.1, 4.7 Hz, 1H), 1.41 (ddd, J = 15.9, 7.8, 4.7 Hz, 1H), 1.16 (dd, J = 14.3, 8.1 Hz, 1H), 1.11 (s,
6H), 1.09 – 1.00 (m, 1H), 0.96 (s, 6H), 0.71 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.0,
135.8, 135.2, 132.0, 128.8 (2C), 128.7 (2C), 128.4 (2C), 128.1, 128.0 (2C), 80.0 (2C), 45.8, 29.4, 25.0 (2C),
24.6 (2C), 21.1, 19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C25H34BNO3 [M]+ 407.2632, found 407.2629.
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N-butyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide
(3a’).
Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 70% (275mg); m.p. 149.8-150.7 ℃. H NMR (400
MHz, CDCl3) δ 7.68 – 7.62 (m, 2H), 7.60 – 7.53 (m, 1H), 7.50 (m, 2H), 7.34 – 7.27 (m, 2H), 7.19 (dd, J =
10.0, 3.9 Hz, 3H), 3.91 (s, 1H), 3.55 (ddd, J = 13.8, 9.4, 6.9 Hz, 1H), 3.10 (ddd, J = 14.0, 9.5, 4.8 Hz, 1H),
1.54 (dqd, J = 18.8, 9.3, 5.0 Hz, 1H), 1.47 – 1.37 (m, 1H), 1.17 (m, 1H), 1.11 (s, 6H), 1.08 – 1.00 (m, 1H),
0.95 (s, 6H), 0.71 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.2, 139.0, 132.0, 128.7 (2C),
128.4 (2C), 128.1 (2C), 128.0 (3C), 125.9, 80.1 (2C), 46.0, 29.4, 25.0 (2C), 24.6 (2C), 19.6, 13.4. HRMS
(EI-TOF, m/z) calcd for C24H32BNO3 [M]+ 393.2475, found 393.2470.
N-butyl-N-((4-methoxyphenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide
(3b).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 75% (317mg); m.p. 155.1-156.3 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.67 – 7.59 (m, 2H), 7.59 – 7.53 (m, 1H), 7.49 (dd, J = 11.5, 4.4 Hz, 2H), 7.15 (d, J =
8.6 Hz, 2H), 6.86 (d, J = 8.6 Hz, 2H), 3.86 (s, 1H), 3.81 (s, 3H), 3.51 (ddd, J = 13.8, 9.4, 6.8 Hz, 1H), 3.06
(ddd, J = 14.0, 9.5, 4.7 Hz, 1H), 1.61 – 1.47 (m, 1H), 1.47 – 1.35 (m, 1H), 1.20 – 1.14 (m, 1H), 1.12 (s, 6H),
1.08 – 1.00 (m, 1H), 0.96 (s, 6H), 0.72 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 173.9, 157.9,
132.0, 130.8, 129.4 (2C), 128.7 (2C), 128.4 (2C), 128.0, 113.5 (2C), 80.1 (2C), 55.2, 45.8, 29.4, 25.0 (2C),
24.5 (2C), 19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C25H34BNO4 [M]+ 423.2581, found 423.2574.
N-butyl-N-((4-(methylthio)phenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (3c).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 72% (316mg); m.p. 158.7-159.9 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.65 – 7.61 (m, 2H), 7.60 – 7.55 (m, 1H), 7.53 – 7.47 (m, 2H), 7.25 – 7.20 (m, 2H),
7.16 – 7.12 (m, 2H), 3.88 (s, 1H), 3.54 (ddd, J = 13.8, 9.4, 6.8 Hz, 1H), 3.07 (ddd, J = 14.0, 9.5, 4.8 Hz,
1H), 2.49 (s, 3H), 1.53 (dtdd, J = 14.0, 9.3, 6.3, 4.9 Hz, 1H), 1.47 – 1.38 (m, 1H), 1.21 – 1.13 (m, 1H), 1.11
(s, 6H), 1.05 (ddd, J = 14.4, 9.0, 6.9 Hz, 2H), 0.97 (s, 6H), 0.72 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 174.2, 136.0, 135.3, 132.1, 128.7 (2C), 128.6 (2C), 128.4 (2C), 127.9, 126.7 (2C), 80.2
(2C), 46.0, 29.4, 25.0 (2C), 24.6, 24.5 (2C), 19.6, 16.1, 13.4. HRMS (EI-TOF, m/z) calcd for C25H34BNO3S
[M]+ 439.2352, found 439.2350.
N-butyl-N-((4-fluorophenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (3d). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 79% (325mg); m.p. 168.9-169.4 ℃. H NMR (400
MHz, CDCl3) δ 7.66 – 7.61 (m, 2H), 7.60 – 7.55 (m, 1H), 7.54 – 7.47 (m, 2H), 7.22 – 7.15 (m, 2H), 7.05 –
6.97 (m, 2H), 3.89 (s, 1H), 3.55 (ddd, J = 13.8, 9.5, 6.8 Hz, 1H), 3.05 (ddd, J = 14.0, 9.6, 4.7 Hz, 1H), 1.54
(dtdd, J = 13.9, 9.4, 6.3, 4.8 Hz, 1H), 1.47 – 1.36 (m, 1H), 1.22 – 1.13 (m, 1H), 1.11 (s, 6H), 1.09 – 0.99
(m, 1H), 0.95 (s, 6H), 0.72 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.2, 161.4 (d, JCF
=
243.5 Hz), 134.6 (d, JCF = 3.1 Hz), 132.1, 129.6 (d, JCF = 7.9 Hz, 2C), 128.7 (2C), 128.4 (2C), 127.8, 114.9
(d, JCF = 21.3 Hz, 2C), 80.2, 46.0, 29.3, 25.0, 24.5, 19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C24H31BFNO3
[M]+ 411.2381, found 411.2380.
