Asymmetric cyclization via oxygen cation radical: Enantioselective synthesis of cis-4b,9b-dihydrobenzofuro[3,2-b]benzofurans

Article abstract of DOI:10.1246/cl.2002.36

Aerobic oxidative cyclization of 2,2′-dihydroxystilbenes via oxygen cation radical to give cis-4b,9b-dihydrobenzofuro[3,2-b]benzofurans was carried out in an enantioselective manner (up to 89% ee) by using (nitrosyl)Ru(salen) 10 as the catalyst under phot

Full text of DOI:10.1246/cl.2002.36

36
Chemistry Letters 2002
Asymmetric Cyclization via Oxygen Cation Radical:
Enantioselective Synthesis of cis-4b,9b-Dihydrobenzofuro[3,2-b]benzofurans
Kouta Masutani, Ryo Irie, and Tsutomu Katsukiꢀ
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University, 33,
CREST, Japan Science and Technology (JST), Hakozaki, Higashi-ku, Fukuoka 812-8581
(Received October 22, 2001; CL-011028)
Aerobic oxidative cyclization of 2,20-dihydroxystilbenes via
benzofuran 6 (Scheme 2).5d
oxygen cation radical to give cis-4b,9b-dihydrobenzofuro[3,2-
b]benzofurans was carried out in an enantioselective manner (up
to 89% ee) by using (nitrosyl)Ru(salen) 10 as the catalyst under
photo-irradiated conditions.
Catalytic asymmetric reaction promoted by molecular
oxygen is one of the goals of organic synthesis because of its
high atom economy and environmental benignancy.
We recently demonstrated that (ON)Ru(salen) 1 catalyzed
enantiomer-differentiating aerobic oxidation of racemic second-
ary alcohols under photo-irradiated conditions. Photo-irradiation
has been considered to promote dissociation of the nitrosyl ligand
to give a coordinatively unsaturated Ru(III) species that is
oxidized to Ru(IV) species 2 by oxygen. Alcohol is coordinated to
2 and undergoes single electron transfer to give a cation radical
intermediate 3 that gives ketone via hydrogen atom and proton
abstraction (Scheme 1).1 This reaction mechanism was supported
by the fact that ꢀ-naphthols underwent oxidative coupling under
the same conditions.2;3
On the other hand, radical cyclization is an important tool for
construction of cyclic compounds4 and oxygen radical cycliza-
tion is also a useful method for the formation of cyclic ethers.5
However, its synthetic application is rather limited.6 Although
several diastereoselective oxygen radical cyclizations have been
reported,5a{c) few study on enantioselective cyclization has been
reported.7 Thus, we studied Ru(salen)-catalyzed enantioselective
cyclization of an oxygen cation radical.
Scheme 2.
We expected that asymmetric version of this unique
bicyclization reaction could be achieved by using (ON)Ru(salen)
complex as the catalyst which would promote aerobic oxidation
via a cation radical (vide supra).8;9 Thus, we examined oxidative
cyclization of 4 in the presence of 1 in chlorobenzene (Table 1,
entry 1). The desired cyclization proceeded smoothly to give the
desired 5 of 34% ee accompanied with 6 (14%).
Although the transition state structure of this reaction is
unclear at present, the resulting phenol cation radical is
considered to reside on the ruthenium ion and close to the 200-
phenyl group, and the other hydroxyphenyl group to be located
close to the ethylenediamine. This spatial arrangement of the
intermediate suggests that enantioselectivity of the reaction
would be affected by the steric repulsion between the substrate
and the 200- and 100-substituents of the catalyst.
Accordingly, we examined the oxidative cyclization of 4
with various Ru(salen)s 7-11 as the catalyst (Table 1). As
expected, enantioselectivity of the reactions depended on the
catalyst used. ðR; RÞ-1 showed slightly better enantioselectivity
than its ðR; SÞ-diastereomer 7 (entries 1 and 2). Replacement of
the 200-phenyl group of 1 with biphenylyl group resulted in a small
improvement of enantioselectivity (entry 3). The remarkable
improvement was brought by the modification of the diamine
moiety: the complex 10 bearing 1,2-diphenylethylenediamine as
its diamine unit induced high enantioselection of 81% ee (entry
5). On the other hand, the catalyst 11 showed poor enantioselec-
tivity (entry 6).
In 1975, Cardillo et al. reported that oxidative cyclization of
2,20-dihydroxystilbene 4 provided a mixture of cis-4b,9b-
dihydrobenzofuro[3,2-b]benzofuran 5 and 2-(2-hydroxyphenyl)-
We next examined the effect of solvent on enantioselectivity
(Table 2). Clear relationship was not observed between solvent
polarity and enantioselectivity. Amongst the reactions examined,
the highest enantioselectivity (89% ee) was achieved when t-
BuOH was used asthe solvent (entry 1), though thechemical yield
