Cross-dehydrogenative coupling strategy for phosphonation and cyanation of secondary N-alkyl anilines by employing 2,3-dichloro-5,6-dicyanobenzoquinone

Article abstract of DOI:10.1016/j.tet.2018.10.058

The cross-dehydrogenative coupling strategy for metal-free phosphonation and cyanation of secondary N-alkyl anilines has been developed firstly under mild reaction conditions. Based on detailed optimization of reaction conditions, the substrate generality of N-alkyl anilines and various hydrogen phosphonates has been investigated, and a series of versatile α-aminophosphonates and α-aminonitriles were therefore furnished in good to excellent yields. A plausible collective reaction mechanism through dehydrogenation to imine formation, then to respective α-aminophosphonates and α-aminonitriles was proposed.

Full text of DOI:10.1016/j.tet.2018.10.058

Accepted Manuscript
Cross-dehydrogenative coupling strategy for phosphonation and cyanation of
secondary N-alkyl anilines by employing 2,3-dichloro-5,6-dicyanobenzoquinone
Qing Liu, Shuchen Yu, Liangzhen Hu, Muhamad Ijaz Hussain, Xiaohui Zhang, Yan
Xiong
PII:
S0040-4020(18)31281-X
https://doi.org/10.1016/j.tet.2018.10.058
TET 29891
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 August 2018
Revised Date: 8 October 2018
Accepted Date: 23 October 2018
Please cite this article as: Liu Q, Yu S, Hu L, Hussain MI, Zhang X, Xiong Y, Cross-dehydrogenative
coupling strategy for phosphonation and cyanation of secondary N-alkyl anilines by employing 2,3-
dichloro-5,6-dicyanobenzoquinone, Tetrahedron (2018), doi: https://doi.org/10.1016/j.tet.2018.10.058.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Cross-dehydrogenative coupling strategy for
phosphonation and cyanation of secondary
N-alkyl anilines by employing 2,3-dichloro-
5,6-dicyanobenzoquinone
Leave this area blank for abstract info.
Qing Liu,1,a Shuchen Yu,1,a Liangzhen Hu,a Muhamad Ijaz Hussain,a Xiaohui Zhang,a and Yan Xiong*,a,b
a School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China.
b State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Cross-dehydrogenative coupling strategy for phosphonation and cyanation of
secondary N-alkyl anilines by employing 2,3-dichloro-5,6-dicyanobenzoquinone
Qing Liu,1,a Shuchen Yu,1,a Liangzhen Hu,a Muhamad Ijaz Hussain,a Xiaohui Zhang,a and Yan Xiong*,a,b
a School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China.
b State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.
1 These authors contributed equally to this work.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The cross-dehydrogenative coupling strategy for metal-free phosphonation and cyanation of
secondary N-alkyl anilines has been developed firstly under mild reaction conditions. Based on
detailed optimization of reaction conditions, the substrate generality of N-alkyl anilines and
various hydrogen phosphonates has been investigated, and
a series of versatile α-
Available online
aminophosphonates and α-aminonitriles were therefore furnished in good to excellent yields. A
plausible collective reaction mechanism through dehydrogenation to imine formation, then to
respective α-aminophosphonates and α-aminonitriles was proposed.
Keywords:
α-aminonitriles
α-aminophosphonates
anilines
2009 Elsevier Ltd. All rights reserved
.
cyanation
cyanation
1. Introduction
in the area of oxidative Strecker reaction have been exploited as
well for tertiary amines12, 13 and it provided an important class of
useful and multifunctional α-aminonitriles, which can be
hydrolysed to form α-amino acids and can be converted into α-
amino carbonyl compounds, α-amino alcohols and vicinal
diamines by nucleophilic addition (eqns. 2 and 3, Scheme 1).
However, the reports on oxidative Strecker reaction of secondary
amines was few, such as Chen and our group, in which metal
oxidant and iron catalysis have been employed, respectively (eqn.
4, Scheme 1).14, 15
Since organophosphorus compounds performed a vital role in
biological activities and medical chemistry, the corresponding C-
P bond formation has attracted considerable attentions in organic
synthesis.1 Among these compounds, α-aminophosphonates2
show increasing importance and have gained widespread
application in both biological and pharmaceutical industries due
to their biological activities such as anticancer,3 antibacterial4 and
antitumor5. Especially in the recent years, a number of synthetic
methods for them have been developed through imine or iminium
formation, and these methods can be divided into two categories,
i.e. imine or iminium was generated from nonoxidative
condensation of aldehydes and amines via Kabachnik-Fields
reaction6 and Pudovik reaction7, and from oxidative
dehydrogenation of alkylamines with cross-dehydrogenative
coupling (CDC) strategy8. Oxidative phosphonation of α-Csp3-H
bond for tertiary amines has been well-evaluated, free of
preparation and tedious isolation of relatively unstable imine
intermediates, and transition-metal catalysis or metal-free method
with peroxides such as H2O2, tert-butyl hydroperoxide (TBHP),
di-tert-butyl hydrogen peroxide (DTBP), O2 as well as DDQ has
been reported (eqn. 1, Scheme 1).9,10 However, the
phosphonation of the secondary amine remains undiscovered and
challengeable, presumably due to its reactive N-H bond. For
example, in Zhao’s and Jia’s phosphination, secondary amines as
feedstock resulted directly in the phosphonated product
formation of tertiary amines and α-aminophosphonates.11
Mild organic oxidants like quinones, especially electron
deficient 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) has
been extensively utilized in oxidative transformation.16,17 It
prompted us to attempt phosphonation and cyanation of
alkylanilines through an oxidative dehydrogenation of
benzylaniline in the presence of quinones. As expected, the
separation, purification and characterization of the phosphonic
acid and cyanide products proceeded smoothly. Herein, we
would like to report the DDQ-oxidized direct phosphonation and
cyanation of secondary amines with phosphites and trimethylsilyl
cyanide (TMSCN), respectively (eqn. 5, Scheme 1).
Scheme 1. Oxidatively dehydrogenative phosphonation and
cyanation of amines.
The synthesis of versatile α-aminonitriles has attracted as
much attention as α-aminophosphonates, thus numerous methods

2
Tetrahedron
ACCEPTED MANUSCRIPT
Entry
Oxid. Solvent
Oxid.
t (h)
T (oC)
Yield (%)b
(x eq.)
1
Q1
Q2
Q3
Q4
Q5
Q1
Q1
Q1
Q1
Q1
Q1
Q1
Q1
Q1
Q1
Q1
Q1
Q1
Q1
Q1
THF
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.8
1.0
0.8
1.0
1.0
1.0
1.0
1.0
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
4
5
2
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
60
100
80
80
80
90
0
2
THF
3
THF
85
0
4
THF
5
THF
0
6
DMF
DMSO
CH3CN
dioxane
DCM
CH3NO2
CH3OH
THF
68
83
77
66
79
57
43
78
95
70
77
90
98
98
90
7
8
2. Results and disscussion
9
At the outset of our study, we chose the treatment of N-
benzylphenylamine 1a with dimethyl phosphate 2a as the model
reaction under the conditions of DDQ as the oxidant at 80 oC for
3 h, with the results summarized in Table 1. Firstly, when THF
was used as a solvent, high activity was observed and
phosphination product 3aa was provided in yield of 90% (entry
1). Different quinones such as benzoquinone (Q2), chloranil
10
11
12
13
14
15
16
17
18
19
20
THF
THF
(Q3),
chloranilic
acid
(Q4)
and
3,3',5,5'-tetra-tert-
butyldiphenoquinone (Q5) were subsequently examined, and as a
result only tetrachlorobenzoquinone gave rise to the product 3aa
in lower yield of 85% and other quinones did not work for this
reaction (entries 2-5). Inspired by this promising result, some
commonly used solvents were screened such as DMF, DMSO,
CH3CN, dioxane, DCM, CH3NO2, CH3OH and the results
showed that they were less favorable to the reaction compared
with THF (entries 6-12). The amount of DDQ was tested, and as
a result we found that the yield of 3aa dropped to 78% when
increasing to 1.8 equivalents (entry 13). To our delight,
decreasing the amount of DDQ to 1.0 equivalent gave an
increasing yield of up to 95% (entry 14). However, further
decrease in oxidant amount led to the inferior result (entry 15). A
range of additives was explored as well. Unfortunately, none of
the yields of 3aa increased when the reaction occurred in the
existence of various additives (For the details, see SI). It is worth
to note that the yield declined precipitously with addition of 0.2
equivalent of base as additives, while the use of organic acid
showed no influences on the yield. As a comparison, nitrogen
atmosphere and dark reaction were executed, and as a result in
both cases the model reaction worked well, which excludes the
process of oxygen and light promotion. Then, we evaluated the
effect of time and temperatures. Consequently, the yield
THF
THF
THF
THF
THF
a
Reaction conditions: N-benzylphenylamine (0.5 mmol), quinone (specified)
and dimethylphosphite (1.5 equiv., see SI for detailed optimization) in solvent
(1 mL) at T oC for t h.
b Determined by 1H NMR using mesitylene as internal standard.