N-butyl-N-((4-chlorophenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide
(3e).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 78% (333mg); m.p. 185.6-186.0 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.66 – 7.61 (m, 2H), 7.61 – 7.55 (m, 1H), 7.50 (ddd, J = 6.8, 4.5, 1.3 Hz, 2H), 7.31 –
7.27 (m, 2H), 7.18 – 7.11 (m, 2H), 3.89 (s, 1H), 3.56 (ddd, J = 13.9, 9.5, 6.8 Hz, 1H), 3.06 (ddd, J = 14.0,
9.5, 4.7 Hz, 1H), 1.53 (dtdd, J = 13.9, 9.4, 6.3, 4.8 Hz, 1H), 1.47 – 1.35 (m, 1H), 1.22 – 1.13 (m, 1H), 1.11
(s, 6H), 1.10 – 1.01 (m, 1H), 0.96 (s, 6H), 0.72 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
174.4, 137.7, 132.2, 131.5, 129.3 (2C), 128.8 (2C), 128.4 (2C), 128.3 (2C), 127.8, 80.2 (2C), 46.1, 29.3,
25.0 (2C), 24.6 (2C), 19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C24H31B35ClNO3 [M]+ 427.2086, found
427.2083; calcd for C24H31B37ClNO3 [M]+ 429.2056, found 429.2058.
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N-((4-bromophenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-N-butylbenzamide (3f). Eluent:
petroleum ether/ethyl acetate (3:1). White solid; yield 80% (377mg); m.p. 199.0-200.2 ℃. H NMR (400
1
MHz, CDCl3) δ 7.63 (m, 2H), 7.61 – 7.55 (m, 1H), 7.54 – 7.48 (m, 2H), 7.46 – 7.41 (m, 2H), 7.13 – 7.06
(m, 2H), 3.87 (s, 1H), 3.57 (ddd, J = 13.9, 9.5, 6.8 Hz, 1H), 3.06 (ddd, J = 14.0, 9.5, 4.7 Hz, 1H), 1.53 (dtdd,
J = 14.0, 9.4, 6.2, 4.9 Hz, 1H), 1.46 – 1.35 (m, 1H), 1.18 (dd, J = 14.2, 6.7 Hz, 1H), 1.11 (s, 6H), 1.09 –
1.00 (m, 1H), 0.96 (s, 6H), 0.71 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.4, 138.2, 132.2,
131.2 (2C), 129.7 (2C), 128.8 (2C), 128.4 (2C), 127.7, 119.6, 80.2 (2C), 46.1, 29.3, 25.0 (2C), 24.6 (2C),
19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C24H31B79BrNO3 [M]+ 471.1580, found 471.1573; calcd for
C24H31B81BrNO3 [M]+ 473.1560, found 473.1556.
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N-butyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(4-(trifluoromethyl)phenyl)methyl)benzamide
(3g). Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 65% (300mg); m.p. 144.6-145.3 ℃. 1H
NMR (400 MHz, CDCl3) δ 7.67 – 7.60 (m, 2H), 7.58 – 7.53 (m, 1H), 7.49 (t, J = 7.4 Hz, 2H), 7.14 – 7.07
(m, 4H), 3.87 (s, 1H), 3.52 (ddd, J = 13.8, 9.4, 6.9 Hz, 1H), 3.08 (ddd, J = 14.0, 9.5, 4.7 Hz, 1H), 2.34 (s,
3H), 1.53 (dtd, J = 14.0, 9.1, 4.7 Hz, 1H), 1.41 (ddd, J = 15.9, 7.8, 4.7 Hz, 1H), 1.16 (dd, J = 14.3, 8.1 Hz,
1H), 1.11 (s, 6H), 1.09 – 1.00 (m, 2H), 0.96 (s, 6H), 0.71 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 174.7, 143.6 (d, JCF = 1.0 Hz, 2C), 132.3, 128.8 (2C), 128.4 (2C), 128.1 (q, JCF = 32.3 Hz), 127.8,
127.6, 125.1 (q, JCF = 3.7 Hz, 2C), 124.4 (q, JCF = 271.7 Hz), 80.3 (2C), 46.3, 29.4, 25.0 (2C), 24.6 (2C),
19.6, 13.3. HRMS (EI-TOF, m/z) calcd for C25H31BF3NO3 [M]+ 461.2349, found 461.2352.
Methyl
4-((N-butylbenzamido)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzoate
(3h).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 85% (383mg); m.p. 162.3-162.9 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.67 – 7.60 (m, 2H), 7.58 – 7.53 (m, 1H), 7.49 (t, J = 7.4 Hz, 2H), 7.14 – 7.07 (m,
4H), 3.87 (s, 1H), 3.52 (ddd, J = 13.8, 9.4, 6.9 Hz, 1H), 3.08 (ddd, J = 14.0, 9.5, 4.7 Hz, 1H), 2.34 (s, 3H),
1.53 (dtd, J = 14.0, 9.1, 4.7 Hz, 1H), 1.41 (ddd, J = 15.9, 7.8, 4.7 Hz, 1H), 1.16 (dd, J = 14.3, 8.1 Hz, 1H),
1.11 (s, 6H), 1.09 – 1.00 (m, 2H), 0.96 (s, 6H), 0.71 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3)
δ 174.6, 167.2, 145.0, 132.3, 129.5 (2C), 128.8 (2C), 128.4 (2C), 127.8, 127.6, 127.6 (2C), 80.3 (2C), 52.0,
46.4, 29.3, 25.0 (2C), 24. 6 (2C), 19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C26H34BNO5 [M]+ 451.2530,
found 451.2527.
