Amberlyst-15 mediated decomposition of α-diazo carbonyl compounds

Article abstract of DOI:10.1016/S0040-4039(01)00936-4

An efficient heterogeneous catalytic method for the synthesis of α-hydroxy ketones from α-diazo carbonyl compounds 1, 3 and 6 in the presence of Amberlyst-15, a macro reticular ion exchange resin, is reported. The desired products were obtained at room temperature or by ultrasonication in good yield. Interestingly, novel fused 3-furanones and bicycloalkane-1,3-diones were obtained as unusual products in the case of alicyclic α-diazo carbonyl compounds.

Full text of DOI:10.1016/S0040-4039(01)00936-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5113–5116
Amberlyst-15 mediated decomposition of a-diazo carbonyl
compounds
Sengodagounder Muthusamy,* Srinivasarao Arulananda Babu, Chidambaram Gunanathan and
Raksh Vir Jasra
Silicates and Catalysis Discipline, Central Salt and Marine Chemicals Research Institute, Bhavnagar 364 002, India
Received 1 March 2001; revised 17 April 2001; accepted 31 May 2001
Abstract—An efficient heterogeneous catalytic method for the synthesis of a-hydroxy ketones from a-diazo carbonyl compounds
1, 3 and 6 in the presence of Amberlyst-15, a macro reticular ion exchange resin, is reported. The desired products were obtained
at room temperature or by ultrasonication in good yield. Interestingly, novel fused 3-furanones and bicycloalkane-1,3-diones were
obtained as unusual products in the case of alicyclic a-diazo carbonyl compounds. © 2001 Elsevier Science Ltd. All rights
reserved.
a-Diazo carbonyl compounds are important intermedi-
ates and have been exploited in synthetic organic chem-
istry for the synthesis of a variety of complex molecules
in recent years.1 Reactions of a-diazo carbonyl com-
pounds have been extensively studied using various
acids, bases and metal complexes including Lewis acids
as catalysts.1 The reaction of a-diazo carbonyl com-
pounds with several Lewis acids such as BF3·Et2O,2
Amberlyst-15 has customarily been applied to the
deprotection of acetals,10 protection of carbonyl com-
pounds in the presence of 1,2-ethanedithiol,11 Michael
reaction,12 preparation of enol ethers13 and tetra-
hydropyranyl ethers.14 Herein, we wish to report our
extensive studies on the reaction of a-diazo carbonyl
compounds with the macro reticular ion-exchange resin
of the type Amberlyst-15 as applied to the synthesis of
a-hydroxy ketones and novel bicycloalkane-1,3-diones,
as well as fused 3-furanone ring systems in a hetero-
geneous manner.
InCl3,3 SnCl2,4 TiCl4,5 Sc(OTf)3 and Cu(OTf)2 has
been applied as a general strategy for the synthesis of
1,3-dicarbonyl compounds and natural products. The
reaction of a-diazo carbonyl compounds with protic/
aprotic acids8 such as aqueous or concentrated acetic
acid, HCl, H2SO4, SiO2/acetic acid, perchloric acid,
trifluoroacetic acid and trifluoromethanesulfonic acid
has been studied. These acidic media are often
employed even though they are corrosive, require care-
ful handling, generate by-products and always require
an aqueous work-up.
6
7
To a solution of a-diazo ketone 1a (125 mg) in 5 ml of
commercial grade dichloromethane was added
Amberlyst-15 (150 mg) and the reaction mixture was
allowed to stir at room temperature for 8 h (Scheme 1).
The reaction was followed by TLC until the disappear-
ance of starting material; the reaction mixture was
filtered and concentrated under reduced pressure. The
crude reaction mixture was purified by silica gel column
chromatography and formed the corresponding a-
hydroxy ketone 2a15 in 82% yield (Table 1). In order to
To the best of our knowledge, there is no report1
dealing with the reaction of a-diazo carbonyl com-
pounds and a solid ionic matrix such as Amberlyst-15.9
R3 COCHN2
R3 COCH2OH
Amberlyst-15
DCM
R2
R1
R2
( )n
( )n
r.t. / ultrasonication
R1
2
1
Scheme 1.
Keywords: Amberlyst-15; diazo carbonyl compounds; heterogeneous catalyst; hydroxy ketones.
