Efficient solid/liquid phase-transfer catalytic diazo transfer synthesis

Article abstract of DOI:10.1080/00397910903100742

A simple and efficient solid/liquid phase-transfer catalytic diazo transfer reaction for the synthesis of diazocarbonyl, diazophosphonyl, and diazophosphinyl compounds is reported. Copyright

Full text of DOI:10.1080/00397910903100742

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Efficient Solid/Liquid Phase-Transfer
Catalytic Diazo Transfer Synthesis
a
b
b
Zsuzsa M. Jászay , Truong Son Pham , Katalin Gönczi , Imre
b
b
Petneházy & László Tőke
a
Research Group of Organic Chemical Technology of the Hungarian
Academy of Sciences, Budapest, Hungary
b
Department of Organic Chemistry and Technology, Budapest
University of Technology and Economics, Budapest, Hungary
Version of record first published: 06 May 2010.
To cite this article: Zsuzsa M. Jászay , Truong Son Pham , Katalin Gönczi , Imre Petneházy & László
Tőke (2010): Efficient Solid/Liquid Phase-Transfer Catalytic Diazo Transfer Synthesis, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:11, 1574-1579
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1
Synthetic Communications , 40: 1574–1579, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903100742
EFFICIENT SOLID/LIQUID PHASE-TRANSFER
CATALYTIC DIAZO TRANSFER SYNTHESIS
1
Zsuzsa M. J a´ szay, Truong Son Pham, Katalin G o¨ nczi,
2
2
2
2
Imre Petneh a´ zy, and L a´ szl o´ T }o ke
1
Research Group of Organic Chemical Technology of the Hungarian
Academy of Sciences, Budapest, Hungary
2
Department of Organic Chemistry and Technology, Budapest University of
Technology and Economics, Budapest, Hungary
A simple and efficient solid/liquid phase-transfer catalytic diazo transfer reaction for the
synthesis of diazocarbonyl, diazophosphonyl, and diazophosphinyl compounds is reported.
Keywords: Diazo phosphinates; diazo phosphonates; diazo transfer; phase-transfer catalysis; solid
potassium carbonate
Diazoketones, diazo carboxylates, and diazo phosphonates are extremely
useful intermediates as carbene precursors in insertion reactions and 1,3-dipolar
[1]
cycloadditions.
The usual synthesis for these compounds is the diazo transfer reaction, which
involves the reaction of an active methylene group with a sulfonyl azide in the pres-
ence of a suitable base. Numerous diazo transfer reactions have been described and
[
2]
reviewed. They differ in terms of the structure of the azide reagents, the bases, and
[
3]
the solvents. Although the most commonly used reagent is p-toluenesulfonyl azide,
numerous alternative sulfonyl azides have been developed that are superior in
[
4]
[5]
stability or safety or offer better separability of product and reagent. To over-
[6]
[
come the latter problem, polystyrene-supported benzenesulfonyl azide and soluble
7]
[8]
oligomeric sulfonyl azide have also been applied. The most often used basic
catalysts are potassium tert-butylate,
[3,5]
[9]
sodium hydride, pyridine, and triethyl
[
6b,6c]
[6d,10]
amine,
but bases on solid supports are also used.
Solid potassium carbon-
[
11]
ate as a base has also been described both in an ionic liquid
reaction (i.e., without any solvent).
or in a solid-state
To avoid the problem of separating the
product from the reagent and the by-products, a liquid=liquid phase-transfer cata-
lytic (PTC) method has also been developed.
In connection with our interest in the synthesis of cyclopropane phosphonates
[12]
[
13]
[14]
and phosphinates,
a simple, efficient, solid=liquid PTC method was developed
Received April 28, 2009.
Address correspondence to Zsuzsa M. J a´ szay, Research Group of Organic Chemical Technology of
the Hungarian Academy of Sciences, H-1521, Budapest, Hungary. E-mail: zsjaszay@mail.bme.hu
1
574

