Reaction of β-trimethylsiloxy α-diazocarbonyl compounds with trimethylsilyl halides: A novel diazo decomposition process

Article abstract of DOI:10.1016/j.tetlet.2005.10.070

When β-trimethylsiloxy α-diazocarbonyl compounds were treated with trimethylsilyl halide, a mixture of α- and γ-halide substituted unsaturated carbonyl compounds was obtained. The mechanism of this novel diazo decomposition process is discussed.

Full text of DOI:10.1016/j.tetlet.2005.10.070

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8873–8875
Reaction of b-trimethylsiloxy a-diazocarbonyl compounds with
trimethylsilyl halides: a novel diazo decomposition process
Fengping Xiao, Zhenhua Zhang, Jian Zhang and Jianbo Wang*
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking University, Beijing 100871, China
Received 7 September 2005; revised 17 October 2005; accepted 18 October 2005
Available online 2 November 2005
Abstract—When b-trimethylsiloxy a-diazocarbonyl compounds were treated with trimethylsilyl halide, a mixture of a- and c-halide
substituted unsaturated carbonyl compounds was obtained. The mechanism of this novel diazo decomposition process was
discussed.
Ó 2005 Elsevier Ltd. All rights reserved.
O
a-Diazocarbonyl compounds as the metal carbene pre-
cursors in catalytic reactions have attracted great atten-
tion over the past decades.1 On the other hand, the
relatively stable a-diazocarbonyl compounds can toler-
ate a number of chemical transformations with the diazo
functionality keeping unchanged. For example, ethyl
diazoacetate can be deprotonated with LDA or NaH,
and the resulting anion can further react with C@O or
C@N groups to give a-diazocarbonyl compounds with
b-hydroxy or b-amino substituent.2 Our recent study
TMS
O
O
O
1) Base
R1
H
R1
R2
+
R2
H
2) TMSCl, Et3N
CH2Cl2, 0 oC
N2
R1
N2
1a~g
3a~g
2
O
O
R1
TMSX
R2
+
R2
CH2Cl2
0 oC-RT
X
X
5a~h
4a~h
Scheme 1.
suggests that
b position of the a-diazocarbonyl
compound is liable to nucleophilic substitution.3 This
observation makes it possible to prepare the diazo
compounds with various b-substituents. We have used
this strategy to prepare some new a-diazocarbonyl
compounds with different b-substituents such as Ts
and SR, and their reactions catalyzed by Rh(II) have
been studied.4,5
The nucleophilic addition of acyldiazomethane 2 with
aldehyde 1a–g gave b-hydroxy a-diazocarbonyl com-
pounds, which were followed by the reaction with
TMSCl in the presence of triethylamine in CH2Cl2
at 0 °C to room temperature. The b-trimethylsiloxy
a-diazocarbonyl compounds 3a–g were obtained in high
yields (Table 1).6,7 The diazo compounds 3a–g are rela-
tively stable and can be kept at room temperature for
days without detectable decomposition.
To further explore the utility of a-diazocarbonyl com-
pounds in organic synthesis, we have converted the b-
hydroxyl group in diazo compound into b-siloxy group
to afford b-siloxy substituted diazo compound 3a–g
(Scheme 1).6 When 3a–e was further treated with tri-
methylsilyl halide, a novel diazo decomposition process
occurred to give a- and c-halide substituted unsaturated
carbonyl compounds 4a–h and 5a–h.
b-Trimethylsiloxy a-diazocarbonyl compounds 3a were
further treated with trimethylsilyl chloride with the
expectation that b-chloro substituted a-diazo com-
pounds may be obtained, as shown in Scheme 2.
