Application of pentacoordinated spirophosphorane as a new organocatalyst for the Michael addition reaction

Article abstract of DOI:10.1080/10426507.2021.1946062

Pentacoordinated spirophosphorane as a simple, effective and novel organocatalyst for the Michael addition reaction has been investigated. The bisaminoacyl spirophosphorane that possessed a thiourea-like moiety and an amine group was applied to the Michae

Full text of DOI:10.1080/10426507.2021.1946062

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Application of pentacoordinated
spirophosphorane as a new organocatalyst for the
Michael addition reaction
Peipei Wang, Wanjiao Li, Kehui Han, Yanchun Guo, Yufen Zhao & Shuxia Cao
To cite this article: Peipei Wang, Wanjiao Li, Kehui Han, Yanchun Guo, Yufen Zhao & Shuxia
Cao (2021): Application of pentacoordinated spirophosphorane as a new organocatalyst for
the Michael addition reaction, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2021.1946062
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2021.1946062
Application of pentacoordinated spirophosphorane as a new organocatalyst
for the Michael addition reaction
a
a
a
a
a,b
a
Peipei Wang , Wanjiao Li , Kehui Han , Yanchun Guo , Yufen Zhao , and Shuxia Cao
a
b
College of Chemistry, Zhengzhou University, Zhengzhou, PR China; Institute of Drug Discovery Technology, Ningbo University, Ningbo,
PR China
ABSTRACT
ARTICLE HISTORY
Pentacoordinated spirophosphorane as a simple, effective and novel organocatalyst for the
Michael addition reaction has been investigated. The bisaminoacyl spirophosphorane that pos-
sessed a thiourea-like moiety and an amine group was applied to the Michael addition reaction of
Received 8 February 2021
Accepted 17 June 2021
KEYWORDS
1, 3-dicarbonyl compound with b-nitrostyrene, affording the desired adduct in good yield.
Pentacoordinated spiro-
phosphorane; organocata-
lyst; Michael addition
reaction; catalytic
mechanism; hydrogen
bonds
Furthermore, the mechanism of the Michael addition reaction catalyzed by spirophosphorane was
proposed with the help of the analysis of single crystal structure, NMR experiments. It was identi-
fied that 1, 3-dicarbonyl compound and b-nitrostyrene formed hydrogen bonds with amine group
and N-H groups of spirophosphorane catalyst, respectively. Then the two reactants approached
each other, and the methylene of 1, 3-dicarbonyl compound attacked the olefin carbon of b-nitro-
styrene to form nucleophilic addition product. This report is the first example of spirophosphorane
as a novel organocatalyst to successfully catalyze the Michael addition reaction.
GRAPHICAL ABSTRACT
[
5–8]
1
. Introduction
amino acid, hereinafter abbreviated as AA-HSP.
It is
well known that the thiourea catalyst with two N-H bonds
as hydrogen bond donor is one of the most powerful system
in organocatalytic field. AA-HSP as shown in Scheme 1
Organocatalysis is a kind of catalysis reaction that can be
accelerated by adding a small account of organic com-
[
1–4]
pounds.
In the past few decades, organocatalysis has
(1a–1d) has two N-H groups located on their rigid spiro
become a very important synthetic tool, which is now a
complement to organometallic catalysis, although organo-
metallic catalysis has been widely applied in many fields. It
is well known that the catalytic effect of some metal catalyst
is greatly affected by water and oxygen, and enzyme catalysis
is influenced by acid and base in the reaction system.
However, organocatalysis typically has the advantages of
mild reaction conditions, easy recovery of the catalyst and
environmentally friendly processes. Therefore, organocatalyst
skeleton, which is similar to the structure of thiourea, so it
can be inferred to act as a hydrogen bond donor to activate
substrate. Nowadays, most organic catalyst in use is bifunc-
[9]
tional, usually with acid and Lewis base sites,
and a
bifunctional catalyst leads to a considerable acceleration of
reaction rate by the activation of donor and acceptor.
Considering recent success using AA-HSPs to synthesize a
series of spirophosphorane derivatives in our labora-
[
10–15]
tory,
we envisaged that the P-H bond of AA-HSP was
becomes a third type of catalyst after metal and enzyme well suited for the introduction of new functional group
catalyst, and has been widely used in organic synthesis.
containing activation sites. Therefore, spirophosphorane
Hydrospirophosphorane (HSP) is a type of pentacoordi- derivatives with bifunctional groups might be designed and
nated phosphorus compound with P-H bond. The penta- synthesized to act as
prospective organocatalyst.
a
coordinated bisaminoacyl spirophosphorane with a P-H Furthermore, different pentacoordinated phosphorus config-
bond is a special type of HSP, which is synthesized from urations of AA-HSP might provide more selectivity for
CONTACT Yanchun Guo
ycguo@zzu.edu.cn; Shuxia Cao
csx@zzu.edu.cn
College of Chemistry, Zhengzhou University, Zhengzhou 450052, PR China.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2021.1946062.
ß 2021 Taylor & Francis Group, LLC

2
P. WANG ET AL.
Scheme 1. Structures of pentacoordinated spirophosphorane catalyst.
catalytic processes. It is worthy to note that simple synthesis analogous N-H functional group, they have two types of
process, mild reaction condition and long-time stable stor- phosphorus configurations, which might bring unexpected
age of pentacoordinated spirophosphoranes make them selectivity and catalytic activity for the Michael addition
attractive to be used as a potential organocatalyst.
reaction. Therefore, spirophosphorane molecules with differ-
Compared with the structure of thiourea catalyst, the ent phosphorus configurations were also prepared.
feasibility of bisaminoacyl spirophosphorane derivatives as a
The AA-HSPs 1a–1d (Scheme 1) were synthesized from
new organocatalysis framework was investigated. Since thio- L-valine and L-phenylalanine according to the literature.
[
5]
urea derivatives are often used to catalyze the Michael add- They had two N-H bonds on the spiro-ring, which was
ition reaction, the reaction of 1, 3-dicarbonyl compound similar to N-H bond of thiourea. Our group has investigated
and b-nitrostyrene catalyzed by bisaminoacyl spirophosphor- the reactivity of N-H bond of spirophosphoranes by H/D
[
20]
anes was firstly studied. Moreover, the catalytic mechanism exchange and NMR experiments.
The results showed that
of the Michael addition reaction was proposed by the ana- the reactivity of N-H bond was influenced by steric hin-
drance and the substituents at phosphorus atom. In add-
ition, when we investigated the CO2 insertion reaction
related to pentacoordinated P-C bond, the N-H bond of the
product could participate in the reaction unexpectedly, and
spirophosphorane 1e was obtained. Here, it was used to
explore the effect of N-H site in catalytic process. It was
reported that bifunctional catalyst usually has both a thio-
urea moiety and an amine group on a chiral scaffold to
achieve remarkably catalytic activity in the Michael addition
lysis of single crystal structure, NMR experiments. The
investigation of pentacoordinated bisaminoacyl spirophos-
phorane as a new type of small molecular organocatalyst
would enrich the type of organocatalyst and expand the
application of pentacoordinated spirophosphorane.
2
. Results and discussion
2.1. Synthesis of pentacoordinated spirophosphorane
[
16–19]
reaction.
The bifunctional catalyst could activate both
organocatalysts
b-nitrostyrene and nucleophile, and sometimes even control
At present, a bifunctional thiourea catalyst is often used in the approach direction of nucleophile to b-nitrostyrene. On
the Michael addition reaction by dual functional activation the basis of this concept, bifunctional spirophosphoranes
of substrates. According to the mechanism of bifunctional 1f–1m with an amine group as a hydrogen bond receptor
thiourea catalysis, an effective catalyst needs not only two were synthesized as shown in Scheme 1. The derivatives
N-H sites as hydrogen bond donors, but also another activa- 1f–1i with new P-O bond were produced by the Atherton-
[
16–19]
tion site as a hydrogen bond receptor.
concept, a series of bifunctional spirophosphorane catalysts lines.
were designed and synthesized from AA-HSPs. Obviously, by P-alkylation reaction following literature method.
Based on this Todd-type reaction of AA-HSP 1a–1d with 3-hydroxylani-
[
10,21]
Spirophosphoranes 1j and 1k were synthesized
[
11]
pentacoordinated spirophosphoranes have different struc- Spirophosphorane derivatives 1l and 1m were prepared
tural characteristics from thiourea derivatives. In addition to from diethylamine by a CO2 insertion reaction into the

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Table 1. Optimization of the reaction conditions.
o
a
Entry
Solvent
CH OH
CHCl
CH CN
DMSO
THF
T ( C)
The amount of catalyst (mmol%)
Additive
The amount of additive (equ.)
Yield (%)
1
2
3
4
5
6
7
8
9
3
20
20
20
20
20
20
20
ꢀ15
10
30
40
80
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
15
15
15
15
15
15
15
15
15
15
15
15
15
5
30
20
25
10
10
10
10
10
10
10
10
10
10
10
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
3
N
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.25
1.5
2.0
2.5
1.0
1.0
1.0
1.0
1.0
1.0
14
25
19
26
32
29
50
28
30
51
53
32
55
34
28
38
32
56
47
45
32
24
58
65
41
34
35
32
3
3
2 2
CH Cl
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
Et
(CH
DBU
CO
CO
2
NH
CH
3
2
)
2
NH
2
K
Cs
2
3
2
3
Isolated yield.
[
12]
pentacoordinate P–N bond developed by our group.
the influence of catalyst loading was examined, and the
Among them, spirophosphoranes 1f–1k were first synthe- results showed that 10 mmol% of catalyst was the most suit-
sized for the investigation of their catalytic effects.
able ratio (entries 13–18). Similarly, increasing or reducing
the amount of Et N weakened activation ability of catalyst
3
(
entries 18–23). Moreover, it could be seen diethylamine
2.2. Optimization of reaction conditions
was an ideal additive for the Michael addition reaction cata-
In order to optimize the reaction conditions, 1a as an orga- lyzed by spirophosphorane (entries 23–28). Therefore, using
nocatalyst was initially examined for the Michael addition 10 mmol% of catalyst and 1 equivalent amount of diethyl-
reaction between b-nitrostyrene 2a and diethyl malonate 3a. amine as an additive provided the most suitable environ-
Firstly, taking Et N as an additive, various solvents were ment for this reaction.
3
screened. As shown in Table 1, the catalytic efficiency of 1a
Subsequently, the effect of different catalysts was investi-
significantly depended on the solvent used. Protic solvents gated, and the results were listed in Table 2. The Michael
and polar solvents, which might reduce the activity of 1a, addition reaction between b-nitrostyrene 2a and diethyl
resulted in poor yields of product 4a. It was presumed that malonate 3a only gave 31% yield in the absence of spiro-
the hydrogen bond interaction between spirophosphorane phosphorane catalyst (entry 14). However, even using AA-
and nitro group of substrate might be weakened by H-bond- HSP 1a–1d as a catalyst, the target products were obtained
[
22]
ing acceptor or donor solvent (entries 1–6).
As expected, with good yields (entries 1–4). It proved that the substrates
toluene without H-bonding acceptor or donor sites effi- could be actually activated by spirophosphorane AA-HSP,
ciently promoted the reaction and gave a better yield (entry although AA-HSP only had N-H activation site. Considering
7
). Accordingly, toluene was chosen to be the best solvent the concept of bifunctional catalyst, organocatalysts 1f–1m
for further investigation. By changing the reaction tempera- bearing an amine group achieved better yields as expected
ꢁ
ꢁ
ture from ꢀ15 C to 80 C, the yield of the desired adduct (entries 6–13). On the whole, the catalytic effect of bifunc-
ꢁ
reached the maximum 55% at 60 C (entries 7–13). Next, tional catalyst 1f–1m was better than that of single

4
P. WANG ET AL.
Table 2. The Michael addition reaction of 2a and 3a with various catalyst 1x.
a
Entry
Catalyst 1x
Yield (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
65
55
61
48
36
90
77
60
65
66
63
71
85
31
1
1
1
1
1
a
0
1
2
3
4
no catalyst
Isolated yield.
functional catalyst 1a–1d. Finally, the highest yield of the 2.4. Proposed mechanism of the Michael addition
desired product was obtained utilizing catalyst 1f. Therefore,
the spirophosphorane skeleton with bifunctional activation
sites proved to be more effective for the Michael addition
reaction. Then, the optimal conditions of the Michael add-
ition reaction were determined to be using 10 mmol% of 1f
as a catalyst, 1 equivalent amount of diethylamine as addi-
reaction catalyzed by spirophosphorane
[
17,23]
As reported in the literature,
diethyl malonate could be
easily deprotonated by a tertiary amine moiety, and b-nitro-
styrene could be activated by a thiourea moiety through
hydrogen bond interaction simultaneously, furnishing the
corresponding vinylogous carbanion. Through a subsequent
cyclization sequence, the desired final product could be
smoothly obtained. Based on this process, N-H group on
five-membered ring of 1f–1m was presumed to form a
hydrogen bond with b-nitrostyrene, and amine group of
1f–1m might activate diketone at the same time. Finally, spi-
rophosphoranes 1f–1m as a bifunctional catalyst, which pos-
sessed both two N-H groups and an amine group, were
possible to be effective to catalyze the Michael add-
ition reaction.
ꢁ
tive in toluene at 60 C.
2.3. The Michael addition reaction of 1,3-dicarbonyl
compound with b-nitrostyrene
With the optimal conditions in hand, the substrate scope of
the Michael addition reaction of 1, 3-dicarbonyl compound
with b-nitrostyrene catalyzed by spirophosphorane 1f was
examined (Table 3). When a bulkier ester group was intro-
duced to malonate, such as tert-butyl ester, the reaction
exhibited lower yield (entries 1–4). The results revealed that
the bulk of ester group of malonate apparently influenced
the yield of addition adduct. If a-substituted malonate was
employed as a nucleophile in the Michael reaction, various
products bearing a quaternary carbon center would be
obtained. For example, when dimethyl methylmalonate or
diethyl 2-chloromalonate as a nucleophile was applied to the
present catalytic system, the reaction proceeded smoothly to
To verify our conjecture and evaluate the actual three-
dimensional structure of spirophosphoranes 1f–1m, the sin-
gle crystal of spirophosphorane catalyst was cultivated by
different methods. Although the single crystal of 1f was not
prepared, the single crystal structure of 1g was obtained.
(
Tables S 1 – S 4, Supplemental Materials). Based on the
X-ray analysis of 1g (Figure 1), it could be seen that the
orientation of two N-H bonds of 1g was spatially pointing
in the opposite directions. As shown in Figure 1, the direc-
tion of N(1)-H was approximately toward the front of the
paper and the direction of N(2)-H was approximately
give the desired adduct in good yield (entries 5, 6). toward the back of the paper. Furthermore, the angle of
ꢁ
Furthermore, the results showed that the position and the P(1)-O(5)-C(11) was determined to be 123.8 , and then ter-
electronic property of substituents on the aromatic ring of tiary amine group -N(3)Et on the meta position of the ben-
2
nitroalkene were well tolerated by the Michael addition reac- zene ring was closer to N(1)-H bond compared with the
tion. Whether electron-withdrawing (entries 7–9, 13, 14), distance to N(2)-H bond. Therefore, as shown in Figure 1, a
electron-donating (entries 10, 12), or electron-neutral (entry cavity composed of an N(1)-H bond, a P(1)-O(5) bond, a
1
1) groups were on the aromatic ring, the reactions pro- benzene ring, and a tertiary amine group -N(3)Et2 was
vided the product 4a in moderate to good yields (65–86%). formed, which might provide an active region to catalyze

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
Table 3. The Michael addition reaction of nitroolefin 2 and malonate 3 catalyzed by 1f.
1
2
3
4
a
Entry
R
R
R
R
Adduct
Yield (%)
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
F
Cl
NO
OCH
CH
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OCH
Cl
Et
H
H
H
H
Me
Cl
H
H
H
H
H
H
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
85
70
65
60
79
90
67
65
72
68
65
75
71
86
Me
i
Pr
t
Bu
Me
Et
i
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
i
i
2
i
1
1
1
1
1
a
0
1
2
3
4
3
i
3
i
3
i
i
NO
2
H
Isolated yield.
the tertiary amine group of 1f might form hydrogen bonds
to activate b-nitrostyrene and diketone, respectively. It was
presumed that 1f could act as a hydrogen bond donor and a
hydrogen bond acceptor similar to thiourea derivatives. To
identify the hydrogen bond between catalyst 1f and reaction
1
substrates, we collected the H NMR spectrum of spirophos-
phonane 1f in the presence of b-nitrostyrene 2a, diethyl
6
malonate 3a, and additive diethylamine in DMSO-d accord-
ing to the reaction ratio. Then, the spectra of 1f (Figure 2A)
and 3a (Figure 2B) were compared with the spectrum of
reaction mixture (Figure 2C). Although there was only a lit-
1
tle change in the H NMR spectrum of reaction mixture, the
change revealed some information about hydrogen bond
interaction between 1f and the substrates. It was observed
that the chemical shift of N-H proton of 1f, which was split
by phosphorus atom and exhibited doublet, shifted from
Figure 1. X-ray crystal structure of 1g (Thermal ellipsoids are drawn at the 30%
probability level).
the substrates simultaneously. Although the single-crystal of 6.11 to 6.17 ppm as shown in enlarged images, while other
other catalyst had not been obtained, the analogues of peaks did not change. It was speculated that N-H proton of
[
21]
[11]
[12]
1h,
1j,
1l
had been reported. The other catalysts catalyst 1f was one of reaction sites, acting as a hydrogen
were presumed to be structurally similar to 1g. Therefore, bond donor to interact with the nitro group of 2a, so the
they might also have an activating cavity in the spatial struc- chemical shift of N-H proton changed. In addition, the
tures, which could catalyze the reaction substrates by N-H chemical shift of methylene of 3a shifted from 3.48 to
and amine site. In short, the X-ray analysis of catalyst 1g 3.46 ppm after mixing with 1f and 3a. Although the chem-
further illustrated that the structures of 1f–1m could provide ical shift changed little, the peak width of methylene broad-
two active sites in one cavity to catalyze the reac- ened significantly from 0.01 to 0.2 ppm as shown in
tion substrates.
enlarged images. This suggested that the methylene of 3a
To obtain further information about the reaction mech- might have a resonance structure between ketone form and
anism, the reaction process catalyzed by spirophosphonane enol form during the reaction. The result was consistent
31
1
f was monitored by P NMR tracing experiments (Figure with our hypothesis that the enol form of 3a formed a
S 1, Supplemental Materials). The results showed that phos- hydrogen bond with the nitrogen atom of tertiary amine
phorus signal did not change, so the structure of spirophos- group of catalyst 1f.
phonane 1f should be well maintained during the reaction.
Furthermore, the effects of solvent also elucidated the
The reaction was speculated to be indeed catalyzed through formation of hydrogen bonds between catalyst and sub-
the weak interaction rather than the formation of new strates as shown in Table 1. In nonpolar toluene as the solv-
chemical bond. As previously mentioned, N-H groups and ent, the catalyst efficiently promoted the reaction to afford

6
P. WANG ET AL.
1
Figure 2. The H NMR spectra of 1f (A), 3a (B) and the mixture (C) of 1f, 2a, 3a and Et
2
NH in DMSO.
adduct 4a in moderate yield. In contrast, the yields of 4a effect on the yield was achieved. Although the effect of pen-
were apparently low in polar solvents (CH OH, CH CN), tacoordinated phosphorus configuration on the Michael
3
3
since the solvation of nitro group of 2a might disturb the addition reaction was not clarified at this stage, we assumed
hydrogen bond between the catalyst and 2a. Therefore, that it might bring some selectivity for asymmetric Michael
hydrogen bonds between catalyst and substrates were the addition reaction in the future.
main interaction mode in the Michael addition reaction. In
Based on the analysis of single crystal structure of 1g,
the case of the effect of structure of spirophosphoranes as NMR experiments and the comparison of catalytic results by
shown in Table 2, the results indicated that both N-H group different spirophosphoranes, a plausible reaction cascade
[
24–26]
and amine group were indispensable moieties for catalyst. was proposed in Scheme 2.
Taking catalyst 1f as an
On the whole, the catalytic effect of bifunctional catalyst example, the tertiary amine group of 1f could firstly deprot-
1
1
f–1m was better than that of single functional catalyst onate the acidic proton of diethyl malonate 3a through
a–1d. It implied that the amine group promoted the cata- hydrogen-bond interaction, generating the complex I of 3a
lytic activity of spirophosphoranes. Moreover, spirophos- and 1f. The enol form as a resonance structure of 3a had
phorane 1e had a special structure, that the hydrogen been identified by NMR spectra as previously mentioned. At
attached to the nitrogen atom on five-membered ring was about the same time, b-nitrostyrene 2a interacted with cata-
substituted by benzyl group. With 1e as a catalyst, the reac- lyst 1f through the hydrogen bonding between nitro group
tion provided desired adduct 4a in only 36% yield (Table 2, and N-H proton on five-membered ring, and a ternary com-
entry 5). Apparently, the result of 1e indicated that the N-H plex II was formed. Thus, the reactants 2a and 3a
group on five-membered ring was an essential factor for spi- approached each other in one cavity composed by N-H
rophosphorane catalyst to catalyze the Michael addition bond, benzene ring and tertiary amine group. Next, the
reaction. Comparing the catalytic result of 1f and 1h with methylene of 3a attacked the olefin carbon of b-nitrostyrene,
the same tertiary amino group and phosphorus configur- forming the complex III. Finally, the hydrogen bond
ation, it was found that the substituent on five-membered between N-H group of catalyst 1f and nitro group of 2a was
ring also had a significant effect on the addition reaction cleaved, and the nitronate captured the proton from the
amino group of catalyst to produce 4a along with cata-
lyst 1f.
(
Table 2, entries 6, 8). When a bulkier benzyl group replaced
an isopropyl group adjacent to the N-H group of catalyst,
the yield of 4a decreased from 90% to 60%. It implied that
steric hindrance around the N-H group was indeed related
to the catalytic activity of spirophosphorane. In this context,
3. Conclusions
it could be concluded that the N-H sites and amine site of In summary, pentacoordinated spirophosphorane as a sim-
spirophosphorane catalysts played a vital role on this cata- ple, effective and novel organocatalyst for the Michael add-
lytic process. Subsequently, the catalytic results of spirophos- ition reaction has been investigated. Firstly, a variety of
phorane catalysts with different phosphorus configuration novel bifunctional spirophosphorane catalysts that possess a
were also compared (entry 8/9, 10/11, 12/13), but no special thiourea-like moiety and an amine group were synthesized.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
7
Scheme 2. The proposed mechanism of the Michael addition reaction catalyzed by spirophosphorane 1f.
Then, the Michael addition reaction of 1, 3-dicarbonyl com- with 85% H PO as the internal standard. Melting points
3
4
pound and b-nitrostyrene in the presence of bifunctional were determined with a XT-4 micro melting point appar-
catalyst 1f–1m was investigated, obtaining the desired atus. ESI-HRMS was performed on a Q-TOF mass spec-
adduct in good yields ranging from 60% to 90%. trometer (Waters, Manchester, UK). The crystal data was
Furthermore, the mechanism of the Michael addition reac- collected on an Oxford Gemini E diffractometer. The
1
13
31
tion catalyzed by spirophosphorane catalysts was proposed Supplemental Materials contains sample H, C and
P
by the analysis of single crystal structure and NMR experi- NMR spectra of novel products 1 and 4 (Figures S 2 –
ments. The N-H sites and amine site of spirophosphorane S 28).
were testified to be necessary for the catalytic process. The
Michael addition reaction was catalyzed by spirophosphor-
4
.1. Synthesis of spirophosphorane catalysts
ane catalyst through hydrogen bonds between catalyst and
substrates. It was identified that 1, 3-dicarbonyl compound
and b-nitrostyrene formed hydrogen bond with amine group
and N-H groups of spirophosphorane catalyst, respectively.
Then two reactants approached each other in one cavity,
and the methylene of 1, 3-dicarbonyl compound attacked
the olefin carbon of b-nitrostyrene to form nucleophilic
addition product. This report is a first example of the suc-
cessful Michael addition reaction catalyzed by spirophos-
phorane as a novel organocatalyst in metal-free conditions.
The investigation of pentacoordinated spirophosphorane as
a new type of small molecular organocatalyst would enrich
the type of organocatalyst and expand the application of
pentacoordinated spirophosphorane.
The AA-HSP 1a, 1b, 1c, 1d and derivatives 1e, 1l and 1m
were prepared according to literature procedures.
[
5,12]
General procedure Preparation of 1fꢂ1i: To a stirred solution
of AA-HSP (0.5 mmol) and 3-(diamino) phenol (0.5 mmol)
in CH CN (5 mL), CCl4 (1 mmol) and Cs CO (3 mmol)
3
2
3
were added. The reaction mixture was stirred at room tem-
31
perature until the P NMR signal of reactant AA-HSP dis-
appeared. Then the reaction solution was filtered and dried
to obtain a crude product. The residue was purified by col-
umn chromatography (PE-EA) to afford the desired prod-
[
10]
ucts 1f, 1g, 1h and 1i.
Preparation of (3S,8S)-5-(3-(dimethylamino)phenoxy)-3,8-dii-
5
sopropyl-1,6-dioxa-4,9-diaza-5k -phosphaspiro[4.4]nonane-
4
. Experimental
2
,7-dione 1f: The general procedure was followed using 1a
1
13
The H NMR and C NMR spectra were recorded in (131 mg, 0.5 mmol) and 3-(dimethylamino) phenol (68.6 mg,
CDCl with tetramethylsilane (TMS) as the internal standard 0.5 mmol). The crude product was purified by column chro-
3
on a Bruker Avance 400 MHz spectrometer operating at matography (silica gel/PE: EA ¼ 8:1) to give 1f as a white
3
1
ꢁ
4
00.13 and 100.61 MHz, respectively. The P NMR spectra solid. MP 187–189 C; FTIR: ꢀ
3308 (N-H) , 2964, 1751
max
ꢀ
1 31
were measured with a Bruker Avance 400 MHz spectrometer (C ¼ O), 1598, 1454 (Ar-H) , 1281, 1227, 829, 657 cm
;
P

8
P. WANG ET AL.
1
ꢁ
NMR (162 MHz, CDCl , H PO ): d ꢀ 54.77 ppm; H NMR
1i: MP 190–191 C; FTIR: ꢀ
3317 (N-H), 2937, 1751
max
3
3
4
ꢀ
1 31
(
400 MHz, CDCl , TMS): d (ppm) 0.96 (d, 6H, J ¼ 6.7 Hz, (C ¼ O), 1607, 1498 (Ar-H), 1263, 1001, 856, 693 cm
;
P
3
1
2
2
1
2
ꢃ CH ), 1.02 (d, 6H, J ¼ 6.9 Hz, 2 ꢃ CH ), 2.18–2.21 (m, NMR (162 MHz, CDCl , H PO ): d ꢀ 53.90 ppm; H NMR
3
3
3
3
4
2
H, 2 ꢃ CH), 2.94 (s, 6H, 2 ꢃ CH ), 3.68 (d, 2H, J
¼
(400 MHz, CDCl , TMS): d (ppm) 2.29 (dd, 2H, J ¼ 11.3 Hz,
3
H-N-P
3
6.5 Hz, 2 ꢃ NH), 3.77 (dd, 2H, J ¼ 8.5 Hz, J ¼ 2.9 Hz, J ¼ 13.5 Hz, 1 ꢃ CH ), 3.02 (s, 6H, 2 ꢃ CH ), 3.18 (d, 2H,
2
3
2
ꢃ CH), 6.40–6.42 (2H, Ar-H), 6.52 (d, 1H, J ¼ 8.4 Hz, Ar- J ¼ 13.6 Hz, 1 ꢃ CH ), 3.56 (d, 2H,
J
¼ 17.5 Hz,
2
H-N-P
13
H), 7.15 (t, 1H, J ¼ 8.0 Hz, Ar-H); C NMR (100 MHz, 2 ꢃ NH), 3.95–4.02 (m, 2H, 2 ꢃ CH), 6.54–6.62 (m, 3H, Ar-
1
3
CDCl , TMS): d (ppm) 16.4, 19.0, 30.7 (d, J ¼ 6.4 Hz), 40.4, H), 7.14–7.15 (m, 4H, Ar-H), 7.28–7.37 (m, 7H, Ar-H);
C
3
2
6
1
1
0.1 (d,
J
¼ 3.3 Hz) , 105.3 (d, J ¼ 5.1 Hz), 108.7, NMR (100 MHz, CDCl
3
, TMS): d (ppm) 39.6 (d, J ¼ 3.6 Hz),
C-N-P
2
09.2, 129.9 (d, J ¼ 2.1 Hz), 151.8, 152.5 (d, J ¼ 10.2 Hz), 40.5, 56.2 (d, JC-N-P ¼ 5.6 Hz), 109.7, 127.4, 129.0, 129.1,
2
þ
2
69.3 (d, J
¼ 11.5 Hz); HRMS (ESI): m/z [M þ H] , 129.4, 130.0, 136.5,152.1, 152.2, 169.2 (d,
J
C(O)-O-P
¼
C(O)-O-P
þ
þ
calcd for C H N O P 398.1839, found 398.1844.
11.9 Hz); HRMS (ESI): m/z [M þ H] , calcd for
1
8
19 3 5
þ
C H N O P 484.1839, found 494.1846.
2
6
29
3
5
Preparation of (3S,8S)-5-(3-(diethylamino)phenoxy)-3,8-diiso-
5
propyl-1,6-dioxa-4,9-diaza-5k -phosphaspiro[4.4]nonane-2,7-
Preparation of 2-((3S,8S)-3,8-diisopropyl-2,7-dioxo-1,6-dioxa-
5
dione 1g: The general procedure was followed using 1b 4,9-diaza-5k -phosphaspiro[4.4]nonan-5-yl)-N,N-diethylaceta-
131 mg, 0.5 mmol) and 3-(diethylamino) phenol (82.6 mg, mide 1j and 2-((3S,8S)-3,8-diisopropyl-2,7-dioxo-1,6-dioxa-
.5 mmol). The crude product was purified by column chro- 4,9-diaza-5k -phosphaspiro[4.4]nonan-5-yl)-N,N-diethylaceta-
(
0
5
matography (silica gel/PE: EA ¼ 5:1) to give 1g as a white mide 1k: To a stirred solution of compounds 1a (131 mg,
ꢁ
solid. MP 135–136 C; FTIR: ꢀ
3280 (N-H), 2963, 1732 0.5 mmol) and 2-chloro-N, N-diethylacetamide (74.8 mg,
max
ꢀ
1
31
1
(
(
(
C ¼ O), 1606, 1506, 1270, 836, 655 cm
;
P NMR 0.5 mmol) in CH
CN (5 mL), TBAI (2 mmol) and Cs CO
3 2 3
162 MHz, CDCl , H PO ): d ꢀ 54.47 ppm;
H
NMR (3 mmol) were added. The reaction mixture was stirred at
3
3
4
31
400 MHz, CDCl , TMS): d (ppm) 0.96 (d, 6H, J ¼ 6.8 Hz, room temperature until the P NMR signal of reactant 1a
3
2
ꢃ CH ), 1.02 (d, 6H, J ¼ 7.0 Hz, 2 ꢃ CH ), 1.16 (t, 6H, disappeared. Then the reaction solution was filtered and
3
3
J ¼ 7.04 Hz, 2 ꢃ CH ), 2.18–2.22 (m, 2H, 2 ꢃ CH), 3.32 (q, dried to obtain a crude product. The residue was purified by
3
2
4
2
H, J ¼ 7.08 Hz, 2 ꢃ CH ), 3.65 (d, 2H, J
¼ 15.96 Hz, column chromatography (silica gel/PE: EA ¼ 2:1) to give 1j
[11]
2
H-N-P
ꢃ NH), 3.77 (dd, 2H, J ¼ 8.4 Hz, J ¼ 2.6 Hz, 2 ꢃ CH), 6.32 and 1k as a white solid.
ꢁ
(
7
d, 2H, J ¼ 6.5 Hz, Ar-H), 6.46 (d, 1H, J ¼ 8.1 Hz, Ar-H),
1j: MP 130–132 C; FTIR: ꢀmax 3361 (N-H), 2981, 2918,
1
3
ꢀ1 31
.11 (t, 1H, J ¼ 8.4 Hz, Ar-H); C NMR (100 MHz, CDCl , 1750 (C ¼ O), 1642, 1506, 1270, 1235, 809 cm ;1 P NMR
3
TMS): d (ppm) 12.5, 16.4, 19.1, 30.7 (d, J ¼ 6.5 Hz), 44.4, (162 MHz, CDCl
,
H
PO
): d ꢀ 50.66 ppm;
H
NMR
3
3
4
2
6
0.1 (d, J
¼ 3.4 Hz), 104.6, 107.7, 108.7, 130.1, 149.2, (400 MHz, CDCl
3
, TMS): d (ppm) 0.94 (d, 6H, J ¼ 6.8 Hz,
), 1.11 (t, 3H,
), 1.21 (t, 3H, J ¼ 7.2 Hz, 1 ꢃ CH ),
C-N-P
2
1
(
52.7 (d, J ¼ 10.2 Hz), 169.3(d, J
¼ 11.2 Hz); HRMS 2 ꢃ CH
3
), 1.01 (d, 6H, J ¼ 7.0 Hz, 2 ꢃ CH
3
C(O)-O-P
þ
þ
ESI): m/z [M þ H] , calcd for C H N O P 426.2152, J ¼ 7.0 Hz, 1 ꢃ CH
20
33 3 5
3
3
found 426.2157.
2.13–2.20 (m, 2H, 2 ꢃ CH), 3.12–3.50 (m, 8H, 3 ꢃ CH
,
2
2
ꢃ NH), 3.88 (ddd, 2H, J ¼ 12.2 Hz, J ¼ 3.4 Hz, J ¼ 1.2 Hz),
13
Preparation of (3S,8S)-3,8-dibenzyl-5-(3-(dimethylamino)phe-
C NMR (100 MHz, CDCl , TMS): d (ppm) 12.8, 14.5, 16.7,
3
5
noxy)-1,6-dioxa-4,9-diaza-5k -phosphaspiro[4.4]nonane-2,7- 19.1, 30.8 (d, J ¼ 3.5 Hz), 38.8, 40.6 (d, J ¼ 23.35 Hz), 43.1,
2
dione 1h and (3S,8S)-3,8-dibenzyl-5-(3-(dimethylamino)phe- 60.3 (d, JC-N-P ¼ 3.5 Hz), 166.0 (d, J ¼ 6.3 Hz), 170.3 (d,
5
þ
noxy)-1,6-dioxa-4,9-diaza-5k -phosphaspiro[4.4]nonane-2,7- J ¼ 7.3 Hz); HRMS (ESI): m/z [M þ H] , calcd for
þ
dione 1i: The general procedure was followed using 1d
C
16
H
31
N
3
O
5
P 376.1996, found 376.1995.
ꢁ
(
0
179 mg, 0.5 mmol) and 3-(dimethylamino) phenol (68.6 mg,
1k: MP 130–132 C; FTIR: ꢀmax 3352 (N-H), 2963, 2918,
ꢀ
1
31
.5 mmol). The crude products were purified by column 1750 (C ¼ O), 1624, 1515, 1270, 1226, 800 cm ; P NMR
1
chromatography (silica gel/PE: EA ¼ 5:1) to give 1h and 1i (162 MHz, CDCl
as a white solid.
(400 MHz, CDCl
, TMS): d (ppm) 0.98 (d, 6H, J¼ 6.4 Hz,
h: MP 190–191 C; FTIR: ꢀ
), 1.7 (d, 6H, J¼ 6.6 Hz, 2ꢃ CH ), 1.13 (t, 3H,
P NMR J¼ 6.8 Hz, 1ꢃ CH ), 1.21 (t, 3H, J¼ 6.8 Hz, 1ꢃ CH ),
,
3
H PO ): d ꢀ 49.87 ppm;
3 4
H
NMR
3
ꢁ
1
3316 (N-H), 2918, 1741 2ꢃ CH
3
3
max
ꢀ
1
31
(
(
(
C ¼ O), 1597, 1506 (Ar-H), 1270, 855, 682 cm
;
3
3
1
162 MHz, CDCl , H PO ): d ꢀ 57.05 ppm;
H
NMR 2.19–2.24 (m, 2H, 2ꢃ CH), 3.19–3.67 (m, 10H, 3ꢃ CH
2
,
3
3
4
1
3
400 MHz, CDCl , TMS): d (ppm) 2.72 (dd, 2H, J ¼ 8.4 Hz, 2ꢃ NH, 2ꢃ CH), C NMR (100 MHz, CDCl
, TMS): d
3
3
J ¼ 13.8 Hz, 1 ꢃ CH ), 2.91 (s, 6H, 2 ꢃ CH ), 3.16 (dd, 2H, (ppm) 12.7, 14.4, 17.9, 19.4, 31.1 (d, J¼ 6.1 Hz), 40.4 (d,
2
3
2
2
J ¼ 3.0 Hz, J ¼ 13.8 Hz, 1 ꢃ CH ), 3.54 (d, 2H,
J
¼
J¼ 15.4 Hz), 42.0, 42.9, 60.0 (d, JC-N-P ¼ 2.9 Hz), 165.2 (d,
2
H-N-P
þ
1
2
6.9 Hz, 2 ꢃ NH), 4.00 (dt, 2H, J ¼ 3.6 Hz, J ¼ 8.6 Hz, J¼ 6.1 Hz), 170.3 (d, J¼ 5.9 Hz); HRMS (ESI): m/z [M þ Na] ,
þ
ꢃ CH), 6.28–6.50 (m, 4H, Ar-H), 7.10–7.15 (m, 5H, Ar- calcd for C16
H
30
N
NaO
P 398.1815, found 398.1831.
3
5
1
3
H), 7.29–7.38 (m, 5H, Ar-H); C NMR (100 MHz, CDCl ,
3
2
TMS): d (ppm) 39.3 (d, J ¼ 6.6 Hz), 40.4, 56.0 (d, J
¼
C-N-P
4
.2. Synthesis of 4x by the Michael addition reaction
4
1
.9 Hz), 105.1, 109.3, 127.4, 128.9, 129.4, 129.9, 130.1, 135.9,
2
52.2, 156.7, 169.1 (d, J
m/z [M þ H] , calcd for C H N O P
¼ 11.5 Hz); HRMS (ESI): General procedure: To a stirred solution of nitroolefin 2a
C(O)-O-P
þ
þ
484.1839, (0.5 mmol), malonate 3a (1 mmol) and Et NH (0.5 mmol) in
2
6
29
3
5
2
found 494.1846.
toluene was added catalyst 1f (10mmol%). After being stirred

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
9
ꢁ
at 60 C for 48h, the reaction solution was extracted with (400 MHz, CDCl , TMS): d (ppm) 1.22 (s, 9H, 3 ꢃ CH ),
3
3
dichloromethane and saturated NH Cl solution and dried 1.47 (s, 9H, 3 ꢃ CH ), 3.62 (d, 1H, J ¼ 9.8 Hz, 1 ꢃ CH), 4.12
4
3
with anhydrous Mg SO . The residue was purified by column (dt, 1H, J ¼ 4.3 Hz, J ¼ 9.7 Hz, 1 ꢃ CH), 4.80 (dd, 1H,
2
4
chromatography (PE-EA) to afford the desired product.
J ¼ 9.8 Hz, J ¼ 12.7 Hz, 0.5 ꢃ CH ), 4.93 (dd, 1H, J ¼ 4.3 Hz,
2
13
J ¼ 12.7 Hz, 0.5 ꢃ CH ), 7.23–7.32 (m, 5H, Ar-H); C NMR
2
Preparation of diethyl 2-(2-nitro-1-phenylethyl)malonate (100 MHz, CDCl , TMS): d (ppm) 27.5, 27.9, 43.1, 56.5,
3
[
27]
4
a:
The general procedure was followed using (E)-2-
7
8.3, 82.3, 82.9, 128.2, 128.3, 128.8, 136.6, 166.0, 166.9;
þ
þ
nitrovinyl) benzene (74.6 mg, 0.5 mmol) and diethyl malon-
ate (152 lL, 1 mmol). The crude product was purified by
HRMS (ESI): m/z [M þ Na] , calcd for C H NNaO
19
27
6
3
88.1731, found 388.1731.
column chromatography (silica gel/PE: EA ¼ 15:1) to give
Preparation of dimethyl 2-methyl-2-(2-nitro-1-phenylethyl)-
1
[
18]
4
(
1
a (131.4 mg, 85% yield) as a white solid. H NMR
malonate 4e:
The general procedure was followed using
400 MHz, CDCl , TMS): d (ppm) 1.05 (t, 3H, J ¼ 7.1 Hz,
3
(E)-2-nitrovinyl) benzene (74.6 mg, 0.5 mmol) and dimethyl
methylmalonate (133 lL, 1 mmol). The crude product was
purified by column chromatography (silica gel/PE: EA ¼
ꢃ CH ) 1.27 (t, 3H, J ¼ 7.2 Hz, 1 ꢃ CH ), 3.82 (d, 1H,
3
3
J ¼ 9.3 Hz, 1 ꢃ CH), 4.01 (q, 2H, J ¼ 7.1 Hz, 1 ꢃ CH ),
2
1
4
1
.20–4.27 (m, 3H, 1 ꢃ CH, 1 ꢃ CH ), 4.84–4.95 (m, 2H,
13
2
10:1) to give 4e (116.6 mg, 79% yield) as a white solid. H
ꢃ CH ), 7.23–7.34 (m, 5H, Ar-H); C NMR (100 MHz,
2
NMR (400 MHz, CDCl , TMS): d (ppm) 1.35 (s, 3H,
3
CDCl , TMS): d (ppm) 13.7, 13.9, 42.9, 54.9, 61.8, 62.1, 77.6,
3
1
ꢃ CH ), 3.73 (s, 3H, 1 ꢃ CH ), 3.78 (s, 3H, 1 ꢃ CH ), 4.18
3
3
3
1
[
28.0, 128.3, 128.9, 136.2, 166.8, 167.5; HRMS (ESI): m/z
M þ H] , calcd for C H NO 310.1285, found 310.1287.
(
1
dd, 1H, J ¼ 4.8 Hz, J ¼ 9.6 Hz, 1 ꢃ CH), 5.01–.09 (m, 2H,
þ
þ
6
13
15
20
ꢃ CH ) 7.15–7.31 (m, 5H, Ar-H); C NMR (100 MHz,
2
CDCl , TMS): d (ppm) 20.3, 48.4, 52.8, 53.0, 56.8, 77.5,
3
Preparation of dimethyl 2-(2-nitro-1-phenylethyl)malonate
1
28.5, 128.8, 128.9, 135.0, 170.7, 171.4; HRMS (ESI): m/z
[
27]
4
b:
The general procedure was followed using (E)-2-
þ
þ
[
M þ H] , calcd for C H NO 296.1129, found 296.1131.
14
18
6
nitrovinyl)benzene (74.6 mg, 0.5 mmol) and dimethyl malon-
ate (114 lL, 1 mmol). The crude product was purified by
Preparation of diethyl 2-chloro-2-(2-nitro-1-phenylethyl)malo-
column chromatography (silica gel/PE: EA ¼ 5:1) to give 4b
[29]
nate 4f:
The general procedure was followed using (E)-2-
1
(
98.4 mg, 70% yield) as a white solid. H NMR (400 MHz,
nitrovinyl) benzene (74.6 mg, 0.5 mmol) and diethyl 2-chlor-
omalonate (162.8 lL, 1 mmol). The crude product was puri-
fied by column chromatography (silica gel/PE: EA ¼ 10:1)
CDCl , TMS): d (ppm) 3.56 (s, 3H, 1 ꢃ CH ), 3.76 (s, 3H,
3
3
1
ꢃ CH ), 3.86 (d, 1H, J ¼ 9.0 Hz, 1 ꢃ CH), 4.25 (dt, 1H,
3
J ¼ 5.3 Hz, J ¼ 8.9 Hz, 1 ꢃ CH), 4.85–4.95 (m, 2H, 1 ꢃ CH )
1
2
to give 4f (154.4 mg, 90% yield) as a white solid. H NMR
13
7
.22–7.34 (m, 5H, Ar-H); C NMR (100 MHz, CDCl ,
3
(
400 MHz, CDCl , TMS): d (ppm) 1.11 (t, 3H, J ¼ 7.2 Hz,
3
TMS): d (ppm) 42.9, 52.8, 53.0, 54.8, 77.4, 127.9, 128.4,
þ
1 ꢃ CH
3
) 1.29 (t, 3H, J ¼ 7.1 Hz, 1 ꢃ CH
3
), 3.96–4.11 (m,
), 4.63 (dd, 1H,
2
1
29.0, 136.1, 167.2, 167.8; HRMS (ESI): m/z [M þ H] , calcd
þ
2H, 1 ꢃ CH
2
), 4.26–4.35 (m, 2H, 1 ꢃ CH
for C H NO 282.0972, found 282.0976.
1
3
16
6
J ¼ 3.4 Hz, J ¼ 10.4 Hz, 1 ꢃ CH), 4.99 (dd, 1H, J ¼ 10.4 Hz,
J ¼ 13.5 Hz, 0.5 ꢃ CH ), 5.23 (dd, 1H, J ¼ 3.4 Hz,
2
Preparation of diisopropyl 2-(2-nitro-1-phenylethyl)malonate
1
3
[
28]
J ¼ 13.5 Hz, 0.5 ꢃ CH
2
), 7.30–7.39 (m, 5H, Ar-H);
C
4
c:
The general procedure was followed using (E)-2-
NMR (100 MHz, CDCl , TMS): d (ppm) 13.6, 13.7, 48.2,
3
nitrovinyl) benzene (74.6 mg, 0.5 mmol) and diisopropyl
malonate (190 lL, 1 mmol). The crude product was purified
by column chromatography (silica gel/PE: EA ¼ 15:1) to
6
1
3.5, 63.6, 71.8, 77.3, 128.7, 129.1, 129.3, 133.5, 164.3,
þ
66.0; HRMS (ESI): m/z [M þ H] , calcd for
þ
1
C H ClNO 344.0895, found 344.0898.
1
5
19
6
give 4c (109.6 mg, 65% yield) as a white solid. H NMR
(
1
400 MHz, CDCl , TMS): d (ppm) 1.02 (d, 3H, J ¼ 6.2 Hz,
3
Preparation of diisopropyl 2-(1-(4-fluorophenyl)-2-nitroethyl)-
malonate 4g: The general procedure was followed using (E)-
ꢃ CH ), 1.07 (d, 3H, J ¼ 6.2 Hz, 1 ꢃ CH ), 1.24 (d, 3H,
3
3
J ¼ 6.3 Hz, 1 ꢃ CH ), 1.25 (d, 3H, J ¼ 6.3 Hz, 1 ꢃ CH ), 3.76
3
3
1
-fluoro-4-(2-nitrovinyl)benzene (83.5 mg, 0.5 mmol) and
(
d, 1H, J ¼ 9.6 Hz, 1 ꢃ CH), 4.23 (dt, 1H, J ¼ 4.6 Hz,
J ¼ 9.4 Hz, 1 ꢃ CH), 4.80–4.87 (m, 2H, 1 ꢃ CH, 0.5 ꢃ CH ),
diisopropyl malonate (190 lL, 1 mmol). The crude product
was purified by column chromatography (silica gel/PE: EA
2
4
.93 (dd, 1H, J ¼ 4.6 Hz, J ¼ 12.9 Hz, 0.5 ꢃ CH ), 5.05–5.12
13
2
¼
20:1) to give 4g (119.0 mg, 67% yield) as a white solid.
(
(
m, 1H, 1 ꢃ CH), 7.23–7.33 (m, 5H, Ar-H); C NMR
ꢁ
1
MP 82–84 C; H NMR (400 MHz, CDCl , TMS): d (ppm)
100 MHz, CDCl , TMS): d (ppm) 21.3, 21.3, 21.5, 21.6,
3
3
1
1
.04 (d, 3H, J ¼ 6.2 Hz, 1 ꢃ CH ), 1.08 (d, 3H, J ¼ 6.3 Hz,
4
1
3
2.9, 55.2, 69.5, 69.9, 77.9, 128.1, 128.3, 128.8, 136.3, 166.3,
3
þ
þ
6
ꢃ CH ), 1.24–1.26 (m, 6H, 2 ꢃ CH ), 3.72 (d, 1H,
67.1; HRMS (ESI): m/z [M þ H] , calcd for C H NO
3
3
1
7
24
J ¼ 9.6 Hz, 1 ꢃ CH), 4.20 (dt, 1H, J ¼ 4.5 Hz, J ¼ 9.6 Hz,
ꢃ CH), 4.77–4.88 (m, 2H, 0.5 ꢃ CH , 1 ꢃ CH), 4.91 (dd,
38.1598, found 338.1597.
1
2
Preparation of di-tert-butyl 2-(2-nitro-1-phenylethyl)malonate 1H, J ¼ 4.5 Hz, J ¼ 12.9 Hz, 0.5 ꢃ CH
) 5.05–5.12 (m, 1H,
2
[
17]
4
d:
The general procedure was followed using (E)-2- 1 ꢃ CH), 6.99–7.03 (m, 2H, Ar-H), 7.21–7.25 (m, 2H, Ar-
13
nitrovinyl) benzene (74.6 mg, 0.5 mmol) and di-tert-butyl H); C NMR (100 MHz, CDCl
, TMS): d (ppm) 21.3, 21.4,
3
malonate (223.7 lL, 1 mmol). The crude product was puri- 21.6, 42.2, 55.1, 69.7, 70.0, 77.9, 115.7, 115.9, 129.9 (d,
þ
fied by column chromatography (silica gel/PE: EA ¼ 15:1) J ¼ 8.2 Hz), 132.1, 166.2, 166.9; HRMS (ESI): m/z [M þ H] ,
1
þ
6
to give 4d (109.6 mg, 60% yield) as a white solid. H NMR calcd for C H FNO 356.1504, found 356.1507.
17
23

1
0
P. WANG ET AL.
methyl-4-(2-nitrovinyl)benzene (81.5 mg, 0.5 mmol) and dii-
Preparation of diisopropyl 2-(1-(4-chlorophenyl)-2-nitroethyl)- sopropyl malonate (190 lL, 1 mmol). The crude product was
malonate 4h: The general procedure was followed using (E)- purified by column chromatography (silica gel/PE: EA ¼
1
1
-chloro-4-(2-nitrovinyl)benzene (91.5 mg, 0.5 mmol) and 15:1) to give 4k (114.1 mg, 65% yield) as a white solid. H
diisopropyl malonate (190 lL, 1 mmol). The crude product NMR (400 MHz, CDCl , TMS): d (ppm) 1.03 (d, 3H,
3
was purified by column chromatography (silica gel/PE: EA J ¼ 6.2 Hz, 1 ꢃ CH ), 1.08 (d, 3H, J ¼ 6.2 Hz, 1 ꢃ CH ),
3
3
¼
15:1) to give 4h (120.6 mg, 65% yield) as a white solid. 1.24–1.26 (m, 6H, 2 ꢃ CH ), 2.29 (s, 3H, 1 ꢃ CH ), 3.73 (d,
3
3
ꢁ
1
MP 80–81 C; H NMR (400 MHz, CDCl , TMS): d (ppm) 1H, J ¼ 9.6 Hz, 1 ꢃ CH), 4.16 (dt, 1H, J ¼ 4.6 Hz, J ¼ 9.4 Hz,
3
1
1
.05 (d, 3H, J ¼ 6.2 Hz, 1 ꢃ CH ), 1.09 (d, 3H, J ¼ 6.2 Hz, 1 ꢃ CH), 4.78–4.92 (m, 3H, 1 ꢃ CH , 1 ꢃ CH), 5.05–5.11 (m,
3
2
13
ꢃ CH ), 1.24–1.26 (m, 6H, 2 ꢃ CH ), 3.71 (d, 1H, 1H, 1 ꢃ CH), 7.09–7.13 (m, 4H, Ar-H); C NMR (100 MHz,
3
3
J ¼ 9.5 Hz, 1 ꢃ CH), 4.18 (dt, 1H, J ¼ 4.5 Hz, J ¼ 9.5 Hz, CDCl , TMS): d (ppm) 21.1, 21.3, 21.3, 21.5, 21.6, 42.6, 55.2,
3
1
1
1
ꢃ CH), 4.78–4.87 (m, 2H, 0.5 ꢃ CH , 1 ꢃ CH), 4.91 (dd, 69.5, 69.9, 78.1, 127.9, 129.5, 133.2, 138.0, 166.4, 167.1;
2
þ
þ
H, J ¼ 4.6 Hz, J ¼ 13.0 Hz, 0.5 ꢃ CH ), 5.03–5.13 (m, 1H, HRMS (ESI): m/z [M þ H] , calcd for C H NO
2
18 26
6
ꢃ CH), 7.18–7.20 (m, 2H, Ar-H), 7.28–7.30 (m, 2H, Ar- 352.1755, found 352.1758.
1
3
H); C NMR (100 MHz, CDCl , TMS): d (ppm) 21.3, 21.3,
3
2
1
1.4, 21.6, 42.3, 55.0, 69.8, 70.1, 77.7, 129.1, 129.5, 134.3, Preparation of diisopropyl 2-(1-(2-methoxyphenyl)-2-nitroe-
þ
34.9, 166.1, 166.8; HRMS (ESI): m/z [M þ H] , calcd for thyl)malonate 4l: The general procedure was followed using
þ
C H ClNO 372.1208, found 372.1210.
(E)-1-methoxy-2-(2-nitrovinyl)benzene (89.5 mg, 0.5 mmol)
1
7
23
6
and diisopropyl malonate (190 lL, 1 mmol). The crude product
Preparation of diisopropyl 2-(2-nitro-1-(4-nitrophenyl)ethyl)- was purified by column chromatography (silica gel/PE: EA ¼
[
30]
malonate 4i:
(
The general procedure was followed using 15:1) to give 4l (137.7 mg, 75% yield) as a white solid. MP
ꢁ
1
E)-1-nitro-4-(2-nitrovinyl)benzene (97.0 mg, 0.5 mmol) and 55–57 C; H NMR (400 MHz, CDCl , TMS): d (ppm) 0.97 (d,
3
diisopropyl malonate (190 lL, 1 mmol). The crude product 3H, J¼ 6.2 Hz, 1ꢃ CH ), 1.03 (d, 3H, J¼ 6.2 Hz, 1ꢃ CH ),
3
3
was purified by column chromatography (silica gel/PE: EA 1.24–1.26 (m, 6H, 2 ꢃ CH ), 3.86 (s, 3H, 1 ꢃ CH ), 4.09 (d,
3
3
1
¼
10:1) to give 4i (137.6 mg, 72% yield) as a white solid. H 1H, J¼ 10.5 Hz, 1ꢃ CH), 4.34 (dt, 1H, J¼ 4.2 Hz, J¼ 9.8 Hz,
NMR (400 MHz, CDCl , TMS): d (ppm) 1.07 (d, 3H, 1ꢃ CH), 4.73–4.79 (m, 1H, 1ꢃ CH), 4.86 (dd, 1H, J¼ 4.2 Hz,
3
J ¼ 6.2 Hz, 1 ꢃ CH ), 1.10 (d, 3H, J ¼ 6.3 Hz, 1 ꢃ CH ), J¼ 12.7 Hz, 0.5ꢃ CH ), 4.98–5.11 (m, 2H, 1ꢃ CH, 0.5ꢃ CH ),
3
3
2
2
13
1
1
4
.24–1.26 (m, 6H, 2 ꢃ CH ), 3.77 (d, 1H, J ¼ 9.2 Hz, 6.85–6.87 (m, 2H, Ar-H), 7.13–7.26 (m, 2H, Ar-H); C NMR
3
ꢃ CH), 4.34 (dt, 1H, J ¼ 4.5 Hz, J ¼ 9.4 Hz, 1 ꢃ CH), (100 MHz, CDCl , TMS): d (ppm) 21.2, 21.3, 21.5, 21.6, 40.6,
3
.84–4.92 (m, 2H, 0.5 ꢃ CH , 1 ꢃ CH), 4.97 (dd, 1H, 52.9, 55.4, 69.1, 69.7, 76.4, 111.0, 120.7, 123.7, 129.6, 131.2,
2
þ
J ¼ 4.5 Hz, J ¼ 13.4 Hz, 0.5 ꢃ CH ), 5.06–5.13 (m, 1H, 157.5, 166.7, 167.5; HRMS (ESI): m/z [M þ H] , calcd for
2
þ
1
ꢃ CH), 7.47 (d, 2H, J ¼ 8.7 Hz, Ar-H), 8.20 (d, 2H, C H NO 368.1704, found 368.1706.
18
26
7
1
3
J ¼ 8.7 Hz, Ar-H); C NMR (100 MHz, CDCl , TMS): d
3
(
ppm) 21.3, 21.4, 21.4, 21.6, 42.5, 54.6, 70.1, 70.5, 77.1, Preparation of diisopropyl 2-(1-(2-chlorophenyl)-2-nitroethyl)-
1
[
24.1, 129.3, 143.8, 147.8, 165.9, 166.5; HRMS (ESI): m/z malonate 4m: The general procedure was followed using (E)-
þ
þ
C H N NaO
8
M þ Na] ,
calcd
found 405.1270.
for
405.1268, 1-chloro-2-(2-nitrovinyl)benzene (91.5 mg, 0.5 mmol) and dii-
sopropyl malonate (190 lL, 1 mmol). The crude product was
purified by column chromatography (silica gel/PE: EA ¼
17
22
2
Preparation of diisopropyl 2-(1-(4-methoxyphenyl)-2-nitroe- 10:1) to give 4m (131.7 mg, 71% yield) as a white solid. MP
thyl)malonate 4j:
using (E)-1-methoxy-4-(2-nitrovinyl)benzene
[
30]
ꢁ
The general procedure was followed 52–54 C; H NMR (400 MHz, CDCl , TMS): d (ppm) 1.09
3
1
(89.5mg, (t, 6H, J ¼ 6.1 Hz, 2ꢃ CH ), 1.21 (d, 3H, J ¼ 6.3 Hz, 1ꢃ CH ),
3
3
0
.5 mmol) and diisopropyl malonate (190lL, 1 mmol). The 1.24 (d, 3H, J ¼ 6.2 Hz, 1ꢃ CH ), 4.05 (d, 1H, J ¼ 9.2 Hz,
3
crude product was purified by column chromatography (silica 1ꢃ CH), 4.71 (dt, 1H, J ¼ 4.3 Hz, J ¼ 8.6 Hz, 1 ꢃ CH),
gel/PE: EA ¼ 15:1) to give 4j (124.8 mg, 68% yield) as a white 4.85–4.94 (m, 2H, 1ꢃ CH ), 5.04–5.12 (m, 2H, 2ꢃ CH),
2
1
13
solid. H NMR (400 MHz, CDCl , TMS): d (ppm) 1.04 (d, 7.21–7.26 (m, 3H, Ar-H), 7.39–7.41 (m, 1H, Ar-H); C NMR
3
3
1
1
H, J ¼ 6.2 Hz, 1 ꢃ CH ), 1.08 (d, 3H, J ¼ 6.2 Hz, 1 ꢃ CH ), (100 MHz, CDCl , TMS): d (ppm) 21.2, 21.3, 21.5, 21.6, 39.4,
3
3
3
.24–1.26 (m, 6H, 2 ꢃ CH ), 3.72 (d, 1H, J ¼ 9.7 Hz, 53.4, 69.7, 70.0, 76.0, 127.2, 129.1, 129.4, 130.4, 133.8, 134.2,
3
þ
ꢃ CH), 3.76 (s, 3H, 1 ꢃ CH ), 4.15 (dt, 1H, J ¼ 4.6 Hz, 166.3, 167.0; HRMS (ESI): m/z [Mþ H] , calcd for
3
þ
J ¼ 9.5 Hz, 1 ꢃ CH), 4.76–4.91 (m, 3H, 1 ꢃ CH , 1 ꢃ CH), C H ClNNaClO 394.1031, found 394.1028.
2
17 22
6
5
7
.05–5.11 (m, 1H, 1 ꢃ CH), 6.82–6.84 (m, 2H, Ar-H),
1
3
.15–7.17 (m, 2H, Ar-H); C NMR (100 MHz, CDCl , Preparation of diisopropyl 2-(2-nitro-1-(2-nitrophenyl)ethyl)-
3
TMS): d (ppm) 21.3, 21.4, 21.5, 21.6, 42.3, 55.2, 55.3, 69.5, malonate 4n: The general procedure was followed using (E)-
9.9, 78.2, 114.2, 128.1, 129.3, 159.4, 166.4, 167.1; HRMS 1-nitro-2-(2-nitrovinyl)benzene (97.0 mg, 0.5 mmol) and dii-
6
þ
þ
7
(
ESI): m/z [M þ H] , calcd for C H NO
368.1698, sopropyl malonate (190 lL, 1 mmol). The crude product was
purified by column chromatography (silica gel/PE: EA ¼
1
8
26
found 368.1707.
1
5:1) to give 4n (164.3 mg, 86% yield) as a white solid. MP
ꢁ
1
Preparation of diisopropyl 2-(2-nitro-1-(p-tolyl)ethyl)malonate 50–51 C; H NMR (400 MHz, CDCl , TMS): d (ppm) 1.04
3
[
30]
4
k:
The general procedure was followed using (E)-1- (d, 3H, J ¼ 6.2 Hz, 1ꢃ CH ), 1.09 (d, 3H, J ¼ 6.3 Hz,
3

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
11
1
ꢃ CH ), 1.23–1.26 (m, 6H, 2ꢃ CH ), 4.14 (d, 1H, [11] Ma, W.; Dai, W.; Liu, Q.; Chen, Y.; Zhao, Y.; Cao, S. Synthesis
3
3
of Novel Spirophosphanes Containing a Pentacoordinated P–C
Bond by P-Alkylation Reaction. Tetrahedron 2020, 76,
J ¼ 8.8 Hz, 1ꢃ CH), 4.70 (dt, 1H, J ¼ 4.2 Hz, J ¼ 8.1 Hz,
1
1
ꢃ CH), 4.84–4.90 (m, 1H, 1 ꢃ CH), 5.02–5.18 (m, 3H,
ꢃ CH 1ꢃ CH), 7.46 (dd, 2H, J ¼ 7.8 Hz, J ¼ 18.6Hz, Ar-
1
30886–130897. DOI: 10.1016/j.tet.2019.130886.
2
,
[12] Cao, S.; Gao, P.; Guo, Y.; Zhao, H.; Wang, J.; Liu, Y.; Zhao, Y.
Unexpected Insertion of CO2 into the Pentacoordinate P-N
bond: Atherton-Todd-type reaction of hydrospirophosphorane
with amines. J. Org. Chem. 2013, 78, 11283–11293. DOI: 10.
1021/jo4018342.
H), 7.58 (t, 1H, J ¼ 7.6 Hz, Ar-H), 7.93 (d, 1H, J ¼ 8.1 Hz, Ar-
1
3
H); C NMR (100 MHz, CDCl , TMS): d (ppm) 21.2, 21.3,
3
2
1
1.5, 21.6, 37.8, 53.8, 70.0, 70.2, 76.6, 125.4, 129.2, 129.4,
þ
31.5, 133.2, 150.0, 166.2, 166.9; HRMS (ESI): m/z [Mþ H] ,
[
13] You, X.; Qi, L.; Zheng, J.; Dai, W.; Guo, Y.; Zhao, Y.; Cao, S.
Synthesis and Characterization of New Pyrospirophosphoranes
Containing a P-O-P Bond by the Atherton–Todd Reaction.
Heteroatom Chem. 2015, 26, 168–174. DOI: 10.1002/hc.21243.
þ
calcd for C H N O 383.1449, found 383.1447.
1
7 23 2 8
Disclosure statement
[14] Cao, S.; Zhao, Y. Progress in the Atherton-Todd Reaction and
Its Stereochemical Mechanism. Sci. Sin-Chim. 2015, 45,
No potential conflict of interest was reported by the authors.
283–294. DOI: 10.1360/N032014-00294.
[
[
[
15] Dai, W.; Liu, Q.; You, X.; Zhou, Z.; Guo, Y.; Zhao, Y.; Cao, S.
Synthesis and Characterization of Alkoxy Spirophosphoranes
Prepared from Hydrospirophosphoranes and Sodium
Alcoholates. Heteroatom Chem. 2016, 27, 63–71. DOI: 10.1002/
hc.21302.
16] Peng, F.-Z.; Shao, Z.-H.; Fan, B.-M.; Song, H.; Li, G.-P.; Zhang,
H.-B. Organocatalytic Enantioselective Michael Addition of 2,4-
Pentandione to Nitroalkenes Promoted by Bifunctional
Thioureas with Central and Axial Chiral Elements. J. Org.
Chem. 2008, 73, 5202–5205. DOI: 10.1021/jo800774m.
Funding
This work was funded by the National Natural Science Foundation of
China (No. 21172201).
ORCID
17] Okino, T.; Hoashi, Y.; Furukawa, T.; Xu, X.; Takemoto, Y.
Enantio- and Diastereoselective Michael Reaction of 1,3-
Shuxia Cao
http://orcid.org/0000-0002-4325-5527
Dicarbonyl Compounds to Nitroolefins Catalyzed by
a
Bifunctional Thiourea. J. Am. Chem. Soc. 2005, 127, 119–125.
DOI: 10.1021/ja044370p.
References
[
[
18] Okino, T.; Hoashi, Y.; Takemoto, Y. Enantioselective Michael
Reaction of Malonates to Nitroolefins Catalyzed by Bifunctional
Organocatalysts. J. Am. Chem. Soc. 2003, 125, 12672–12673.
DOI: 10.1021/ja036972z.
19] Hayama, N.; Kuramoto, R.; F o€ ldes, T.; Nishibayashi, K.; Kobayashi,
Y.; P ꢀa pai, I.; Takemoto, Y. Mechanistic Insight into Asymmetric
Hetero-Michael Addition of a,b-Unsaturated Carboxylic Acids
Catalyzed by Multifunctional Thioureas. J. Am. Chem. Soc. 2018,
[
[
[
[
[
1] Dalko, P. I.; Moisan, L. In the Golden Age of Organocatalysis.
Angew. Chem. Int. Ed. Engl. 2004, 43, 5138–5175. DOI: 10.
002/anie.200400650.
2] Palomo, C.; Oiarbide, M.; L ꢀo pez, R. Asymmetric Organocatalysis
by Chiral Brønsted Bases: implications and Applications. Chem.
Soc. Rev. 2009, 38, 632–653. DOI: 10.1039/B708453F.
3] Kaur, J.; Chauhan, P.; Singh, S.; Chimni, S. S. Journey Heading
towards Enantioselective Synthesis Assisted by Organocatalysis.
Chem. Rec. 2018, 18, 137–153. DOI: 10.1002/tcr.201700020.
4] Giacalone, F.; Gruttadauria, M.; Agrigento, P.; Noto, R. Low-
Loading Asymmetric Organocatalysis. Chem. Soc. Rev. 2012, 41,
1
140, 12216–12225. DOI: 10.1021/jacs.8b07511.
[
20] Sun, C.; Cao, S.; Zhao, P.; Ma, W.; Guo, Y.; Zhao, Y. The
Investigation on the NH Reactivity of Pentacoordinate
Spirophosphoranes by H/D Exchange and NMR Experiments.
Tetrahedron Lett. 2018, 59, 3833–3838. DOI: 10.1016/j.tetlet.
2
406–2447. DOI: 10.1039/C1CS15206H.
5] Yu, L.; Liu, Z.; Fang, H.; Zeng, Q. L.; Zhao, Y. F. Synthesis,
Characteristics and Biological Activity of Pentacoordinated
Spirophosphoranes Derived from Amino Acids. Amino Acids.
2018.09.020.
[
21] Han, K.; Wang, Y.; Zhao, P.; You, X.; Wang, J.; Guo, Y.; Zhao,
Y.; Cao, S. Investigation of the Stereochemical Mechanism of
the Nucleophilic Substitution Reaction at Pentacoordinate
Phosphorus of Spirophosphorane. J. Org. Chem. 2021, 86,
2
005, 28, 369–372. DOI: 10.1007/s00726-005-0207-8.
[
6] Hou, J.-B.; Zhang, H.; Guo, J.-N.; Liu, Y.; Xu, P.-X.; Zhao, Y.-
F.; Blackburn, G. M. Chirality at Phosphorus in
Pentacoordinate Spirophosphoranes: stereochemistry by X-Ray
Structure and Spectroscopic Analysis. Org. Biomol. Chem. 2009,
4512–4531. DOI: 10.1021/acs.joc.0c02953.
[
22] Wang, J.; Li, H.; Duan, W.; Zu, L.; Wang, W. Organocatalytic
Asymmetric Michael Addition of 2,4-Pentandione to Nitroolefins.
Org. Lett. 2005, 7, 4713–4716. DOI: 10.1021/ol0519137.
7
, 3020–3023. DOI: 10.1039/b909786d.
[
[
[
7] Yang, G.; Xu, Y.; Hou, J.; Zhang, H.; Zhao, Y. Diastereomers of
the Pentacoordinate Chiral Phosphorus Compounds in Solution:
absolute Configurations and Predominant Conformations. Dalton
Trans. 2010, 39, 6953–6959. DOI: 10.1039/C001872D.
8] Garrigues, B.; Munoz, A.; Koenig, M.; Sanchez, M.; Wolf, R.
Spirophosphoranylation D’a-Aminoacides—I: Preparation et
tautomerie. Tetrahedron 1977, 33, 635–643. DOI: 10.1016/0040-
[
23] Wang, S.-G.; Liu, X.-J.; Zhao, Q.-C.; Zheng, C.; Wang, S.-B.;
You, S.-L. Asymmetric Dearomatization of b-Naphthols
through a Bifunctional-Thiourea-Catalyzed Michael Reaction.
Angew. Chem. Int. Ed. Engl. 2015, 54, 14929–14932. DOI: 10.
1
002/anie.201507998.
24] Hong, B.-C.; Kotame, P.; Lee, G.-H. Asymmetric Synthesis of
,4-Dihydrocoumarin Motif with an All-Carbon Quaternary
[
3
4
020(77)80303-7.
Stereocenter via a Michael-acetalization sequence with bifunc-
tional amine-thiourea organocatalysts. Org. Lett. 2011, 13,
9] Ma, J.-A.; Cahard, D. Towards Perfect Catalytic Asymmetric
Synthesis: Dual Activation of the Electrophile and the
5758–5761. DOI: 10.1021/ol202331j.
Nucleophile. Angew. Chem. Int. Ed. Engl. 2004, 43, 4566–4583. [25] Shi, X.-M.; Dong, W.-P.; Zhu, L.-P.; Jiang, X.-X.; Wang, R.
DOI: 10.1002/anie.200300635.
Asymmetric Vinylogous Michael Addition/Cyclization Cascade
Reaction for the Construction of Diversely Structured Spiro-
Oxindole Skeletons. Adv. Synth. Catal. 2013, 355, 3119–3123.
DOI: 10.1002/adsc.201300329.
[
10] Cao, S.; Guo, Y.; Wang, J.; Qi, L.; Gao, P.; Zhao, H.; Zhao, Y.
Preliminary Stereochemical Investigation of the Atherton–Todd-
Type Reaction between Valine Hydrospirophosphorane and
Phenols. Tetrahedron Lett. 2012, 53, 6302–6305. DOI: 10.1016/j. [26] Concell oꢀ n, C.; Mart ꢀı n, J.; Gallegos, M.; Fanjul-Mosteir ꢀı n, N.;
ꢀ
Costales, A.; Pend ꢀa s, A. M.; del Amo, V. Mimicking Enzymes:
tetlet.2012.09.056.

1
2
P. WANG ET AL.
Asymmetric Induction inside a Carbamate-Based Steroidal Cleft. [29] Garc ꢀı a-Garc ꢀı a, P.; Zagdoun, A.; Cop ꢀe ret, C.; Lesage, A.; D ꢀı az,
Org. Lett. 2019, 21, 3994–3997. DOI: 10.1021/acs.orglett.9b01170.
27] Shumaila, A. M. A. K2CO3/Al2O3: An Efficient and Recyclable
Catalyst under Solvent Free Conditions for the Reaction of
U.; Corma, A. In Situ Preparation of a Multifunctional
Chiral Hybrid Organic–Inorganic Catalyst for Asymmetric
Multicomponent Reactions. Chem. Sci. 2013, 4, 2006–2012.
DOI: 10.1039/c3sc22310h.
[
Electron-Deficient
Nitro-Olefins
with
1,3-Dicarbonyl
Compounds. Cogent Chem. 2018, 4, 1455346–1455354. DOI: [30] Naicker, T.; Arvidsson, P. I.; Kruger, H. G.; Maguire, G. E. M.;
1
0.1080/23312009.2018.1455346.
28] Tsubogo, T.; Yamashita, Y.; Kobayashi, S. Calcium Chloride
CaCl2) as Catalyst for Asymmetric Organic Reactions.
Top. Catal. 2014, 57, 935–939. DOI: 10.1007/s11244-014-
254-z.
Govender, T. Microwave-Assisted Synthesis of Guanidine
Organocatalysts Bearing a Tetrahydroisoquinoline Framework and
Their Evaluation in Michael Addition Reactions. Eur. J. Org.
Chem. 2012, 2012, 3331–3337. DOI: 10.1002/ejoc.201200303.
[
(
0