Unusual reaction of β-hydroxy α-diazo carbonyl compounds with TsNHN=CHCOCl/Et3N

Article abstract of DOI:10.1016/j.tetlet.2004.04.037

The reaction of β-hydroxy α-diazo carbonyl compounds with TsNHN=CHCOCl/Et₃N gave β-(p-tolylsulfonyl) α,β- unsaturated carbonyl compounds or β-(p-tolylsulfonyl) α-diazo esters. The reaction mechanism is discussed.

Full text of DOI:10.1016/j.tetlet.2004.04.037

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4563–4566
Unusual reaction of b-hydroxy a-diazo carbonyl compounds with
TsNHN@CHCOCl/Et3N
Weifeng Shi, Bo Zhang, Binge Liu, Feng Xu, Fengping Xiao, Jian Zhang, Shiwei 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 20 February 2004; revised 29 March 2004; accepted 2 April 2004
Abstract—The reaction of b-hydroxy a-diazo carbonyl compounds with TsNHN@CHCOCl/Et3N gave b-(p-tolylsulfonyl) a,b-
unsaturated carbonyl compounds or b-(p-tolylsulfonyl) a-diazo esters. The reaction mechanism is discussed.
Ó 2004 Elsevier Ltd. All rights reserved.
a-Diazo carbonyl compounds have attracted great
attention over the past decades due to their diverse
reactivities.1 In addition to serve as metal carbene pre-
cursors in catalytic metal carbene transfer reactions, the
relatively stable a-diazo carbonyl compounds them-
selves can also tolerate a number of chemical transfor-
mations without decomposition of the diazo
functionality. 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-diazo carbonyl compounds with b-hydroxy or
b-amino substituent.2 We have recently studied the
reaction of b-substituted a-diazo carbonyl compounds,
which are easily prepared by these nucleophilic con-
densations and have found that the b-substituent dra-
matically affects the subsequent metal catalyzed reaction
of the corresponding a-diazo carbonyl compounds.3 To
further explore the chemistry of b-hydroxy a-diazo
carbonyl compounds, we have intended to convert the
hydroxyl group in diazo compound 1 into a diazoester
group with a well-established diazotization reaction
(Scheme 1).1a;4 Since there are two diazo functional
groups in the resulting diazoester compound 3, novel
reactivity may be expected. However, when trying to
convert the b-hydroxyl group into diazoester group, we
observed quite unexpected results.
O
N2
R'
OH
O
O
O
NNHTs
HCCOCl
R
R'
+
R
N2
1
R = Aryl
N2
2
3
Et3N
CH2Cl2, 0 oC
4a R = Ph, R' = CH3
4b R = Ph, R' = OEt
84 %
76 %
65 % *
p-CH3C6H4
O S O O
4c R = p-PhPh, R' = OEt
4d R = p-MeOPh, R' = OEt 90 %
R
H
R'
*18 % Trans isomer was also isolated.
Scheme 1.
chloride p-toluenesulfonylhydrazone 2 in the presence of
triethylamine in CH2Cl2 at 0 °C to room temperature.4
The reaction proceeded cleanly to give a major product
in 76% isolated yield. The structure of this product was
elucidated to be ethyl cis-3-(p-tolylsulfonyl)-3-phenyl-2-
propenoate 4b, rather than the expected bisdiazo com-
pound 3 (R ¼ Ph, R0 ¼ OEt), based on the spectral data.
Initially, the b-hydroxy-b-phenyl a-diazo ester
1
The formation of b-(p-tolylsulfonyl) a,b-unsaturated
carbonyl compounds were found to be general for b-aryl
(R ¼ Ph, R0 ¼ OEt) was treated with glyoxylic acid
b-hydroxy diazo substrates
1
(R ¼ Ph, R0 ¼ CH3;
R ¼ p-PhPh, p-MeOPh, R0 ¼ OEt). The normal diazoti-
* Corresponding author. Tel.: +86-10-6275-7248; fax: +86-10-6275-
1708; e-mail: wangjb@pku.edu.cn
zation reactions with these substrates all proceeded in
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.037

