Synthesis of Sulfonyldiazomethanes and Acetyldiazomethanes via an Alumina-Mediated Decarboxylation Strategy

Article abstract of DOI:10.1071/CH15637

Diazo compounds are widely adopted in organic synthesis due to their carbine characteristics. One of the most interesting diazo compounds is diazolsulfonyl. Here, in the current study, we found that diazolsufonyl compounds could be prepared with moderate

Full text of DOI:10.1071/CH15637

CSIRO PUBLISHING
Aust. J. Chem.
Communication
http://dx.doi.org/10.1071/CH15637
Synthesis of Sulfonyldiazomethanes and
Acetyldiazomethanes via an Alumina-Mediated
Decarboxylation Strategy
A C
,
B
B
A B C
, ,
Yiyong Yan,
Gaoyuan Ma, Wei Wei, and Jing Zhao
A
School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate
School, Shenzhen 51800, China.
B
State Key laboratory of Pharmaceutical Biotechnology, Institute of Chemistry and
Biomedical Sciences, School of Life Sciences, Nanjing University,
Nanjing 210093, China.
C
Corresponding authors. Email: yanyy@pkusz.edu.cn; jingzhao@nju.edu.cn
Diazo compounds are widely adopted in organic synthesis due to their carbine characteristics. One of the most interesting
diazo compounds is diazolsulfonyl. Here, in the current study, we found that diazolsufonyl compounds could be prepared
with moderate to excellent yield through decarboxylation of diazosulfonyl acetates by neutral alumina. We hope that this
mild and simple method might inspire wider application of these useful compounds.
Manuscript received: 10 October 2015.
Manuscript accepted: 14 December 2015.
Published online: 18 January 2016.
Diazo compounds are very useful in organic synthesis.[1] Due
to their carbene characteristics, these types of compounds
have been studied extensively for their applications including
cyclopropanation,[2] C–H insertion reaction,[3] and Wolff
rearrangement.[4] a-Diazocarbonyls are well-known species
regarding their synthesis and reactivity,[5] whereas a-
diazosulfonyl compounds have been less explored in spite
of the expected reactivity resemblance with that of a-
diazocarbonyls.[6] Due to their metabolic stability and gener-
ally favourable physical properties of the sulfonyl groups,[7]
a-diazosulfonyl compounds could potentially provide
straightforward access to structurally unique small libraries for
medicinal chemistry. Here, we describe a simple procedure for
the preparation of diazosulfones through a novel neutral
alumina-mediated decarboxylation of diazosulfonyl acetates.
Interesting substrate dependence is discussed, which led to our
proposed mechanism.
Currently, the most widely used methods to synthesize
diazosulfonyl compounds are via the alumina-promoted decar-
boxylation of nitroso compound 1 (Scheme 1)[8] and the deace-
tylation of acetyl compounds.[9] Notably, the former process
required the use of highly toxic nitrosyl chloride gas.
While attempting to synthesize tosyldiazomethane using the
deacetylation protocol, we discovered that the formation of
the desired product was much more facile when we replaced
the acetyl group with a 3,5,5-trimethylcyclohex-2-enol-derived
Previous method
O
O
O
O
O
Alumina
CINO
N
S
S
O
N2
N
S
O
H
Et2O, 10–15ЊC
O
O
Pyridine
O
NO
1
Our method
O
S
O
O
O
S
O
Alumina
S
N2
p-AcNHC6H4SO2N3
O
O
O
O
CH2Cl2, 0ЊC to r.t.
O
N2
Et3N
Scheme 1. Methods employed to synthesize sulfonyldiazomethane. ClNO ¼ nitrosyl chloride; r.t. ¼ room temperature.
Journal compilation Ó CSIRO 2016 www.publish.csiro.au/journals/ajc

