Oxidative dehydrogenation and the aromatization of polycycles using o-iodoxybenzoic acid (IBX)

Article abstract of DOI:10.1055/s-2004-829580

An efficient and convenient method for the dehydrogenation and aromatization of various polycycles using o-iodoxybenzoic acid (IBX) is described.

Full text of DOI:10.1055/s-2004-829580

LETTER
2043
Oxidative Dehydrogenation and the Aromatization of Polycycles Using
o-Iodoxybenzoic Acid (IBX)
O
xidative De
h
a
ydrogenati
m
on
a
ndthe
A
romatiz
b
a
tionof Pol
a
ycycles sivarao Kotha,* Shaibal Banerjee, Kalyaneswar Mandal
IIT Bombay, Powai, Mumbai-400 076, India
Fax +91(22)25723480; E-mail: srk@chem.iitb.ac.in
Received 12 January 2004
supramolecular structures.5 Some of these compounds can
be used as model substrates for storage of solar energy.6
Several methods are available for their preparation, but
many of these procedures are multi-step processes involv-
ing metal-based oxidants and require drastic reaction con-
ditions. This transformation has also been reported using
expensive samarium diiodide as a dehydrogenating re-
agent.7
Abstract: An efficient and convenient method for the dehydro-
genation and aromatization of various polycycles using o-iodoxy-
benzoic acid (IBX) is described.
Key words: dehydrogenation, Diels–Alder reaction, IBX, quino-
nes, aromatization
o-Iodoxybenzoic acid (IBX), a much overlooked reagent,
has recently attracted the attention of organic chemists
worldwide for various synthetic transformations.1 The
limited utility of this reagent in the past has been attribut-
ed to its insolubility in common solvents such as acetone,
ethyl acetate and chloroform.2
Conventional chromium based oxidants such as PCC have
failed to bring about the desired dehydrogenation at the
ring junction of the corresponding Diels–Alder adducts in
a single step.5c In this regard, we found IBX to be an ef-
fective reagent, for carrying out the oxidation in a single
step from the corresponding Diels–Alder adducts. The
substituted aromatic quinones are important components
of many natural products such as Vitamin K. Several
methods are available in the literature for their prepara-
tion.12
HO
O
I
O
O
There are several reports available in the literature for the
preparation of IBX.2 However, some of these methods
provide IBX contaminated with residual bromine and the
IBX prepared by this procedure is found to be explosive
in nature.8 By following Santagostino’s process, we pre-
pared IBX that is free from bromine contamination.9
Figure 1 IBX
The ready availability of IBX and mild reaction condi-
tions for effecting the oxidation reactions underpin the
popularity of this reagent.3 IBX is predominantly used as
an oxidizing agent for the oxidation of alcohols to alde-
hydes or ketones and the dehydrogenation of simple ke- The required Diels–Alder adducts were prepared by
tones to the corresponding enones.4 However, its utility adopting the literature methods.10 These Diels–Alder ad-
towards the preparation of complex unsaturated keto de- ducts were subjected to dehydrogenation reactions using
rivatives remains to be tested. To fill this gap, we report IBX in DMSO at elevated temperature (80–85 °C) result-
the utilization of IBX for the dehydrogenation of Diels– ing the corresponding triene-dione moiety. The results are
Alder adducts derived from cyclopentadiene with various shown in Table 1.11
substituted quinones as shown in Scheme 1.
In the course of application of IBX towards the dehydro-
genation of polycyclic compounds, we found that IBX
also induces aromatization of the 1,4-dihydro precursors
O
IBX
DMSO
R1
R2
O
O
forming the rehybridized aromatic compounds (Table 1,
entry 6). To generalize the aromatization reaction, various
polycyclic substrates were subjected to dehydrogenation
using IBX as shown in Table 2. It is noteworthy that IBX
preferentially aromatizes the Diels–Alder adducts
(Table 2, entry 1–3) without oxidizing the benzylic posi-
tion. The presence of allylic functionality does not affect
the formation of the desired product (Table 2, entry 4).
R1
R1
80–85 °C
O
R2
O
R2
O
Scheme 1
The tricyclic diene-dione moiety found in 1 is an impor-
tant precursor for various interesting compounds such as
‘Garudane’, quadricyclanes, U-turn templates and rigid
The reaction time varies from 10–24 hours, however, pro-
longed heating of the reaction mixture results in decompo-
sition and reduced yields. The plausible mechanism for
this transformation involves single electron transfer
(SET) as postulated by Nicolaou et al.4b
SYNLETT 2004, No. 11, pp 2043–2045
Advanced online publication: 28.07.2004
DOI: 10.1055/s-2004-829580; Art ID: D00604ST
© Georg Thieme Verlag Stuttgart · New York
0
6
.0
9
.2
0
0
4