4564
W. Shi et al. / Tetrahedron Letters 45 (2004) 4563–4566
Figure 2. X-ray structure of 5b.
compounds 5a–c are found to be exceptionally stable. In
EI-MS spectra, they all give molecular ion peak. They
are stable when refluxed in 1,2-dichloroethane. When
catalyzed with Rh2(OAc)4 in CH2Cl2 at room tempera-
ture, 5b reacted very slowly to give an oxidized product
6b, rather than the product due to 1,2-hydride shift, in
45% yield after 12 h (Scheme 3).
Figure 1. X-ray structure of 4c.
good isolated yields of 4b–d. For 1 (R ¼ p-PhPh,
R0 ¼ OEt), the reaction gave an isomeric mixture in a
ratio of 78:22. In other cases, only cis isomers were
isolated.5 For 4c, the structure was further confirmed by
single crystal X-ray diffraction (Fig. 1).6
A reaction mechanism is proposed to account for the
formation of 4 and 6 (Scheme 4). As suggested by Corey
and Mayers, the reaction of b-hydroxy diazo com-
pound 1 with TsNHN@CHCOCl/Et3N gave bisdiazo
ester 3 together with p-toluenesulfinate ester 9.4b We
speculate that the existence of the neighboring electron-
withdrawing diazo group and the carbonyl group makes
the b-position in 3 and 9 liable to nucleophilic attack.
The p-toluenesulfinate group in 9 is a good leaving
group, which is easily replaced by the p-toluenesulfinyl
anion through the attack of the more nucleophilic sul-
fur. The diazo ester group in 3, on the other hand, may
also be easily replaced by the p-toluenesulfinyl anion
after protonation. The SN2 type nucleophilic substitu-
tion gives the b-(p-tolylsulfonyl) a-diazo ester 5. When
R of 5 is an aryl group, the diazo decomposition occurs
under the reaction conditions to give the 1,2-hydride
shift product 4.9
We then examined the reaction of b-hydroxy a-diazo
carbonyl compounds bearing b-alkyl substituents
(Scheme 2). Unexpectedly again, the isolated products in
this case were neither bisdiazo esters 3, nor b-(p-tolyl-
sulfonyl) a,b-unsaturated carbonyl compounds 4. The
spectral data suggested their structures as b-(p-tolyl-
sulfonyl) a-diazo esters 5a–c.5 The structure of a-diazo
compound 5b was confirmed by single crystal X-ray
diffraction (Fig. 2).6
The X-ray structure of 5b shows some interesting fea-
tures. The O@C–C@N2 group is found to have s–Z
conformation, while the other b-substituted a-diazo
carbonyl compounds that we have studied all have s–E
conformation.3c;7 The diazo group and the carbonyl
group are almost coplanar with a dihedral angle of
)0.93°. The dihedral angle between b C–H bond and the
diazo group is )169.5°. Thus, the b C–H is in an anti-
periplanar position, which is not favorable for 1,2-
hydride shift in diazo decomposition.8 The diazo
The important point in this mechanism is the suggestion
that the b-position is liable to nucleophilic attack in
these compounds. This speculation is supported by the
fact that b-acetoxy group in compound 7 is readily
replaced by p-CH3C6H4SO2 group when treating with
sodium p-toulenesulfinate (Scheme 5) in DMF at room
temperature.10
p-CH
3C6H4
OH
O
O S O O
Et3N
CH2Cl2
0 oC
NNHTs
HCCOCl
p-CH
3C6H4
p-CH3C6H4
R
R' +
R
OEt
N2
O S O O
O S O O
N2
Rh2(OAc)4
CH2Cl2
0 oC~r.t.
45 %
R
OEt
R
O
OEt
1
5a R = CH3CH2
76 %
N2
R = Alkyl
R' = OEt
5b R = CH3(CH2)2 65 %
82 %
5b R = CH3(CH2)2
6b R = CH3(CH2)2
5c R = CH3(CH2)5
Scheme 2.
Scheme 3.