PHASE-TRANSFER CATALYTIC DIAZO TRANSFER SYNTHESIS
1575
that provides the sensitive diazo intermediates in excellent yield and high purity. The
method is generally applicable for the synthesis of diazo carbonyl, phosphonyl, and
phosphinyl compounds.
The diazo transfer reaction is carried out by stirring the active methylene
compound 1 with the sulfonyl azide 2 in toluene in the presence of solid potassium
carbonate as a base and a quaternary ammonium chloride as catalyst. The reaction pro-
ꢀ
ceeds smoothly at 60 C and is complete within 10–60 min, depending on the substrate 1
and the sulfonyl azide 2. In a general procedure, equivalent amounts of substrate 1 and
sulfonyl azide 2 are stirred in toluene with an excess of solid potassium carbonate and a
catalytic amount of benzyltriethylammonium chloride (TEBAC) (Scheme 1).
The reaction does not require an inert atmosphere. Because of the high conver-
sion, workup is simple: it involves filtering the potassium salt, followed by washing
the filtrate with diluted sodium hydroxide and water, and evaporating of the solvent.
The products can be isolated without column chromatography or distillation.
The results of the diazo transfer reaction with three different sulfonyl azides
with a variety of substrates are collected in Table 1.
The data in Table 1 demonstrate that all the three sulfonyl azides reacted
smoothly under the reported solid=liquid PTC conditions. The reactions were very
fast with tosyl azide (2a), which is still the most common diazo transfer reagent,
and also with trisyl azide (2,4,6-triisopropylbenzenesulfonyl azide, 2b), which has
[
15]
been mainly used as an azidation reagent so far.
and 2b were 100% in the presence of TEBAC, but somewhat lower, 80 and 85%
entries 2 and 14), without the catalyst. The reaction proceeded smoothly with
The conversions of 1 with 2a
(
[
4]
imidazole-1-sulfonyl azide hydrochloride (2c), a new shelf-stable reagent, but diazo
transfer was slower and the conversion was less than with 2a and 2b (entries 3, 6, 8,
1
yield and shorter reaction time than in non-PTC circumstances.
2, 15, 20). Note that under our reaction condition, 2c also provided much greater
[
4]
In conclusion, a simple solid=liquid PTC method using solid potassium
carbonate as base has been elaborated, which is superior to other procedures in
terms of reaction time and conversion. In most cases, all the three sulfonyl azides
(2a–c) proved to be better reagents in our circumstances than using procedures
described in the literature. We found our method especially convenient for the
Scheme 1. PTC diazo transfer method starting from active methylene compound 1 using aromatic sulfonyl
azide 2a–c.

´
Z. M. JASZAY ET AL.
1576
Table 1. Preparation of compounds 3a–i in a solid=liquid PTC reaction
Time
(min)
Conv.
of 1 (%)
Yield of
3 (%)
Reported
yield (%)
Entry
Product 3
Azide 2
a
[6b]d
95
1
2
2a
2b
10
10
100
91 (3a)
90 (3a)
a
100
3
2c
90
96
84 (3a)
a
[12]
4
5
2a
2b
10
10
100
93 (3b)
91 (3b)
94
a
100
–
a
[4]
6
7
8
2c
2a
2c
90
10
90
97
88 (3b)
89 (3c)
75 (3c)
65
a
[12]
86 , 90
[13]
100
a
92
[4]
59
a
[10]
[12]
[5]
9
2a
15
100
91 (3d)
90 , 96
b
[3]
37 , 61
1
1
0
1
2a
2b
20
20
100
92 (3e)
87 (3e)
b
100
–
b
98
[4]
0
12
2c
150
85 (3e)
b
[3]
1
1
3
4
2a
2b
20
20
100
89 (3f)
86 (3f)
6
b
100
–
b
15
16
17
2c
2a
2b
150
100
84 (3f)
–
b
c
75
100
93 (3g)
b
75
100
88 (3g)
b
c
18
2a
75
100
94 (3h)
b
c
1
2
9
0
2a
2c
75
100
91 (3i)
b
86
240
74 (3i)
a
b
c
1
Conversion is based on H NMR analysis.
31
Conversion is based on P NMR analysis.
New compound.
With p-acetamidobenzenesulfonyl azide.
d
synthesis of the sensitive and nonvolatile phophonyl and phosphinyl derivatives.
The reaction has a wide scope; the method presented does not require special circum-
stances and can be scaled up easily.