2044
S. Kotha et al.
LETTER
Table 1 IBX-Mediated Dehydrogenation of Various Polycycles at
Table 2 IBX-Mediated Aromatization of Various Polycyclic
the Ring Junction
Compounds
Entry Substrate
1
Product
Yield (%)a
41b
Entry Substrate
Product
Yield (%)a
79
O
1
O
O
O
O
O
O
O
Me
Me
Me
17
Me
O
O
O
O
O
O
1
75b
13
2
88
76
2
88
76
94
Me
Me
Me
Me
Me
Me
Me
Me
O
O
O
O
O
O
2
86b
14
18
Me
Me
3
3
Me
Me
O
O
O
O
O
O
96b
19
15
3
4
4
46
48
42
O
O
Me
Me
Me
Me
Me
Me
O
Me
O
O
Me
O
O
O
4
106b
5
16
20
a Isolated yield of chromatographically pure compound.
O
Me
O
Me
5
11
6
O
O
References
(1) (a) Wirth, T.; Hirt, U. H. Synthesis 1999, 1271. (b) Wirth,
T. Angew. Chem. Int. Ed. 2001, 40, 2812.
Me
Me
O
O
(2) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277; and references therein.
(3) Thottumkara, A. P.; Vinod, T. K. Tetrahedron Lett. 2002,
43, 569.
Me
Me
126b
6
a Isolated yield of chromatographically pure compound.
b Yield based on starting material recovered.
(4) (a) Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994,
35, 8019. (b) Nicolaou, K. C.; Montagnon, T.; Baran, P. S.;
Zong, Y. L. J. Am. Chem. Soc. 2002, 124, 2245.
(5) (a) Mehta, G.; Padma, S. J. Am. Chem. Soc. 1987, 109,
7230. (b) Mehta, G.; Padma, S.; Karra, S. R.; Gopidas, K. R.;
Cyr, D. R.; Das, P. K.; George, M. V. J. Org. Chem. 1989,
54, 1342. (c) Stoermer, M. J.; Butler, D. N.; Warrener, R. N.;
Weerasuria, K. D. V.; Fairlie, D. P. Chem.–Eur. J. 2003, 9,
2068; and references therein.
(6) (a) Scharf, H. D.; Fleischhaner, J.; Liesman, H.; Ressler, I.;
Schleker, W.; Weitz, R. Angew. Chem., Int. Ed. Engl. 1979,
18, 652. (b) Suzuki, T.; Yamashita, Y.; Mukai, T.; Miyahsi,
T. Tetrahedron Lett. 1988, 29, 1405.
In summary, we have developed a convenient procedure
for dehydrogenation of the Diels–Alder adducts at the ring
junction mediated by o-iodoxybenzoic acid (IBX). This
protocol is far superior to the other conventional proce-
dures. The ready availability of these triene-dione inter-
mediates and aromatic quinones would significantly
expand their utility in the design of complex polycyclic
targets and natural products.
(7) Pandey, B.; Saravanan, K.; Rao, A. T.; Nagamani, D.;
Kumar, P. Tetrahedron Lett. 1995, 36, 1145.
(8) Plumb, J. B.; Harper, D. J. Chem. Eng. News 1990, 68, 3.
(9) Frigerio, M.; Santagostino, M.; Sputore, S. J. Org. Chem.
1999, 64, 4537.
(10) (a) Diels, O.; Alder, K. Chem. Ber. 1929, 62, 2337.
(b) Meinwald, J.; Wiley, G. A. J. Am. Chem. Soc. 1958, 80,
3667. (c) Paquette, L. A.; Bellamy, F.; Boehm, M. C.;
Gleiter, R. J. Org. Chem. 1980, 45, 4913. (d)Knavles, D. E.
J. Am. Chem. Soc. 1934, 56, 2478.
Acknowledgment
We thank the DST, New Delhi for the financial support and RSIC,
Mumbai for recording the spectroscopic data. SB and KM thank
U.G.C. and C.S.I.R., New Delhi respectively for the award of their
research fellowship.
Synlett 2004, No. 11, 2043–2045 © Thieme Stuttgart · New York