* Corresponding author. Tel.: +91 278 567760; fax: +91 278 567562; e-mail: salt@csir.res.in
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00936-4

5114
S. Muthusamy et al. / Tetrahedron Letters 42 (2001) 5113–5116
reduce the reaction time, the reaction was carried out
under ultrasonication to afford the product 2a in 30
minutes (Table 1). The remarkable reactivity of
Amberlyst-15 gave us impetus to study it further in
reaction with other a-diazo carbonyl compounds in a
heterogeneous manner.
alicyclic a-diazo carbonyl compounds (Scheme 2) with
Amberlyst-15, which afforded unexpected results. The
reaction of diazo compounds 3a–c having a two/three-
carbon chain length in the presence of Amberlyst-15
resulted in the corresponding a-hydroxy ketones15
(Table 2). In the case of diazo compound 3d, having a
three-carbon chain length tethered to a cyclohexanone
ring system, reaction with Amberlyst-15 furnished the
1,3-dione 5d instead of the corresponding a-hydroxy
ketone 4d. We confirmed this curious cyclization by
performing the reaction with diazo compound 3e. It is
interesting to note that these bicycloalkane-1,3-diones 5
have also been synthesized from diazo ketones 3d,e
Initially we studied other aromatic compounds 1b–e
and aliphatic diazo compounds 1f,g which afforded the
respective a-hydroxy ketones 2b–g both room tempera-
ture and under ultrasonication. These reactions were
also carried out in acetone as a solvent for all the diazo
compounds 1, which afforded 2 in comparable yield.
The resulting intermediate undergoes an O–H insertion
reaction16 to give the a-hydroxy ketone 2. Moreover,
the a-hydroxy ketones are versatile intermediates in the
synthesis of several natural products such as frontalin.17
5
using SnCl24b/TiCl4 as a catalyst.
We were further interested in studying the effect of ring
size with only one carbon in the chain in the a-diazo
carbonyl compounds. Diazo carbonyl compounds 1, 3
and 6 involved in this work were prepared based on
literature precedents.1,18 Then, we extended our investi-
Encouraged by these results with aromatic compounds;
we subsequently investigated the reaction of various
Table 1. Reaction of aromatic a-diazo carbonyl compounds 1a–g with Amberlyst-15
Substrate
R1
R2
R3
n
Time
Yielda (%)
Room temp. (h)
Ultrasonication (min)
1a
1b
1c
1d
1e
1f
OMe
H
Me
H
H
H
H
H
H
Me
H
H
H
H
0
0
0
0
0
1
2
8
7
5.5
6
7
30
20
20
25
35
30
25
82
77
92
80
79
75
76
-CHꢀCH-CHꢀCH-
H
H
H
H
7
6
1g
H
a Yields (unoptimized) refer to isolated and chromatographically pure compounds 2.
O
R1
( )m
O
R1
( )m
O
O
Amberlyst-15, DCM
room temp.
COCH
2OH
COCHN2
(or)
( )n
( )n
( )m
R1
( )n
4
3
5
Scheme 2.
Table 2. Reaction of alicylcic a-diazo carbonyl compounds with Amberlyst-15
Substrate
R1
n
m
Time (h)
Yieldb of 4%
Yieldb of 5%
3a
3b
3c
3d
3e
H
H
H
H
1
1
2
2
2
1
2
1
2
2
5
5
5
2.5
6
76
82
85
–
–
–
–
714b,5
69
Me
–
b Yields (unoptimized) refer to isolated and chromatographically pure compounds 4 and 5.
O
O
R
OH
O
R
Amberlyst-15, DCM
room temp.
+
COCHN2
COCH2OH
( )n
( )n
( )n
R
7
O
6
8
Scheme 3.