W. Shi et al. / Tetrahedron Letters 45 (2004) 4563–4566
4565
O
O
OH
O
H
Cl3CCN, NaH
NHCCCl3
R'
Cl
R
R'
N
N2, PhCH3
0 oC ~ r.t.
ref. 3c
NHSO2
R
N2
N2
11
2
Glyoxyl Chloride
Tosylhydrazone
1
Et3N
Normal
imidation
NH
O
S
N2
NH
O
CCl3
R'
O
O
O
b
H
S
O
O
CCl3
R
O
O
R
R
R'
a
b
8
N2
10
N2
O
S
OH
O
9
NH
O
R'
CCl3
N2
1
Scheme 6.
O
a
S
O
H
O
compound 1 can be easily replaced by other functional
group through nucleophilic substitution opens the way
to the diazo compounds with more diverse b-substitu-
tions. These diazo compounds may have novel reactiv-
ities when catalyzed with transition metal complex or
acid. The investigation along this line is under the way in
our laboratory and the results will be reported in due
course.
H
p-CH
O
O
3C6H4
N
2R
R'
O
S
O O
N2
R
R'
O
S
O
N2
CO2
CH2N2
3
5
R = Aryl
p-CH
3C6H4
Acknowledgements
O
O
S O
R
R'
The project is generously supported by Natural Science
Foundation of China (Grant No. 20225205, 20172002,
20390050).
H
4
Scheme 4.
References and notes
p-CH
3C6H4
O S O O
1. For comprehensive reviews, see: (a) Doyle, M. P.;
McKervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds; Wiley–Inter-
science: New York, 1998; (b) Ye, T.; McKervey, M. A.
Chem. Rev. 1994, 94, 1091–1160.
OAc O
CH3C6H4SO2Na
R
OEt
R
OEt
DMF
40 %
N2
N2
5c
7
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.; Wang, J. Tetrahedron Lett. 2002, 43, 1285–1287.
3. (a) Jiang, N.; Qu, Z.; Wang, J. Org. Lett. 2001, 3, 2989–
2992; (b) Jiang, N.; Ma, Z.; Qu, Z.; Xing, X.; Xie, L.;
Wang, J. J. Org. Chem. 2003, 68, 893–900; (c) Shi, W.;
Jiang, N.; Zhang, S.; Wu, W.; Du, D.; Wang, J. Org. Lett.
2003, 5, 2243–2246.
Scheme 5.
In our previous study, we have observed a direct con-
version of hydroxyl group to trichloroacetylamino
group by treatment of b-hydroxy a-diazo carbonyl
compound 1 with Cl3CCN and NaH (Scheme 6).3c
Similar SN2 type mechanism is most likely followed in
that case too, thereby supporting the argument made in
this paper that the b-position in a-diazo carbonyl com-
pounds is liable to nucleophilic attack.
In summary, we have observed unexpected reactions of
b-hydroxy a-diazo carbonyl compounds with
TsNHN@CHCOCl/Et3N, which give b-(p-tolylsulfonyl)
a-diazo esters or b-(p-tolylsulfonyl) a-diazo esters. These
transformations may find synthetic applications.11
Moreover, the fact that the b-hydroxyl group in diazo
4. (a) House, H. O.; Blankley, L. J. Org. Chem. 1968, 33, 53–
60; (b) Corey, E. J.; Mayers, A. G. Tetrahedron Lett. 1984,