However, when 3a was treated with TMSCl in CH2Cl2
at 0 °C to room temperature, the diazo compound was
decomposed to give two major products, none of them
was the expected b-chloro substituted a-diazo com-
pound. Inspection of the two products with IR, 1H
*
Corresponding author. Tel./fax: +86 10 6275 7248; e-mail: wangjb@
pku.edu.cn
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.070

8874
F. Xiao et al. / Tetrahedron Letters 46 (2005) 8873–8875
Table 1. Reaction of b-hydroxy a-diazo esters with trimethylsilyl
chloride
O
TMSO
O
TMSI
OEt
OEt
Aldehyde R1
Diazo R2
Product
Yielda (%)
CH2Cl2
0 oC, 58 %
Entry
I
N2
3a
1CH
OEt
OEt
OEt
OEt
OEt
CH3
CH3
3a
3b
3c
3d
3e
3f
91
90
90
89
88
89
88
3
6
2
3
4
5
6
7
CH3CH2
CH3(CH2)2
CH3(CH2)4
Ph
CH3
CH3(CH2)2
Scheme 3.
3g
TMS
O
TMS
O
TMSO
O
O
a Yields after column chromatographic purification with silica gel.
TMSX
OEt
OEt
OEt
CH2Cl2
N2
N2
H
X
N2
8
3a
7
SiMe3
O
X
O
Me3Si
TMSO
R1
O
TMSX
R1
O
R1
R2
H
O
R2
R2
N2
N2
N2
X
a
b
4a
5a
not observed
X =Cl, Br
OEt
a
H
N2
Scheme 2.
X
b
9
NMR and MS spectra indicated one product was (E)-
ethyl 4-chloropent-2-enoate 4a (R1 = CH3, R2 = Et,
X = Cl), the other one was (E)-ethyl 2-chloropent-3-
enoate 5a (R1 = CH3, R2 = OEt, X = Cl). The diazo
decomposition with TMSCl was surprising, and to the
best of our knowledge, this type of reaction of a-diazo-
carbonyl compound has not been reported before. The
reaction of TMSCl with other b-trimethylsiloxyl a-di-
azocarbonyl compounds gave similar results (Table
2),8 except in the case of 3e, in which case a complex
mixture was formed. For the reactions with substrates
3f and 3g, same results were obtained but the products
were all volatile and unstable compounds. Accurate data
of yields could not be determined for these two cases.
Scheme 4.
only product in 58% yield. No isomeric product similar
to 5 could be identified from the reaction mixture. The
c-iodo substituted product 6 was highly unstable at
room temperature (Scheme 3).
A plausible reaction mechanism was proposed to
account for the formation of 4 and 5 (Scheme 4). The
reaction of 3a with TMSX generated an intermediate
7, in which the b substituent became a better leaving
group. E2 type elimination gave vinyl diazo carbonyl
compound 8, which could be further protonated at the
diazo carbon. Nucleophilic attack by XÀ could occur
at both a- and c-position to give 4a and 5a with the
extrusion of N2.
When trimethylsilyl bromide was used instead of tri-
methylsilyl chloride, the corresponding mixture of bro-
mide 4 (X = Br) and 5 (X = Br) were obtained in similar
yields (Table 2). It was noted that the reaction had no
selectivity with two isomeric products 4 and 5 isolated
in almost 1:1 ratio.
This proposed mechanism was supported by the follow-
ing experiments. When vinyl diazocarbonyl compound
10 was treated with aqueous HCl in acetone, a mixture
of 4g and 5g was isolated in moderate yield (combined
yield of 65 %) with a ratio of 60:40 (Scheme 5).
It was also noted that compound 4a–h was not stable
even in refrigerator. Partial conversion of 4 to 5 was
observed. Trimethylsilyl iodide (TMSI) could also react
with 3. Compound 3a was treated with TMSI in CH2Cl2
at 0 °C to give (E)-ethyl 4-iodopent-2-enoate 6 as the
On the other hand, when 3a was treated with Rh2(OAc)4
(1mol %) in CH 2Cl2 at room temperature, 1,2-hydrogen
shift product 11 was isolated in almost quantitative yield
(Scheme 6). Other diazo compounds gave similar results
Table 2. Reaction of 3a–e with TMSCl or TMSBr
TMSX (X = ) Products Yielda (%) Ratiob (4:5)
O
Entry
3
( )4
1
2
3
4
5
6
7
8
a
a
b
b
c
Cl
Br
Cl
Br
Cl
Br
Cl
Br
4a+5a
4b+5b
4c+5c
4d+5d
4e+5e
4f+5f
56
52
64
63
55
60
64
55
41:59
48:52
39:61
57:43
35:65
47:53
50:50
45:55
O
O
Cl
4g
HCl (aq.)