B
Y. Yan et al.
ester. During initial substrate screening, we were surprised to
find that decarboxylation seemed to occur exclusively for this
particular ester. Simpler ethyl, benzyl, or saturated analogues
did not afford any desired tosyldiazomethane product under
otherwise identical conditions (Table 1).
Table 1. Decarboxylation of various ester analogues
Substrates
ProductA
Entry
1
O
O
S
O
These seemingly peculiar results inspired us to propose a
carbocation decarboxylation pathway (Scheme 2). In the case
of 3,5,5-trimethylcyclohex-2-enyl ester, decarboxylation occurs
through the formation of thermodynamically stable tertiary
allylic carbocation. Either the esters lack the double bond or
substitution does not proceed due to the resulting higher energetic
cationic species. To verify this hypothesis, we examined t-Bu and
3-methylbut-2-enyl esters. To our delight, decarboxylation
occurred smoothly for both substrates in the presence of neutral
alumina. Spectroscopically pure product was obtained by simple
filtrationand concentration. Noflash column isrequired for most
substrates. It is noted that certain tosyldiazomethanes decom-
posed slightly on Al2O3, as evidenced by the pink colour on the
alumina surface. The yield and purity were nevertheless not
affected. Silica gel can also promote this reaction, although
yields were lower. Decarboxylation under basic conditions
(KOH, LiOH, or pyrrolidine) also led to tosyldiazomethane
formation, however, with a lower efficiency.
H
S
O
O
O
N2
N2
2a (98 %)
1a
2
No reaction
O
O
S
O
O
O
N2
1b
3
4
No reaction
No reaction
O
O
S
O
N2
1c
O
O
This method is general for various benzene-sulfonyldiazo-
methanes-bearing substituents, regardless of electronic proper-
ties. Interestingly, it can also be extended to simple alkyl
sulfonyldiazomethane synthesis. Those compounds were
obtained at slightly lower yields, partially due to product
instability in the presence of alumina (Table 2).
This method can be also used for decarboxylation of
acetyldiazomethanes, and the yield was modest (Scheme 3).
In summary, we have developed a simple method for the
synthesis of a-diazosulfonyl compounds. The products were
obtained in high yield and purity through neutral alumina-
mediated decarboxylation. The formation of a stable allylic
carbocation was proposed to be the driving force for the facile
decarboxylation, supported by experimental data. Further stu-
dies and applications of these useful diazo analogues will be
reported in due course.
S
O
O
N2
1d
5
6
No reaction
O
O
S
O
O
N2
1e
2a (70 %)
O
S
O
O
O
N2
1f
7
2a (61 %)
O
S
O
O
Experimental
O
N2
General Procedure for Decarboxylation by Neutral Al2O3
1g
AThe numbers in parentheses represent the yields.
To the white solid of 5 g Al2O3 in a Schlenk tube was added
anhydrous dichloromethane (DCM; 15 mL) under the protection
of nitrogen, and the suspension was stirred at 08C. The Schlenk
O
O
S
O
O
S
O
O
S
S
O
H
CO2
ϩ
ϩ
ϩ
Ϫ
O
O
O
N2
O
O
O
O
N2
N2
N2
ϩ
ϩ
Al2O3-OϪ
Al2O3-OH
ϩ
Scheme 2. Proposed mechanism for decarboxylation.

Synthesis of Sulfonyldiazomethanes and Acetyldiazomethanes
C
Table 2. Synthesis of sulfonyldiazomethanes
The reaction mixture was filtrated and washed with DCM to
ensure that the product was thoroughly washed out. The yellow
filtrate was concentrated by rotary evaporation at room tem-
perature to obtain a yellow oil or solid. The raw product was
purified by chromatography column (ethyl acetate/petroleum
ether). The product was stored well at ꢀ208C in the dark.
N2
O
O
O
Alumina, DCM
O
S
S
0ЊC to r.t.
R
N2
O
R
O
Supplementary Material
Entry
1
R
Yield [%]
73
Additional experimental details and spectroscopic data are
available on the journal’s website.
MeO
Acknowledgement
2b
This work was financed by Grant 31200607 from the National Natural
Science Foundation of China, Grant 2014M550563 from the China Post-
doctoral Science Foundation, and Grant JCYJ20140627145302109 from
Shenzhen Municipal Science and Technology Innovation Council.
2
3
99
98
2c
2d
References
Cl
[1] (a) M. P. Doyle, M. A. McKervey, T. Ye, Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds 1998 (Wiley Interscience:
New York, NY)
(b) T. Ye, M. A. McKervey, Chem. Rev. 1994, 94, 1091. doi:10.1021/
CR00028A010
(c) M. P. Doyle, M. A. McKervey, Chem. Commun. 1997, 11, 983.
doi:10.1039/A604927C
4
77
Cl
(d) Y. Zhang, J. Wang, Eur. J.Org. Chem. 2011, 2011, 1015. doi:10.1002/
EJOC.201001588
[2] (a) H. Lebel, J.-F. Marcoux, C. Molinaro, A. B. Charette, Chem. Rev.
2e
5
6
96
90
2003, 103, 977. doi:10.1021/CR010007E
(b) G. Maas, Chem. Soc. Rev. 2004, 33, 183. doi:10.1039/B309046A
(c) M. P. Doyle, J. Org. Chem. 2006, 71, 9253. doi:10.1021/JO061411M
(d) A. Caballero, A. Prieto, M. Diaz-Requejo, P. J. Perez, Eur. J. Inorg.
Chem. 2009, 2009, 1137. doi:10.1002/EJIC.200800944
(e) D. Qian, J. Zhang, Chem. Soc. Rev. 2015, 44, 677. doi:10.1039/
C4CS00304G
2f
F
2g
[3] (a) A. Padwa, D. J. Austin, Angew. Chem., Int. Ed. Engl. 1994, 33, 1797.
doi:10.1002/ANIE.199417971
7
8
70
64
(b) M. P. Doyle, D. C. Forbes, Chem. Rev. 1998, 98, 911. doi:10.1021/
CR940066A
(c) H. M. L. Davies, R. E. J. Beckwith, Chem. Rev. 2003, 103, 2861.
doi:10.1021/CR0200217
(d) M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev. 2010, 110,
704. doi:10.1021/CR900239N
2h
Me
(e) H. M. L. Davies, D. Morton, Chem. Soc. Rev. 2011, 40, 1857.
doi:10.1039/C0CS00217H
2i
(f) Z. Liu, J. Wang, J. Org. Chem. 2013, 78, 10024. doi:10.1021/
JO401850Q
[4] (a) H. Meier, K.-P. Zeller, Angew. Chem., Int. Ed. Engl. 1975, 14, 32.
doi:10.1002/ANIE.197500321
(b) W. Kirmse, Eur. J. Org. Chem. 2002, 2002, 2193. doi:10.1002/1099-
0690(200207)2002:14,2193::AID-EJOC2193.3.0.CO;2-D
(c) J. Wang, Y. Hou, J. Chem. Soc., Perkin Trans. 1 1998, 12, 1919.
doi:10.1039/A801953C
O
N2
H
O
Alumina
CH2Cl2, 0 C to r.t.
N2
O
Њ
(d) H. Yang, K. Foster, C. R. J. Stephenson, W. Brown, E. Roberts, Org.
O
Lett. 2000, 2, 2177. doi:10.1021/OL006146K
(e) B. Ma, F.-L. Chen, X.-Y. Xu, Y.-N. Zhang, L.-H. Hu, Adv. Synth.
Catal. 2014, 356, 416. doi:10.1002/ADSC.201300763
[5] (a) H. M. L. Davies, Eur. J. Org. Chem. 1999, 1999, 2459. doi:10.1002/
(SICI)1099-0690(199910)1999:10,2459::AID-EJOC2459.3.0.CO;2-R
(b) Z. Zhang, J. Wang, Tetrahedron 2008, 64, 6577. doi:10.1016/J.TET.
2008.04.074
1h
2j (60 %)
Scheme 3. Decarboxylation of acetyldiazomethanes.
tube was covered with aluminium foil for protection from light.
Then, diazo acetate was introduced into the tube at 08C and
reacted at room temperature. The reaction was monitored by
thin layer chromatography until diazo acetate was consumed.
(c) Y. Zhang, J. Wang, Chem. Commun. 2009, 36, 5350. doi:10.1039/
B908378B
(d) J. Kaschel, T. F. Schneider, D. B. Werz, Angew. Chem., Int. Ed.
2012, 51, 7085. doi:10.1002/ANIE.201203829

D
Y. Yan et al.
[6] (a) M. Hrytsak, N. Etkin, T. Durst, Tetrahedron Lett. 1986, 27, 5679.
doi:10.1016/S0040-4039(00)85299-5
(c) K. F. Morgan, I. A. Hollingsworth, J. A. Bull, Org. Biomol. Chem.
2015, 13, 5265. doi:10.1039/C5OB00549C
(b) J. P. John, A. V. Novikov, Org. Lett. 2007, 9, 61. doi:10.1021/
OL062592H
[8] (a) A. M. van Leusen, J. Strating, Recl. Trav. Chim. Pays-Bas 1965, 84,
151. doi:10.1002/RECL.19650840203
(c) S. Zhu, J. V. Ruppel, H. Lu, L. Wojtas, X. P. Zhang, J. Am. Chem.
Soc. 2008, 130, 5042. doi:10.1021/JA7106838
(b) A. M. van Leusen, J. Strating, Org. Synth. 1977, 57, 95. doi:10.15227/
ORGSYN.057.0095
(d) C. J. Flynn, C. J. Elcoate, S. E. Lawrence, A. R. Maguire, J. Am.
Chem. Soc. 2010, 132, 1184. doi:10.1021/JA909713A
[7] (a) D. A. Bachovchin, A. M. Zuhl, A. E. Speers, M. R. Wolfe,
E. Weerapana, S. J. Brown, H. Rosen, B. F. Cravatt, J. Med. Chem.
2011, 54, 5229. doi:10.1021/JM200502U
[9] (a) M. P. Doyle, V. Bagheri, T. J. Wandless, N. K. Harn, D. A. Brinker,
C. T. Eagle, K.-L. Loh, J. Am. Chem. Soc. 1990, 112, 1906. doi:10.1021/
JA00161A040
(b) F. G. West, B. N. Naidu, J. Org. Chem. 1994, 59, 6051. doi:10.1021/
JO00099A041
(b) K. Shyam, P. G. Penketh, R. P. Baumann, R. A. Finch, R. Zhu,
Y.-L. Zhu, A. C. Sartorelli, J. Med. Chem. 2015, 58, 3639. doi:10.1021/
JM501459C
(c) X. Qi, J. M. Ready, Angew. Chem., Int. Ed. 2007, 46, 3242.
doi:10.1002/ANIE.200700069