With the optimal reaction conditions in hand, we next
examined the scope of N-alkyl anilines (Table 2). We firstly
explored the range of secondary amine bearing various
phenylamine moieties. For electron-rich groups, methyl-
substituted phenylamine 1b was unfortunately harmful to this
transformation to obtain product 3ba in 35% NMR yield,
compared with model product 3aa in 98%. The methoxyl group
and trifluoromethoxyl group were found to be properly suitable,
and the desired products were gave both in 95% yield (3ca and
3da). Different halogen groups proved to be compatible, and the
NMR yields were generally high and varied from 89% to 97%
(3ea-ha). A wide variety of substituents at the benzyl moieties
were also investigated continuously and the corresponding
products (3ia-oa) were furnished with good to excellent yields
(75-99%). Whether the electron-withdrawing or the electron-
donating substituents on benzene ring were tolerated, and showed
insignificant electronic nature of substitution groups. The
benzylamines with methyl and ethyl substitutions gave excellent
yields (3ia and 3ja). The halogen-substituents also afforded high
yields, in which the yield of dichloro-substituent was slightly
lower than mono-halogen substituted substrates (3ka-ma). The
relatively strong electron-withdrawing groups, such as cyano and
trifluoromethyl groups were examined and yielded 3na and 3oa
o
diminished with temperature decreased to 60 C or increased to
100 oC (entries 16 and 17); prolonging the reaction time to above
4 hour led to formation of 3aa in approximately 98% yield and
shortening the reaction time to 2 hours, the yield dropped to 90%
(entries 18-20). The combination of catalytic amount of DDQ
and oxygen balloon to improve this reaction has been attempted
as well, however the phosphonation failed under present
conditions.
Table 1. Optimization of reaction conditions.a

3
in 75% and 99%, respectively. Moreover, the naphthyl group was
ACCEPTED MANUSCRIPT
also compatible with the reaction and gave the desired product
3pa in 88% yield. In addition, some heterocyclic substituents,
such as furylmethylamine and thiophenylmethylamine were both
compatible and produced the corresponding products 3qa and
3ra in 90% and 89% yields, respectively. The reaction of linear
alkyl amines such as N-ethylaniline, N-isobutylaniline and N-
octylaniline failed to occur and the reason of the failure was
speculated from their relatively low reductive states. Importantly,
the cyclic aliphatic secondary amines also could be
functionalized into α-aminophosphonates (3sa and 3ta) in yields
of 77% and 42%, respectively.
3pa, 88% (85%)
3sa, 77% (70%)
3ac, 95% (93%)
3qa, 90% (88%)
3ta, 42% (41%)
3ad, 44% (44%)
3ra, 89% (82%)
3ab, 96%b (94%)
3ae, 34% (33%)
Various P-sources was investigated subsequently and the
corresponding results are listed. It is noteworthy that the
oxidative system worked well with hydrogen phosphonites, such
as diethyl phosphite, dibutyl phosphite, diphenyl phosphite,
bis(2,2,2-trifluoroethyl)phosphite and long-chain phosphite,
giving the desired products in moderate to excellent yields, which
indicated broad substitution scope and great compatibility
towards synthesis of diverse α-aminophosphonates (3ab-af). For
compound 3af, just one diasteromer was observed from 1H NMR
spectrum in our execution.
3af, 76% (61%)
Table 2. Substrate scope of the N-alkyl anilines.a
a
Reaction conditions: aniline (0.5 mmol), DDQ (0.5 mmol) and
alkylphosphite (0.75 mmol) in THF (1 mL) at 80 oC for 4 h.
b Yield of 3 determined by 1H NMR using mesitylene as internal standard.
c Isolated yield shown within parentheses.
It was worth noting that the product of the substrate 7-
nitrotetrahydroquinoline through oxidation reaction was 7-
nitroquinoline 4 (Scheme 2). Moreover, when the DDQ-oxidized
reaction was magnified to a gram scale of 10 mmol, 3aa could
also be isolated in a good yield of 78%, and demonstrated the
practicability of the method.
3aa, 98%b (85%)c
3ba, 35% (15%)
3ea, 89% (78%)
3ca, 95% (85%)
3fa, 97% (85%)
Scheme 2. Conversion of 7-nitrotetrahydroquinoline into 7-
nitroquinoline
3da, 95% (85%)
We turned our attention to derivation of hydrogenated salen
ligand N,N-dibenzylbenzene-1,2-diamine with 3.0 eq. of
dimethyl phosphite and 2.0 eq. of DDQ at 80 oC for 4 h.
However, a hetero aromatic benzimidazole 5 was obtained in
isolated yield of 74% (Scheme 3).
3ga, 96% (88%)
3ja, 86% (79%)
3ma, 93% (88%)
3ha, 96% (96%)
3ka, 90% (85%)
3na, 75% (73%)
3ia, 97% (80%)
3la, 89% (77%)
3oa, 99% (99%)
Scheme 3. Substrate expansion
We also moved toward interesting application of α-
aminophosphonate for Horner–Wadsworth–Emmons reaction
with aldehyde. The reaction of dimethyl (phenyl (phenylamino)
methyl) phosphonate and octanal afforded long chain ketone 1-
phenylnonan-1-one (6) with isolated yield of 50% under
modified conditions (Scheme 4).

4
Tetrahedron
Scheme 4. Application of α-aminophosphonate and convenient
formed reversibly from BHT through H-[1,6] shift from oxygen
ACCEPTED MANUSCRIPT
preparation of ketone from aldehyde
free radical to para-methyl group, and benzylphenylamine
radical was produced readily from the deprotonation of amine
radical cation 9.
Following our continuous interests on cyanation and synthesis
of nitriles,18 we focused on oxidative strecker reaction through
DDQ-oxidized dehydrogenation of secondary amine towards
imine formation. After optimization of reaction conditions (see
SI), the generality of phenylamines bearing methyl, methoxyl,
trifluoromethoxyl and halogen groups were investigated.
Different from model product (7a), methyl substituent 7b led to
unsatisfactory yield like in phosphonation. As expected, alkoxyl,
trifluoromethoxyl and halogen substituents showed good
activities to the transformation (7c-e). Besides, benzyl group
having various substituents such as alkyl, halogen, methoxy,
trifluoromethyl and heterocyclic groups were investigated as
well. Methyl (7f) and ethyl (7g) substituents were suitable for the
reaction and gave the desired product in 87% and 75% yield,
respectively. Halogen substituents (7h-m) gave good to excellent
yields. Among halogen substituents, the steric effect of
substitution groups has little effect on the yield, which is
confirmed by ortho-, para- and meta- bromine substitution in 7i-
k. Methoxyl and trifluoromethyl groups were also detected and
good results were obtained (7n and 7o). Moreover, heterocyclic
amines such as N-(furan-2-ylmethyl)aniline and N-(thiophen-2-
ylmethyl)aniline were considered as well, and as a result
moderate and moderate and good yields of isolated product (7p
and 7q) were obtained, respectively.
Scheme 5. Radical trap by utility of BHT
Accordingly, a plausible and collective reaction mechanism
for the synthesis of α-aminophosphonates and α-aminonitriles is
proposed (Figure 1). First, a radical cation 9 could be generated
from N-benzylphenylamine upon oxidative single electron
transfer (SET) with DDQ and a DDQ•- is released. 9 produces
the imine 11 through interaction of DDQ•- and α-H of 9, π-bond
formation, and then deprotonating of intermediate cation 10.
Next, the nucleophile addition of unshared pair electrons on
phosphine to the imine 11 generates the corresponding
intermediate of phosphate cation and the desired product 3aa was
afforded by deprotonating of cation. In the same way, the α-
aminonitriles 7a was also produced through attack of cyanide
anion to imine 11.
Table 3. Substrate scope for cyanation.a
Entry
1
R1
R2
Product
7a
Yield (%)b
84
H
Ph
2
p-Me
Ph
7b
7c
27
3
p-OCH3
Ph
75
4
p-OCF3
p-Cl
H
Ph
7d
7e
79
5
Ph
81
6
p-Me-Ph
p-Et-Ph
p-F-Ph
p-Br-Ph
m-Br-Ph
o-Br-Ph
p-Br-Ph
p-Br-Ph
p-OCH3-Ph
p-CF3-Ph
2-thiophen
2-furan
7f
87
7
H
7g
75
8
H
7h
7i
69
9
H
79
10
11
12
13
14
15
16
17
H
7j
89
Figure 1. Plausible mechanism.
H
7k
7l
81
3. Conclusions
p-Cl
p-Br
H
89
In summary, we have developed a metal-free method for the
synthesis of various α-aminophosphonates and α-aminonitriles. A
wide range of functional group tolerance with good to excellent
yields makes this protocol attractive and practicable in the
construction of C-P and C-C bonds for secondary amines. Based
on control experiments, a tandem pathway, i.e. dehydrogenative
imine formation-nucleophilic addition of phosphate and cyanide
anion, was proposed to clearly present reaction processes.
7m
7n
7o
81
83
H
91
H
7p
72
H
7q
44
a Reaction conditions: aniline (0.5 mmol), DDQ (0.5 mmol) and TMSCN (0.9
mmol) in MeCN (2 mL) at 30 oC for 8 h. b Isolated yield.
To gain insight into reaction mechanism, to phosphonation
system was added 5.0 equivalents of radical scavenger 2,6-di-
tert-butyl-4-methylphenol (BHT), however no desired product
was obtained (Scheme 5), which suggested the free radical
pathway. Fortunately, a small amount of product 8 was isolated.
The formation of tertiary amine 8 was speculatively generated
from the coupling of 4-hydroxyl-3,5-di-tert-butyl benzyl radical
and benzylphenyl amine radical. 4-Hydroxyl-3,5-di-tert-butyl
benzyl radical exists p-π conjugation of stable factor and was
4. Experimental section
4.1. General procedures
The 1H and 13C NMR spectra were recorded in CDCl3 solution
o
1
on a Bruker Avance 500/125 MHz spectrometer at 20-25 C. H
NMR chemical shifts were reported in ppm using
tetramethylsilane (TMS, δ = 0.00 ppm) as the internal standard.