( )4
O
+
CH3COCH3
CH2Cl2, 0 oC
65 %
N2
10
O
( )4
c
O
d
d
4g+5g
4h+5h
Cl
4g : 5g = 60 : 40
5g
a Yields after column chromatographic purification with silica gel.
b Ratios after column chromatographic purification with silica gel.
Scheme 5.

F. Xiao et al. / Tetrahedron Letters 46 (2005) 8873–8875
8875
4. Shi, W.; Zhang, B.; Zhang, J.; Liu, B.; Zhang, S.; Wang, J.
Org. Lett. 2005, 7, 3103–3106.
Me3SiO
O
Me3SiO
O
Rh (OAc)
2
4
5. Xu, F.; Shi, W.; Wang, J. J. Org. Chem. 2005, 70, 4191–
4194.
OEt
CH Cl , RT
OEt
2
2
N2
H
99 %
´
´
´
6. Sarabia Garcıa, F.; Pedraza Cebrian, G. M.; Heras Lopez,
´
A.; Lopez Herrera, F. J. Tetrahedron 1998, 54, 6867–
6896.
11
3a
Scheme 6.
7. General procedure for the reaction of b-hydroxy a-diazo
carbonyl compounds with TMSCl: In a flamed three-necked
round bottom flask, b-hydroxy a-diazocarbonyl compound
(1.0 mmol) was dissolved in CH2Cl2 (5 mL). Triethylamine
(3.0 mmol) was added to the solution at 0 °C. After stirring
for 10 min, TMSCl (1.2 mmol) was added with syringe. The
mixture was allowed to stir for 4 h between 0 °C and room
temperature. The reaction mixture was quenched by water
and was extracted twice with CH2Cl2, washed with
saturated brine and dried. After evaporation of the solvent,
a residue was obtained which was purified by column
chromatography on silica gel (petroleum ether/ace-
tone = 100:0.1) to afford pure products 3a–g. Ethyl 2-diazo
3-trimethylsiloxy pentanoate (3a): 1H NMR (300 MHz,
CDCl3): d 0.00 (s, 9H), 0.79 (t, J = 7.5 Hz, 3H), 1.13–1.15
(t, J = 7.2 Hz, 3H), 1.49–1.56 (m, 2H), 4.10 (qd, J = 7.2,
1.5 Hz, 2H), 4.40 (t, J = 6.8, 1H); 13C NMR (75 MHz,
CDCl3): d À0.31, 9.87, 14.16, 29.29, 60.62, 67.84, 165.86.
8. General procedure for the reaction of 3a–d with TMSX: In a
flamed three-necked round bottom flask, b-trimethylsiloxy
a-diazocarbonyl compound 3a–d (1.0 mmol) was dissolved
in CH2Cl2 (5 mL). TMSX (X = Cl or Br, 1.0 mmol) was
added by syringe at 0 °C. The mixture was allowed to stir at
0 °C until all the diazo substrate disappeared as judged by
IR spectra. Evaporation of the solvent gave a residue,
which was purified by column chromatography on silica gel
(petroleum ether/ether = 200:1) to afford the pure products
of 4a–h and 5a–h. Representative data: (E)-ethyl 2-chlo-
when treated with Rh2(OAc)4. This reaction may be
served as a good method for preparing this type of enol
trimethylsilyl ethers.
In summary, we have observed a novel reaction of b-tri-
methylsiloxyl a-diazocarbonyl compounds with TMSX
(X = Br, Cl), which give a- and c-halide substituted
unsaturated carbonyl compounds. This reaction may
find synthetic application as a new entry to these halides.
As far as our knowledge is concerned, there are only lim-
ited methods to prepare these halides.9
Acknowledgements
The project is generously supported by Natural Science
Foundation of China (Grant No. 20225205, 20390050).