LETTER
Oxidative Dehydrogenation and the Aromatization of Polycycles
2045
(11) Typical Experimental Procedure: To a solution of IBX
(0.2–0.4 mmol) in DMSO (10 mL) was added Diels–Alder
adduct (0.1 mmol) and the mixture was stirred at 80–85 °C
for 10–24 h, until the starting material disappeared. At the
conclusion of the reaction (TLC monitoring), the reaction
mixture was quenched with H2O. The insoluble
CDCl3): d = 1.98 (s, 6 H), 2.20–2.30 (m, 2 H), 4.08–4.09 (m,
2 H), 6.83 (dd, J1 = J2 = 1.8 Hz, 2 H). 13C NMR (75 MHz,
CDCl3): d = 12.3, 48.6, 73.5, 139.6, 142.6, 160.2, 184.3. MS:
m/z = 201 [M + H+]. Compound 11: 1H NMR (400 MHz,
CDCl3): d = 2.17 (s, 3 H), 2.33–2.38 (m, 2 H), 4.14–4.16 (m,
2 H), 6.49 (s, 1 H), 6.91 (dd, J1 = J2 = 2.0 Hz, 2 H), 7.06–
7.09 (m, 1 H), 7.20–7.33 (m, 3 H). 13C NMR (100 MHz,
CDCl3): d = 20.4, 48.4, 48.7, 73.8, 125.6, 129.1, 129.4,
130.3, 133.5, 133.8, 136.2, 142.5, 142.7, 147.7, 160.6,
160.8, 182.9, 184.3. MS: m/z = 263 [M + H+]. Compound 12:
1H NMR (300 MHz, CDCl3): d = 2.29–2.39 (m, 8 H), 4.21–
4.23 (m, 2 H), 6.89 (dd, J1 = J2 = 1.8 Hz, 2 H), 7.79 (s, 2
H).13C NMR (75 MHz, CDCl3): d = 182.0, 162.8, 142.8,
142.6, 130.8, 127.4, 73.3, 48.7, 20.1. Compound 17: mp
117 °C. Lit mp 117–119 °C.13 Compound 18: 1H NMR (300
MHz, CDCl3): d = 2.15 (s, 6 H), 2.38 (s, 6 H), 7.81 (s, 2 H).
13C NMR (75 MHz, CDCl3): d = 183.5, 143.2, 143.1, 130.2,
127.4, 20.2, 12.9. Compound 19: mp 209 °C. Lit mp 209–
210 °C.14 Compound 20: 1H NMR (400 MHz, CDCl3): d =
2.44 (s, 6 H), 4.65 (dt, J1 = 5.2 Hz, J2 = 1.6 Hz, 4 H), 5.30
(d, J = 10.4 Hz, 2 H), 5.52 (d, J = 17.2 Hz, 2 H), 6.13–6.23
(m, 2 H), 6.61 (s, 2 H), 7.99 (s, 2 H). 13C NMR (100 MHz,
CDCl3): d = 148.2, 135.6, 133.9, 125.4, 121.6, 117.2, 103.9,
69.4, 20.4.
iodosobenzoic acid (IBA) was filtered off with the aid of a
Celite® pad. The filtrate was extracted with Et2O (3 × 30 mL)
and the combined organic layers were washed with sat.
NaHCO3 solution and finally with brine. The organic layer
was dried over anhyd MgSO4 and removal of solvent gave
the crude compound which was purified by the column
chromatography (silica gel) using petroleum ether and
EtOAc to afford the pure dehydrogenated compound.
Selected spectral data: Compound 7: 1H NMR (300 MHz,
CDCl3): d = 2.31–2.34 (m, 2 H), 4.09–4.12 (m, 2 H), 6.57 (s,
2 H), 6.86 (dd, J1 = J2 = 1.8 Hz, 2 H). 13C NMR (100 MHz,
CDCl3): d = 48.5, 73.9, 135.8, 142.6, 160.8, 184.1. MS:
m/z = 172 [M+]. Compound 8: 1H NMR (300 MHz, CDCl3):
d = 2.30–2.40 (m, 2 H), 4.24–4.27 (m, 2 H), 6.90 (dd,
J1 = J2 = 1.8 Hz, 2 H), 7.69 (dd, J1 = 5.5 Hz, J2 = 3.3 Hz, 2
H), 8.07 (dd, J1 = 5.6 Hz, J2 = 3.3 Hz, 2 H). 13C NMR (75
MHz, CDCl3): d = 48.8, 73.4, 126.3, 132.9, 133.4, 142.6,
163.2, 181.8. MS: m/z = 223 [M + H+]. Compound 9:
1H NMR (400 MHz, CDCl3): d = 2.36–2.42 (m, 2 H), 4.30–
4.32 (m, 2 H), 6.94 (dd, J1 = J2 = 1.8 Hz, 2 H), 7.64–7.67 (m,
2 H), 8.02–8.05 (m, 2 H), 8.59 (s, 2 H). 13C NMR (100 MHz,
CDCl3): d = 48.8, 73.2, 128.4, 129.2, 129.8, 130.1, 134.6,
142.5, 164.6, 181.3. Compound 10: 1H NMR (300 MHz,
(12) Labahn, A.; Schmid, R.; Goebel, F.; Warnecke, A. J. Chem.
Soc., Perkin Trans. 2 1999, 1199.
(13) Skarzewski, J. Tetrahedron 1984, 40, 4997.
(14) Allen, C. F. H.; Bell, A. Org. Synth. Coll Vol. III 1955, 310.
Synlett 2004, No. 11, 2043–2045 © Thieme Stuttgart · New York