PHASE-TRANSFER CATALYTIC DIAZO TRANSFER SYNTHESIS
1577
EXPERIMENTAL
1
1
13
H NMR spectra were recorded on a Bruker DRX-500 instrument; C NMR
3
and P NMR spectra were measured on a Bruker 300 Avance instrument using
1
13
tetramethylsilane ( H, C) as internal standard and 85% H PO ( P) as external
31
3
4
standard, all in CDCl solution.
3
Typical Procedure
The stirred suspension of the substrate 1 (2 mmol), TEBAC (0.2 mmol,
.045 g), and solid anhydrous K CO (8 mmol, 0.78 g) in 5 mL of toluene was heated
to 60 C, and the sulfonyl azide 2 (2 mmol) in toluene (3 mL) was added. After the
reaction was complete (as indicated in Table 1), the solid parts were filtered off.
The filtrate was extracted twice with 0.5 M NaOH, twice with water, dried over
0
2
3
ꢀ
MgSO , and concentrated under reduced pressure. The products 3 obtained were
4
pure enough according to their spectroscopic data and did not require further
purification.
Compounds 3a–f are known compounds. The spectroscopical data of 3a–d
have been described and are in good agreement with those reported.
Ethyl Diazo(diethoxyphosphoryl)acetate (3e)
1
H NMR: d (ppm) 1.33 (3H, t, JHH ¼ 7.1 Hz, CH ); 1.39 (6H, t, J ¼ 7.1 Hz,
3
HH
3
1
CH ); 4.29 (2H, q, J ¼ 7.1 Hz, CH ); 4.22 (4H, m, CH ). P NMR: d (ppm) 10.2.
3
HH
2
2
Diethyl (1-Diazo-2-oxo-2-phenyl)ethylphosphonate (3f)
1
H NMR: d (ppm) 1.31 (6H, t, J ¼ 7.1 Hz, CH ); 4.19 (4H, m, CH );
HH
3
2
3
1
7
.4–7.76 (m, 5H, CHAr). P NMR: d (ppm) 10.6.
Phenyl Propenyl Diazo(diethoxyphosphoryl)acetate (3g)
1
H NMR: d (ppm) 1.42 (6H, t, JHH ¼ 7.1 Hz, CH ); 4.21 (4H, m, CH ); 4.77 (2H,
3
2
d, JHH ¼ 6.5 Hz, CH ); 6.17 (1H, dt, J ¼ 6.5 Hz, J ¼ 15.9 Hz, CH); 6.58 (1H, d,
2,
HH
HH
1
3
JHH ¼ 15.9 Hz CH); 7.3–7.6 (m, 5H, CH ). C NMR d (ppm) 12.6 (CH ); 16.9
Ar
3
(
1
CH ); 62.4, 62.6 (OCH ); 123.8 (C
3
); 131.5 (CH ); 128.3; 132.8; 136.1; 135.7;
vinyl
2
vinyl
3
1
46.3 (CH ); 155.2 (CO) 171.4 (d, Jpc ¼ 50 Hz, C=N ). P NMR: d (ppm) 10.0.
ar
2
But-2-enyl Diazo(ethoxy-phenylphosphinyl)acetate (3h)
1
H NMR: d (ppm) 1.41 (3H, t, JHH ¼ 7.0 Hz, CH ); 1.69 (2H, d, J ¼ 7.3 Hz),
3
HH
4
.18 (2H, m, CH ); 4.53 (2H, d, J ¼ 6.4 Hz, CH ); 5.42 (1H, m, CH); 5.70 (1H, m,
3 2
2
HH
2,
1
3
CH); 7.4–8.1 (m, 5H, CHAr). C NMR d (ppm) 16,39 (CH ); 62.25 (OCH ); 65.8
(
(
C=N ); 122,4 (C ); 126.7 (CHvinil); 128.3–146.3 (CHarom a´ s); 163.3 (CO); 171.4
d, JPC ¼ 50 Hz, C=N2). P NMR: d (ppm) 23.2.
2 vinil
3
1