References and notes
1. For comprehensive reviews, see: (a) Doyle, M. P.; McKer-
vey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; Wiley-Interscience: New
York, 1998; (b) Ye, T.; McKervey, M. A. Chem. Rev. 1994,
94, 1091–1160.
rohept-3-enoate (4e). IR (film): m 1264, 1743 cmÀ1 1H
;
NMR (200 MHz, CDCl3): d 0.91(t, J = 7.2 Hz, 3H), 1.30
(t, J = 7.2 Hz, 3H), 1.38–1.49 (m, 2H), 2.02–2.13 (m, 2H),
4.21(q, J = 7.2, 2H), 4.74 (d, J = 8.6 Hz, 1H), 5.61–5.74
(m, 1H), 5.82–5.96 (m, 1H); 13C NMR (50 MHz, CDCl3): d
3.52, 13.96, 21.71, 34.09, 58.10, 62.15, 124.66, 137.82,
168.56; MS m/z (EI) 155 [(MÀCl)+, 75], 127 (23), 117 (2),
109 (11), 97 (4), 81 (100), 75 (58). (E)-Ethyl 4-chlorohept-2-
2. (a) Schollkopf, U.; Frasnelli, H.; Hoppe, D. Angew. Chem.,
Int. Ed. Engl. 1970, 9, 300–301; (b) Schollkopf, U.;
Banhidai, B.; Frasnelli, H.; Meyer, R.; Beckhaus, H.
Liebigs Ann. Chem. 1974, 1767–1783; (c) Pellicciari, R.;
Natalini, B. J. Chem. Soc., Perkin Trans. 1 1977, 1822–
1824; (d) Pellicciari, R.; Natalini, B.; Sadeghpour, B. M.;
Marinozzi, M.; Snyder, J. P.; Williamson, B. L.; Kuethe,
J. T.; Padwa, A. J. Am. Chem. Soc. 1996, 118, 1–12; (e)
Moody, C. J.; Taylor, R. J. Tetrahedron Lett. 1987, 28,
5351–5352; (f) Wenkert, E.; McPherson, A. A. J. Am.
Chem. Soc. 1972, 94, 8084–8090; (g) Burkoth, T. L.
Tetrahedron Lett. 1969, 10, 5049–5052; (h) Woolsey,
N. F.; Khalil, M. H. J. Org. Chem. 1972, 37, 2405–2408;
(i) Jiang, N.; Qu, Z.; Wang, J. Org. Lett. 2001, 3, 2989–
2992; (j) Jiang, N.; Wang, J. Tetrahedron Lett. 2002, 43,
1285–1287; (k) Jiang, N.; Ma, Z.; Qu, Z.; Xing, X.; Xie, L.;
Wang, J. J. Org. Chem. 2003, 68, 893–900.
enoate (5e). IR (film): m 228, 1268, 1723 cmÀ1 1H NMR
;
(200 MHz, CDCl3): d 0.94 (t, J = 7.2 Hz, 3H), 1.30 (t,
J = 7.2 Hz, 3H), 1.40–1.55 (m, 2H), 1.78–1.89 (m, 2H), 4.22
(q, J = 7.2, 2H), 4.40–4.51(m, H1 ), 6.02 (dd,
J = 1.0,
15.4 Hz, 1H), 6.89 (dd, J = 7.8, 15.4 Hz, 1H); 13C NMR
(50 MHz, CDCl3): d 3.34, 14.18, 19.41, 39.59, 59.61, 60.65,
122.31, 146.2, 165.84; MS m/z (EI) 190 (M+, 6), 162 (15),
155 (71), 145 (35), 127 (30), 120 (30), 109 (24), 81 (97), 29
(100).
9. (a) Duclos, J. F.; Outurquin, F.; Paulmier, C. Tetrahedron
Lett. 1993, 34, 7417–7420; (b) Dussault, P. H.; Eary, C. T.;
Lee, R. J.; Zope, U. R. J. Chem. Soc., Perkin Trans. 1 1999,
2189–2204; (c) Tunge, J. A.; Mellegaard, S. R. Org. Lett.
2004, 6, 1205–1207.
3. Shi, W.; Zhang, B.; Liu, B.; Xu, F.; Xiao, F.; Zhang, J.;
Zhang, S.; Wang, J. Tetrahedron Lett. 2004, 45, 4563–4566.