1
The data of H NMR was reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =

5
multiplet), coupling constant (J value) in Hz and integration. 13C
CDCl3) δ 146.2, 135.7, 129.3, 128.8, 128.2, 127.9, 118.6, 114.0,
56.3, 55.1, 53.9; 31P NMR (202 MHz, CDCl3) δ 25.09.
ACCEPTED MANUSCRIPT
NMR spectra were reported in parts per million using solvent
CDCl3 (δ = 77.2 ppm) as an internal standard. All the reagents
used were of analytical grade, purchased locally and used without
any purification unless otherwise specified. Solvents purchased
from chemical supplier were firstly dried over 4Å molecular
sieve for one week. Column chromatography was performed
using silica gel, and analytical thin-layer chromatography (TLC)
was used to monitor the reactions, performed on silica gel plates.
4.2.2. Dimethyl (phenyl(p-tolylamino)methyl)phosphonate (3ba)21
o
1
White solid; m.p. 77.9-80.7 C; 15% yield, 46 mg; H NMR
(500 MHz, CDCl3) δ 7.47-7.45 (m, 2H), 7.34 (t, J = 7.5 Hz, 2H),
7.28-7.27 (m, 1H), 6.91 (d, J = 8.5 Hz, 2H), 6.51 (d, J = 8.5 Hz,
2H), 4.78 (dd, J1 = 6.0 Hz, J2 = 24.0 Hz, 1H), 4.70-4.64 (m, 1H),
3.76 (d, J = 10.5 Hz, 3H), 3.47 (d, J = 10.5 Hz, 3H), 2.18 (s, 3H).
13C NMR (125 MHz, CDCl3) δ 143.9, 143.8, 129.9, 128.9, 128.2,
128.0, 127.9, 114.2, 56.7, 55.5, 54.0, 20.5; 31P NMR (202 MHz,
CDCl3) δ 24.97.
General procedure for synthesis of secondary amine 1.19
To a 100 mL round flask that was equipped with a stirring bar,
aniline (10.0 mmol), aldehyde (11.0 mmol), NaOEt (1.36 g, 20.0
mmol) and methanol (20 mL) was added successively. The
resulting mixture was stirred at 80 oC in atmosphere and
monitored by TLC. When aniline was converted completely, the
mixture was cooled to room temperature, and NaBH4 (0.416 g,
11.0 mmol) was added to the reaction mixture in portions. The
4.2.3.
Dimethyl
(((4-
methoxyphenyl)amino)(phenyl)methyl)phosphonate (3ca)21
White solid; m.p. 90.8-92.0 oC; 85% yield, 137 mg; 1H NMR
(500 MHz, CDCl3) δ 7.46 (d, J = 7.0 Hz, 2H), 7.33 (t, J = 7.5
Hz, 2H), 7.27-7.24 (m, 1H), 6.68 (d, J = 8.5 Hz, 2H)ꢀ6.55ꢁd, J
= 8.5 Hz, 2Hꢂ, 4.73(dd, J1 = 8.0 Hz, J2 = 24.0 Hz, 1H), 4.59 (t,
J = 8.5 Hz, 1H), 3.75 (d, J = 11.0 Hz, 3H), 3.66 (s, 3H), 3.47 (d, J
= 10.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 152.8, 140.1,
135.8, 128.8, 128.1, 127.9, 115.4, 114.8, 57.3, 56.1, 55.7, 53.9;
31P NMR (202 MHz, CDCl3) δ 25.23.
o
continuous stirring was kept for additional 1-4 hours at 80 C.
TLC monitored the completion of the reaction. The solvent was
evaporated and the resulting residue was purified by column
chromatography on silica gel column using EtOAc−petroleum
ether solution as eluent to afford secondary amine.
Synthesis of 6.
4.2.4.
Dimethyl
(phenyl((4-
(trifluoromethoxy)phenyl)amino)methyl)phosphonate (3da)
NaH (40mg, 60%wt) was added to the stirred solution of 3aa
(0.5 mmol) and Octanal (0.5 mmol) in THF (2 mL) at room
temperature. When phosphonate 3aa was converted completely,
added water quenching reaction and extracted with ethyl acetate,
dried over magnesium sulfate, filtered and concentrated in vacuo.
The residue was chromatographed on a silica gel column to give
product 6.
o
1
White solid; m.p. 61.0-63.2 C; 85%, 159 mg; H NMR (500
MHz, CDCl3) δ 7.47(d, J = 7.5 Hz, 2H), 7.35 (t, J = 7.5 Hz, 2H),
7.30-7.28 (m, 1H), 6.95 (d, J = 8.5 Hz, 2H), 6.56 (d, J = 8.5 Hz,
2H), 5.07 (t, J = 9.0 Hz, 1H), 4.75 (dd, J1 = 8.0 Hz, J2 = 24.5 Hz,
1H), 3.76 (d, J = 11.0 Hz, 3H), 3.46 (d, J = 10.5 Hz, 3H). 13C
NMR (125 MHz, CDCl3) δ 145.1, 141.3, 135.3, 129.0, 128.4,
127.9, 122.4, 114.3, 56.6, 55.4, 54.0; 31P NMR (202 MHz,
4.2. Synthesis of 3 and 7.
Synthesis of 3.
CDCl3)
C16H17F3NO4P: 398.0740; found: 398.0742
δ
24.63; HRMS (ESI): m/z [M+Na]+ calcd for
DDQ (114mg, 0.5mmol) was added to the stirred solution of
secondary amine 1 (0.50 mmol) and phosphite (0.75 mmol) in
THF (1mL) at room temperature. The resulting mixture was kept
4.2.5.
Dimethyl
(((4-
fluorophenyl)amino)(phenyl)methyl)phosphonate (3ea)22
o
1
White solid; m.p. 108.7-110.2 C; 78% yield, 121 mg; H
NMR (500 MHz, CDCl3) δ 7.46 (d, J = 7.5 Hz, 2H), 7.34 (t, J =
7.5 Hz, 2H), 7.29-7.26 (m, 1H), 6.79 (t, J = 8.5 Hz, 2H), 6.54-
6.51 (m, 2H), 4.87-4.81 (m, 1H), 4.73 (dd, J1 = 8.0 Hz, J2 = 24.0
o
stirring at 80 C for 4 h. Subsequently, the mixture was poured
into aqueous Na2S2O3 solution, and extracted with ethyl acetate
(5 mL×3). The organic layers were combined, washed with
saturated NaHCO3 solution, dried over magnesium sulfate,
filtered and concentrated in vacuo. The residue was
Hz, 1H), 3.76 (d, J = 10.5 Hz, 3H), 3.46 (d, J = 10.5 Hz, 3H). 13
C
NMR (125 MHz, CDCl3) δ 156.3, 142.5, 135.5, 128.9, 128.3,
127.9, 115.7, 115.0, 57.0, 55.8, 53.9; 31P NMR (202 MHz,
CDCl3) δ 24.93.
chromatographed on
a
silica gel column to give α-
aminophosphonate 3.
Synthesis of 7.
4.2.6.
Dimethyl
(((4-
DDQ (114mg, 0.5mmol) was added to the stirred solution of
secondary amine 1 (0.50 mmol) and TMSCN (0.9 mmol) in
MeCN (2 mL) at room temperature. The resulting mixture was
chlorophenyl)amino)(phenyl)methyl)phosphonate (3fa)21
White solid; m.p. 93.5-94.3 oC; 85% yield, 138 mg; H NMR
(500 MHz, CDCl3) δ 7.45 (d, J = 7.5 Hz, 2H), 7.33 (t, J = 7.5 Hz,
2H), 7.28-7.26 (m, 1H), 7.02 (d, J = 9.0 Hz, 2H), 6.52 (d, J = 8.5
Hz, 2H), 5.04 (t, J = 9.0 Hz, 1H), 4.75 (dd, J1 = 8.0 Hz, J2 = 24.5
1
o
kept stirring at 30 C for 8 h. Subsequently, the mixture was
poured into aqueous Na2S2O3 solution, and extracted with ethyl
acetate (5 mL×3). The organic layers were combined, washed
with saturated NaHCO3 solution, dried over magnesium sulfate,
filtered and concentrated in vacuo. The residue was
chromatographed on a silica gel column to give α-aminonitrile 7.
Hz, 1H), 3.75 (d, J = 10.5 Hz, 3H), 3.45 (d, J = 10.5 Hz, 3H). 13
C
NMR (125 MHz, CDCl3) δ 144.8, 135.2, 129.1, 128.9, 128.3,
127.8, 123.1, 115.1, 56.4, 55.2, 53.9. 31P NMR (202 MHz,
CDCl3) δ 24.72.
4.2.1.
Dimethyl
(phenyl(phenylamino)methyl)phosphonate
4.2.7.
