Catalyst-controlled switchable phosphination of α-diazoesters

Article abstract of DOI:10.1039/c3ob40429c

Organocatalyst and metal provide different products: a catalyst-controlled switchable phosphination of α-diazoesters has been developed by using DBU and copper as catalysts. It provided an efficient synthetic method for the construction of various phospho

Full text of DOI:10.1039/c3ob40429c

Organic &
Biomolecular Chemistry
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Catalyst-controlled switchable phosphination of
α-diazoesters†
Cite this: Org. Biomol. Chem., 2013, 11,
3612
Honglai Jiang,a Hongming Jin,a Ablimit Abdukader,a,b Aijun Lin,a Yixiang Chenga
Received 1st March 2013,
Accepted 13th April 2013
and Chengjian Zhu*a,c
DOI: 10.1039/c3ob40429c
www.rsc.org/obc
Organocatalyst and metal provide different products: a catalyst-
controlled switchable phosphination of α-diazoesters has been
developed by using DBU and copper as catalysts. It provided an
efficient synthetic method for the construction of various phos-
phorus compounds via the formation of N–P and C–P bonds.
The synthetic and biological importance of phosphorus com-
pounds has stimulated increasing research on the construc-
tion of structurally sophisticated phosphorus compounds.1
P–E bond-forming reactions have been extensively studied via
transition-metal catalysed coupling with organohalides,
addition to unsaturated C–C bonds, homo- and heterodehydro
coupling or coupling through decarboxylation.1,2 However the
search for economical, high yielding, and technically simple
methods for the synthesis of useful phosphorus compounds
remains a burgeoning field of synthetic research.
Much attention has been paid to α-diazocarbonyl com-
pounds because of their extensive applications in synthetic
chemistry,3 which includes cyclopropanation,4 cyclopropena-
tion,5 X–H (X = C, O, S, N, Si) bond insertions6 and ylide for-
mations.7 Although α-diazocarbonyl compounds have been
studied extensively, the reactions between phosphorus com-
pounds and α-diazocarbonyl compounds are rarely studied.8
The reported method was limited to high temperature, low
yields and an excess of aliphatic phosphonates. For diversity
reaction properties, the α-diazocarbonyl compounds can not
only form carbenes but also can be used as nucleophiles
under special conditions.9 To the best of our knowledge, the
important chemoselective reaction of α-diazocarbonyl com-
pounds with the same partners both at the carbon (C1) and
Scheme 1 The switchable phosphination of α-diazoesters.
the terminal nitrogen (N1) has not been reported. It is particu-
larly interesting for substrates with multiple reactive sites
capable of undergoing different reactions switched by different
catalysts. Furthermore, developing approaches that can con-
struct different phosphorous compounds in an effective way is
actively required, since the process can afford the desired pro-
ducts through rapid, easily obtained substrates and minimal
synthetic manipulations.10 Herein we disclose a new method-
ology for chemoselectively constructing N–P and C–P bonds:
organocatalyst- and copper-catalysed switchable reactions
between α-diazoesters and phosphorus compounds (Scheme 1).
In our initial study, we observed that the reaction between
dimethyl phosphonate 2a and methyl 2-diazo-2-phenylacetate
1a could be catalysed by K2CO3 and CuBr (Table 1, entry 1). To
our surprise, the result was the phosphinamide from the phos-
phonate nucleophilic addition to the terminal nitrogen of
α-diazoester rather than the P–H bond insertion into the
carbene. Additionally, the metal CuBr was unnecessary during
the process (Table 1, entry 2). To uncover this unprecedented,
base-catalysed phosphinamide synthesis, we put our attention
to studying the feasibility of this novel finding. No conversion
of 1a was observed in the absence of any catalyst (Table 1,
entry 3). Meanwhile, Li2CO3 did not furnish the desired coup-
ling product either (Table 1, entry 4). Intriguingly, DBU effec-
tively catalysed the reaction even at ambient temperature,
which indicated that inorganic salts usually gave unsatisfactory
aState Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical
Engineering, Nanjing University, Nanjing 210093, People’s Republic of China.
E-mail: cjzhu@nju.edu.cn
bDepartment School of Chemistry and Chemical Engineering, Xinjiang University,
Urumqi 830046, People’s Republic of China
cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Shanghai 200032, People’s Republic of China