4566
W. Shi et al. / Tetrahedron Letters 45 (2004) 4563–4566
25, 3559–3562; (c) Corey, E. J.; Mayers, A. G. J. Am.
Chem. Soc. 1985, 107, 5574–5576; (d) Clive, D. L. J.;
Daigneault, S. J. Org. Chem. 1991, 56, 3801–3814.
6. The crystallographic measurement was made on a Rigaku
R-AXIS RAPID image plate diffractometer with graphite
ꢀ
monochromated Mo-Ka radiation (k ¼ 0:71073 A). An
5. General procedure for the reaction of b-hydroxy a-diazo
carbonyl compounds with TsNHN@CHCOCl/Et3N. In a
flamed three-necked round bottom flask, b-hydroxy-a-
diazo compound (1.0 mmol) was dissolved in 5 mL
CH2Cl2. Triethylamine (4.0 mmol) was added to the
solution at 0 °C, after 10 min the glyoxylic acid chloride
p-toluenesulfonylhydrazone (3.0 mmol) was added drop-
wise. The mixture was allowed to stir for 8 h between 0 °C
and room temperature. The reaction mixture was concen-
trated under reduced pressure with rotvap. The residue
was subjected to silica gel chromatography (petroleum
ether–acetone ¼ 12:1) to afford the pure products. Repre-
sentative analytical data:
absorption correction was applied by correction of sym-
metry-equivalent reflections using the ABSCOR program.
The structure was solved by direct methods and successive
difference maps (SHELXS 97) and refined by full-matrix
least squares on F 2 using all unique data (SHELXL 97). The
non-hydrogen atoms were refined anisotropically. The
hydrogen atoms were included in their calculated positions
with geometrical constraints and refined in the riding
model. Lists of refined coordinates have been deposited in
the Cambridge Crystallographic Data Center (deposition
number 4c, CCDC 231762; 5b, CCDC 231761). Copies of
the available material can be obtained free of charge on
application to the CCDC, 12, Union Rd, Cambridge, CB2
1EZ, UK. E-mail: deposit@ccdc.cam.ac.uk.
(E)-Ethyl 3-(p-tolylsulfonyl)-3-phenyl-3-buten-2-one (4a).
1
IR 3058, 1706, 1147, 700, 561 cmꢀ1; H NMR (200 MHz,
7. For a discussion on the conformation of a-diazo carbonyl
compounds, see: Kirmse, W. Eur. J. Org. Chem. 2002,
2193–2256.
8. (a) Evanseck, J. D.; Houk, K. N. J. Phys. Chem. 1990, 94,
5518–5523; (b) Nickon, A. Acc. Chem. Res. 1993, 26, 84–
89; (c) Schaefer, H. F., III Acc. Chem. Res. 1979, 12, 288–
296; (d) Keating, A. E.; Garcia-Garibay, M. A.; Houk, K.
N. J. Phys. Chem. A 1998, 102, 8467–8476; (e) Calvo-
CDCl3): d 2.37 (s, 3H), 2.60 (s, 3H), 6.44 (s, 1H), 7.21 (d,
2H, J ¼ 8:4 Hz), 7.27–7.33 (m, 5H), 7.56 (d, 2H,
J ¼ 8:4 Hz); 13C NMR (50 MHz, CDCl3): d 21.6, 31.3,
128.3, 128.6, 129.5, 129.5, 129.6, 132.2, 135.4, 139.8, 144.1,
144.9, 200.7; MS m=z (EI) 300 (Mþ, 9), 235 (12), 221 (25),
193 (38), 150 (38), 139 (50), 102 (51.8), 91 (68), 65 (43), 43
(100); Anal. Calcd for C17H16O3S: C, 67.98; H, 5.37; S,
10.67. Found: C, 67.87; H, 5.23; S, 10.70.
ꢁ
Losada, S.; Suarez, D.; Sordo, T. L.; Quirante, J. J.
Ethyl 2-diazo-3-(p-tolylsulfonyl)-nonanoate (5c). IR 2929,
2098, 1698, 1324, 1141 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d 0.87 (t, 3H, J ¼ 6:7 Hz), 1.07 (br, 3H), 1.26–1.43 (m,
8H), 1.61–1.73 (m, 1H), 2.27 (br, 1H), 2.43 (s, 3H), 3.86–
3.98 (m, br, 3H), 7.33 (d, 2H, J ¼ 8:1 Hz), 7.76 (d, 2H,
J ¼ 8:2 Hz); 13C NMR (100 MHz, CDCl3): d 13.9, 14.2,
21.6, 22.4, 23.5, 26.4, 28.5, 31.3, 59.6, 61.2, 128.8, 129.6,
134.5, 145.0; MS m=z (EI) 366 (Mþ, 0.38), 338 (0.69), 293
(3), 211 (10), 183 (62), 155 (51), 139 (52), 109 (100), 91
(81), 67 (39), 55 (47), 29 (99). Anal. Calcd for
C18H26SO4N2: C, 58.99; H, 7.15; N, 7.64. Found: C,
58.96; H, 7.10; N, 7.51.
J. Phys. Chem. B 1999, 103, 7145–7150; (f) Shin, S. H.;
Keating, A. E. J. Am. Chem. Soc. 1998, 118, 7626–7627.
9. When crude TsNHN@CHCOCl was used in the reaction,
the b-aryl-b-tosyl a-diazo carbonyl compounds could also
be isolated in 21–30% yield for the b-aryl substrates 1
(R ¼ aryl).
10. The reaction gave essentially only one product. The
isolated yield was not optimized.
11. For example, a,b-unsaturated sulfones have been applied
in the synthesis of pyrrole derivatives, see: Uno, H.;
Tanaka, M.; Inoue, T.; Ono, N. Synthesis 1999, 471–
474.