According to our previous report,5 benzyloxy benzylidene
malonate 5 was chosen as a suitable substrate for the
proposed reaction, which was easily synthesized from
salicylaldehyde (3). Benzylation of the hydroxy group of 3
followed by Knoevenagel condensation with dimethyl ma-
lonate gave 5 in quantitative yield (Scheme 3).
Scheme 1. C-H Functionalization via Internal Redox Process
Scheme 3. Preparation of Benzylidene Malonate 5
internal redox processes typically proceeded under thermal condi-
tions or, in some cases, under Brønsted or Lewis acid catalysis.3,4
As part of our ongoing effort to develop new catalytic
transformations, we found that the imine derivative was also
viable for the internal redox processes.5 Seidel and co-
workers recently reported the Gd(OTf)3-facilitated [1,5]
hydride shift without heating (room temperature), affording
tetrahydroisoquinoline derivatives.6 A number of related
reactions with nitrogen-containing substrates have been
reported. Although Sames and co-workers have extensively
studied the oxygen version,2a,b,e,h the formation of benzopy-
ran derivatives remains to be investigated.7
Having the requisite substrate, the planned cyclization was
attempted: a solution of 5 in ClCH2CH2Cl was exposed to
several acids (Table 1). On treatment of 5 with TsOH·H2O,
We report herein a highly efficient method for the construc-
tion of a benzopyran skeleton via Lewis acid catalyzed C-H
bond functionalization (Scheme 2). It is noted that the presence
Table 1. Examination of Reaction Conditionsa
Scheme 2. Expeditious Construction of Benzopyran Skeleton
yield (%)
entry
catalyst
solvent
6b
7c
1
2
3
4
5
6
7
8
TsOH·H2O
TfOH
MgBr2
Yb(OTf)3
Sc(OTf)3
TiCl4
SnCl4
SnCl4
SnCl4
SnCl4
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
CH3CN
85
83
- (80)
- (95)
69c
9
6
18
7
31
61
8
- (61)
of a substituent ortho to the alkoxy group had a remarkable
influence on the reactivity, affording the desired benzopyrans
in excellent chemical yields with short reaction times.
64c
- (80)
15 (50)
35
9d
10
11
toluene
benzene
cyclohexane
(3) These types of reactions have been classified under the term tert-
amino effect. For reviews, see: (a) Meth-Cohn, O.; Suschitzky, H. AdV.
Heterocycl. Chem. 1972, 14, 211. (b) Verboom, W.; Reinhoudt, D. N. Recl.
TraV. Chim. Pays-Bas 1990, 109, 311. (c) Meth-Cohn, O. AdV. Heterocycl.
Chem. 1996, 65, 1. (d) Quintela, J. M. Recent Res. DeV. Org. Chem. 2003,
7, 259. (e) Matyus, P.; Elias, O.; Tapolcsanyi, P.; Polonka-Balint, A.; Halasz-
SnCl4
2 (85)
a Unless otherwise noted, all reactions were performed with 0.2 mmol
of 5 and 30 mol % of catalyst in solvent (2.0 mL) at refluxing temperature.
1H NMR yield. Recovery of 5 is indicated in parentheses. c Isolated yield.
b
d At 90 °C.
Dajka, B. Synthesis 2006, 2625
.
(4) (a) Verboom, W.; Reinhoudt, D. N.; Visser, R.; Harkema, S. J. Org.
Chem. 1984, 49, 269. (b) Nijhuis, W. H. N.; Verboom, W.; Reinhoudt,
D. N.; Harkema, S. J. Am. Chem. Soc. 1987, 109, 3136. (c) Nijhuis,
W. H. N.; Verboom, W.; Reinhoudt, D. N. Synthesis 1987, 641. (d) Nijhuis,
W. H. N.; Verboom, W.; Abu El-Fadl, A.; Harkema, S.; Reinhoudt, D. N.
J. Org. Chem. 1989, 54, 199. (e) Nijhuis, W. H. N.; Verboom, W.; Abu
El-Fadl, A.; Van Hummel, G. J.; Reinhoudt, D. N. J. Org. Chem. 1989, 54,
209. (f) De Boeck, B.; Jiang, S.; Janousek, Z.; Viehe, H. G. Tetrahedron
1994, 50, 7075. (g) De Boeck, B.; Janousek, Z.; Viehe, H. G. Tetrahedron
1995, 51, 13239. (h) Ojea, V.; Muinelo, I.; Quintela, J. M. Tetrahe-
dron 1998, 54, 927. (i) Kaval, N.; Halasz-Dajka, B.; Vo-Thanh, G.; Dehaen,
W.; Van der Eycken, J.; Matyus, P.; Loupy, A.; Van der Eycken, E.
Tetrahedron 2005, 61, 9052. (j) Zhang, C.; Kanta De, C.; Mal, R.; Seidel,
D. J. Am. Chem. Soc. 2008, 130, 416. (k) Ruble, J. C.; Hurd, A. R.; Johnson,
T. A.; Sherry, D. A.; Barbachyn, M. R.; Toogood, P. L.; Bundy, G. L.;
Graber, D. R.; Kamilar, G. M. J. Am. Chem. Soc. 2009, 131, 3991. (l)
starting material 5 was almost completely consumed after 24 h
(entry 1). Disappointingly, the resulting product was not the
desired product 6 but coumarin 7, which was produced by
debenzylation followed by internal cyclization. TfOH also gave
(5) Mori, K.; Ohshima, Y.; Ehara, K.; Akiyama, T. Chem. Lett. 2009,
38, 524. Seidel reported a similar redox process promoted by TfOH: Zhang,
C.; Murarka, S.; Seidel, D. J. Org. Chem. 2009, 74, 419.
(6) Murarka, S.; Zhang, C.; Konieczynska, M. D.; Seidel, D. Org. Lett.
2009, 11, 129.
(7) During the preparation of our manuscript, Sames reported a similar
redox process promoted by Sc(OTf)3: McQuaid, K. M.; Long, J. Z.; Sames,
D. Org. Lett. 2009, 11, 2972.
Tobisu, M.; Nakai, H.; Chatani, N. J. Org. Chem. 2009, 74, 5471
.
Org. Lett., Vol. 12, No. 8, 2010
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