´
Z. M. JASZAY ET AL.
1578
Phenylpropenyl Diazo(ethoxy-phenylphosphinyl)acetate (3i)
1
H NMR: d (ppm) 1.4 (3H, t, JHH ¼ 7.0 Hz, CH ); 4.23 (2H, qd, J ¼ 7.3 Hz,
3
HH
JHH ¼ 21.2 Hz, CH ); 4.75 (2H, d, J ¼ 6.5 Hz, CH ); 6.15 (1H, dt, J ¼ 6.5 Hz,
2
HH
2,
HH
J
¼ 15.8 Hz, CH); 6.53 (1H, d, J ¼ 15.8 Hz, CH); 7.1–7.6 (m, 10H, CH ).
3 2 2 vinyl
HH
HH
Ar
1
3
C NMR: d (ppm) 16.39 (CH ); 62.25 (OCH ); 65.8 (CH ); 122.4 (C
); 131.7
P
3
1
(
CHvinyl); 128.3–146.3 (CH ); 163.3 (CO); 1721.3 (d, J ¼ 50 Hz, C=N2).
ar
PC
NMR: d (ppm) 21.7.
ACKNOWLEDGMENT
Financial support by the Hungarian Scientific Research Fund (OTKA No.
K60284) is gratefully acknowledged.
REFERENCES
1
. (a) Callant, P.; D’Haenens, L.; Vandewalle, M. An efficient preparation and the intramol-
ecular cyclopropanation of a-diazo-b-ketophosphonates and a-diazophosphonoacetates.
Synth. Commun. 1984, 14(2), 155–161; (b) Davies, H. M.; McAfee, M. J.; Oldenburg,
C. E. M. Scope and stereochemistry of the tandem intramolecular cyclopropanation=
Cope rearrangement sequence. J. Org. Chem. 1989, 54(4), 930–936; (c) Davies, H. M.;
Antoulinakis, E. G.; Hansen, T. Catalytic asymmetric synthesis of syn-aldol products
from intermolecular C-H insertions between allyl silyl ethers and methyl aryldiazoace-
tates. Org. Lett. 1999, 1(3), 383–385; (d) Padwa, A.; Sheehan, S. M.; Straub, C. S. An
¨
isomunchnone-based method for the synthesis of highly substituted 2(1H)-pyridones. J.
Org. Chem. 1999, 64(23), 8648–8659; (e) Davies, H. M.; Beckwith, E. J. Catalytic enantio-
selective C-H activation by means of metal-carbenolid-induced C-H insertion. Chem. Rev.
2
003, 103(8), 2861–2903; (f) Mu
Asymmetric cyclopropanation and cycloaddition of dioxocarbenes. Synthesis 2006, (10),
689–1696; (g) Fenlon, T. W.; Schwaebisch, D.; Mayweg, V. W.; Lee, V.; Adlington,
¨
ller, P.; Allenbach, Y. F.; Chappellet, S.; Ghanem, A.
1
R. M. Studies towards the synthesis of lindenene: Unexpected stereochemical outcome
of an intramolecular cyclopropanation reaction and synthesis of (ꢁ)-epi-lindenene and
(
ꢁ)-iso-lindenene. Synlett 2007, (17), 2679–2682.
2
. (a) Regicz, M. Transfer of diazo groups. Angew. Chem., Int. Ed. Engl. 1967, 6, 733–743;
(
b) Hendrickson, J. B.; Wolf, W. A. The direct introduction of the diazo function in
organic synthesis. J. Org. Chem. 1968, 33(9), 3610–3618; (c) Regicz, M.; Maas, G. Diazo
Compounds: Properties and Synthesis; Academic Press: Orlando, 1986.
3
4
5
6
. Regitz, M.; Ansch u¨ tz, W.; Liedhegener, A. Synthese von a-Diazo-phosphons a¨ ureestern.
Chem. Ber. 1968, 101, 3734–3743.
. Goddard-Borger, E. D.; Stick, R. V. An efficient, inexpensive, and shelf-stable diazotrans-
fer reagent: Imidazole-1-sulfonyl azide hydrochloride. Org. Lett. 2007, 9(19), 3797–3800.
. Khare, A. B.; McKenna, C. E. An improved synthesis of tetraalkyl diazomthylenedipho-
sphonates and alkyl diazo(dialkoxyphosphoryl)acetates. Synthesis 1991, 405–406.
. (a) Taber, D. F.; Ruckle, R. E. Jr.; Hennessy, M. J. Mesyl azide: A superior reagent for
diazo transfer. J. Org. Chem. 1986, 51(21), 4077–4078; (b) Baum, J. S.; Shook, D. Diazo-
transfer reactions with p-acetamidobenzenesulfonyl azide. Synth. Commun. 1987, 17(14),
1709–1716; (c) Wurz, R. P.; Lin, W.; Charette, A. B. Trifluoromethanesulfonyl azide: An
efficient reagent for the preparation of a-cyano-a-diazo carbonyls and an a-sulfonyl-a-
diazo carbonyl. Tetrahedron Lett. 2003, 44(49), 8845–8848; (d) Rianelli, R. S.; deSouza,

PHASE-TRANSFER CATALYTIC DIAZO TRANSFER SYNTHESIS
1579
M. C. B. V.; Ferreira, V. F. Mild diazo transfer reaction catalyzed by modified clays.
Synth. Commun. 2004, 34(5), 951–959.
7
. Green, G. M.; Peet, N. P.; Metz, W. A. Polystyrene supported benzenesulfonyl azide: A
diazo transfer reagent that is both efficient and safe. J. Org. Chem. 2001, 66(7), 2509–2511.
. Harned, A. M.; Sherrill, W. M.; Flynn, D. L.; Hanson, P. R. High-load, soluble oligo-
meric benzenesulfonyl azide: Application to facile diazo-transfer reactions. Tetrahedron
8
2
005, 61(51), 12093–12099.
. Shiraki, C.; Saito, H.; Takahashi, K.; Urakawa, C.; Hirata, T. Preparation of amino
diethoxyphosphoryl) acetic esters: Catalytic hydrogenation of diazo compounds to
amines. Synthesis 1988, 399–401.
9
(
1
1
0. Alloum, A. B.; Villemin, D. Potassium fluoride on alumina: An easy preparation of
diazocarbonyl compounds. Synth. Commun. 1989, 19, 2567–2571.
1. Ramachary, D. B.; Narayana, V. V.; Ramakumar, K. Direct ionic liquid–promoted orga-
nocatalyzed diazo-transfer reactions, diversity-oriented synthesis of diazo-compounds.
Tetrahedron Lett. 2008, 49, 2704–2709.
1
1
1
2. Ghosh, S.; Datta, I. Diazo transfer reaction in solid state. Synth. Commun. 1991, 21(2),
1
91–200.
3. Ledon, H. An improved preparation of a-diazocarbonyl compounds. Synthesis 1974,
47–348.
3
4. T o} ke, L.; J a´ szay, M. Z.; Petneh a´ zy, I.; Clementis, G.; Vereczkey, D. G.; K o¨ vesdi, I.;
Rockenbauer, A.; Kov a´ ts, K. A versatile building block for the synthesis of substituted
cyclopropanephosphonic acid esters. Tetrahedron 1995, 51(33), 9167–9178.
1
5. Evans, D. A.; Britton, T. C.; Ellman, J. A.; Dorow, R. L. The asymmetric synthesis of
a-amino acids: Electrophilic azidation of chiral imide enolates, a practical approach to
the synthesis of (R)-, and (S)-a-azido carboxylic acids. J. Am. Chem. Soc. 1990,
112(10), 4011–4030.