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3ob40429c
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Table 1 Optimization of the direct phosphination of methyl 2-diazo-2-
phenylacetatea
Table 2 DBU catalysed N-phosphination of α-diazoestersa
Entry
Cat (mol%)
R
Solvent
Yieldc (%)
1
2
3
4
5
6
7
8
K2CO3–CuBrb
K2CO3 (20)
—
Li2CO3 (20)
DBU (20)
DMAP (20)
DMEDA (20)
DBU (20)
DBU (20)
DBU (20)
CuBr (5)
CuBr (5)
CuBr (5)
CuBr (5)
CuBr (5)
CuBr (5)
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OEt
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
DMSO
THF
CH2Cl2
CH2Cl2
CH2Cl2
ClCH2CH2Cl
Toluene
Hexane
3a/20
3a/20
3a/0
3a/trace
3a/55
3a/0
3a/0
3a/66
3a/45
3a/24
4a/0
9
10
11
12
13
14
15
16
4a/0
OPh
OPh
OPh
OPh
4a/45
4a/87
4a/12
4a/0
a A mixture of 1a (0.5 mmol), 2 (0.55 mmol) and catalyst in solvent
(2 mL) was stirred at room temperature for 48 h (3a), 12 h (4a). b K2CO3
(20 mol%) and CuBr (5 mol%). c Yield of isolated product.
results. It is noteworthy that the reaction using DMAP and
DMEDA gave no product (Table 1, entries 6–7). We further
examined the efficacy of this transformation in the presence
20 mol% DBU as the catalyst by varying the solvents. Only
acetonitrile provided a moderate result and produced the
corresponding N–P bond formation product in 66% yield,
whereas all other tested solvents gave unsatisfactory yields
(Table 1, entries 9–10).
During our research on the α-diazoesters, we also investi-
gated the C–P bond formation reactions since C–P bond con-
struction is highly important in the synthesis of phosphine-
containing compounds. Although X–H (X = C, O, S, N, Si) bond
a Reaction conditions: 1 (0.5 mmol), 2 (0.55 mmol), DBU (20 mol%,
0.1 mmol), CH3CN (2.0 mL), room temperature, yield of isolated
product.
insertions6 and copper-catalysed synthesis of alkylphospho- bond formation included 5 mol% of copper(I) bromide at
nates from phosphonates and N-tosylhydrazones have been room temperature in the presence of ClCH2CH2Cl as solvent.
reported,11 C–P bond formation by P–H insertion into the Therefore, chemoselective phosphination can be easily
carbene has hardly been developed.8 To our disappointment, obtained through the selective N–P and C–P bond formation
we found that P–H insertion into the carbene did not happen by controlling the DBU and copper catalyst.
when the α-diazoester and aliphatic phosphonate was treated
With the optimized reaction conditions in hand, the scope
with copper-catalyst (Table 1, entries 11–12). Realizing it may of the phosphination via N–P bond formation between various
due to its low activity,12 we turned our attention to diphenyl α-diazoesters and phosphorous compounds was investigated.
phosphonate which has high activity. As anticipated, the C–P As described in Table 2, a broad range of α-diazoesters are
bond formation reaction did occur under copper(I) bromide compatible with this operationally simple DBU-catalysed phos-
(5 mol%) catalysis with dry CH2Cl2 as solvent, affording the phination. When the methyl ester group of the α-diazoester
product in 45% yield (Table 1, entry 13). Among the solvents was switched to ethyl or isopropyl ester, a satisfactory yield
screened, toluene and hexane decreased the yields dramati- was obtained (Table 2, 3a–3c). Notably, the ester group of the
cally, while the utilization of ClCH2CH2Cl gave an excellent α-diazoesters had a limited effect on the yield. Moreover, sub-
yield, and the yield can be improved to 87% (Table 1, entries strates with various electron-withdrawing and electron-donat-
14–16). Consequently, the optimal reaction conditions for C–P ing functional groups were well tolerated, and gave the
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Table 3 Copper catalysed P–H insertion into carbene reactionsa
toward establishing a new horizon for controlling reactions via
different catalysts types.
Acknowledgements
We gratefully acknowledge the National Natural Science Foun-
dation of China (21172106, 21074054), the National Science
Fund for Talent Training in Basic Science (No. J1103310), the
National Basic Research Program of China (2010CB923303),
and the Research Fund for the Doctoral Program of Higher
Education of China (20120091110010) for their financial
support.
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α-diazoesters that could be controlled by organomolecule and
metal. The new methodology offered facile access to various
phosphorus compounds and provided an excellent option
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