Dimethyl
(((4-
(3aa)20
bromophenyl)amino)(phenyl)methyl)phosphonate (3ga)21
o
1
White solid; m.p. 92.5-94.2 C; 85% yield, 124 mg; H NMR
(500 MHz, CDCl3) δ 7.48-7.47 (m, 2H), 7.34 (t, J = 7.5 Hz, 2H),
7.28-7.27 (m, 1H), 7.10 (t, J = 7.5 Hz, 2H), 6.69 (t, J = 7.0 Hz,
1H), 6.60 (d, J = 7.5 Hz, 2H), 4.86-4.77 (m, 2H), 3.75 (d, J =
11.0 Hz, 3H), 3.46 (d, J = 10.5 Hz, 3H). 13C NMR (125 MHz,
o
1
White solid; m.p. 96.5-97.1 C; 88% yield, 163 mg; H NMR
(500 MHz, CDCl3) δ 7.45 (d, J = 7.5 Hz, 2H), 7.33 (t, J = 7.5 Hz,
2H), 7.29-7.26 (m, 1H), 7.16 (d, J = 8.5 Hz, 2H), 6.48 (d, J = 8.5
Hz, 2H), 5.07-5.04 (m, 1H), 4.74 (dd, J1 = 8.0 Hz, J2 = 24.0 Hz,
1H), 3.75 (d, J = 10.5 Hz, 3H), 3.45 (d, J = 10.5 Hz, 3H). 13C

6
Tetrahedron
NMR (125 MHz, CDCl3) δ 145.3, 135.2, 132.0, 129.0, 128.3,
145.9, 135.0, 132.0, 129.6, 129.4, 122.2, 119.0, 114.0, 55.9, 54.7,
ACCEPTED MANUSCRIPT
127.8, 115.6, 110.3, 56.3, 55.1, 53.9; 31P NMR (202 MHz,
54.0; 31P NMR (202 MHz, CDCl3) δ 24.27.
CDCl3) δ 24.64.
4.2.14.
Dimethyl
((4-
4.2.8.
Dimethyl
(((4-
cyanophenyl)(phenylamino)methyl)phosphonate (3na)23
iodophenyl)amino)(phenyl)methyl)phosphonate (3ha)
o
1
White solid; m.p. 112.4-114.0 C; 73% yield, 115 mg; H
NMR (500 MHz, CDCl3) δ 7.64-7.60 (m, 4H), 7.11 (t, J = 8.0
Hz, 2H), 6.74 (t, J = 7.0 Hz, 1H), 6.54 (d, J = 7.5 Hz, 2H), 4.90-
4.83 (m, 2H), 3.78 (d, J = 10.5 Hz, 3H), 3.60 (d, J = 10.5 Hz,
3H). 13C NMR (125 MHz, CDCl3) δ 145.6, 141.7, 132.6, 129.5,
128.6, 119.3, 118.7, 113.9, 112.0, 56.3, 55.1, 54.1; 31P NMR (202
MHz, CDCl3) δ 23.50.
o
1
White solid; m.p. 112.3-113.1 C; 96% yield, 200 mg; H
NMR (500 MHz, CDCl3) δ 7.45 (d, J = 7.5 Hz, 2H), 7.34-7.32
(m, 4H), 7.28-7.27 (m, 1H), 6.39 (d, J = 9.0 Hz, 2H), 5.11 (s,
1H), 4.75 (d, J = 24.0 Hz, 1H), 3.75 (d, J = 11.0 Hz, 3H), 3.44 (d,
J = 10.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 145.9, 137.8,
135.1, 128.8, 128.3, 127.8, 116.1, 79.6, 56.1, 54.8, 53.9; 31P
NMR (202 MHz, CDCl3) δ 24.63; HRMS (ESI): m/z [M+H]+
calcd for C15H17INO3P: 418.0064; found: 418.0084.
4.2.15.
Dimethyl
((phenylamino)(4-
(trifluoromethyl)phenyl)methyl)phosphonate (3oa)
4.2.9. Dimethyl ((phenylamino)(p-tolyl)methyl)phosphonate (3ia)
o
1
White solid; m.p. 107.0-108.1 C; 99% yield, 178 mg; H
NMR (500 MHz, CDCl3) δ 7.61 (m, 4H), 7.12 (t, J = 7.0 Hz,
2H), 6.73 (t, J = 7.0 Hz, 1H), 6.57 (d, J = 8.0 Hz, 2H), 4.89-4.84
o
1
White solid; m.p. 122.9-123.4 C; 80% yield, 122 mg; H
NMR (500 MHz, CDCl3) δ 7.35-7.34 (m, 2H), 7.14 (d, J = 7.5
Hz, 2H), 7.10 (t, J = 8.0 Hz, 2H), 6.69 (t, J = 7.5 Hz, 1H), 6.59
(d, J = 7.5 Hz, 2H), 4.80-4.73 (m, 2H), 3.76 (d, J = 10.5 Hz, 3H),
3.48 (d, J = 11.0 Hz, 3H), 2.31 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 146.3, 138.0, 132.6, 129.6, 129.3, 127.8, 118.7, 114.1,
56.1, 54.9, 54.0, 21.3. 31P NMR (202 MHz, CDCl3) δ 25.29.
(m, 2H), 3.78 (d, J = 10.5 Hz, 3H), 3.56 (d, J = 11.0 Hz, 3H). 13
C
NMR (125 MHz, CDCl3) δ 145.8, 140.2, 129.5, 128.2, 125.8,
119.1, 113.9, 56.2, 55.0, 54.1; 31P NMR (202 MHz, CDCl3) δ
24.00; HRMS (ESI): m/z [M+H]+ calcd for C16H17F3NO3P:
360.0971; found: 360.0958.
4.2.16.
Dimethyl
(naphthalen-2-
yl(phenylamino)methyl)phosphonate (3pa)23
4.2.10.
Dimethyl
((4-
o
1
ethylphenyl)(phenylamino)methyl)phosphonate (3ja)
White solid; m.p. 148.0-148.7 C; 85% yield, 145 mg; H
NMR (500 MHz, CDCl3) δ 8.23 (d, J = 8.5 Hz, 1H), 7.89 (d, J =
8.0 Hz, 1H), 7.79 (d, J = 7.5 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1H),
7.54 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.04 (t, J = 7.0
Hz, 2H), 6.65 (t, J = 7.0 Hz, 1H), 6.54 (d, J = 8.0 Hz, 2H), 5.67
(dd, J1 = 7.0 Hz, J2 = 24.0 Hz, 1H), 5.07 (t, J = 8.5 Hz, 1H), 3.81
(d, J = 10.5 Hz, 3H), 3.13 (d, J = 10.5 Hz, 3H). 13C NMR (125
MHz, CDCl3) δ 146.0, 134.0, 131.5, 129.4, 129.3, 128.8, 126.7,
125.9, 125.8, 125.7, 122.7, 118.6, 113.7, 53.9, 51.9, 50.6; 31P
NMR (202 MHz, CDCl3) δ 25.40.
o
1
White solid; m.p. 96.5-97.8 C; 79% yield, 126 mg; H NMR
(500 MHz, CDCl3) δ 7.38-7.37 (m, 2H), 7.16 (d, J = 7.5 Hz, 2H),
7.09 (t, J = 8.0 Hz, 2H), 6.68 (t, J = 7.5 Hz, 1H), 6.60 (d, J = 8.0
Hz, 2H), 4.83-4.75 (m, 2H), 3.75 (d, J = 10.5 Hz, 3H), 3.47 (d, J
= 10.5 Hz, 3H), 2.60 (q, J1 = 7.5 Hz, J2 = 15.5Hz, 2H), 1.19 (t, J
= 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 146.2, 144.1,
132.7, 129.2, 128.3, 127.8, 118.5, 113.9, 56.0, 54.8, 53.8, 28.6,
15.5; 31P NMR (202 MHz, CDCl3) δ 25.29; HRMS (ESI): m/z
[M+H]+ calcd for C17H22NO3P: 320.1410; found: 320.1417.
4.2.17. Dimethyl (furan-2-yl(phenylamino)methyl)phosphonate
4.2.11.
Dimethyl
((4-
(3qa)20
chlorophenyl)(phenylamino)methyl)phosphonate (3ka)20
White solid; m.p. 82-83 oC; 88% yield, 124 mg; 1H NMR (500
MHz, CDCl3) δ 7.21 (s, 1H), 7.16-7.12 (m, 3H), 6.96-6.95 (m,
1H), 6.74 (t, J = 7.0 Hz, 1H), 6.67 (d, J = 7.5 Hz, 2H), 5.08 (dd,
J1 = 8.0 Hz, J2 = 23.5 Hz, 1H), 4.71 (t, J = 7.5 Hz, 1H), 3.77 (d, J
= 10.5 Hz, 3H), 3.60 (d, J = 10.5 Hz, 3H). 13C NMR (125 MHz,
CDCl3) δ 145.9, 139.5, 129.3, 127.2, 126.4, 125.5, 119.1, 114.0,
54.1, 52.3, 51.0; 31P NMR (202 MHz, CDCl3) δ 23.19.
o
1
White solid; m.p. 138.4-138.7 C; 85% yield, 138 mg; H
NMR (500 MHz, CDCl3) δ 7.41 (d, J = 7.5 Hz, 2H), 7.32 (d, J =
8.0 Hz, 2H), 7.11 (t, J = 7.0 Hz, 2H), 6.72 (t, J = 6.5 Hz, 1H),
6.56 (d, J = 7.5 Hz, 2H), 4.79-4.74 (m, 2H), 3.77 (d, J = 10.5 Hz,
3H), 3.54 (d, J = 10.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ
145.9, 134.4, 134.0, 129.4, 129.2, 129.1, 119.0, 114.0, 55.9, 54.7,
54.1; 31P NMR (202 MHz, CDCl3) δ 24. 70.
4.2.18.
Dimethyl
((phenylamino)(thiophen-2-
4.2.12.