N-((3-bromophenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-N-butylbenzamide (3i). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 71% (334mg); m.p. 127.3-128.1 ℃. H NMR (400
MHz, CDCl3) δ 7.65 (d, J = 7.2 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.4 Hz, 2H), 7.39 – 7.31 (m,
2H), 7.22 – 7.11 (m, 2H), 3.87 (s, 1H), 3.60 (ddd, J = 14.0, 9.5, 6.8 Hz, 1H), 3.11 (ddd, J = 14.0, 9.6, 4.7
Hz, 1H), 1.61 – 1.48 (m, 1H), 1.48 – 1.35 (m, 1H), 1.18 (dd, J = 14.2, 6.9 Hz, 1H), 1.12 (s, 6H), 1.11 – 1.00
(m, 1H), 0.97 (s, 6H), 0.73 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.6, 141.7, 132.3,
130.6, 129.7, 129.0, 128.8 (2C), 128.5 (2C), 127.6, 126.4, 122.2, 80.3 (2C), 46.3, 29.4, 25.1 (2C), 24.5 (2C),
19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C24H31B79BrNO3 [M]+ 471.1580, found 471.1568; calcd for
C24H31B81BrNO3 [M]+ 473.1560, found 473.1553.
N-((2-bromophenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-N-butylbenzamide (3j). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 52% (245mg); m.p. 147.9-148.8 ℃. H NMR (400
MHz, CDCl3) δ 7.67 – 7.61 (m, 2H), 7.60 – 7.48 (m, 4H), 7.32 – 7.26 (m, 1H), 7.22 – 7.15 (m, 1H), 7.05
(td, J = 8.0, 1.6 Hz, 1H), 4.56 (s, 1H), 3.63 – 3.49 (m, 1H), 3.00 (ddd, J = 13.9, 9.4, 4.6 Hz, 1H), 1.58 (dtdd,
J = 13.8, 9.2, 6.3, 4.7 Hz, 1H), 1.46 (qdd, J = 7.3, 5.5, 3.5 Hz, 1H), 1.24 – 1.14 (m, 1H), 1.12 (s, 6H), 1.11
– 1.00 (m, 1H), 0.97 (s, 6H), 0.74 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.5, 138.6,
132.5, 132.1, 129.4, 128.8 (2C), 128.4 (2C), 127.8, 127.3, 127.2, 123.9, 80.2 (2C), 46.4, 29.3, 25.0 (2C),
24.5 (2C), 19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C24H31B79BrNO3 [M]+ 471.1580, found 471.1562;
calcd for C24H31B81BrNO3 [M]+ 473.1560, found 473.1557.
N-butyl-N-((2,4-dichlorophenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (3k).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 55% (254mg); m.p. 178.3-179.1 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.65 – 7.56 (m, 3H), 7.50 (dd, J = 11.4, 4.3 Hz, 2H), 7.39 (d, J = 2.1 Hz, 1H), 7.23
(dd, J = 8.4, 2.1 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 4.49 (s, 1H), 3.57 (ddd, J = 13.9, 9.2, 7.2 Hz, 1H), 2.98
(ddd, J = 13.9, 9.4, 4.7 Hz, 1H), 1.61 – 1.49 (m, 1H), 1.43 (tdd, J = 13.4, 6.6, 2.4 Hz, 1H), 1.25 – 1.14 (m,
1H), 1.12 (s, 6H), 1.05 (m, 7H), 0.74 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.7, 135.6,
133.9, 132.3, 131.8, 129.1, 128.8 (2C), 128.4 (2C), 127.6, 127.0 (2C), 80.3 (2C), 46.5, 29.3, 25.0 (2C), 24.5
(2C), 19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C24H30B35Cl2NO3 [M]+ 461.1696, found 461.1680; calcd
for C24H30B35Cl37ClNO3 [M]+ 463.1666, found 463.1674; calcd for C24H30B37Cl2NO3 [M]+ 465.1637, found
465.1654.
N-butyl-N-(naphthalen-2-yl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (3l). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 88% (390mg); m.p. 142.8-144.1 ℃. H NMR (400
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MHz, CDCl3) δ 7.85 – 7.78 (m, 3H), 7.69 (dt, J = 3.7, 1.5 Hz, 3H), 7.56 – 7.52 (m, 1H), 7.51 – 7.46 (m,
2H), 7.46 – 7.37 (m, 3H), 4.12 (s, 1H), 3.58 (ddd, J = 13.9, 9.3, 6.9 Hz, 1H), 3.10 (ddd, J = 14.0, 9.4, 4.8
Hz, 1H), 1.62 – 1.50 (m, 1H), 1.50 – 1.39 (m, 1H), 1.21 – 1.09 (m, 7H), 1.09 – 0.73 (m, 7H), 0.68 (t, J =
7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.3, 136.8, 133.5, 132.2, 132.1, 128.7 (2C), 128.3 (2C),