was modest. The yield of 6 was low (2%). The reaction in toluene
gave better chemical yield, but enantioselectivity was slightly
diminished (entry 3). Thus, use of mixed solvent was examined
Scheme 1.
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
37
Table 1. Asymmetric aerobic oxidative cyclization of 2,20-
dihydroxystilbene 4 using Ru(salen) as catalysta
Scheme 3.
tivity in the cyclization of an oxygen cation radical for the first
time, though there is still a room for improvement. Further study
is in progress in our laboratory.
Dedicated with respect and admiration to Professor Teruaki
Mukaiyama on the occasion of his 75th birthday.
References and Notes
1
K. Masutani, T. Uchida, R. Irie, and T. Katsuki, Tetrahedron Lett., 41,
5119 (2000).
2
3
R. Irie, K. Masutani, and T. Katsuki, Synlett, 2000, 1433.
For other asymmetric aerobic oxidative coupling of ꢀ-naphthol see: a)
M. Nakajima, I. Miyoshi, K. Kanayama, and S. Hashimoto, J. Org.
Chem., 66, 2264 (1999). b) S.-W. Hon, C.-H. Li, J.-H. Kuo, N. B.
Barhate, Y.-H. Liu, Y. Wang, and C.-T. Chen, Org. Lett., 3, 869 (2001).
c) X. Li, J. Yang, and M. C. Kozlowski, Org. Lett., 3, 1137(2001). d) C.-
Y. Chu, D.-R. Hwang, S.-K. Wang, and B.-J. Uang, Chem. Commun.,
2001, 980.
4
5
‘‘Radicals in Organic Synthesis,’’ ed. by P. Renaud and M. Sibi, Wiley-
VCH, New York (2001), Vol. I and II.
a) Y. Guindon and R. C. Denis, Tetrahedron Lett., 39, 339 (1998). b) J.
Hartungand F. Gallou, J. Org. Chem., 60, 6706 (1995). c) J. Hartungand
R. Kneuer, Eur. J. Org. Chem., 2000, 1677. d) B. Cardillo, M. Cornia,
and L. Merlini, Gazz. Chim. Ital., 105, 1151 (1975).
Table 2. Solvent effect on asymmetric oxidative cyclization of 4
using 10 as the catalysta
6
7
a) M. Newcomb, ‘‘Radicals in Organic Synthesis,’’ ed. by P. Renaud and
M. Sibi, Wiley-VCH, New York (2001), Vol. I, Chap. 3. b) H. Togo and
M. Katohgi, Synlett, 2001, 565.
To our knowledge, asymmetric oxygen radical cyclization (1.3% ee)
using copper-amine complex as the oxidant has been reported: B.
Feringa and H. Wynberg, Bioorg. Chem., 7, 397 (1978).
8A possibilitythat the cation radicalspecies undergoesdeprotonation and
the resulting radical species undergoes cyclization can not be removed.
9
During the reviewing process, one referee suggested that the present
reaction might proceed via Michael-type addition of phenol to
mesomeric radical enone. Indeed, Wallis have reported that 2,40-
dihydroxystilbene derivative cyclizes via Michael-type addition of
phenol to mesomeric dienone.11 We, however, believe that the present
cyclization occurs in the vicinity of the metal center from its moderate to
high enantioselectivity and proceeds through intramolecular addition of
phenoxy radical to olefin as proposed by Cardillo et al. (Scheme 2).
and acceptable enantioselectivity and chemical yield were
achieved by using mixed toluene-t-butyl alcohol (2 : 3) (entry
4), though a small amount of 6 (13%) was formed.10
To understand the mechanism of asymmetric induction by
10, we next examined the reactions of substituted 2,20-
dihydroxystilbenes (Scheme 3). From the proposed arrangement
of the intermediate (vide supra), the introduction of the
substituents onto the benzene ring of the substrate is considered
to cause the undesired steric repulsion with the 200- and 100-
substituent and to lower the enantioselectivity. Indeed, the
reaction of 4,40-dimethyl derivative 12 proceeded with moderate
enantioselectivity of 66% ee (Scheme 3). The reaction of 5,50-
dimethyl derivative 14 showed further reduced enantioselectivity
of 10% ee. Use of diisopropyl ether as the solvent improved
enantioselectivity of both the reactions, though the chemical
yields were insufficient.
10 Experimental procedure for oxidative cyclization of 4:12 4 (21.2 mg,
0.1 mmol) and 11 (4.4 mg, 4 mol%) were dissolved in t-BuOH (1.2 ml)
and toluene (0.8ml). The solution was stirred under irradiation with a
halogen lamp in air for 1 h at room temperature and kept stirred for 3 h
without irradiation. The procedure was further repeated seven times.
Then, the mixture was chromatographed on silica gel
(hexane : ethyl acetate ¼ 9 : 1) to give 5 (17.0 mg, 81%) of 84% ee
and 6 (2.0 mg, 10%).
11 A. F. A. Wallis, Aust. J. Chem., 25, 1529 (1972).
12 Experiments described in Tables 1 and 2 and Scheme 3 were carried out
in25 ꢁmolscaleand irradiationwas continuedduringthereactions. The
exemplified experiment was performed in 0.1 mmol scale (Ref. 10) and
irradiated every four hours to avoid temperature-rising.
In conclusion, we were able to achieve high enantioselec-