Dimethyl
((3,4-
yl)methyl)phosphonate (3ra)
dichlorophenyl)(phenylamino)methyl)phosphonate (3la)
o
1
White solid; m.p. 81.0-81.5 C; 82% yield, 122 mg; H NMR
(500 MHz, CDCl3) δ 7.21 (d, J = 5.0 Hz, 1H), 7.17-7.12 (m, 3H),
6.96 (t, J = 4.0 Hz, 1H), 6.74 (t, J = 7.0 Hz, 1H), 6.67 (d, J = 8.0
Hz, 2H), 5.08 (d, J = 23.5 Hz, 1H), 4.67 (s, 1H), 3.77 (d, J = 10.5
Hz, 3H), 3.61 (d, J = 10.5 Hz, 3H). 13C NMR (125 MHz, CDCl3)
δ 146.0, 139.6, 129.3, 127.2, 126.4, 125.5, 119.1, 114.1, 54.1,
52.4, 51.1; 31P NMR (202 MHz, CDCl3) δ 23.21; HRMS (ESI):
m/z [M+H]+ calcd for C13H16NO3PS: 298.0662; found: 298.0655.
White solid; m.p. 96-97 oC; 77% yield, 139 mg; 1H NMR (500
MHz, CDCl3) δ 7.57 (s, 1H), 7.42-7.41 (m, 1H), 7.33-7.32 (m,
1H), 7.14-7.10 (m, 2H), 6.76-6.72 (m, 1H), 6.56 (d, J = 8.0 Hz,
2H), 4.79-4.71 (m, 2H), 3.80-3.76 (m, 3H), 3.62-3.53 (m, 3H).
13C NMR (125 MHz, CDCl3) δ 145.7, 136.5, 132.7, 130.9, 129.8,
129.5, 129.2, 127.2, 119.3, 114.0, 55.6, 54.4, 54.2; 31P NMR (202
MHz, CDCl3) δ 23.79; HRMS (ESI): m/z [M+H]+ calcd for
C15H16Cl2NO3P: 360.0318; found: 360.0305.
4.2.19. Dimethyl (cyclopropyl(phenylamino)methyl)phosphonate
(3sa)
4.2.13.
Dimethyl
((4-
bromophenyl)(phenylamino)methyl)phosphonate (3ma)21
o
1
White solid; m.p. 80.0-81.4 C; 70% yield, 89 mg; H NMR
(500 MHz, CDCl3) δ 7.15 (t, J = 8.0 Hz, 2H), 6.72 (t, J = 7.0 Hz,
1H), 6.64 (d, J = 8.0 Hz, 2H), 3.91 (m, 1H), 3.79 (d, J = 10.5 Hz,
3H), 3.71 (d, J = 10.5 Hz, 3H), 3.38-3.31 (m, 1H), 1.22-1.17 (m,
1H), 0.65-0.57 (m, 2H), 0.48-0.43 (m, 1H), 0.41-0.36 (m, 1H).
o
1
White solid; m.p. 144.0-144.3 C; 88% yield, 163 mg; H
NMR (500 MHz, CDCl3) δ 7.47 (d, J = 7.5 Hz, 2H), 7.35 (d, J =
8.0 Hz, 2H), 7.11 (t, J = 7.0 Hz, 2H), 6.72 (t, J = 7.5 Hz, 1H),
6.56 (d, J = 8.0 Hz, 2H), 4.81-4.72 (m, 2H), 3.77 (d, J = 11.0 Hz,
3H), 3.54 (d, J = 10.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ

7
13C NMR (125 MHz, CDCl3) δ 147.2, 129.3, 118.2, 113.4, 54.8,
4.2.25. Decyl methyl (phenyl(phenylamino)methyl)phosphonate
(3af)
ACCEPTED MANUSCRIPT
53.6, 52.9, 11.6, 3.3, 3.0; 31P NMR (202 MHz, CDCl3) δ 27.53;
HRMS (ESI): m/z [M+H]+ calcd for C12H18NO3P: 256.1097;
found: 256.1090.
1
Brown liquid; 61%, 127 mg; H NMR (500 MHz, CDCl3) δ
7.46 (s, 2H), 7.33 (s, 2H), 7.28-7.26 (m, 1H), 7.10 (t, J = 7.0 Hz,
2H), 6.69 (t, J = 7.0 Hz, 1H), 6.59 (d, J = 8.0 Hz, 2H), 4.80-4.75
(m, 2H), 4.07-4.02 (m, 1H), 3.89-3.73 (m, 2H), 3.62-3.45 (m,
2H), 1.63-1.60 (m, 1H), 1.44 (s, 1H), 1.28-1.18 (m, 14H), 0.89-
0.87 (m, 3H). 13C NMR (125 MHz, CDCl3) δ 146.3, 135.9, 129.3,
128.8, 128.1, 128.0, 118.6, 114.0, 67.6, 56.6, 55.4, 53.9, 32.0,
30.6, 29.6, 29.5, 29.2, 25.5, 22.8, 14.3; 31P NMR (202 MHz,
4.2.20. Dimethyl (cyclohexyl(phenylamino)methyl)phosphonate
(3ta)
o
1
White solid; m.p. 92.4-93.7 C; 41% yield, 61 mg; H NMR
(500 MHz, CDCl3) δ 7.09 (t, J = 8.0 Hz, 2H), 6.63 (t, J = 7.5 Hz,
1H), 6.57 (d, J = 8.0 Hz, 2H), 3.83-3.81 (m, 1H), 3.65 (d, J =
10.5 Hz, 3H), 3.62-3.57 (m, 4H), 1.90 (d, J = 12.5 Hz, 1H), 1.82-
1.81 (m, 1H), 1.69-1.65 (m, 3H), 1.56 (d, J = 13.0 Hz, 1H), 1.27-
1.02 (m, 5H). 13C NMR (125 MHz, CDCl3) δ 147.6, 129.4, 118.0,
113.2, 56.6, 55.4, 53.5, 52.5, 40.0, 31.0, 28.4, 26.4, 26.2; 31P
NMR (202 MHz, CDCl3) δ 27.81; HRMS (ESI): m/z [M+H]+
calcd for C15H24NO3P: 298.1567; found: 298.1557.
CDCl3)
δ
23.87; HRMS (ESI): m/z [M+H]+ calcd for
C24H36NO3P: 418.2506, found 418.2502.
4.2.26. 7-nitroquinoline (4)26
o
1
Yellow solid; m.p. 127.3-128.1 C; 42% yield, 37 mg; H
NMR (500 MHz, CDCl3) δ 9.10 (s, 1H), 9.01 (s, 1H), 8.34-8.28
(m, 2H), 8.00 (d, J = 8.5 Hz, 1H), 7.62-7.60 (m, 1H). 13C NMR
(125 MHz, CDCl3) δ 152.9, 148.2, 147.3, 136.1, 131.5, 129.6,
126.0, 124.1, 120.2.
4.2.21. Diethyl (phenyl(phenylamino)methyl)phosphonate (3ab)24
o
1
White solid; m.p. 87.1-88.0 C; 94% yield, 150 mg; H NMR
(500 MHz, CDCl3) δ 7.47 (d, J = 7.5 Hz, 2H), 7.32 (t, J = 7.5 Hz,
2H), 7.26-7.25 (m, 1H), 7.09 (t, J = 7.5 Hz, 2H), 6.68 (t, J = 7.5
Hz, 1H), 6.59 (d, J = 8.0 Hz, 2H), 4.86 (t, J = 8.5 Hz, 1H), 4.76
(dd, J1 = 7.5 Hz, J2 = 24.0 Hz, 1H), 4.17-4.04 (m, 2H), 3.96-3.89
(m, 1H), 3.70-3.62 (m, 1H), 1.27 (t, J = 7.0 Hz, 3H), 1.10 (t, J =
7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 146.4, 136.0, 129.2,
4.2.27. 1-benzyl-2-phenyl-1H-benzo[d]imidazole (5)27
1
White solid; 74% yield, 105 mg; H NMR (500 MHz, CDCl3)
δ 7.87 (d, J = 8.5 Hz, 1H), 7.69-7.67 (m, 2H), 7.46-7.42 (m, 3H),
7.33-7.28 (m, 4H), 7.24-7.19 (m, 2H), 7.09 (d, J = 7.5 Hz, 2H),
5.44 (s, 2H).
128.7, 128.0, 127.9, 118.4, 113.9, 63.3, 56.7, 55.5, 16.5, 16.3; 31
P
4.2.28. 1-phenylnonan-1-one (6)28
NMR (202 MHz, CDCl3) δ 22.76.
Yellow liquid; 50% yield, 55 mg; 1H NMR (500 MHz, CDCl3)
δ 7.96-7.95 (m, 2H), 7.55-7.52 (m, 1H), 7.46-7.43 (m, 2H), 2.95
(t, J = 7.5 Hz, 2H), 1.76-1.70 (m, 2H), 1.39-1.27 (m, 10H), 0.88
(t, J = 7.0 Hz, 3H).
4.2.22. Dibutyl (phenyl(phenylamino)methyl)phosphonate (3ac)
o
1
White solid; m.p. 39.5-41.5 C; 93% yield, 175 mg; H NMR
(500 MHz, CDCl3) δ 7.46 (d, J = 7.5 Hz, 2H), 7.32 (t, J = 7.0 Hz,
2H), 7.27-7.24 (m, 1H), 7.10 (t, J = 8.0 Hz, 2H), 6.69 (t, J = 7.0
Hz, 1H), 6.59 (d, J = 8.0 Hz, 2H), 4.82-4.73 (m, 2H), 4.09-3.98
(m, 2H), 3.90-3.84 (m, 1H), 3.62-3.56 (m, 1H), 1.63-1.57 (m,
2H), 1.46-1.40 (m, 2H), 1.39-1.31 (m, 2H), 1.26-1.18 (m, 2H),
0.89 (t, J = 7.5 Hz, 3H), 0.82 (t, J = 7.5 Hz, 3H). 13C NMR (125
MHz, CDCl3) δ 146.5, 136.1, 129.3, 128.7, 128.0, 127.9, 118.5,
113.9, 67.0, 65.6, 56.7, 55.5, 32.6, 32.5, 18.8, 18.7, 13.7; 31P
NMR (202 MHz, CDCl3) δ 22.66; HRMS (ESI): m/z [M+H]+
calcd for C21H30NO3P: 376.2036; found: 376.2029.