S. Muthusamy et al. / Tetrahedron Letters 42 (2001) 5113–5116
Table 3. Fused 3-furanones ring systems 7 produced via Scheme 3
5115
Substrate
R
n
Time (h)
Yieldc of 7%
Yieldc of 8%
6a
6b
6c
6d
Me
1
1
2
2
1
1
0.5
0.5
39
34
87
74
38
35
–
CH2CHꢀCH2
Me
CH2CHꢀCH2
–
c Yields (unoptimized) refer to isolated and chromatographically pure compounds 7 and 8.
gation on diazo compounds 6a–d (Scheme 3). Treat-
ment of diazo ketones 6a,b with Amberlyst-15 resulted
in the respective novel fused 3-furanone skeleton 7a,b
and a-hydroxy ketones 8a,b. However, in the reaction
of an a-diazo ketone tethered to a cyclohexanone ring
6c,d the corresponding fused 3-furanones 7c,d15 were
formed (Table 3). The reason may be the formation of
a favorable 6,5-fused ring system 7c,d rather than the
strained 5,5-fused ring system 7a,b under the experi-
mental conditions. It is worth noting that the fused
3-furanone skeleton is present in many natural products
such as avermectin B.19 It may also be noted that the
olefin moiety present in the diazo compounds 6b,d
stayed intact under the reaction conditions.
Branca, S. J.; Dieter, R. K. J. Am. Chem. Soc. 1981, 103,
1996–2008; (c) Erman, W. F.; Stone, L. C. J. Am. Chem.
Soc. 1971, 93, 2821–2823.
3. Sengupta, S.; Mondal, S. Tetrahedron Lett. 1999, 40,
8685–8688.
4. (a) Hecker, S. J.; Werner, K. M. J. Org. Chem. 1993, 58,
1762–1765; (b) Padwa, A.; Hornbuckle, S. F.; Zhang, Z.;
Zhi, L. J. Org. Chem. 1990, 55, 5297–5299.
5. Muthusamy, S.; Babu, S. A.; Gunanathan, C. Synth.
Commun. 2001, in press.
6. Pansare, S. V.; Jain, R. P.; Bhattacharyya, A. Tetra-
hedron Lett. 1999, 40, 5255–5258.
7. Doyle, M. P.; Trudell, M. L. J. Org. Chem. 1984, 49,
1196–1199.
8. Regitz, M.; Mass, G. Diazo Compounds-Properties and
Synthesis; Academic Press: New York, 1986; pp. 90–165.
9. Amberlyst-15 is a macroreticular type sulfonic acid based
polystyrene cation exchange resin and used in this study
in the H+ form. Amberlyst is a trademark of the Rohm
and Hass Co.
10. Coppola, G. M. Synthesis 1984, 1021–1023.
11. Perni, R. B. Synth. Commun. 1989, 19, 2383–2387.
12. Ballini, R.; Marziali, P.; Mozzicafreddo, A. J. Org.
Chem. 1996, 61, 3209–3211.
In summary, the reaction of various a-diazo carbonyl
compounds with a solid ionic matrix, Amberlyst-15
under mild heterogeneous conditions furnished a-
hydroxy ketones, novel fused 3-furanones and bicy-
cloalkane-1,3-diones. The mild reaction conditions
together with the heterogeneous manner makes the use
of Amberlyst-15 an important alternative to classic
acidic catalysis and other methods, since both by-prod-
ucts and aqueous work-up are avoided.
13. (a) Patwardhan, S. A.; Dev, S. Synthesis 1974, 11, 348–
349; (b) Gupta, S. K. J. Org. Chem. 1976, 41, 2642–2646;
(c) Dann, A. E.; Davis, J. B.; Nagler, J. J. Chem. Soc.,
Perkin Trans. 1 1979, 158–160.
Acknowledgements
14. Bongini, A.; Cardillo, G.; Orena, M.; Sandri, S. Synthesis
1979, 618–620.
This research was supported by the CSIR, Young
Scientist Scheme and partly by the Department of
Science and Technology, New Delhi. We thank Dr. P.
K. Ghosh, Director, for his encouragement of this
work. We are grateful to Professor G. Mehta, Director,
Indian Institute of Science, Bangalore, for a generous
gift of Amberlyst-15 for this study. S.A.B. and C.G.
thank CSIR, New Delhi, for a Fellowship.