127.8, 127.7, 127.6, 127.5, 126.6, 126.2, 125.7, 125.1, 80.1 (2C), 46.1, 29.3, 25.1 (2C), 24.6 (2C), 19.5,
13.3. HRMS (EI-TOF, m/z) calcd for C28H34BNO3 [M]+ 443.2632, found 443.2625.
N-butyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(thiophen-2-yl)methyl)benzamide (3m). Eluent:
petroleum ether/ethyl acetate (3:1). Yellow solid; yield 56% (223mg); m.p. 152.4-153.6 ℃. 1H NMR (400
MHz, CDCl3) δ 7.64 – 7.58 (m, 2H), 7.58 – 7.52 (m, 1H), 7.48 (dd, J = 10.0, 4.8 Hz, 2H), 7.23 (d, J = 4.7
Hz, 1H), 6.98 (dt, J = 5.0, 3.3 Hz, 2H), 4.23 (s, 1H), 3.50 (ddd, J = 14.0, 9.7, 6.7 Hz, 1H), 3.14 (ddd, J =
14.1, 9.8, 4.6 Hz, 1H), 1.67 – 1.56 (m, 1H), 1.48 – 1.36 (m, 1H), 1.24 – 1.17 (m, 1H), 1.15 (s, 6H), 1.10 (dd,
J = 14.2, 7.0 Hz, 1H), 1.05 (s, 6H), 0.74 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 173.7,
141.2, 132.1, 128.7 (2C), 128.4 (2C), 127.8, 126.7, 126.3, 124.6, 80.4 (2C), 45.8, 29.5, 24.9 (2C), 24.6,
24.6, 19.6, 13.4. HRMS (EI-TOF, m/z) calcd for C22H30BNO3S [M]+ 399.2039, found 399.2042.
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N-ethyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)benzamide
(3n).
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Eluent:
petroleum ether/ethyl acetate (3:1). White solid; yield 82% (311mg); m.p. 157.4-158.1 ℃. H NMR (400
MHz, CDCl3) δ 7.67 – 7.60 (m, 2H), 7.58 – 7.53 (m, 1H), 7.49 (t, J = 7.4 Hz, 2H), 7.14 – 7.07 (m, 4H), 3.87
(s, 1H), 3.52 (ddd, J = 13.8, 9.4, 6.9 Hz, 1H), 3.08 (ddd, J = 14.0, 9.5, 4.7 Hz, 1H), 2.34 (s, 3H), 1.53 (dtd,
J = 14.0, 9.1, 4.7 Hz, 1H), 1.41 (ddd, J = 15.9, 7.8, 4.7 Hz, 1H), 1.16 (m, 1H), 1.11 (s, 6H), 1.09 – 1.00 (m,
1H), 0.96 (s, 6H), 0.71 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 173.8, 135.7, 135.3, 132.1,
128.8 (2C), 128.7 (2C), 128.4 (2C), 128.0 (2C), 127.9, 80.1 (2C), 41.1, 25.0 (2C), 24.6 (2C), 21.1, 13.0.
HRMS (EI-TOF, m/z) calcd for C23H30BNO3 [M]+ 379.2319, found 379.2316.
N-ethyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide
(3n’).
Eluent:
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petroleum ether/ethyl acetate (3:1). White solid; yield 78% (285mg); m.p. 142.8-143.5 ℃. H NMR (400
MHz, CDCl3) δ 7.69 – 7.63 (m, 2H), 7.60 – 7.54 (m, 1H), 7.53 – 7.47 (m, 2H), 7.34 – 7.29 (m, 2H), 7.23 –
7.17 (m, 3H), 3.95 (s, 1H), 3.65 (dq, J = 14.3, 7.2 Hz, 1H), 3.18 (dq, J = 14.3, 7.2 Hz, 1H), 1.10 (dd, J =
12.1, 4.7 Hz, 9H), 0.96 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 173.9, 139.0, 132.1, 128.7 (2C), 128.4
(2C), 128.1 (2C), 127.9 (2C), 127.8, 125.9, 80.1 (2C), 41.2, 25.0 (2C), 24.6 (2C), 13.0. HRMS (EI-TOF,
m/z) calcd for C22H28BNO3 [M]+ 365.2152, found 365.2158.
N-benzyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)benzamide (3o). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 81% (357mg); m.p. 206.0-206.8 ℃. H NMR (400
MHz, CDCl3) δ 7.72 (d, J = 7.2 Hz, 2H), 7.54 (dt, J = 29.1, 6.9 Hz, 3H), 7.26 (d, J = 2.0 Hz, 3H), 7.12 (d,
J = 7.3 Hz, 2H), 7.04 (d, J = 6.9 Hz, 2H), 6.92 (d, J = 2.7 Hz, 2H), 4.85 (d, J = 15.1 Hz, 1H), 4.16 (d, J =
15.1 Hz, 1H), 3.74 (s, 1H), 2.35 (s, 3H), 1.09 (s, 6H), 0.94 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ
174.5, 135.4, 135.4, 133.9, 132.2, 128.9 (2C), 128.9 (2C), 128.8 (2C), 128.5 (2C), 128.4 (2C), 128.2, 128.0
(2C), 127.9, 80.1 (2C), 49.7, 25.0 (2C), 24.5 (2C), 21.2. HRMS (EI-TOF, m/z) calcd for C28H32BNO3 [M]+
441.2475, found 441.2480.
N-benzyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide
(3o’).
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Eluent:
petroleum ether/ethyl acetate (3:1). White solid; yield 75% (320mg); m.p. 189.5-190.7 ℃. H NMR (400
MHz, CDCl3) δ 7.76 – 7.71 (m, 2H), 7.62 – 7.57 (m, 1H), 7.55 – 7.49 (m, 2H), 7.32 (t, J = 7.4 Hz, 2H), 7.28
– 7.25 (m, 3H), 7.24 – 7.20 (m, 1H), 7.16 – 7.12 (m, 2H), 6.95 – 6.89 (m, 2H), 4.89 (d, J = 15.0 Hz, 1H),
4.17 (d, J = 15.1 Hz, 1H), 3.78 (s, 1H), 1.09 (s, 6H), 0.93 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.7,
138.7, 133.7, 132.3, 128.9 (2C), 128.9 (2C), 128.6 (2C), 128.3 (3C), 128.1 (2C), 128.1 (2C), 127.8, 126.0,
80.2 (2C), 49.9, 24.9 (2C), 24.5 (2C). HRMS (EI-TOF, m/z) calcd for C27H30BNO3 [M]+ 427.2319, found
427.2312.
N-(2,4-dimethoxybenzyl)-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)benzamide
(3p). Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 70% (351mg); m.p. 219.4-220.1 ℃. 1H
NMR (400 MHz, CDCl3) δ 7.73 (ddd, J = 7.0, 4.1, 2.0 Hz, 2H), 7.59 – 7.53 (m, 1H), 7.52 – 7.46 (m, 2H),
7.13 (d, J = 7.8 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 6.69 (d, J = 8.3 Hz, 1H), 6.32 (dd, J = 8.3, 2.4 Hz, 1H),
6.27 (d, J = 2.3 Hz, 1H), 4.91 (d, J = 14.3 Hz, 1H), 4.07 (d, J = 14.3 Hz, 1H), 3.75 (s, 3H), 3.65 (s, 1H),
3.41 (s, 3H), 2.35 (s, 3H), 1.06 (s, 6H), 0.88 (s, J = 12.7, 5.8 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ
174.3, 161.2, 158.7, 136.2, 134.9, 131.8, 131.5, 128.7, 128.7, 128.7 (2C), 128.5, 128.4 (2C), 128.2, 126.9,
114.1, 103.8, 98.4, 79.9 (2C), 55.4, 54.7, 45.4, 25.0 (2C), 24.6 (2C), 21.2. HRMS (EI-TOF, m/z) calcd for
C30H36BNO5 [M]+ 501.2687, found 501.2682.
methyl N-benzoyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)glycinate (3q). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 73% (309mg); m.p. 163.8-164.5 ℃. H NMR (400
MHz, CDCl3) δ 7.71 – 7.64 (m, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.10 (s, 4H), 4.17 (d,
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J = 17.4 Hz, 1H), 3.98 – 3.85 (m, 2H), 3.63 (s, 3H), 2.33 (s, 3H), 1.12 (s, 6H), 0.97 (s, 6H). 13C{1H} NMR
(101 MHz, CDCl3) δ 175.7, 167.6, 135.9, 134.6, 132.5, 128.9 (2C), 128.9 (2C), 128.7 (2C), 128.3 (2C),
127.5, 80.3 (2C), 52.7, 48.1, 24.9 (2C), 24.6 (2C), 21.1. HRMS (EI-TOF, m/z) calcd for C24H30BNO5 [M]+
423.2217, found 423.2213.
methyl N-benzoyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)glycinate (3q’). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 69% (282mg); m.p. 145.9-146.7 ℃. H NMR (400
MHz, CDCl3) δ 7.74 – 7.64 (m, 2H), 7.58 (dd, J = 10.8, 4.1 Hz, 1H), 7.48 (dd, J = 11.4, 4.2 Hz, 2H), 7.33
– 7.28 (m, 2H), 7.24 – 7.17 (m, 3H), 4.21 (d, J = 17.4 Hz, 1H), 4.00 – 3.88 (m, 2H), 3.62 (s, 3H), 1.12 (s,
6H), 0.97 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 176.0, 167.5, 137.8, 132.5, 128.9 (2C), 128.5 (2C),
128.3 (2C), 128.1 (2C), 127.3, 126.4, 80.3 (2C), 52.7, 48.3, 24.9 (2C), 24.5 (2C). HRMS (EI-TOF, m/z)
calcd for C23H28BNO5 [M]+ 409.2061, found 409.2063.
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N-phenyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide
(3r).
Eluent:
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petroleum ether/ethyl acetate (3:1). White solid; yield 38% (157mg); m.p. 131.7-132.5 ℃. H NMR (400
MHz, CDCl3) δ 7.50 – 7.45 (m, 2H), 7.42 (t, J = 7.5 Hz, 1H), 7.25 (t, J = 7.8 Hz, 2H), 7.19 (d, J = 4.3 Hz,
4H), 7.16 – 7.12 (m, 3H), 7.09 (dq, J = 8.7, 4.1 Hz, 1H), 6.94 (dd, J = 6.4, 3.1 Hz, 2H), 4.33 (s, 1H), 1.17
(s, 6H), 1.01 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 172.7, 138.9, 138.8, 132.7, 130.5 (2C), 129.3
(2C), 128.7 (2C), 128.1(8), 128.1(5) (2C), 127.7 (2C), 127.2, 126.4, 125.8, 80.3 (2C), 25.1 (2C), 24.5 (2C).
HRMS (EI-TOF, m/z) calcd for C26H28BNO3 [M]+ 413.2162, found 413.2155.