4.2.29. 2-phenyl-2-(phenylamino)acetonitrile (7a)29
o
1
White solid; m.p. 74.2-75.7 C; 89% yield; H NMR (500
MHz, CDCl3) δ 7.58 (d, J = 7.0 Hz, 2H ), 7.46-7.41 (m, 3H), 7.26
(t, J = 8.0 Hz, 2H), 6.89 (t, J = 7.5 Hz, 1H), 6.76 (d, J = 8.0 Hz,
2H ), 5.41 (d, J = 8.5 Hz, 1H ), 4.04 (d, J = 8.0 Hz, 1H ).
4.2.30. 2-phenyl-2-(p-tolylamino)acetonitrile (7b)29
o
1
White solid; m.p. 93.4-97.2 C; 27% yield; H NMR (500
MHz, CDCl3) δ 7.60 (dd, J = 2.0, 8.0 Hz, 2H), 7.48-7.43 (m, 3H),
7.09 (d, J = 8.5 Hz, 2H), 6.71 (d, J = 8.5 Hz, 2H), 5.40 (d, J = 9.0
Hz, 1H), 3.91 (d, J = 8.5 Hz, 1H), 2.28 (s, 3H).
4.2.23. Diphenyl
(phenyl(phenylamino)methyl)phosphonate
(3ad)25
White solid; m.p. 148.2-148.8 oC; 44% yield, 91 mg; 1H NMR
(500 MHz, CDCl3) δ 7.55 (d, J = 7.0 Hz, 2H), 7.34 (t, J = 7.0 Hz,
2H), 7.30-7.24 (m, 3H), 7.20 (t, J = 8.0 Hz, 2H), 7.16-7.07 (m,
6H), 6.84 (d, J = 8.0 Hz, 2H), 6.74 (t, J = 7.0 Hz, 1H), 6.64 (d, J
= 8.0 Hz, 2H), 5.15 (dd, J1 = 8.0 Hz, J2 = 24.5 Hz, 1H), 4.94 (t, J
= 9.0 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 150.4, 146.0,
134.9, 129.9, 129.8, 129.4, 129.0, 128.5, 128.4, 125.6, 125.4,
120.8, 120.48, 119.0, 114.2, 56.1; 31P NMR (202 MHz, CDCl3) δ
15.37.
4.2.31. 2-((4-methoxyphenyl)amino)-2-phenylacetonitrile (7c)29
Yellow oil; 75% yield; 1H NMR (500 MHz, CDCl3) δ 7.61 (d,
J = 6.5 Hz, 2H), 7.48-7.43 (m, 3H), 6.85 (d, J = 9.0 Hz, 2H), 6.77
(d, J = 8.5 Hz, 2H), 5.35 (s, 1H), 3.78 (s, 4H).
4.2.32.
2-phenyl-2-((4-
(trifluoromethoxy)phenyl)amino)acetonitrile (7d)15
o
1
White solid; m.p. 68.6-69.4 C; 79% yield; H NMR (500
MHz, CDCl3) δ 7.57 (d, J = 5.0 Hz, 2H), 7.44 (s, 3H), 7.12 (d, J
= 8.5 Hz, 2H), 6.73 (d, J = 7.5 Hz, 2H), 5.38 (d, J = 7.0 Hz, 1H),
4.18 (d, J = 6.5 Hz, 1H).
4.2.24.
Bis(2,2,2-trifluoroethyl)
(phenyl(phenylamino)methyl)phosphonate (3ae)
White solid; m.p. 75-78 oC; 33% yield, 71 mg; H NMR (500
MHz, CDCl3) δ 7.47 (d, J = 7.5 Hz, 2H), 7.38 (t, J = 7.0 Hz, 2H),
7.35-7.32 (m, 1H), 7.15 (t, J = 7.5 Hz, 2H), 6.77 (t, J = 7.5 Hz,
1H), 6.67 (d, J = 8.0 Hz, 2H), 4.98 (dd, J1 = 9.0 Hz, J2 = 24.5 Hz,
1H), 4.70 (t, J = 8.5 Hz, 1H), 4.50-4.41 (m, 1H), 4.30-4.17 (m,
2H), 3.80-3.71 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 145.5,
134.0, 129.5, 129.3, 129.1, 128.0, 119.6, 114.4, 63.3, 63.0, 62.8,
56.9, 55.7; 31P NMR (202 MHz, CDCl3) δ 25.29; HRMS (ESI):
m/z [M+H]+ calcd for C17H16F6NO3P: 428.0845; found:
428.0839.
1
4.2.33. 2-((4-chlorophenyl)amino)-2-phenylacetonitrile (7e)30
o
1
White solid; m.p. 68.5-73.3 C; 81% yield; H NMR (500
MHz, CDCl3) δ7.56 (t, J = 3.0 Hz, 2H ), 7.43 (d, J = 5.0 Hz, 3H),
7.19 (d, J = 8.5 Hz, 2H), 6.67 (d, J = 8.5 Hz, 2H), 5.36 (d, J = 8.5
Hz, 1H), 4.12 (d, J = 7.5 Hz, 1H).
4.2.34. 2-(phenylamino)-2-(p-tolyl)acetonitrile (7f)29
o
1
White solid; m.p. 63.7-64.4 C; 87% yield; H NMR (500
MHz, CDCl3) δ 7.46 (d, J = 8.5 Hz, 2H), 7.27-7.23 (m, 4H), 6.88

8
Tetrahedron
(t, J = 7.5 Hz, 1H), 6.75 (d, J = 8.0 Hz, 2H), 5.35 (s, 1H), 4.01
6.93 (t, J = 7.5 Hz, 1H), 6.76 (d, J = 7.5 Hz, 2H), 5.51 (s, 1H),
ACCEPTED MANUSCRIPT
(s, 1H), 2.38 (s, 3H).
4.13 (s, 1H).
4.2.35. 2-(4-ethylphenyl)-2-(phenylamino)acetonitrile (7g)31
4.2.44. 2-(phenylamino)-2-(thiophen-2-yl)acetonitrile (7p)30
o
1
o
1
Light yellow solid; m.p. 42.0-42.9 C; 75% yield; H NMR
(500 MHz, CDCl3) δ 7.48 (d, J = 8.0 Hz, 2H), 7.25 (t, J = 8.5 Hz,
4H), 6.87 (t, J = 7.5 Hz, 1H), 6.75 (d, J = 8.0 Hz, 2H), 5.35 (s,
1H), 4.01 (s, 1H), 2.67 (q, J = 8.0 Hz, 2H), 1.24 (t, J = 7.5 Hz,
3H).
White solid; m.p. 88.8-89.5 C; 72% yield; H NMR (500
MHz, CDCl3) δ 7.38-7.35 (m, 2H), 7.28-7.26 (m, 2H), 7.04 (dd, J
= 3.5,5.0 Hz, 1H), 6.92 (t, J = 7.5, 1H), 6.79 (d, J = 8.0 Hz, 2H),
5.63 (d, J = 9.0 Hz, 1H), 4.19 (d, J = 9.0 Hz, 1H).
4.2.45. 2-(furan-2-yl)-2-(phenylamino)acetonitrile (7q)35
4.2.36. 2-(4-fluorophenyl)-2-(phenylamino)acetonitrile (7h)32
o
1
White solid; m.p. 67.8-69.3 C; 44% yield; H NMR (500
MHz, CDCl3) δ 7.48 (dd, J = 0.5, 2.0 Hz, 1H), 7.30-7.26 (m, 2H),
6.92 (t, J = 7.5 Hz, 1H), 6.79-6.77 (m, 2H), 6.58 (d, J = 3.0 Hz,
1H), 6.43 (dd, J = 2.0, 3.5 Hz, 1H), 5.49 (d, J = 8.0 Hz, 1H), 4.19
(d, J = 9.0 Hz, 1H).
o
1
Light yellow solid; m.p. 99.6-103.8 C; 69% yield; H NMR
(500 MHz, CDCl3) δ 7.57 (dd, J = 8.0, 5.5 Hz, 2H), 7.27 (t, J =
8.0 Hz, 2H), 7.13 (t, J = 8.5 Hz, 2H), 6.91 (t, J = 7.5 Hz, 1H),
6.76 (d, J = 8.0 Hz, 2H), 5.40 (d, J = 8.5 Hz, 1H), 4.04 (d, J = 8.5
Hz, 1H).
4.2.46. 4-((benzyl(phenyl)amino)methyl)-2,6-di-tert-butylphenol
4.2.37. 2-(4-bromophenyl)-2-(phenylamino)acetonitrile (7i)29
(8)
o
1
White solid; m.p. 90.2-91.3 C; 79% yield; H NMR (500
MHz, CDCl3) δ 7.55 (d, J = 8.5 Hz, 2H), 7.44 (d, J = 8.5 Hz,
2H), 7.25 (d, J = 8.5 Hz, 2H), 6.90 (t, J = 7.0 Hz, 1H), 6.73 (d, J
= 8.0 Hz, 2H), 5.37 (d, J = 8.5 Hz, 1H), 4.11 (d, J = 8.5 Hz, 1H).