15. All new compounds gave satisfactory spectral data con-
sistent with their structures. Selected spectral data, (2b):
colorless solid mp 103–105°C; IR (KBr) 3391, 2927, 2845,
1678, 1603, 1576, 1512, 1422, 1250, 1181, 1103, 1029, 977,
821 cm−1 1H NMR (200 MHz, CDCl3/CD3CN) l 7.89
;
(d, 2H, J=8.9 Hz, Arom.-H), 6.99 (d, 2H, J=8.9 Hz,
Arom.-H), 4.78 (s, 2H, OCH2), 3.86 (s, 3H, OCH3), 3.49
(br s, 1H, OH); 13C NMR (50 MHz, CDCl3/CD3CN) l
54.9 (OCH3), 64.6 (OCH2), 113.6 (ꢀCH), 126.3 (quat.-C),
129.5 (ꢀCH), 163.8 (quat.-C), 197.0 (CꢀO). Anal. calcd
for C9H10O3: C, 65.05; H, 6.07. Found: C, 65.13; H, 6.12.
(4b): colorless thick liquid; IR (neat) 3445, 2960, 2877,
References
1. (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern
Catalytic Methods for Organic Synthesis with Diazo Com-
pounds. From Cyclopropanes to Ylides; Wiley-Inter-
science: New York, 1998; (b) Padwa, A.; Weingarten, M.
D. Chem. Rev. 1996, 96, 223–269; (c) Ye, T.; McKervey,
M. A. Chem. Rev. 1994, 94, 1091–1160; (d) Padwa, A.;
Hornbuckle, S. A. Chem. Rev. 1991, 91, 263–309; (e)
Calter, M. A. Curr. Org. Chem. 1997, 1, 37–70; (f)
Padwa, A. Topp. Curr. Chem. 1997, 189, 121–158.
1
1731, 1452, 1406, 1274, 1158, 1069, 732 cm−1; H NMR
(200 MHz, CDCl3) l 4.19 (s, 2H, OCH2), 3.32 (br s, 1H,
OH), 2.50 (t, 2H, J=7.0 Hz), 1.40–2.21 (m, 9H); 13C
NMR (50 MHz, CDCl3) l 21.1 (CH2), 23.9 (CH2), 30.1
(CH2), 36.4 (CH2), 38.5 (CH2), 48.4 (CH), 68.6 (OCH2),
210.0 (CꢀO), 221.2 (CꢀO). Anal. calcd for C9H14O3: C,
63.51; H, 8.29. Found: C, 63.59; H, 8.37. (7c): colorless
solid mp 120–122°C; IR (KBr) 3380, 2944, 2911, 1760,
1
1457, 1413, 1232, 1097, 1076, 1020, 938 cm−1; H NMR
2. (a) Srikrishna, A.; Ramachary, D. B. Tetrahedron Lett.
1999, 40, 1605–1606; (b) Smith, III, A. B.; Toder, B. H.;
(200 MHz, CDCl3) l 4.16 (dd, 2H, J1=13.5 Hz, J2=1.6

5116
S. Muthusamy et al. / Tetrahedron Letters 42 (2001) 5113–5116
Hz, OCH2), 2.91 (s, 1H, OH), 1.90–2.00 (m, 1H), 1.35–
10843.
1.75 (m, 7H), 1.22 (s, 3H, CH3); 13C NMR (50 MHz,
CDCl3) l 13.7 (CH3), 21.0 (CH2), 23.5 (CH2), 33.1 (CH2),
34.0 (CH2), 51.3 (quat.-C), 67.9 (OCH2), 106.0 (quat.-C),
217.6 (CꢀO); mass m/z (%): 170 (M+, 24), 153 (20), 142
(6), 124 (8), 112 (63), 97 (48), 83 (48), 69 (69), 55 (96), 41
(100). Anal. calcd for C9H14O3: C, 63.51; H, 8.29. Found:
C, 63.46; H, 8.28.
17. Whitsell, J. K.; Buchanan, C. M. J. Org. Chem. 1986, 51,
5443–5445.
18. Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Suresh, E.;
Dastidar, P.; Jasra, R. V. Tetrahedron 2000, 56, 6307–
6318.
19. White, J. D.; Bolton, G. L.; Dantanarayana, A. P.; Fox,
C. M. J.; Hiner, R. N.; Jackson, R. W.; Sakuma, K.;
Warrier, U. S. J. Am. Chem. Soc. 1995, 117, 1908–1939.
16. Miller, D. J.; Moody, C. J. Tetrahedron 1995, 51, 10811–
.