A Reagent-Controlled Phospha-Michael Addition Reaction of Nitroalkenes with Bifunctional N-Heterocyclic Phosphine (NHP)-Thioureas

Article abstract of DOI:10.1021/acs.joc.6b02490

Bifunctional N-heterocyclic phosphine (NHP)-thioureas have been successfully applied for phospha-Michael addition reaction of nitroalkenes to afford diversely substituted β-nitrodiazaphosphonates. This transformation takes place at room temperature under catalyst-free conditions and exhibits broad functional group tolerance. The key to success in catalyst, additive-free reaction conditions is the suitable hydrogen-bond activation of the nitro group by a Br?nsted acid (thiourea), which artfully combined with the highly nucleophilic NHP motif for a synergetic effect. Importantly, this transformation enables a two-step synthesis of pharmaceutically, biologically significant β-amino phosphonic acids.

Full text of DOI:10.1021/acs.joc.6b02490

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Article
A Reagent-Controlled Phospha-Michael Addition Reaction of Nitroalkenes
with Bifunctional N-Heterocyclic Phosphine (NHP)-Thioureas
Hai Huang, Jake Palmas, and Jun Yong Kang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02490 • Publication Date (Web): 02 Nov 2016
Downloaded from http://pubs.acs.org on November 4, 2016
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The Journal of Organic Chemistry
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A ReagentꢀControlled PhosphaꢀMichael Addition Reaction of Nitroalkenes with Bifunctional Nꢀ
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Heterocyclic Phosphine (NHP)ꢀThioureas
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Hai Huang,†,‡ Jake Palmas,† Jun Yong Kang*,†
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† Department of Chemistry and Biochemistry, University of Nevada Las Vegas, 4505 S. Maryland
Parkway, Las Vegas, Nevada, 89154ꢀ4003, United States
‡ Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Nanjing Tech
University, No. 30 Puzhu Road (S), Nanjing 211816, People’s Republic of China
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Eꢀmail: junyong.kang@unlv.edu
S
R
O
Ph
N
NO2
R
P
N
N
N
NH2
Ph
R
H
H
O
P
O
P
2 steps
N
NHP-thiourea
R
HO
NO2
R = aryl, alkenyl, alkyl
R
N
CHCl3, rt
HO
β-amino phosphonic acid
R
No catalysts
No additives
No bases
20 examples
up to 91% yield
Abstract: Bifunctional Nꢀheterocyclic phosphine (NHP)ꢀthioureas have been successfully applied for
phosphaꢀMichael addition reaction of nitroalkenes to afford diversely substituted βꢀ
nitrodiazaphosphonates. This transformation takes place at room temperature under catalystꢀfree
conditions and exhibits broad functional group tolerance. The key to success in catalyst, additiveꢀfree
reaction conditions is the suitable hydrogenꢀbond activation of the nitro group by a Brønsted acid
(thiourea), which artfully combined with the highly nucleophilic Nꢀheterocyclic phosphine (NHP) motif
for a synergetic effect. Importantly, this transformation enables a twoꢀstep synthesis of
pharmaceutically, biologically significant βꢀamino phosphonic acids.
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Introduction
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βꢀAminophosphonates and their phosphonic acid derivatives have received significant attention in
recent years because of their unique biological properties and broad pharmaceutical applications (Figure
1).1 They are widely used in medicine and drug applications as NꢀmethylꢀDꢀaspartate (NMDA) receptor
antagonists (a, b, c).2 In addition, they exhibit a wide range of enzyme inhibitions such as imidazole
glycerol phosphate dehydratase (IGPD) inhibitors (d)3 and norstatine renin inhibitors (e).4 Therefore, the
development of mild and efficient methods for the synthesis of βꢀaminophosphonate derivatives is
necessitated and currently attracting growing interest.5
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Figure 1. Biologically active and pharmaceutically important βꢀaminophosphonates and their derivatives
Among the various synthetic methods for βꢀaminophosphonates,1a the phosphaꢀMichael reaction of
nitroalkenes with dialkyl phosphonates or trialkyl phosphites6 provides a practical and straightforward
route to the βꢀaminophosphonates, which can be readily transformed from the corresponding Michael
adduct of the βꢀnitrophosphonates, after a simple reduction of the nitro group.7 In addition, this method
allows the construction of many different products available with various substitution patterns, relying
on both the diverse Michael acceptors and donors.
For a successful development of this transformation, three main hurdles should be addressed jointly,
with efforts to promote more efficient, mild reaction conditions; i) activation of the nitroalkene Michael
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The Journal of Organic Chemistry
acceptor, ii) facilitation of the equilibrium between reactive phosphite and unreactive phosphonate form
in favor of the former, iii) nucleophile additives for the transformation of P(III) to P(V). Since the
pioneering early investigation by Pudovik in 1979, various reaction conditions of the phosphaꢀMichael
reaction of nitroalkenes have been developed over the past decades. Terada7c and Zhao8 group
independently reported a Brønsted acidꢀcatalyzed phosphaꢀMichael reaction of nitroalkenes with
diphenylphosphites in which a hydrogenꢀbond activation of the nitroalkene Michael acceptor was
established by thiourea or guanidine groups and additionally molecular sieves were added to achieve the
equilibrium in favor of the phosphite form inꢀsitu. On the other hand, the desired equilibrium towards a
reactive phosphite form was accomplished through a hydrogen bondꢀactivation of the unreactive
phosphonate form by a tertiary amine group tethered to a Brønsted acid, reported by Rawal,9 Wang,7b
Herrera,10 Nagasaw,11 and Zlotin,12 separately. This strategy using the bifunctional amino Brønsted
acids does not require the use of molecular sieves for the favored equilibrium, providing simpler
reaction conditions. Similarly, Lewis acidꢀcatalyzed phosphaꢀMichael reaction reported by Namboothiri
demonstrated molecular sievesꢀfree reaction conditions.13 Other methods to achieve this phosphaꢀ
Michael reaction of nitroalkenes use amines as bases,14 auxiliaries requiring extra synthetic steps,15 LiI
as external nucleophiles,16 or elevated reaction temperatures for inducing the reactive phosphite
nucleophiles.17 Despite great efforts devoted to the synthesis of pharmaceutically, biologically
significant βꢀnitrophosphonate derivatives, there are limitations such as harsh reaction conditions
(strong bases, high reaction temperatures) and requirement of external nucleophilies, additives, or
catalysts. In addition, to the best of our knowledge, there is no efficient method available for the
synthesis of βꢀnitrophosphonates under catalyst, additive freeꢀreaction conditions at mild room
temperature.7b, 9ꢀ12, 16 With our recently developed Nꢀheterocyclic phosphine (NHP)ꢀthioureas as novel
bifunctional phosphonylation reagents,18 we envisioned that this phosphaꢀMichael reaction of
nitroalkenes would be preceded without additives or catalysts under mild reaction conditions. Herein,
we report NHPꢀthioureaꢀpromoted phosphaꢀMichael / intramolecular nucleophilic substitution reaction
of nitroalkenes for the synthesis of βꢀnitrophosphonates as a simple and mild route.
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Results and discussion
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To test our hypothesis, NHPꢀthiourea 1a and (E)ꢀ(2ꢀnitrovinyl)benzene 2a were used as model
substrates to screen for optimal reaction conditions described in Table 1. The initial solvent studies
revealed that the halogenated solvent (CHCl3) proved to be superior to the nonꢀhalogenated solvents and
polar solvents (entry 2 vs entries 6ꢀ7), providing 64% yield of the desired products without additives or
catalysts. A slight increment of the ratio of Michael acceptor 2a helped to improve the product yield
(entry 8, 75%). The reaction under reflux condition provided 71% yield (entry 9). A significant
improvement in reactivity for this phosphaꢀMichael reaction was observed in higher solvent
concentration conditions, which also reduced the reaction time drastically (entry 10, 91%, 4 h).
Table 1. Optimization of reaction conditionsa
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entry
1
ratio (1a : 2a)
1:1
solvent
DCM
time
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
4 h
yield (%) b
54%
2
1:1
CHCl3
DCE
64%
3
1:1
49%
4
1:1
Et2O
55%
5
1:1
toluene
THF
50%
6
1:1
23%
7
1:1
CH3CN
CHCl3
CHCl3
CHCl3
43%
8
1:1.2
1:1.2
1:1.2
75%
9c
10d
71%
91%
a
Reaction conditions: 1a (0.1 mmol), 2a (0.1ꢀ0.12 mmol), and solvent
b
c
d
(0.5 mL) for 4ꢀ18 h. Isolated yield (%). under reflux condition. 0.3
mL solvent was used.
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The Journal of Organic Chemistry
Table 2. Scope of NHPꢀthioureasa
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2
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6
7
8
9
entry
NHP
3a yield (%)b
entry
NHP
3a yield (%)b
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S
S
S
Ph
Ph
O
Ph
1a, n = 1; 91%
1b, n = 2; 83%
1c, n = 3; 52%
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2
3
O
Ph
N
N
P
N
N
N
( )n
P
N
N
H
N
H
40%
6
H
Ph
1f
Ph
O
O
O
Ph
Ph
O
N
N
P
N
N
H
N
H
P
N
Ph
0%
58%
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8
4
5
N
1d
1g
Ph
Ph
CF3
S
Ph
Ph
O
Ts
O
N
N
P
N
H
P
N
N
H
N
H
CF3 47%
trace
N
1h
Ph
Ph
1e
a Reaction conditions: 1 (0.1 mmol), 2a (0.12 mmol), and CHCl3 (0.3 mL) at rt for 4 h.
b Isolated yield (%).
Next, we investigated the effect of Brønsted acid motif on the intramolecular nucleophilic substitution
reaction process of this phosphaꢀMichael reaction (Table 2). The parent NHPꢀthiourea 1a generated the
phosphaꢀMichael adduct 3a in 91% yield (entry 1). Further optimization studies of the bifunctional
NHPs disclosed that the tether length between the NHP motif and a Brønsted acid has a direct influence
on the effective hydrogenꢀbond activation of the nitro group. NHPs with a lengthy tether reduced the
efficiency of this transformation, resulted in the lower product yields (entry 1 vs entries 2ꢀ3). For
instance, a drastic decrement of the product yield was observed with the NHPꢀthiourea having a fourꢀ
carbon length tether (entry 3). In addition, the electronic effects of the thiourea motif on this substitution
reaction were also investigated. NHPs with a strongly electronꢀdonating group (4ꢀmethoxyphenyl
thiourea, 1d) and an electronꢀwithdrawing group (3,5ꢀbis(trifluoromethyl)phenyl, 1e) on the thiourea
moiety were subjected to the standard reaction conditions yet both of them showed inferior results than
the parent NHPꢀthiourea 1a (entry 1 vs entries 4ꢀ5). These outcomes clearly showed an important
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relationship between a suitable hydrogen bondꢀactivation of the nitroalkenes by a Brønsted acid and the
nucleophilicity of an inꢀsituꢀgenerated anionic thiourea intermediate for the intramolecular nucleophilic
substitution reaction. Having a methyl substituent on the nitrogen atom of the Brønsted acid motif such
as Nꢀmethyl thiourea 1f and Nꢀmethyl amide 1g, the reaction efficiency was significantly reduced
(entries 6ꢀ7), seemingly owing to the obstructing of intramolecular nucleophilic substitution reaction
course. Finally, it should be noted that the replacement of a thiourea group with a sulfonic acid amide
totally reduced the reaction efficiency, which reveals the critical role of thiourea group in this Michael
addition reaction (entry 8).
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Having the optimized reaction conditions, we studied the scope of this reaction by treating NHPꢀ
thioureas with nitroalkenes (Table 3). Firstly, it is worth mentioning that this reaction can be easily
scaled up (2.0 mmol) with an excellent yield of the target product (3a, 95%). Next, the study of
electronic and steric effects of the NHP motif on this transformation was performed under the standard
reaction conditions. While the electronics have a negligible influence (3bꢀ3c), the steric effects of the
orthoꢀsubstituents on the NHP motif 1k suppressed the reaction completely (3d). Gratifyingly, this
phosphaꢀMichael addition reaction tolerated a wide range of functional groups on the nitroalkenes
including electronꢀdonating groups (3eꢀ3g) and electronꢀwithdrawing groups (3hꢀ3k), and provided
good to high yields. Nitroalkenes with diꢀsubstituted phenyl groups were also viable substrates for this
phosphaꢀMichael reaction and afforded the corresponding βꢀnitrodiazaphosphonates in high yields (3n,
3o). Heteroaromatic nitroalkenes were also succeeded in producing the desired adduct in 56ꢀ57% yields
(3p, 3q). Aliphatic nitroalkenes such as (E)ꢀ(2ꢀnitrovinyl)cyclohexane 2r, (E)ꢀ1ꢀnitropentꢀ1ꢀene 2s, and
(E)ꢀ(3ꢀnitroallyl)benzene 2t also proved to be useful substrates under the standard reaction conditions
(3rꢀ3t). Finally, highly conjugated nitroalkenes, ((1E,3E)ꢀ4ꢀnitrobutaꢀ1,3ꢀdienꢀ1ꢀyl)benzene 2u,
furnished an allylphosphonate compound 3u in an acceptable yield (28%).
Table 3. Scope of Nitroalkenes and NHPꢀthioureas for PhosphaꢀMichael Reactiona
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The Journal of Organic Chemistry
S
R
1
2
3
4
5
6
7
O
Ph
N
N
R
N
O
R
R
P
N
N
H
N
P
H
NO2
R
+
NO2
1a, 1i-1k
R
CHCl3, rt, 4-6 h
2
3
1a: R = Ph; 1i: R = 4-MePh
1j: R = 4-MeOPh; 1k: R = 2,6-iPrPh
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9
N
N
O
N
N
N
N
O
Ph
Ph
Ph
Ph
R
R
P
P
P
N
3b: R = 4-MePh, 88%
3c: R = 4-MeOPh, 91%
3d: R = 2,6-i-PrPh, NR
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O
NO2
NO2
NO2
3a, 91%b (95%c)
3e, 93%
N
Ph
N
N
N
O
N
N
N
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
P
P
P
P
O
O
NO2
NO2
NO2
NO2
Cl
MeO
N
F
3i, 83%
3f, 70%
3h, 89%
3g, 73%
N
N
O
N
N
N
N
O
N
N
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
P
P
P
P
O
O
NO2
NO2
NO2
NO2
Br
Cl
F3C
F
3j, 76%
3k, 89%
3m, 71%
3l, 74%
N
N
N
N
O
N
N
O
N
N
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
P
P
P
P
O
NO2
NO2
NO2
NO2
S
O
Cl
Br
Cl
3o, 83%
3p, 56%d
3q, 57%d
3n, 76%
N
N
N
N
O
N
N
O
N
N
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
P
P
P
P
O
O
NO2
NO2
NO2
NO2
Ph
3s, 51%
3t, 58%
3u, 28%d
3r, 48%
a Reaction conditions: 1 (0.1 mmol), 2 (0.12 mmol), and CHCl3 (0.3 mL) at rt for 4 h. b Isolated yield.
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c Scaleꢀup experiment with 2.0 mmol of 1a. d Reaction run for 6 h.
We next explored the synthetic utilities of the phosphaꢀMichael adducts (Scheme 1). The
regioselective bromination of electronꢀrich aromatic ring 3a was performed using NBS and benzoyl
peroxide in which only Nꢀarylꢀbrominated product 4a was obtained in 63% yield. The reduction of a
nitro group to an amine was achieved under the modified nickel boride conditions, and this method
afforded a NꢀBocꢀprotected βꢀamino diazaphosphonate 4b in 88% yield and a primary βꢀamino
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diazaphosphonate 4c in 83% yield.10 Gratifyingly, hydrolysis of 4c furnished a βꢀamino phosphonic acid
4d in 67% yield under conc. HCl condition.19
1
2
3
4
5
6
Scheme 1. Synthetic Manipulations of PhosphaꢀMichael adduct 3a
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9
Br
H
NO2
N
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Ph
1) NiCl2•6H2O, NaBH4
MeOH/THF, -10 oC to rt
Boc
Ph
O
P
NO2
Ph
O
P
N
NBS, (PhCOO)2
DCE, rt
N
Ph
O
P
Ph
N
2) (Boc)2O, rt
N
Ph
3a
N
Ph
N
4b, 88%
NiCl2•6H2O, NaBH4
MeOH/THF, -10 oC to rt
Br
4a, 63%
NH2
NH2
Ph
conc. HCl, reflux;
propylene oxide, MeOH
Ph
O
O
P
N
HO
P
N
Ph
HO
Ph
4d, 67%
4c, 83%
On the basis of experimental observations and our previous works,18 a rational mechanism for the
formation of 3 is depicted in Scheme 2. The Michael addition of NHPꢀthiourea 1a to nitroalkene 2
activated through a hydrogen bonding with a thiourea motif generates a diazaphosphonium intermediate
A. Following the sequential proton transfer / tautomerization process furnishes an anionic thiourea
intermediate B. The anionic thioureaꢀinitiated intramolecular nucleophilic substitution reaction
responses to the formation of βꢀnitrodiazaphosphonate 3a and thiazolidine byproduct C.
Scheme 2. A Proposed Mechanism
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The Journal of Organic Chemistry
S
Ph
1
2
3
4
5
6
O
Ph
N
Ph
N
P
N
N
N
N
N
O
H
H
Ph
Ph
P
+
HN
1a
NO2
S
Ph
NO2
Ph
Ph
2
3a
C
7
8
9
intramolecular
nucleophilic
substitution
phospha-
Michael reaction
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S
H
N
Ph
Ph
N
H
O
N
N
H
O
Ph
O
S
Ph
N
O
NO2
N
P
N
proton transfer/
tautomerization
P
N
N
Ph
Ph
B
A
Ph
Ph
Conclusions
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In summary, bifunctional N‑heterocyclic phosphine (NHP)ꢀthioureas recently developed in our
laboratory have been successfully applied in phosphaꢀMichael reaction of nitroalkenes to afford a
variety of substituted βꢀnitrodiazaphosphonates. This work is the first example of phosphaꢀMichael
reaction of nitroalkenes with bifunctional NHPꢀthiourea by combining a phosphonylation reagent with
Brønsted acid motif, which demonstrated a synergetic effect to achieve mild reaction conditions
(catalystꢀ, nucleophile additiveꢀ, and baseꢀfree reaction conditions at room temperature). In addition,
synthetic manipulations of the Michael adduct demonstrated an easy access to a paraꢀselective aryl
bromination product 4a and reductive amination compounds 4b, 4c. Importantly, a threeꢀstep synthesis
of a pharmaceutically valuable βꢀamino phosphonic acid 4d was achieved using this method. Further
studies on the efficient enantioselective phosphaꢀMichael reaction of nitroalkenes with chiral
bifunctional N‑heterocyclic phosphine (NHP)ꢀthioureas are underway and will be reported in due
course.
Experimental Section
General Information
All reactions were carried out under atmospheric conditions in ovenꢀdried glassware with magnetic
stirring bar. Dry solvents (THF, toluene, and DCM) were obtained by solvent purification system under
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argon. All commercially available reagents were used as received without further purification.
Purification of reaction products was carried out by flash column chromatography using silica gel 60
(230ꢀ400 mesh). Analytical thin layer chromatography was performed on 0.25 mm aluminumꢀbacked
silica gel 60ꢀF plates. Visualization was accompanied with UV light and KMnO4 solution.
Concentration under reduced pressure refers to the removal of volatiles using a rotary evaporator
attached to a dry diaphragm pump (10ꢀ15 mm Hg) followed by pumping to a constant weight with an oil
pump (<300 mTorr). Infrared (IR) spectra were recorded on an IR spectrometer with KBr wafers or a
film on KBr plate. Highꢀresolution mass spectra (HRMS) were recorded on LCMSꢀITꢀTOF mass
spectrometer using ESI (electrospray ionization). 1H NMR spectra were recorded in CDCl3 on 400 MHz
NMR spectrometer. The 1H chemical shifts are referenced to residual solvent signals at δi 7.26 (CHCl3)
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or δi 0.00 (TMS). H NMR coupling constants (J) are reported in Hertz (Hz) and multiplicities are
indicated as follows: s (singlet), bs (broad singlet), d (doublet), t (triplet), m (multiplet), dd (doublet of
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doublet), dt (doublet of triplet). C NMR spectra were proton decoupled and recorded in CDCl3 on
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100.5 MHz NMR spectrometer. The C chemical shifts are referenced to solvent signals at δi 77.16
(CDCl3). 31P NMR spectra were proton decoupled and recorded in CDCl3 on 162 MHz NMR
spectrometer. 31P chemical shifts are reported relative to 85% H3PO4 (0.00 ppm) as an external standard.
General Procedure for the Synthesis of NHPꢀThioureas 1
NHPꢀThioureas 1 were synthesized and characterized according to our previously reported
methodology.18a To a solution of 2ꢀchloroꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine20 (1.00 g, 3.62 mmol)
in DCM (25 mL) were added 1ꢀ(2ꢀhydroxyethyl)ꢀ3ꢀphenylthiourea21 (0.711 g, 3.62 mmol) and
triethylamine (0.438 g, 4.34 mmol) at 0 °C. The reaction mixture was warmed up to room temperature
and stirred for 2 h. After stirring for 2 h at room temperature, the reaction mixture was concentrated
under reduced pressure. The residue was subjected to column chromatography on silica gel (gradient
eluent of Hexanes:EtOAc: 7/1 to 5/1) to give colorless crystalline solid 1a
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General Procedure for the PhosphaꢀMichael Reaction of Nitroalkenes with NHPꢀThioureas
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NHPꢀthioureas 1 (0.1 mmol) and nitroalkenes 2 (0.12 mmol) were dissolved in CHCl3 (0.3 mL) in a 2
dram vial. The resulting mixture was stirred for 4 h at room temperature. After stirring for 4 h, the
volatiles were removed under reduced pressure. The residue was subjected to column chromatography
on silica gel to give corresponding products 3.
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2ꢀ(2ꢀNitroꢀ1ꢀphenylethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3a): 37.0 mg, 91% yield;
white solid; mp 150 °C (decomp.); Rf 0.20 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column; IR
ν
1
(KBr, cmꢀ1) 3061, 2958, 2858, 1599, 1554, 1498, 1375, 1269, 1230, 1124, 958; H NMR (400 MHz,
CDCl3) δ 7.46ꢀ7.37 (m, 4 H), 7.34ꢀ7.29 (m, 4 H), 7.28ꢀ7.12 (m, 5 H), 6.75ꢀ6.70 (m, 2 H), 5.28 (ddd, J =
4.0, 7.6, 12.0 Hz, 1 H), 4.90 (ddd, J = 4.4, 11.8, 15.0 Hz, 1 H), 4.78 (ddd, J = 4.0, 14.8, 21.6 Hz, 1 H),
3.53ꢀ3.37 (m, 2 H), 2.93ꢀ2.85 (m, 1 H), 2.80ꢀ2.72 (m, 1 H); 13C NMR (100.5 MHz, CDCl3) δ 141.2 (dd,
J = 74.4, 8.2 Hz), 132.0 (d, J = 7.4 Hz), 129.8 (d, J = 5.2 Hz), 128.6 (d, J = 3.7 Hz), 128.3 (d, J = 3.7
Hz), 128.2 (d, J = 5.2 Hz), 123.0 (d, J = 44.6 Hz), 117.1 (dd, J = 63.3, 4.5 Hz), 74.6 (d, J = 5.9 Hz), 45.8
(d, J = 102.7 Hz), 43.7 (d, J = 8.2 Hz), 42.6 (d, J = 8.1 Hz); 31P NMR (162 MHz, CDCl3): δ 21.7 ppm;
HRMS (ESI+): m/z calcd. for C22H22N3O3P [M+Na]+: 430.1291; Found: 430.1293.
2ꢀ(2ꢀNitroꢀ1ꢀphenylethyl)ꢀ1,3ꢀdiꢀpꢀtolylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3b): 38.2 mg, 88% yield;
white solid; mp 155 °C (decomp.); Rf 0.20 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column; IR
ν
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(KBr, cmꢀ1) 3032, 2960, 2918, 2877, 1618, 1554, 1514, 1473, 1375, 1363, 1269, 1234, 964; H NMR
(400 MHz, CDCl3) δ 7.26ꢀ7.17 (m, 11 H), 6.77ꢀ6.72 (m, 2 H), 5.24 (ddd, J = 3.6, 7.4, 12.2 Hz, 1 H),
4.88 (ddd, J = 4.4, 11.8, 15.0 Hz, 1 H), 4.55 (ddd, J = 3.6, 14.6, 21.4 Hz, 1 H), 3.49ꢀ3.33 (m, 2 H), 2.89ꢀ
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2.81 (m, 1 H), 2.80ꢀ2.72 (m, 1 H), 2.37 (s, 6 H); C NMR (100.5 MHz, CDCl3) δ 138.7 (dd, J = 69.9,
8.1 Hz), 132.5 (d, J = 48.3 Hz), 132.2 (d, J = 6.7 Hz), 130.3 (d, J = 3.0 Hz), 128.5 (d, J = 3.0 Hz), 128.3
(d, J = 5.2 Hz), 128.2 (d, J = 3.7 Hz), 117.4 (dd, J = 63.3, 3.8 Hz), 74.7 (d, J = 5.9 Hz), 45.7 (d, J =
102.7 Hz), 44.0 (d, J = 8.2 Hz), 42.9 (d, J = 9.0 Hz), 20.7 (d, J = 2.2 Hz); 31P NMR (162 MHz, CDCl3):
δ 24.1 ppm; HRMS (ESI+): m/z calcd. for C24H26N3O3P [M+Na]+: 458.1604; Found: 458.1605.
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1,3ꢀBis(4ꢀmethoxyphenyl)ꢀ2ꢀ(2ꢀnitroꢀ1ꢀphenylethyl)ꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3c): 42.4 mg,
91% yield; white solid; mp 185 °C (decomp.); Rf 0.16 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (1/1/4) for
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column; IR
ν
(KBr, cmꢀ1) 3007, 2960, 2910, 2839, 1556, 1510, 1458, 1375, 1273, 1244, 1188, 1031,
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962; H NMR (400 MHz, CDCl3) δ 7.30ꢀ7.19 (m, 7 H), 6.95 (tt, J = 9.2, 2.4 Hz, 4 H), 6.81ꢀ6.77 (m, 2
H), 5.17 (ddd, J = 4.0, 7.6, 12.4 Hz, 1 H), 4.81 (ddd, J = 4.4, 11.8, 15.0, Hz, 1 H), 4.46 (ddd, J = 3.6,
14.2, 21.4 Hz, 1 H), 3.85 (d, J = 1.2 Hz, 6 H), 3.46ꢀ3.33 (m, 2 H), 2.90ꢀ2.80 (m, 2 H); 13C NMR (100.5
MHz, CDCl3) δ 155.8 (d, J = 21.6 Hz), 134.3 (dd, J = 61.0, 8.2 Hz), 132.3 (d, J = 6.7 Hz), 128.5 (d, J =
3.0 Hz), 128.4 (d, J = 5.2 Hz), 128.2 (d, J = 3.7 Hz), 119.6 (dd, J = 69.2, 3.8 Hz), 115.0 (d, J = 8.2 Hz),
74.7 (d, J = 5.3 Hz), 55.5 (d, J = 3.7 Hz), 45.7 (d, J = 103.4 Hz), 44.9 (d, J = 8.2 Hz), 43.8 (d, J = 8.2
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Hz); P NMR (162 MHz, CDCl3): δ 23.9 ppm; HRMS (ESI+): m/z calcd. for C24H26N3O5P [M+Na]+:
490.1502; Found: 490.1511.
2ꢀ(2ꢀNitroꢀ1ꢀ(pꢀtolyl)ethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3e): 39.1 mg, 93% yield;
white solid; mp 168 °C (decomp.); Rf 0.20 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column; IR
ν
(KBr, cmꢀ1) 3061, 2916, 2893, 1599, 1554, 1498, 1371, 1269, 1236, 1120, 958; H NMR (400 MHz,
CDCl3) δ 7.46ꢀ7.37 (m, 4 H), 7.34ꢀ7.29 (m, 4 H), 7.15ꢀ7.11 (m, 2 H), 7.00 (d, J = 8.4 Hz, 2 H), 6.60 (dd,
J = 8.0, 2.4 Hz, 2 H), 5.26 (ddd, J = 3.6, 7.4, 12.2 Hz, 1 H), 4.87 (ddd, J = 4.4, 11.8, 15.0 Hz, 1 H), 4.56
(ddd, J = 3.6, 14.6, 21.4 Hz, 1 H), 3.53ꢀ3.37 (m, 2 H), 2.95ꢀ2.87 (m, 1 H), 2.84ꢀ2.78 (m, 1 H), 2.29 (d, J
1
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= 2.4 Hz, 3 H); C NMR (100.5 MHz, CDCl3) δ 141.3 (dd, J = 75.9, 8.9 Hz), 138.2 (d, J = 3.7 Hz),
129.8 (d, J = 4.5 Hz), 129.3 (d, J = 2.9 Hz), 128.8 (d, J = 6.7 Hz), 128.1 (d, J = 5.9 Hz), 122.9 (d, J =
43.2 Hz), 117.1 (dd, J = 61.0, 4.4 Hz), 74.8 (d, J = 6.0 Hz), 44.4 (d, J = 103.4 Hz), 43.7 (d, J = 8.2 Hz),
42.6 (d, J = 8.2 Hz), 21.1; P NMR (162 MHz, CDCl3): δ 24.8 ppm; HRMS (ESI+): m/z calcd. for
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C23H24N3O3P [M+Na]+: 444.1447; Found: 444.1441.
2ꢀ(1ꢀ(4ꢀMethoxyphenyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3f): 30.8 mg,
70% yield; white solid; mp 174 °C (decomp.); Rf 0.20 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for
column; IR
ν
(KBr, cmꢀ1) 3061, 2957, 2891,1600, 1554, 1512, 1373, 1273, 1255, 1226, 1180, 1035,
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The Journal of Organic Chemistry
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958; H NMR (400 MHz, CDCl3) δ 7.46ꢀ7.37 (m, 4 H), 7.32 (t, J = 8.4 Hz, 4 H), 7.17ꢀ7.11 (m, 2 H),
6.75ꢀ6.70 (m, 2 H), 6.66ꢀ6.61 (m, 2 H), 5.26 (ddd, J = 3.6, 7.4, 11.8 Hz, 1 H), 4.83 (ddd, J = 4.4, 11.8,
15.0 Hz, 1 H), 4.53 (ddd, J = 3.6, 14.6, 21.0 Hz, 1 H), 3.76 (s, 6 H), 3.54ꢀ3.39 (m, 2 H), 3.06ꢀ2.95 (m, 1
H), 2.98ꢀ2.82 (m, 1 H); 13C NMR (100.5 MHz, CDCl3) δ 159.5 (d, J = 2.9 Hz), 141.3 (dd, J = 76.6, 8.9
Hz), 129.8 (d, J = 3.0 Hz), 129.4 (d, J = 5.2 Hz), 123.7 (d, J = 6.7 Hz), 122.9 (d, J = 42.4 Hz), 117.1
(dd, J = 58.8, 4.5 Hz), 114.0 (d, J = 3.0 Hz), 74.9 (d, J = 7.4 Hz), 55.2, 45.0 (d, J = 104.9 Hz), 43.7 (d, J
= 8.2 Hz), 42.6 (d, J = 8.1 Hz); 31P NMR (162 MHz, CDCl3): δ 25.1 ppm; HRMS (ESI+): m/z calcd. for
C23H24N3O4P [M+Na]+: 460.1397; Found: 460.1389.
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2ꢀ(1ꢀ(4ꢀ(Dimethylamino)phenyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3g) ：
32.9 mg, 73% yield; white solid; mp 146 °C (decomp.); Rf 0.14 (vHexane/vEA= 2:1), vHexane/vEA/vDCM
(3/1/1) for column; IR
ν
(KBr, cmꢀ1) 3059, 2951, 2891, 1618, 1599, 1552, 1527, 1375, 1269, 1230,
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1122, 956; H NMR (400 MHz, CDCl3) δ 7.45ꢀ7.37 (m, 4 H), 7.36ꢀ7.29 (m, 4 H), 7.15ꢀ7.10 (m, 2 H),
6.59ꢀ6.48 (m, 4 H), 5.24 (ddd, J = 3.6, 7.4, 11.8 Hz, 1 H), 4.82 (ddd, J = 4.4, 11.0, 15.0 Hz, 1 H), 4.48
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(ddd, J = 3.6, 14.2, 21.0 Hz, 1 H), 3.52ꢀ3.38 (m, 2 H), 3.00ꢀ2.86 (m, 2 H), 2.91 (s, 6 H); C NMR
(100.5 MHz, CDCl3) δ 150.2 (d, J = 2.2 Hz), 141.5 (dd, J = 76.7, 8.9 Hz), 129.7 (d, J = 2.2 Hz), 129.0
(d, J = 5.2 Hz), 122.7 (d, J = 41.0 Hz), 118.7 (d, J = 7.5 Hz), 117.0 (dd, J = 55.8, 4.8 Hz), 112.1 (d, J =
2.2 Hz), 75.0 (d, J = 7.4 Hz), 45.0 (d, J = 104.2 Hz), 43.6 (d, J = 7.5 Hz), 42.5 (d, J = 8.2 Hz), 40.3; 31P
NMR (162 MHz, CDCl3): δ 26.1 ppm; HRMS (ESI+): m/z calcd. for C24H27N4O3P [M+Na]+: 473.1713;
Found: 473.1710.
2ꢀ(1ꢀ(4ꢀFluorophenyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3h): 37.8 mg, 89%
yield; white solid; mp 162 °C (decomp.); Rf 0.20 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column;
IR
ν
(KBr, cmꢀ1) 3066, 2951, 2893, 1599, 1554, 1500, 1477, 1373, 1267, 1232, 1161, 1124, 1105, 956;
1H NMR (400 MHz, CDCl3) δ 7.46ꢀ7.38 (m, 4 H), 7.35ꢀ7.29 (m, 4 H), 7.19ꢀ7.13 (m, 2 H), 6.91 (t, J =
8.4 Hz, 2 H), 6.73ꢀ6.67 (m, 2 H), 5.28 (ddd, J = 2.8, 4.6, 7.8 Hz, 1 H), 4.84 (ddd, J = 4.4, 12.2, 15.0 Hz,
1 H), 4.57 (ddd, J = 3.6, 14.6, 21.4 Hz, 1 H), 3.58ꢀ3.43 (m, 2 H), 3.02ꢀ2.93 (m, 1 H), 2.92ꢀ2.84 (m, 1
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H); 13C NMR (100.5 MHz, CDCl3) δ 162.4 (dd, J = 247.0, 3.7 Hz), 141.1 (dd, J = 75.9, 8.9 Hz), 130.0,
129.9 (d, J = 3.7 Hz), 127.9 (dd, J = 4.6, 2.3 Hz), 123.2 (d, J = 42.5 Hz), 117.2 (dd, J = 59.5, 4.4 Hz),
115.2 (dd, J = 21.6, 3.0 Hz), 74.8 (d, J = 6.7 Hz), 45.0 (d, J = 104.2 Hz), 43.9 (d, J = 8.2 Hz), 42.8 (d, J
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= 8.2 Hz); P NMR (162 MHz, CDCl3): δ 23.3 ppm; HRMS (ESI+): m/z calcd. for C22H21FN3O3P
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[M+Na]+: 448.1197; Found: 448.1200.
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2ꢀ(1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3i): 36.7 mg, 83%
yield; white solid; mp 172 °C (decomp.); Rf 0.22 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column;
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ν
(KBr, cmꢀ1) 3063, 2947, 2895, 1599, 1554, 1491, 1475, 1369, 1267, 1232, 1124, 956; H NMR
(400 MHz, CDCl3) δ 7.46ꢀ7.38 (m, 4 H), 7.35ꢀ7.28 (m, 4 H), 7.22ꢀ7.13 (m, 4 H), 6.69ꢀ6.63 (m, 2 H),
5.26 (ddd, J = 3.6, 7.4, 12.2 Hz, 1 H), 4.83 (ddd, J = 4.4, 11.8, 14.6 Hz, 1 H), 4.56 (ddd, J = 3.6, 14.6,
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21.4 Hz, 1 H), 3.58ꢀ3.42 (m, 2 H), 3.04ꢀ2.95 (m, 1 H), 2.93ꢀ2.85 (m, 1 H); C NMR (100.5 MHz,
CDCl3) δ 141.0 (dd, J = 75.2, 8.2 Hz), 134.3 (d, J = 4.4 Hz), 130.7 (d, J = 6.7 Hz), 129.9 (d, J = 3.8 Hz),
129.6 (d, J = 5.2 Hz), 128.9 (d, J = 2.9 Hz), 123.2 (d, J = 43.2 Hz), 117.2 (dd, J = 60.2, 4.4 Hz), 74.6 (d,
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J = 6.0 Hz), 45.2 (d, J = 103.4 Hz), 44.0 (d, J = 8.2 Hz), 42.8 (d, J = 8.2 Hz); P NMR (162 MHz,
CDCl3): δ 23.6 ppm; HRMS (ESI+): m/z calcd. for C22H21ClN3O3P [M+Na]+: 464.0901; Found:
464.0911.
2ꢀ(1ꢀ(4ꢀBromophenyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3j): 36.9 mg, 76%
yield; white solid; mp 167 °C (decomp.); Rf 0.22 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column;
IR
ν
(KBr, cmꢀ1) 3059, 2918, 2893, 159, 1554, 1500, 1477, 1371, 1265, 1228, 1120, 956; 1H NMR (400
MHz, CDCl3) δ 7.46ꢀ7.38 (m, 4 H), 7.36ꢀ7.28 (m, 6 H), 7.18ꢀ7.13 (m, 2 H), 6.62ꢀ6.57 (m, 2 H), 5.26
(ddd, J = 3.6, 7.4, 12.6 Hz, 1 H), 4.83 (ddd, J = 4.4, 11.8, 15.0 Hz, 1 H), 4.55 (ddd, J = 4.0, 14.4, 21.2
Hz, 1 H), 3.58ꢀ3.42 (m, 2 H), 3.04ꢀ2.95 (m, 1 H), 2.93ꢀ2.85 (m, 1 H); 13C NMR (100.5 MHz, CDCl3) δ
141.0 (dd, J = 75.2, 8.2 Hz), 131.8 (d, J = 3.0 Hz), 131.2 (d, J = 6.7 Hz), 129.9 (d, J = 3.8 Hz), 129.8 (d,
J = 59 Hz), 123.2 (d, J = 43.2 Hz), 122.4 (d, J = 4.4 Hz), 117.2 (dd, J = 59.6, 4.5 Hz), 74.5 (d, J = 5.2
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Hz), 45.3 (d, J = 103.5 Hz), 44.0 (d, J = 8.1 Hz), 42.8 (d, J = 8.2 Hz); P NMR (162 MHz, CDCl3): δ
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23.3 ppm; HRMS (ESI+): m/z calcd. for C22H21BrN3O3P [M+Na]+: 508.0396; Found: 508.0418.
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2ꢀ(2ꢀNitroꢀ1ꢀ(4ꢀ(trifluoromethyl)phenyl)ethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3k):
42.3 mg, 89% yield; white solid; mp 200 °C (decomp.); Rf 0.26 (vHexane/vEA= 2:1), vHexane/vEA/vDCM
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(8/2/1) for column; IR
ν
(KBr, cmꢀ1) 3061, 2920, 2885, 1599, 1558, 1500, 1327, 1263, 1234, 1118,
1070, 960; 1H NMR (400 MHz, CDCl3) δ 7.50ꢀ7.39 (m, 6 H), 7.34ꢀ7.29 (m, 4 H), 7.17 (t, J = 7.2 Hz, 2
H), 6.87 (dd, J = 8.0, 2.0 Hz, 2 H), 5.29 (ddd, J = 3.6, 7.4, 12.6 Hz, 1 H), 4.90 (ddd, J = 4.0, 12.0, 14.8
Hz, 1 H), 4.65 (ddd, J = 3.2, 14.4, 21.2 Hz, 1 H), 3.60ꢀ3.43 (m, 2 H), 3.04ꢀ2.95 (m, 1 H), 2.90ꢀ2.81 (m,
1 H); 13C NMR (100.5 MHz, CDCl3) δ 140.9 (dd, J = 72.2, 8.2 Hz), 136.4 (d, J = 6.0 Hz), 130.0 (d, J =
5.3 Hz), 128.7 (d, J = 5.2 Hz), 125.6 (m), 123.7 (d, J = 270.9 Hz), 123.4 (d, J = 41.7 Hz), 117.4 (dd, J =
56.6, 3.7 Hz), 74.5 (d, J = 5.2 Hz), 45.7 (d, J = 102.8 Hz), 44.1 (d, J = 8.2 Hz), 42.9 (d, J = 8.9 Hz); 31P
NMR (162 MHz, CDCl3): δ 22.7 ppm; HRMS (ESI+): m/z calcd. for C23H21F3N3O3P [M+Na]+:
498.1165; Found: 498.1167.
2ꢀ(2ꢀNitroꢀ1ꢀ(oꢀtolyl)ethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3l): 31.2 mg, 74% yield;
white solid; mp 176ꢀ177 °C; Rf 0.20 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column; IR
ν (KBr,
cmꢀ1) 3092, 3018, 2951, 1599, 1550, 1500, 1371, 1269, 1232, 1116, 960; 1H NMR (400 MHz, CDCl3) δ
7.44ꢀ7.35 (m, 6 H), 7.28 (d, J = 8.0 Hz, 2 H), 7.17ꢀ7.01 (m, 5 H), 6.82 (d, J = 8.0 Hz, 1 H), 5.35ꢀ5.29
(m, 1 H), 4.95ꢀ4.81 (m, 2 H), 3.53ꢀ3.43 (m, 2 H), 3.06ꢀ2.95 (m, 1 H), 2.91ꢀ2.82 (m, 1 H), 1.73 (s, 3 H);
13C NMR (100.5 MHz, CDCl3) δ 141.5 (dd, J = 61.1, 9.0 Hz), 138.3 (d, J = 6.7 Hz), 131.1 (d, J = 3.0
Hz), 130.5 (d, J = 6.7 Hz), 129.8 (d, J = 5.2 Hz), 128.0 (d, J = 3.0 Hz), 127.1 (d, J = 4.5 Hz), 125.9 (d, J
= 3.7 Hz), 122.8 (d, J = 49.9 Hz), 116.8 (dd, J = 63.3, 4.5 Hz), 76.2 (d, J = 6.7 Hz), 43.6 (d, J = 8.2 Hz),
42.2 (d, J = 8.2 Hz), 41.7 (d, J = 104.9 Hz); P NMR (162 MHz, CDCl3): δ 25.4 ppm; HRMS (ESI+):
31
m/z calcd. for C23H24N3O3P [M+Na]+: 444.1447; Found: 444.1455.
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2ꢀ(1ꢀ(2ꢀFluorophenyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3m) ： 30.2 mg,
71% yield; white solid; mp 158 °C (decomp.); Rf 0.14 (vHexane/vEA= 3:1), vHexane/vEA/vDCM (8/2/1) for
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2
3
4
5
6
column; IR
ν
(KBr, cmꢀ1) 3076, 3043, 2960, 2879, 1599, 1554, 1492, 1473, 1267, 1234, 1128, 1107,
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8
9
1
958; H NMR (400 MHz, CDCl3) δ 7.43ꢀ7.28 (m, 8 H), 7.24ꢀ7.17 (m, 1 H), 7.15ꢀ7.09 (m, 2 H), 6.98ꢀ
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6.89 (m, 2 H), 6.76 (tt, J = 7.6, 2.0 Hz, 1 H), 5.28ꢀ5.21 (m, 1 H), 5.00ꢀ4.84 (m, 2 H), 3.61ꢀ3.46 (m, 2 H),
13
3.17ꢀ3.09 (m, 1 H), 3.05ꢀ2.97 (m, 1 H); C NMR (100.5 MHz, CDCl3) δ160.8 (dd, J = 248.6, 6.0 Hz),
141.2 (dd, J = 78.2, 8.2 Hz), 130.0 (dd, J = 8.2, 3.7 Hz), 129.7, 129.2, 124.2 (t, J = 3.0 Hz), 123.0 (d, J
= 20.8 Hz), 119.5 (dd, J = 14.2, 6.7 Hz), 117.3 (dd, J = 24.5, 3.7 Hz), 115.9 (dd, J = 22.3, 3.0 Hz), 74.3
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(dd, J = 5.9, 2.3 Hz), 43.8 (d, J = 9.0 Hz), 42.8 (d, J = 9.0 Hz), 39.4 (d, J = 106.4 Hz); P NMR (162
MHz, CDCl3): δ 23.1 (d, J = 3.6 Hz) ppm; HRMS (ESI+): m/z calcd. for C22H21FN3O3P [M+Na]+:
448.1197; Found: 448.1188.
2ꢀ(1ꢀ(2,4ꢀDichlorophenyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3n): 35.9 mg,
76% yield; white solid; mp 188 °C (decomp.); Rf 0.28 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (5/1/1) for
1
column; IR
ν
(KBr, cmꢀ1) 3028, 2939, 2856, 1599, 1560, 1552, 1500, 1477, 1373, 1269, 1116, 960; H
NMR (400 MHz, CDCl3) δ 7.42ꢀ7.27 (m, 6 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.19 (dd, J = 2.4, 0.8 Hz, 1 H),
7.14ꢀ7.01 (m, 3 H), 6.87 (dd, J = 8.8, 2.4 Hz, 1 H), 5.17ꢀ5.01 (m, 2 H), 4.93ꢀ4.83 (m, 1 H), 3.69ꢀ3.52
13
(m, 2 H), 3.48ꢀ3.39 (m, 1 H), 3.25ꢀ3.17 (m, 1 H); C NMR (100.5 MHz, CDCl3) δ 141.2 (dd, J = 31.3,
8.2 Hz), 135.9 (d, J = 6.7 Hz), 134.5 (d, J = 3.7 Hz), 129.8 (d, J = 2.9 Hz), 129.6 (d, J = 13.4 Hz), 129.5,
128.9 (d, J = 6.7 Hz), 127.1 (d, J = 3.8 Hz), 123.2 (d, J = 8.9 Hz), 117.4 (d, J = 5.2 Hz), 75.2 (d, J = 6.0
31
Hz), 43.8 (d, J = 9.7 Hz), 42.7 (d, J = 9.7 Hz), 41.9 (d, J = 104.2 Hz); P NMR (162 MHz, CDCl3): δ
22.0 ppm; HRMS (ESI+): m/z calcd. for C22H20Cl2N3O3P [M+Na]+: 498.0512; Found: 498.0518.
2ꢀ(1ꢀ(2ꢀBromoꢀ4ꢀchlorophenyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3o): 43.0
mg, 83% yield; white solid; mp 160 °C (decomp.); Rf 0.30 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for
1
column; IR
ν
(KBr, cmꢀ1) 3085, 2958, 2926, 1600, 1554, 1498, 1473, 1375, 1273, 1232, 1126, 958; H
NMR (400 MHz, CDCl3) δ 7.42ꢀ7.34 (m, 5 H), 7.30ꢀ7.25 (m, 2 H), 7.21 (d, J = 8.0 Hz, 2 H), 7.14ꢀ7.04
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(m, 3 H), 6.90 (dd, J = 8.8, 2.84 Hz, 1 H), 5.13ꢀ5.00 (m, 2 H), 4.91ꢀ4.82 (m, 1 H), 3.70ꢀ3.54 (m, 2 H),
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3
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3.54ꢀ3.45 (m, 1 H), 3.31ꢀ3.23 (m, 1 H); C NMR (100.5 MHz, CDCl3) δ 141.2 (dd, J = 17.8, 7.4 Hz),
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7
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134.6 (d, J = 3.7 Hz), 133.1 (d, J = 2.2 Hz), 130.7 (d, J = 6.7 Hz), 129.6 (d, J = 23.1 Hz), 127.6 (d, J =
3.0 Hz), 126.3, 123.2 (d, J = 3.0 Hz), 117.5 (dd, J = 5.9, 4.4 Hz), 75.5 (d, J = 5.3 Hz), 44.7 (d, J = 105.0
Hz), 43.8 (d, J = 8.9 Hz), 42.6 (d, J = 9.7 Hz); 31P NMR (162 MHz, CDCl3): δ 21.9 ppm; HRMS (ESI+):
m/z calcd. for C22H20BrClN3O3P [M+Na]+: 542.0006; Found: 542.0024.
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2ꢀ(1ꢀ(Furanꢀ2ꢀyl)ꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3p): 22.2 mg, 56 %
yield; white solid; mp 120 °C (decomp.); Rf 0.20 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column;
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IR
ν
(KBr, cmꢀ1) 3007, 2957, 2852, 1600, 1554, 1498, 1473, 1307, 1267, 1236, 1155, 1126; H NMR
(400 MHz, CDCl3) δ 7.44ꢀ7.28 (m, 9 H), 7.17ꢀ7.11 (m, 2 H), 6.29 (dd, J = 2.8, 2.0 Hz, 1 H), 5.87 (t, J =
3.6Hz, 1 H), 5.11 (ddd, J = 3.2, 7.6, 12.4 Hz, 1 H), 4.77ꢀ4.59 (m, 2 H), 3.69ꢀ3.60 (m, 1 H), 3.53 (dq, J =
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8.8, 3.6 Hz, 1 H), 3.35 (dq, J = 8.8, 4.0 Hz, 1 H), 3.13ꢀ3.05 (m, 1 H); C NMR (100.5 MHz, CDCl3) δ
146.6 (d, J = 10.4 Hz), 142.4 (d, J = 3.8 Hz), 140.8 (dd, J = 50.6, 8.2 Hz), 129.7 (d, J = 20.8 Hz), 123.3
(d, J = 64.0 Hz), 117.9 (dd, J = 119.8, 3.7 Hz), 110.9 (d, J = 3.7 Hz), 108.9 (d, J = 8.2 Hz), 73.0 (d, J =
5.9 Hz), 43.5 (d, J = 8.9 Hz), 43.0 (d, J = 8.2 Hz), 39.5 (d, J = 105.7 Hz); 31P NMR (162 MHz, CDCl3):
δ 22.0 ppm; HRMS (ESI+): m/z calcd. for C20H20N3O4P [M+Na]+: 420.1084; Found: 420.1093.
2ꢀ(2ꢀNitroꢀ1ꢀ(thiophenꢀ2ꢀyl)ethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3q): 23 mg, 57 %
yield; white solid; mp 122 °C (decomp.); Rf 0.20 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column;
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IR
ν
(KBr, cmꢀ1) 3014, 2957, 2881, 1599, 1558, 1498, 1471, 1267, 1228, 1126, 960; H NMR (400
MHz, CDCl3) δ 7.45ꢀ7.30 (m, 8 H), 7.19ꢀ7.12 (m, 3 H), 6.87 (ddd, J = 0.4, 3.8, 4.6 Hz, 1 H), 6.44ꢀ6.41
(m, 1 H), 5.26 (ddd, J = 2.0, 6.6, 11.4 Hz, 1 H), 4.85 (ddd, J = 3.6, 14.2, 21.0 Hz, 1 H), 4.71 (ddd, J =
3.6, 11.8, 14.2 Hz, 1 H), 3.61ꢀ3.47 (m, 2 H), 3.19ꢀ3.06 (m, 2 H); 13C NMR (100.5 MHz, CDCl3) δ 140.9
(dd, J = 67.7, 8.1 Hz), 134.4 (d, J = 8.2 Hz), 129.8 (d, J = 8.2 Hz), 127.0 (d, J = 3.8 Hz), 126.7 (d, J =
7.5 Hz), 125.5 (d, J = 4.0 Hz), 123.2 (d, J = 50.6 Hz), 117.6 (dd, J = 91.6, 4.5 Hz), 75.9 (d, J = 6.7 Hz),
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44.2 (d, J = 8.2 Hz), 43.1 (d, J = 8.2 Hz), 41.1 (d, J = 107.9 Hz); P NMR (162 MHz, CDCl3): δ 23.1
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ppm; HRMS (ESI+): m/z calcd. for C20H20N3O3PS [M+Na]+: 436.0855; Found: 436.0861.
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2ꢀ(1ꢀCyclohexylꢀ2ꢀnitroethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3r): 19.9 mg, 48% yield;
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white solid; mp 168ꢀ169 °C; Rf 0.17 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column; IR
ν (KBr,
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cmꢀ1) 2924, 2887, 2850, 1599, 1552, 1502, 1491, 1375, 1273, 1215, 1122, 962; H NMR (400 MHz,
CDCl3) δ 7.41ꢀ7.30 (m, 8 H), 7.14ꢀ7.07 (m, 2 H), 4.77 (ddd, J = 5.2, 11.4, 15.4 Hz, 1 H), 4.40 (ddd, J =
8.4, 9.4, 17.0 Hz, 1 H), 3.96ꢀ3.76 (m, 4 H), 3.30ꢀ3.19 (m, 1 H), 1.80ꢀ1.67 (m, 1 H), 1.65ꢀ1.50 (m, 3 H),
1.39 (d, J = 13.2 Hz, 1H), 1.30 (d, J = 13.2 Hz, 1 H), 1.16ꢀ0.89 (m, 4 H), 0.85ꢀ0.74 (m, 1 H); 13C NMR
(100.5 MHz, CDCl3) δ 141.4 (dd, J = 43.2, 8.2 Hz), 129.7 (d, J = 2.3 Hz), 123.3 (d, J = 46.2 Hz), 118.5
(dd, J = 117.6, 4.5 Hz), 72.9 (d, J = 3.0 Hz), 45.1 (d, J = 8.1 Hz), 44.6 (d, J = 3.7 Hz), 44.0 (d, J = 96.0
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Hz), 37.0, 33.0 (d, J = 11.2 Hz), 28.7 (d, J = 3.0 Hz), 26.8, 26.4, 25.6; P NMR (162 MHz, CDCl3): δ
29.2 ppm; HRMS (ESI+): m/z calcd. for C22H28N3O3P [M+Na]+: 436.1760; Found: 436.1764.
2ꢀ(1ꢀNitropentanꢀ2ꢀyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3s): 19.1 mg, 51% yield; white
solid; mp 128ꢀ130 °C; Rf 0.17 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column; IR
ν
(KBr, cmꢀ1)
3061, 2964, 2931, 2895, 1600, 1560, 1500, 1481, 1267, 1220, 1126, 956; 1H NMR (400 MHz, CDCl3) δ
7.41ꢀ7.31 (m, 8 H), 7.14ꢀ7.08 (m, 2 H), 4.83 (ddd, J = 4.8, 11.2, 14.4 Hz, 1 H), 4.21 (ddd, J = 9.2, 9.4,
15.0 Hz, 1 H), 3.97ꢀ3.76 (m, 4 H), 3.38ꢀ3.26 (m, 1 H), 1.74ꢀ1.61 (m, 1 H), 1.31ꢀ1.14 (m, 3 H), 0.74 (t, J
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= 7.2 Hz, 3 H); C NMR (100.5 MHz, CDCl3) δ 141.2 (dd, J = 11.9, 7.4 Hz), 129.7 (d, J = 3.0 Hz),
123.3 (d, J = 27.5 Hz), 118.1 (dd, J = 22.3, 4.4 Hz), 75.8 (d, J = 2.3 Hz), 44.9 (d, J = 8.1 Hz), 44.4 (d, J
= 8.9 Hz), 38.2 (d, J = 111.6 Hz), 30.1 (d, J = 3.0 Hz), 20.5 (d, J = 9.6 Hz), 13.7; 31P NMR (162 MHz,
CDCl3): δ 28.9 ppm; HRMS (ESI+): m/z calcd. for C19H24N3O3P [M+Na]+: 396.1447; Found: 396.1451.
2ꢀ(1ꢀNitroꢀ3ꢀphenylpropanꢀ2ꢀyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3t): 24.4 mg, 58 %
yield; white solid; mp 138ꢀ139 °C; Rf 0.17 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for column; IR
ν
(KBr, cmꢀ1) 3056, 3022, 2957, 2924, 1599, 1558, 1492, 1377, 1271, 1220, 1118, 972; H NMR (400
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MHz, CDCl3) δ 7.44ꢀ7.33 (m, 6 H), 7.25ꢀ7.09 (m, 7 H), 6.92ꢀ6.87 (m, 2 H), 4.90 (ddd, J = 5.6, 11.6,
14.8 Hz, 1 H), 4.29 (ddd, J = 8.0, 10.0, 16.4 Hz, 1 H), 3.80ꢀ3.64 (m, 3 H), 3.62ꢀ3.54 (m, 1 H), 3.30ꢀ3.20
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(m, 1 H), 3.00 (ddd, J = 7.2, 10.8, 14.0 Hz, 1 H), 2.58 (ddd, J = 8.4, 15.4, 19.0 Hz, 1 H); C NMR
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8
9
(100.5 MHz, CDCl3) δ 141.1 (dd, J = 41.7, 7.4 Hz), 136.9 (d, J = 9.6 Hz), 129.8 (d, J = 23.8 Hz), 128.7,
128.4, 127.1, 123.2 (d, J = 30.6 Hz), 117.8 (dd, J = 16.3, 5.2 Hz), 75.5 (d, J = 3.0 Hz), 44.3 (d, J = 8.9
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Hz), 43.5 (d, J = 9.0 Hz), 39.1 (d, J = 111.7 Hz), 34.0 (d, J = 2.3 Hz); P NMR (162 MHz, CDCl3): δ
27.6 ppm; HRMS (ESI+): m/z calcd. for C23H24N3O3P [M+Na]+: 444.1447; Found: 444.1460.
(E)ꢀ2ꢀ(1ꢀNitroꢀ4ꢀphenylbutꢀ3ꢀenꢀ2ꢀyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (3u): 12.1 mg, 28
% yield; white solid; mp 142 °C (decomp.); Rf 0.17 (vHexane/vEA= 2:1), vHexane/vEA/vDCM (8/2/1) for
1
column; IR
ν
(KBr, cmꢀ1) 3024, 2914, 2881, 1599, 1554, 1500, 1491, 1265, 1226, 1122, 960; H NMR
(400 MHz, CDCl3) δ 7.45ꢀ7.37 (m, 6 H), 7.36ꢀ7.26 (m, 5 H), 7.19ꢀ7.15 (m, 4 H), 6.17 (dd, J = 16.0, 5.6
Hz, 1 H), 5.72 (ddd, J = 5.6, 12.0, 13.2 Hz, 1 H), 5.05 (ddd, J = 3.6, 8.2, 11.4 Hz, 1 H), 4.43 (ddd, J =
4.0, 11.2, 14.0 Hz, 1 H), 4.19ꢀ4.06 (m, 1 H), 3.82ꢀ3.69 (m, 4 H); 13C NMR (100.5 MHz, CDCl3) δ 140.9
(dd, J = 47.6, 8.9 Hz), 136.2 (d, J = 12.7 Hz), 135.4 (d, J = 6.3 Hz), 129.9 (d, J = 10.4 Hz), 128.8, 128.5
(d, J = 1.5 Hz), 126.3 (d, J = 1.5 Hz), 123.4 (d, J = 71.4 Hz), 119.5 (d, J = 10.4 Hz), 117.8 (dd, J = 91.6,
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4.5 Hz), 75.6 (d, J = 4.5 Hz), 44.7 (d, J = 12.7 Hz), 43.8 (d, J = 7.4 Hz), 43.6; P NMR (162 MHz,
CDCl3): δ 24.6 ppm; HRMS (ESI+): m/z calcd. for C24H24N3O3P [M+Na]+: 456.1447; Found: 456.1448.
General procedure for the largeꢀscale reaction
To a solution of NHPꢀthiourea 1a (0.86 g, 2.0 mmol) in CHCl3 (6 mL) was added (E)ꢀ(2ꢀ
nitrovinyl)benzene 2a (0.35 g, 0.46 mmol). The reaction mixture was stirred at room temperature for 6
h. After stirring for 6 h, the reaction mixture was concentrated under reduced pressure. The residue was
subjected to column chromatography on silica gel (Hexane/EA/DCM = 8:2:1 and Hexane/EA = 1:2) to
give corresponding product 3a (788 mg, 95%) and byproduct C (303 mg, 85%).
Synthetic Manipulation of PhosphaꢀMichael Adduct 3a
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1,3ꢀBis(4ꢀbromophenyl)ꢀ2ꢀ(2ꢀnitroꢀ1ꢀphenylethyl)ꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (4a): To a solution
of 3a (40.8 mg, 0.1 mmol) in 1,2ꢀdichloroethane (1.0 mL) were added benzoyl peroxide (4.7 mg, 0.012
mmol) and Nꢀbromosuccinimide (44.3 mg, 0.25 mmol) at room temperature. After stirring for 3 h,
volatiles were removed under reduced pressure. The residue was subjected to column chromatography
(Hexanes/ DCM = 1/1) on silica gel to give paleꢀyellow solid 4a (35.6 mg, 63%). mp 178 °C (decomp.);
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Rf 0.31 (vHexane/vDCM= 1:1); IR
ν
(KBr, cmꢀ1) 3028, 2957, 2875, 1591, 1556, 1491, 1473, 1363, 1309,
1267, 1234, 960; 1H NMR (400 MHz, CDCl3) δ 7.56ꢀ7.48 (m, 4 H), 7.30ꢀ7.15 (m, 7 H), 6.75ꢀ6.70 (m, 2
H), 5.23 (ddd, J = 4.0, 8.0, 12.0 Hz, 1 H), 4.86 (ddd, J = 5.6, 11.2, 14.8 Hz, 1 H), 4.54 (ddd, J = 4.0,
14.4, 20.8 Hz, 1 H), 3.49ꢀ3.32 (m, 2 H), 2.87ꢀ2.79 (m, 1 H), 2.75ꢀ2.66 (m, 1 H); 13C NMR (100.5 MHz,
CDCl3) δ 140.2 (dd, J = 78.1, 8.9 Hz), 132.8 (d, J = 3.0 Hz), 131.6 (d, J = 6.7 Hz), 128.9 (d, J = 3.0 Hz),
128.6 (d, J = 3.7 Hz), 128.1 (d, J = 5.2 Hz), 118.7 (dd, J = 63.3, 4.5 Hz), 116.0 (d, J = 42.5 Hz), 74.3 (d,
31
J = 5.2 Hz), 45.7 (d, J = 104.2 Hz), 43.7 (d, J = 7.4 Hz), 42.6 (d, J = 8.2 Hz); P NMR (162 MHz,
CDCl3): δ 24.6 ppm; HRMS (ESI+): m/z calcd. for C22H20Br2N3O3P [M+Na]+: 585.9501; Found:
585.9494.
Tertꢀbutyl(2ꢀ(2ꢀoxidoꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidinꢀ2ꢀyl)ꢀ2ꢀphenylethyl)carbamate (4b): To a
solution of 3a (40.6 mg, 0.1 mmol) in MeOH/THF (3:1, 2.0 mL) were added NiCl2•6H2O (59.6 mg,
0.25 mmol) and NaBH4 (38.1 mg, 1 mmol) at –10 °C. After stirring for 2 h at –10 °C, the reaction
mixture was warmed up to room temperature, then diꢀtertꢀbutyl dicarbonate (68.3 mg, 0.3 mmol) was
added to the mixture and kept stirring for another 2.5 h. The reaction was quenched with 1N aq.
NaHCO3, and the volatiles were removed under reduced pressure. The aqueous phase was extracted
with DCM. The organic phase was dried over anhydrous Na2SO4 and Na2SO4 was filtered off. After
removal of the solvent under reduced pressure, the residue was purified by flash column
chromatography to afford 4b (41.6 mg, 88%); white solid; mp 180ꢀ181 °C; Rf 0.41 (vHexane/vEA= 1:1),
vHexane/vEA/vDCM (8/2/1) for column; IR
ν
(KBr, cmꢀ1) 3448, 3057, 2976, 2889, 1710, 1599, 1500, 1365,
1
1271, 1170, 1126, 954; H NMR (400 MHz, CDCl3) δ 7.41ꢀ7.32 (m, 6 H), 7.27 (dd, J = 8.0, 0.8 Hz, 2
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H), 7.24ꢀ7.13 (m, 3 H), 7.10ꢀ7.05 (m, 2 H), 6.67 (dd, J = 7.2, 1.6 Hz, 2 H), 5.67 (b, 1 H), 3.90ꢀ3.70 (m,
3 H), 3.50ꢀ3.41 (m, 1 H), 3.41ꢀ3.33 (m, 1 H), 2.86 (b, 1 H), 2.70 (b, 1 H), 1.41 (s, 9 H); 13C NMR (100.5
MHz, CDCl3) δ 155.7, 141.9 (dd, J = 90.8, 8.2 Hz), 134.9, 129.6 (d, J = 13.4 Hz), 128.7 (d, J = 5.2 Hz),
128.3 (d, J = 3.0 Hz), 127.6, 122.3 (d, J = 59.5 Hz), 116.9 (dd, J = 98.2, 4.4 Hz), 79.3, 47.5 (d, J = 102.7
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9
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Hz), 43.8 (d, J = 7.4 Hz), 42.4 (d, J = 7.5 Hz), 40.7; P NMR (162 MHz, CDCl3): δ 29.1 ppm; HRMS
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(ESI+): m/z calcd. for C27H32N3O3P [M+Na]+: 500.2073; Found: 500.2076.
2ꢀ(2ꢀAminoꢀ1ꢀphenylethyl)ꢀ1,3ꢀdiphenylꢀ1,3,2ꢀdiazaphospholidine 2ꢀoxide (4c): To a solution of 3a
(145.7 mg, 0.36 mmol) in MeOH/THF (2.5:1, 7.0 mL) were added NiCl2•6H2O (211.9 mg, 0.90 mmol)
and NaBH4 (136.4 mg, 3.6 mmol) at –10 °C. After stirring for 2 h at –10 °C, the reaction mixture was
warmed up to room temperature and quenched with 1N aq. NaHCO3, and the volatiles were removed
under reduced pressure. The aqueous phase was extracted with DCM. The organic phase was dried over
anhydrous Na2SO4 and Na2SO4 was filtered off. After removal of the solvent under reduced pressure,
the residue was purified by flash column chromatography to afford 4c (112.3 mg, 83%); white solid; mp
130ꢀ131 °C; Rf 0.05 (vEA/vMeOH= 9:1), vEA/vMeOH (9/1) for column; IR
ν
(KBr, cmꢀ1) 3436, 3368, 3059,
1
2943, 2880, 1598, 1493, 1472, 1270, 1229, 1125, 997, 957; H NMR (400 MHz, CDCl3) δ 7.40ꢀ7.34
(m, 6 H), 7.27 (dd, J = 7.6, 0.8 Hz, 2 H), 7.24ꢀ7.16 (m, 3 H), 7.10ꢀ7.04 (m, 2 H), 6.73ꢀ6.69 (m, 2 H),
3.77 (ddd, J = 6.4, 12.4, 17.2 Hz, 1 H), 3.66 (ddd, J = 6.4, 10.0, 10.0 Hz, 1 H), 3.50ꢀ3.34 (m, 2 H), 3.21
13
(ddd, J = 9.2, 9.4, 17.4 Hz, 1 H), 2.84ꢀ2.72 (m, 2 H), 1.91 (b, 2 H); C NMR (100.5 MHz, CDCl3) δ
142.0 (dd, J = 88.6, 8.2 Hz), 134.9 (d, J = 6.0 Hz), 129.5 (d, J = 16.4 Hz), 128.9 (d, J = 6.0 Hz), 128.4
(d, J = 3.8 Hz), 127.5 (d, J = 3.7 Hz), 122.2 (d, J = 49.9 Hz), 116.9 (dd, J = 101.3, 4.5 Hz), 51.2 (d, J =
31
102.0 Hz), 43.8 (d, J = 7.4 Hz), 42.4 (d, J = 7.4 Hz), 42.1; P NMR (162 MHz, CDCl3): δ 29.4 ppm;
HRMS (ESI+): m/z calcd. for C22H24N3OP [M+H]+: 378.1730; Found: 378.1735.
(2ꢀAminoꢀ1ꢀphenylethyl)phosphonic acid (4d): A mixture of 4c (29.4 mg, 0.078 mmol) in 36% aq. HCl
(0.3 mL) was refluxed for 20 h. The mixture allowed to cool down, and coꢀevaporated two times with
water. The crude reside was dissolved in water (2.0 mL), and the solution was stirred for 30 min after
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addition of Na2CO3 (4.0 equiv). After sttiring for 30 min, the water was evaporated under reduced
pressure. The resulting solid was dissolved in MeOH (2.0 mL) and filtered to remove the undissolved
solid. Propylene oxide (100 ꢁL) was added to the filtrate and the solution was stirred for 30 min at 0 °C.
After stirring for 30 min, a white precipitate formed. The solid was filtered and dried to give 4d:19 (10.5
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9
1
mg, 67%); white solid; H NMR (400 MHz, D2O) δ 7.43ꢀ7.30 (m, 5 H), 3.63ꢀ3.55 (m, 1 H), 3.53ꢀ3.43
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(m, 1 H), 3.28 (ddd, J = 5.2, 13.4, 19.4 Hz, 1 H); C NMR (100.5 MHz, D2O) δ 134.4 (d, J = 7.4 Hz),
129.2 (d, J = 2.3 Hz), 129.0 (d, J = 5.9 Hz), 128.0 (d, J = 2.2 Hz), 44.6 (d, J = 128.0 Hz), 40.6 (d, J =
3.0 Hz); 31P NMR (162 MHz, D2O): δ 15.6 ppm;
Acknowledgment
This work was financially supported by University of Nevada Las Vegas (Faculty Opportunity
Awards). Dr. Katarzyna LorencꢀKukula at SCAAC is acknowledged for mass spectra data.
Supporting information
1H and 13C NMR spectra of new compounds. This material is available free of charge via the Internet at
http://pubs.acs.org.
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