1H NMR (500 MHz, CDCl3) δ 7.31-7.28 (m, 2H), 7.24-
7.23(m, 3H), 7.17 (t, J = 7.5 Hz, 2H), 7.03 (s, 2H), 6.78 (d, J =
7.5 Hz, 2H), 6.69 (t, J = 6.5 Hz, 1H), 5.11 (s, 1H), 4.56 (d, J =
16.5 Hz, 4H), 1.38 (s, 18H).
4.2.38. 2-(3-bromophenyl)-2-(phenylamino)acetonitrile (7j)31
Acknowledgments
o
1
Light yellow solid; m.p. 63.2-65.1 C; 89% yield; H NMR
(500 MHz, CDCl3) δ 7.82 (s, 1H), 7.61 (t, J = 9.5 Hz, 2H), 7.40-
7.31 (m, 3H), 6.98 (t, J = 7.5 Hz, 1H), 6.82 (d, J = 8.0 Hz, 2H),
5.47 (d, J = 8.5 Hz, 1H), 4.13 (d, J = 8.5 Hz, 1H).
We thank the National Natural Science Foundation of China
(no. 21372265) for financial support.
References and notes
4.2.39. 2-(2-bromophenyl)-2-(phenylamino)acetonitrile (7k)33
o
1
1. (a) Hirachmann, R.; Smith, III, A. B.; Taylor, C. M.; Benkovic, P.
A.; Taylor, S. D.; Yager, K. M.; Sprengeler, P. A.; Benkovis, S. J.
Science 1994, 265, 234-237. (b) Demmer, C. S.; Krogsgaard-
Larsen, N.; Bunch, L. Chem. Rev. 2011, 111, 7981-8006. (c)
Horsman, G. P.; Zechel, D. L. Phosphonate Biochemistry. Chem.
Rev. 2017, 117, 5704-5783. (d) Nakamura, S.; Hayama, D. Angew.
Chem. Int. Ed. 2017, 56, 8785-8789.
2. (a) Ma, J. A. Chem. Soc. Rev. 2006, 35, 630-636. (b) Gao, Y.;
Huang, Z.; Zhuang, R.; Zhang, P.; Tang, G.; Zhao, Y. Org. Lett.
2013, 15, 4214-4217. (c) Cheng, M.; Ma, R.; Yang, Q.; Yang, S.
Org. Lett. 2016, 18, 3262-3265. (d) Ghafuri, H.; Rashidizadeh, A.;
Zand, H. R. E. RSC Adv. 2016, 6, 16046-16054.
3. (a) Troev, K. D. Chemistry and Application of H-Phosphonates,
Elsevier, Amsterdam, 2006.
4. (a) Atherton, F. R.; Hassall, C. H.; Sain, R. J. Med. Chem. 1986,
29, 29-40. (b) Pratt, R. F. Science. 1989, 246, 917-919. (c) Smith,
III, A. B.; Yager, K. M.; Taylor, C. M. J. Am. Chem. Soc. 1995,
117, 10879-10888.
Light yellow solid; m.p. 79.0-80.2 C; 81% yield; H NMR
(500 MHz, CDCl3) δ 7.76 (d, J =7.5 Hz, 1H), 7.66 (d, J = 7.5 Hz,
1H), 7.43 (t, J = 7.5 Hz, 1H), 7.32-7.26 (m, 3H), 6.91 (t, J = 7.5
Hz, 1H), 6.79 (d, J = 7.5 Hz, 2H), 5.71 (d, J = 8.0 Hz, 1H), 4.02
(d, J = 7.0 Hz, 1H).
4.2.40. 2-(4-bromophenyl)-2-((4-chlorophenyl)amino)acetonitrile
(7l)
o
1
White solid; m.p. 109.6-111.1 C; 89% yield; H NMR (500
MHz, CDCl3) δ 7.58 (d, J =8.5 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H),
7.21 (d, J = 8.5 Hz, 2H), 6.77 (d, J = 8.5 Hz, 2H), 5.35 (d, J = 8.5
Hz, 1H), 4.10 (d, J = 8.5 Hz, 1H)ꢃ13C NMR (125 MHz, CDCl3)
δ 143.0, 132.7, 132.6, 129.6, 128.9, 125.5, 124.0, 117.7, 115.7,
49.8. HRMS (ESI): m/z [M+H]+ calcd for C14H10BrClN2:
320.9789, found 320.9778.
5. (a) Huang, J.; Chen, R. Heteroat. Chem. 2000, 11, 480-492.
6. (a) Fields, E. K. J. Am. Chem. Soc. 1952, 74, 1528-1531. (b)
Bhagat, S.; Chakraborti, A. K. J. Org. Chem. 2007, 72, 1263-
1270. (c) Cheng, X.; Goddard, R.; Buth, G.; List, B. Angew.
Chem. Int. Ed. 2008, 47, 5079-5081. (d) Bhagat, S.; Chakraborti,
A. K. J. Org. Chem. 2008, 73, 6029-6032. (e) Zhou, X.; Zhang,
D.; Zhang, Q.; Lin, L.; Liu, X.; Feng, X. Org. Lett. 2009, 11,
1401-1404. (f) Keglevich, G.; Bálint, E. Molecules 2012, 17,
12821-12835.
7. (a) Sasai, H.; Arai, S.; Tahara, Y.; Shibasaki, M. J. Org. Chem.
1995, 60, 6656-6657. (b) Grӧger, H.; saida, Y.; Sasai, H.;
Yamaguchi, K.; Martens, J.; Shibasaki, M. J. Am. Chem. Soc.
1998, 120, 3089-3103. (c) Schlemminger, I.; Saida, Y.; Grӧger,
H.; Maison, W.; Durot, N.; Sasai, H.; Shibasaki, M.; Martens, J. J.
Org. Chem. 2000, 65, 4818-4825. (d) Davis, F. A.; Lee, S.; Yan,
H.; Titus, D. D. Org. Lett. 2001, 3, 1757-1760. (e) Davis, F. A.;
Lee, S. H.; Xu, H. J. Org. Chem. 2004, 69, 3774-3781. (f) Joly, G.
D.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 4102-4103. (g)
Pettersen, D.; Marcolini, M.; Bernardi, L.; Fini, F.; Herrera, R. P.;
Sgarzani, V.; Ricci, A. J. Org. Chem. 2006, 71, 6269-6272. (h)
Saito, B.; Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2007, 129,
1978-1986. (i) Abell, J. P.; Yamamoto, H. J. Am. Chem. Soc.
2008, 130, 10521-10523. (j) Merino, P.; Marqués-López, E.;
Herrera, R. P. Adv. Synth. Catal. 2008, 350, 1195-1208. (k)
4.2.41. 2-(4-bromophenyl)-2-((4-bromophenyl)amino)acetonitrile
(7m)
o
1
White solid; m.p. 126.2-127.5 C;81% yield; H NMR (500
MHz, CDCl3) δ 7.59-7.56 (m, 2H), 7.45-7.43 (m, 2H), 7.36-7.33
(m, 2H), 6.64-6.61 (m, 2H), 5.35 (d, J = 9.0 Hz, 1H), 4.14 (d, J =
8.5 Hz, 1H)ꢃ13C NMR (125 MHz, CDCl3) δ 143.5, 132.7,
132.5, 128.9, 124.0, 117.6, 116.1, 112. 7, 49.7. HRMS (ESI): m/z
[M+H]+ calcd for C14H10Br2N2: 364.9284, found 364.9276.
4.2.42. 2-(4-methoxyphenyl)-2-(phenylamino)acetonitrile (7n)30
o
1
White solid; m.p. 96.4-97.5 C; 83% yield; H NMR (500
MHz, CDCl3) δ 7.52-7.49 (m, 2H), 7.29-7.25 (m, 2H), 6.98-6.95
(m, 2H), 6.89 (t, J = 7.5 Hz, 1H), 6.77 (d, J = 8.5 Hz, 2H), 5.36
(d, J = 8.0 Hz, 1H), 3.97 (d, J = 8.0 Hz, 1H), 3.83 (s, 3H).
4.2.43. 2-(phenylamino)-2-(4-(trifluoromethyl)phenyl)acetonitrile
(7o)34
o
1
White solid; m.p. 90.2-91.5 C; 91% yield; H NMR (500
MHz, CDCl3) δ 7.72 (q, J = 8.5 Hz, 4H), 7.27 (t, J = 8.0 Hz, 2H),

9
Nakamura, S.; Hayashi, M.; Hiramatsu, Y.; Shibata, N.;
Funahashi, Y.; Toru, T. J. Am. Chem. Soc. 2009, 131, 18240-
18241. (l) Ingle, G. K.; Liang, Y.; Mormino, M. G.; Li, G.;
Fronczek, F. R.; Antilla, J. C. Org. Lett. 2011, 13, 2054-2057. (m)
Motevalli, S.; Iranpoor, N.; Etemadi-Davan, E.; Moghadam, K. R.
RSC Adv. 2015, 5, 100070-100076.
Tetrahedron 2016, 72, 2359-2363. (r) Yang, W.; Wei, L.; Yi, F.;
ACCEPTED MANUSCRIPT
Cai, M. Tetrahedron 2016, 72, 4059-4067. (s) Liu, P.; Zhang, C.;
Zhao, S.; Yu, F.; Li, F.; He,Y. J. Org. Chem. 2017, 82, 12786-
12790. (t) Patil, M. R.; Dedhia, N. P.; Kapdi, A. R.; Kumar, A.V.
J. Org. Chem. 2018, 83, 4477−4490. (u) Sun, M.; Wang, Y.; Xu,
B.; Ma, X.; Zhang, S. Org. Biomol. Chem. 2018, 16, 1971-1975.
13. (a) Shen, H.; Zhang, X.; Liu, Q.; Pan, J.; Hu, W.; Xiong, Y.