N-((4-chlorophenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-N-phenylbenzamide
(3s).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 26% (116mg); m.p. 163.4-164.1 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.48 – 7.40 (m, 3H), 7.27 – 7.23 (m, 2H), 7.19 (d, J = 4.3 Hz, 3H), 7.16 – 7.13 (m,
3H), 7.09 (td, J = 8.7, 7.7, 3.3 Hz, 1H), 6.97 – 6.92 (m, 2H), 4.34 (s, 1H), 1.17 (s, 6H), 1.02 (s, 6H). 13C{1H}
NMR (101 MHz, CDCl3) δ 172.8, 139.0, 138.8, 132.6, 130.5 (2C), 129.5 (2C), 129.3 (2C), 128.7, 128.2,
128.2 (2C), 127.7 (2C), 126.5 (2C), 125.8, 80.4 (2C), 25.0 (2C), 24.5 (2C). HRMS (EI-TOF, m/z) calcd for
C26H27B35ClNO3 [M]+ 447.1773, found 447.1771; calcd for C26H27B37ClNO3 [M]+ 449.1743, found
449.1738.
N-phenyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)benzamide
(3t).
Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 60% (256mg); m.p. 148.9-149.8 ℃. H NMR (400
MHz, CDCl3) δ 7.48 – 7.43 (m, 2H), 7.40 (t, J = 7.5 Hz, 1H), 7.23 (t, J = 7.8 Hz, 2H), 7.16 – 7.12 (m, 3H),
7.07 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 7.9 Hz, 2H), 6.95 – 6.89 (m, 2H), 4.28 (s, 1H), 2.24 (s, 3H), 1.17 (s,
6H), 1.02 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 172.5, 139.0, 135.6, 135.2, 132.6, 130.4 (2C), 129.2
(2C), 128.8 (2C), 128.4 (2C), 128.1 (3C), 127.3, 126.5 (2C), 80.3 (2C), 25.1 (2C), 24.6 (2C), 21.1. HRMS
(EI-TOF, m/z) calcd for C27H30BNO3 [M]+ 427.2319, found 427.2310.
N-((4-methoxyphenyl)(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-N-phenylbenzamide (3u).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 68% (301mg); m.p. 138.2-139.5 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.47 – 7.38 (m, 3H), 7.23 (t, J = 7.8 Hz, 2H), 7.17 – 7.10 (m, 5H), 6.73 (d, J = 8.6 Hz,
2H), 4.25 (s, 1H), 3.72 (s, 3H), 1.18 (s, 6H), 1.03 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 172.43,
157.83, 138.92, 132.57, 130.72, 130.42(2C), 130.3 (2C), 129.3 (2C), 128.1, 128.1 (2C), 127.3, 126.6 (2C),
113.1 (2C), 80.3 (2C), 55.0, 25.0 (2C), 24.5 (2C). HRMS (EI-TOF, m/z) calcd for C27H30BNO4 [M]+
443.2268, found 443.2262.
N-(4-methoxyphenyl)-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)benzamide (3v).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 73% (334mg); m.p. 154.1-155.0 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.49 – 7.45 (m, 2H), 7.44 – 7.38 (m, 1H), 7.28 – 7.23 (m, 2H), 7.07 (d, J = 8.0 Hz,
2H), 6.99 (d, J = 7.9 Hz, 2H), 6.85 – 6.80 (m, 2H), 6.68 – 6.62 (m, 2H), 4.20 (s, 1H), 3.69 (s, 3H), 2.26 (s,
3H), 1.17 (s, 6H), 1.01 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 172.43, 158.94, 135.74, 135.17, 132.47,
131.84, 130.47(2C), 128.82(2C), 128.42(2C), 128.11(2C), 127.61(2C), 127.4, 114.4 (2C), 80.3 (2C), 55.3,
25.1 (2C), 24.6 (2C), 21.1. HRMS (EI-TOF, m/z) calcd for C28H32BNO4 [M]+ 457.2424, found 457.2419.
N-ethyl-4-fluoro-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (4a). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 78% (299mg); m.p. 147.0-147.8 ℃. H NMR (400
MHz, CDCl3) δ 7.74 – 7.67 (m, 2H), 7.34 – 7.28 (m, 2H), 7.24 – 7.17 (m, 5H), 3.95 (s, 1H), 3.64 (dq, J =
14.3, 7.2 Hz, 1H), 3.21 (dq, J = 14.3, 7.2 Hz, 1H), 1.15 – 1.08 (m, 9H), 0.96 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 172.9, 164.8 (d, JCF = 254.5 Hz), 138.8, 131.0 (d, JCF = 9.0 Hz, 2C), 128.2 (2C), 127.9 (2C),
126.0, 123.9 (d, JCF = 3.5 Hz), 116.2 (d, JCF = 22.2 Hz, 2C), 80.2 (2C), 41.3, 25.0 (2C), 24.5 (2C),
12.95.HRMS (EI-TOF, m/z) calcd for C22H27BFNO3 [M]+ 383.2068, found 383.2065.
4-chloro-N-ethyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (4b). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 82% (327mg); m.p. 164.5-165.3 ℃. H NMR (400
MHz, CDCl3) δ 7.67 – 7.58 (m, 2H), 7.52 – 7.46 (m, 2H), 7.34 – 7.29 (m, 2H), 7.19 (dd, J = 10.3, 4.1 Hz,
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3H), 3.96 (s, 1H), 3.62 (dq, J = 14.3, 7.2 Hz, 1H), 3.20 (dq, J = 14.3, 7.2 Hz, 1H), 1.16 – 1.06 (m, 9H), 0.96
(s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 172.8, 138.5, 138.4, 129.7 (2C), 129.0 (2C), 128.0 (2C), 127.7
(2C), 126.0, 125.9, 80.0 (2C), 41.1, 24.9 (2C), 24.4 (2C), 12.8. HRMS (EI-TOF, m/z) calcd for
C22H27B35ClNO3 [M]+ 399.1773, found 399.1770; calcd for C22H27B37ClNO3 [M]+ 401.1743, found
401.1754.
4-bromo-N-ethyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (4c). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 85% (377mg); m.p. 178.8-179.6 ℃. H NMR (400
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MHz, CDCl3) δ 7.66 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.33 – 7.28 (m, 2H), 7.20 (t, J = 8.4 Hz,
3H), 3.94 (s, 1H), 3.60 (dq, J = 14.3, 7.1 Hz, 1H), 3.19 (dq, J = 14.2, 7.1 Hz, 1H), 1.14 – 1.06 (m, 9H), 0.95
(s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 173.0, 138.7, 132.2 (2C), 129.9 (2C), 128.2 (2C), 127.9 (2C),
127.0, 126.7, 126.0, 80.2 (2C), 41.3, 25.0 (2C), 24.5 (2C), 13.0. HRMS (EI-TOF, m/z) calcd for
C22H27B79BrNO3 [M]+ 443.1267, found 443.1250; calcd for C22H27B81BrNO3 [M]+ 445.1247, found
445.1237.
N-ethyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)-4-(trifluoromethyl)benzamide
(4d). Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 70% (303mg); m.p. 136.8-137.3 ℃. 1H
NMR (400 MHz, CDCl3) δ 7.80 (s, 4H), 7.36 – 7.31 (m, 2H), 7.25 – 7.19 (m, 3H), 3.98 (s, 1H), 3.56 (dq, J
= 14.3, 7.2 Hz, 1H), 3.20 (dq, J = 14.3, 7.2 Hz, 1H), 1.17 – 1.06 (m, 9H), 0.97 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 172.7, 138.4, 133.8 (q, JCF = 33.1 Hz), 131.5 (d, JCF = 1.0 Hz, 2C), 128.7 (2C), 128.2 (2C),
127.9 (2C), 126.1, 125.9 (q, JCF = 3.7 Hz, 2C), 123.3 (q, JCF = 272.8 Hz), 80.3 (2C), 41.2, 25.0 (2C), 24.5
(2C), 12.9. HRMS (EI-TOF, m/z) calcd for C23H27BF3NO3 [M]+ 433.2036, found 433.2030.
N-ethyl-4-methoxy-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)benzamide
(4e).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 78% (319mg); m.p. 163.8-164.7 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.68 – 7.63 (m, 2H), 7.13 – 7.07 (m, 4H), 7.00 – 6.95 (m, 2H), 3.90 (s, 1H), 3.85 (s,
3H), 3.71 (dq, J = 14.1, 7.1 Hz, 1H), 3.20 (dq, J = 14.3, 7.2 Hz, 1H), 2.32 (s, 3H), 1.15 – 1.09 (m, 9H), 0.97
(s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 173.1, 162.6, 136.0, 135.1, 130.7 (2C), 128.7 (2C), 127.9 (2C),
119.6, 114.0 (2C), 79.8 (2C), 55.4, 41.2, 25.1 (2C), 24.6 (2C), 21.1, 13.0. HRMS (EI-TOF, m/z) calcd for
C24H32BNO4 [M]+ 409.2424, found 409.2421.
3-bromo-N-ethyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (4f). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 62% (275mg); m.p. 153.8-154.6 ℃. H NMR (400
MHz, CDCl3) δ 7.82 (t, J = 1.6 Hz, 1H), 7.75 – 7.66 (m, 1H), 7.57 (d, J = 7.8 Hz, 1H), 7.38 (t, J = 7.9 Hz,
1H), 7.35 – 7.29 (m, 2H), 7.21 (t, J = 6.7 Hz, 3H), 3.95 (s, 1H), 3.59 (dq, J = 14.3, 7.2 Hz, 1H), 3.18 (dq, J
= 14.3, 7.2 Hz, 1H), 1.15 – 1.07 (m, 9H), 0.96 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 172.5, 138.5,
135.1, 131.3, 130.3, 129.8, 128.2 (2C), 127.9 (2C), 126.7, 126.0, 122.9, 80.2 (2C), 41.2, 25.0 (2C), 24.5
(2C), 12.9. HRMS (EI-TOF, m/z) calcd for C22H27B79BrNO3 [M]+ 443.1267, found 443.1259; calcd for
C22H27B81BrNO3 [M]+ 445.1247, found 445.1229.
2-bromo-N-ethyl-N-(phenyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)benzamide (4g). Eluent:
1
petroleum ether/ethyl acetate (3:1). White solid; yield 34% (150mg); m.p. 134.3-135.8 ℃. H NMR (400
MHz, CDCl3) δ 7.67 (dd, J = 8.0, 0.8 Hz, 1H), 7.50 (dd, J = 7.6, 2.0 Hz, 1H), 7.46 (td, J = 7.4, 1.1 Hz, 1H),
7.42 – 7.37 (m, 1H), 7.35 – 7.26 (m, 4H), 7.23 – 7.18 (m, 1H), 3.94 (s, 1H), 3.22 (dq, J = 14.5, 7.2 Hz, 1H),
3.11 (dq, J = 14.2, 7.2 Hz, 1H), 1.12 (s, 6H), 1.03 (t, J = 7.2 Hz, 3H), 0.96 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 172.6, 138.6, 133.3, 132.4, 130.6, 129.2, 128.1 (2C), 128.1 (2C), 127.8, 125.9, 120.2, 80.2,
40.9, 25.0 (2C), 24.6 (2C), 12.5. HRMS (EI-TOF, m/z) calcd for C22H27B79BrNO3 [M]+ 443.1267, found
443.1260; calcd for C22H27B81BrNO3 [M]+ 445.1247, found 445.1239.
N-ethyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)acetamide
(4h).
Eluent:
1
petroleum ether/ethyl acetate (2:1). White solid; yield 69% (219mg); m.p. 156.5-157.4 ℃. H NMR (400
MHz, CDCl3) δ 7.08 (d, J = 7.9 Hz, 2H), 7.00 (d, J = 8.1 Hz, 2H), 3.71 (s, 1H), 3.39 (dq, J = 14.4, 7.2 Hz,
1H), 3.09 (dq, J = 14.4, 7.2 Hz, 1H), 2.32 (s, 3H), 2.27 (d, J = 1.1 Hz, 3H), 1.13 – 1.06 (m, 9H), 0.92 (s,
6H). 13C{1H} NMR (101 MHz, CDCl3) δ 174.6, 135.7, 135.3, 128.7 (2C), 128.1 (2C), 79.9 (2C), 40.1, 25.0
(2C), 24.5 (2C), 21.1, 15.8, 12.6. HRMS (EI-TOF, m/z) calcd for C18H28BNO3 [M]+ 317.2162, found
317.2164.
N-ethyl-3-methyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)but-2-enamide (4i).
Eluent: petroleum ether/ethyl acetate (2:1). White solid; yield 70% (250mg); m.p. 178.3-179.1 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.07 (d, J = 7.9 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 5.88 (s, 1H), 3.69 (s, 1H), 3.47 (dq,
J = 14.5, 7.2 Hz, 1H), 3.09 (dq, J = 14.4, 7.2 Hz, 1H), 2.31 (s, 3H), 2.28 (s, 3H), 2.02 (s, 3H), 1.11 – 1.06
(m, 9H), 0.94 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 169.7, 161.4, 136.7, 135.0, 128.6 (2C), 128.0
(2C), 108.6, 79.7 (2C), 39.8, 28.7, 25.0 (2C), 24.5 (2C), 21.6, 21.1, 13.1. HRMS (EI-TOF, m/z) calcd for
C21H32BNO3 [M]+ 357.2475, found 357.2472.
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N-ethyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)furan-2-carboxamide
(4j).
Eluent: petroleum ether/ethyl acetate (3:1). Yellow solid; yield 85% (314mg); m.p. 137.2-138.1 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.66 (dd, J = 1.6, 0.8 Hz, 1H), 7.48 (dd, J = 3.6, 0.6 Hz, 1H), 7.11 – 7.04 (m, 4H), 6.62
(dd, J = 3.6, 1.8 Hz, 1H), 4.18 (dq, J = 14.3, 7.2 Hz, 1H), 3.91 (s, 1H), 3.25 (dq, J = 14.3, 7.2 Hz, 1H), 2.32
(s, 3H), 1.17 (t, J = 7.2 Hz, 3H), 1.12 (s, 6H), 0.97 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 161.3, 147.2,
142.6, 136.0, 135.3, 128.7 (2C), 128.2 (2C), 122.8, 112.5, 80.0 (2C), 41.0, 25.1 (2C), 24.5 (2C), 21.1, 13.5.
HRMS (EI-TOF, m/z) calcd for C21H28BNO4 [M]+ 369.2111, found 368.2123.
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N-ethyl-N-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)(p-tolyl)methyl)thiophene-2-carboxamide (4k).
Eluent: petroleum ether/ethyl acetate (3:1). White solid; yield 88% (339mg); m.p. 158.9-159.4 ℃. 1H NMR
(400 MHz, CDCl3) δ 7.86 (dd, J = 3.9, 1.1 Hz, 1H), 7.73 (dd, J = 5.0, 1.1 Hz, 1H), 7.20 (dd, J = 5.0, 3.9 Hz,
1H), 7.12 – 7.05 (m, 4H), 3.99 – 3.89 (m, 2H), 3.34 (dq, J = 14.5, 7.2 Hz, 1H), 2.33 (s, 3H), 1.22 (t, J = 7.2
Hz, 3H), 1.13 (s, 6H), 0.99 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 166.1, 135.9, 135.4, 135.0, 133.6,
128.8 (2C), 128.2 (2C), 128.1, 127.9, 80.0 (2C), 41.2, 25.1 (2C), 24.5 (2C), 21.1, 12.9. HRMS (EI-TOF,
m/z) calcd for C21H28BNO3S [M]+ 385.1883, found 385.1886.
ASSOCIATED CONTENT
Supporting information
1H and 13C NMR spectra of all compounds (PDF).
AUTHOR INFORMATION
Corresponding Authors
*E-mail: ghsong@ecust.edu.cn.
ORCID
Gong-Hua Song: 0000-0002-4673-6561.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Financial supports for this study from National Natural Science Foundation of China (Grant No.
21572060) and National Key Research and Development Plan (Grant No. 2017YFD0200504) are gratefully
acknowledged.
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