Tetrahedron Lett. 2015, 56, 5628-5631. (b) Shen, H.; Hu, L.; Liu,
Q.; Hussain, M. I.; Pan, J.; Huang, M.; Xiong, Y. Chem. Commun.
2016, 52, 2776-2779. (c) Shen, H.; Deng, Q.; Liu, R.; Feng, Y.;
Zheng, C.; Xiong, Y. Org. Chem. Front. 2017, 4, 1806-1811. (d)
Sundberg, R.; Théret, M. H.; Wright, L. Org. Prep. Proc. Int.
1994, 26, 386-389.
14. Zhu, C.; Xia, J.; Chen, C. Tetrahedron Letters 2014, 55, 232-234.
15. Huang, M.; Deng, Q.; Gao, Q.; Shi, J.; Zhang, X.; Xiong, Y. Asian
J. Org. Chem. 2018, 7, 404-410.
16. (a) Zhang, Y.; Li, C. Angew. Chem. Int. Ed. 2006, 45, 1949-1952.
(b) Zhang, Y.; Li, C. J. Am. Chem. Soc. 2006, 128, 4242-4243. (c)
Zhang, H.; Liu, L.; Chen, J.; Wang, D.; Li, C. Adv. Synth. Catal.
2006, 348, 229-235. (d) Zhang, Y.; Xu, J.; Li, X.; Tian, S. Eur. J.
Org. Chem. 2013, 3648-3652.
17. Ying, B.; Trogden, B. G.; Kohlman, D.T.; Liang, S. X.; Xu, Y.
Org. Lett. 2004, 6, 1523-1526.
18. (a) Shen, H.; Li, J. Q.; Liu, Q.; Pan, J.; Huang, R. F.; Xiong, Y. J.
Org. Chem. 2015, 80, 7212-7218. (b) Hussain, M. I.; Feng, Y. Y.;
Hu, L. Z.; Deng, Q. F.; Zhang, X. H.; Xiong, Y. J. Org. Chem.
2018, DOI: 10.1021/acs.joc.8b00729.
19. (a) Ling, X.; Xiong, Y.; Huang, R.; Zhang, X.; Zhang, S.; Chen,
C. J. Org. Chem. 2013, 78, 5218-5226.
20. Srikant, B. J. Org. Chem. 2007, 72, 1263-1270.
21. WSS: Spectral data were obtained from Wiley Subscription
Services, Inc. (US)
8. (a) Li, C. J. Acc. Chem. Res. 2009, 42, 335-344. (b) Girard, S. A.;
Knauber, T.; Li, C. J. Angew. Chem. Int. Ed. 2014, 53, 74-100.
9. (a) Zhou, X.; Liu, X.; Yang, X.; Shang, D.; Xin, J.; Feng, X.
Angew. Chem. Int. Ed. 2008, 47, 392-394. (b) Han, W.; Ofial, A.
R. Chem. Commun. 2009, 6023-6025. (c) Baslé, O.; Li, C. J.
Chem. Commun. 2009, 4124-4126. (d) Han, W.; Mayer, P.; Ofial,
A. R. Adv. Synth. Catal. 2010, 352, 1667-1676. (e) Rueping, M.;
Zhu, S.; Koenigs, R. M. Chem. Commun. 2011, 47, 8679–8681. (f)
Xie, J.; Li, H.; Xue, Q.; Cheng, Y.; Zhu, C. Adv. Synth. Catal.
2012, 354, 1646-1650. (g) Yoo, W.; Kobayashi,S. Green Chem.
2014, 16, 2438. (h) Zhang, H.; Mao, L.; Yang, B.; Yang, S. D.
Chem. Commoun. 2015, 51, 4101-4104. (i) Gao, Y.; Lu, G.;
Zhang, P.; Zhang, L.; Tang, G.; Zhao, Y. Org. Lett. 2016, 18,
1242-1245.
10. (a) Hari, D. P.; Kӧnig, B. Org. Lett. 2011, 13, 3852-3855. (b)
Wang,H.; Li,X.; Wu, F.; Wan, B. Tetrahedron Lett. 2012, 53,
681–683. (c) Rueping, M.; Vila, C.; Bootwicha, T. ACS Catal.
2013, 3, 1676−1680. (d) Gandy, M. N.; Raston, C. L.; Stubbs, K.
A. Chem. Commun. 2015, 51, 11041. (e) Wang, X. Z.; Meng, Q.
Y.; Zhong, J.; Gao, X.; Lei, T.; Zhao, L.; Li, Z.; Chen, B.; Tung,
C.; Wu, L. Chem. Commun. 2015, 51, 11256. (f) Huo, C.; Xie, H.;
Wu, M.; Jia, X.; Wang, X.; Chen, F.; Tang, J. Chem. Eur. J. 2015,
21, 5723 – 5726. (g) Dhineshkumar, J.; Samaddar, P.; Prabhu, K.
R. ACS Omega, 2017, 2, 4885-4893.
11. (a) Hu, G.; Chen, W.; Ma, D.; Zhang, Y.; Xu, P.; Gao, Y.; Zhao,
Y. J. Org. Chem. 2016, 81, 1704-1711. (b) In our preparation for
submission, a same reaction was reported, see: Jia, X. D.; Liu, X.
F.; Yuan, Y.; Li, P. F.; Hou, W. T.; He, K. X. Chem. Asian J.
2018, 13, 1911-1914..
22. Rosi, R. K. Chem. Lett. 2005, 34, 444-445.
23. Srikant, B. J. Org. Chem. 2008, 73, 6029-6032.
24. Mazaahir, K. Catal. Sci. & Technol. 2011, 1, 426-430.
25. Mohsen, R. Phosphorus Sulfur. 2011, 186, 334-337.
26. Mark H., N. J. Med. Chem. 2007, 50, 3497-3514.
27. Murali Mohan, G. J. Org. Chem. 2011, 76, 5295-5308.
28. Nicolas R., V. Chem. Commun. 2011, 47, 6635-6637.
29. Li, P.; Zhang, Y.; Chen, Z.; Zhang, X. Tetrahedron Lett. 2017, 58,
1854-1858.
12. (a) Zhdankin, V. V.; Kuehl, C. J. ; Krasutsky, A. P.; BOG, J. T.;
Mismashl, B.; Woodwardl, J. K.; Simonseal, A. J. Tetrahedron
Letters 1995, 36, 7975-7978. (b) Murahashi, S.; Komiya, N.;
Terai, H.; Nakae, T. J. Am. Chem. Soc. 2003, 125, 15312-15313.
(c) Murahashi, S.; Komiya, N.; Terai, H. Angew. Chem. Int. Ed.
2005, 44, 6931-6933. (d) Singhal, S.; Jain, S. L.; Sain, B. Chem.
Commun. 2009, 2371-2372. (e) Zhang, Y.; Peng, H.; Zhang, M.;
Cheng, Y.; Zhu, C. Chem. Commun. 2011, 47, 2354-2356. (f)
Rueping, M.; Zhu, S.; Koenigs, R. M. Chem. Commun. 2011, 47,
12709-12711. (g) Liu, P.; Liu, Y.; Wong, E.; Xiang, S.; Che, C.
Chem. Sci. 2011, 2, 2187-2195. (h) Alagiri, K.; Prabhu, K. R.
Org. Biomol. Chem. 2012, 10, 835-842. (i) Reddy, K. H. V.;
Satish, G.; Reddy, V. P.; Anil Kumar, B. S. P.; Nageswar, Y. V.
D. RSC Advances 2012, 2, 11084-11088. (j) Kumar, S.; Kumar,
P.; Jain, S. L. RSC Adv. 2013, 3, 24013-24016. (k) Panwar, V.;
Ray, S. S.; Jain, S. L. Tetrahedron Letters 2015, 56, 4184-4186.
(l) Legacy, C. J.; Wang, A.; O‘Day, B. J.; Emmert, M. H. Angew.
Chem. Int. Ed. 2015, 54, 14907-14910. (m) Verma, S.; Nasir Baig,
R. B.; Han, C.; Nadagouda, M. N.; Varma, R. S. Chem. Commun.
2015, 51, 15554-15557. (n) Zheng, Y.; Mao, J.; Chen, J.; Rong,
G.; Liu, D.; Yan, H.; Chi, Y.; Xu, X. RSC Adv. 2015, 5, 50113-
50117. (o) Patil, M.; Kapdi, A. R.; Kumar, A. V. RSC Adv. 2015,
5, 54505-54509. (p) Wagner, A.; Ofial, A. R. J. Org. Chem. 2015,
80, 2848-2854. (q) Zhang, L.; Gu, X.; Lu , P.; Wang, Y.
30. Shen, Z. L.; Ji, S. J.; Loh, T.P. Tetrahedron 2008, 64, 8159-8163.
31. Chaturvedi, D.; Chaturvedi, A. K.; Mishra, N.; Mishra, V.
Tetrahedron Lett. 2012, 53, 5398-5401.
32. Khan, N. H.; Agrawal, S.; Kureshy, R. I.; Abdi, S. H. R.; Singh,
S.; Suresh, E.; Jasra, R. V. Tetrahedron Lett. 2008, 49, 640-644.
33. Surendra, K.; Krishnaveni, N. S.; Mahesh, A.; Rao, K. R. J. Org.
Chem. 2006, 71, 2532-2534.
34. Cioc, R. C.; Preschel, H. D.; Heijden, G. V. D.; Ruijter, E.; Orru,
R. V. A. Chem. Eur. J. 2016, 22, 7837-7842.
35. Maihi, A.; Kim, S. S.; Kadam, S. T. Tetrahedron 2008, 64, 5509-
5514.
Supplementary Material
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic