ORGANIC LETTERS
Photochemical Cyclization with Release of Carboxylic Acids and Phenol from Pyrrolidino-Substituted 1,4-Benzoquinones Using Visible Light
2005 Vol. 7, No. 17 3729-3732
Yugang Chen and Mark G. Steinmetz* Department of Chemistry, Marquette UniVersity, Milwaukee, Wisconsin 53201-1881
[email protected] Received June 10, 2005
ABSTRACT
Visible light irradiation of 5-acyloxymethyl- and 5-phenoxymethyl-2-pyrrolidino-1,4-benzoquinones effects photoisomerization to labile oxazolidines, which undergo elimination of carboxylate or phenolate leaving groups in high yields to generate trappable o-quinone methide intermediates.
Early studies have shown that the photochemical cyclization of 2-amino-1,4-benzoquinones to oxazolidines can be effected with sunlight.1 This photocyclization is exemplified by 2-pyrrolidino-1,4-benzoquinone 1, which gives oxazolidine 2 as a photoproduct (Scheme 1).2 In the case of the
Scheme 2
Scheme 1
respect to “dark” elimination of a leaving group (LG), such as a carboxylate group or a phenolate group. Thus, visible light would serve to activate a photoremovable protecting group for release or unmasking of functionality in a structurally related 2-pyrrolidino-1,4-benzoquinone 3 (Scheme 2), the photocyclization product 4 should be unstable with (1) (a) Cameron, D. W.; Giles, R. G. F. Chem. Commun. 1965, 573574. (b) Cameron, D. W.; Giles, R. G. F. J. Chem. Soc. C 1968, 14611464. (c) Giles, R. G. F.; Mitchell, P. R. K.; Roos, G. H. P.; Baxter, I. J. Chem. Soc., Perkin Trans. 1 1973, 493-496. 10.1021/ol051362k CCC: $30.25 Published on Web 07/27/2005
© 2005 American Chemical Society
(2) (a) Oxazolidine 2 could be isolated in excellent yield after silica gel column chromatography, eluting with EtOAc in hexane. The high-field spectral data were as follows: 1H NMR (CDCl3) δ 1.87 (m, 2 H), 2.07 (s, 3 H), 2.14 (s, 3 H), 2.21 (m, 2 H), 2.97 (m, 1 H), 3.35 (m, 1 H), 5.15 (br s, 1 H), 5.81 (t, J ) 3.3 Hz, 1 H), 6.61 (s, 1 H); 13C NMR (CDCl3) δ 10.8, 15.3, 24.2, 32.8, 55.8, 102.8, 110.8, 111.1, 115.2, 140.5, 145.0, 148.3. (b) Falci, K. J.; Franck, R. W.; Smith, G. P. J. Org. Chem. 1977, 42, 33173319.
subsequent step. The use of visible light for unmasking of functionality is of fundamental importance for the development of selective methods for photodeprotection of polyfunctional molecules,3 where selectivity in the deprotection would depend on the color of the incident light. Progress in this area has been hindered by the dearth of photocleavable protecting groups that can be removed with visible light. With few exceptions,4,5 the usable wavelength region for photoremoval of protecting groups typically lies below about 400 nm. 2-Amino-1,4-benzoquinones generally absorb light in the 450-650 nm wavelength region.6 Although the available energy in this wavelength region (44-63 kcal mol-1) is insufficient to directly cleave relatively strong bonds, it is capable of effecting the photocyclization of 1. In the case of 3, the release of the leaving group is expected to occur after such a photocyclization, in a dark elimination step that would be expected to be pH dependent. Nevertheless, one concern is that no quantum yield has been reported for the photocyclization of a 2-amino-1,4-benzoquinone. We thus conducted a preliminary investigation with 1 and found that upon irradiation at 458 nm the photocyclization occurs in 100% chemical yield with a quantum efficiency of 0.091 in CH2Cl2 as the solvent.7 The photocyclizations with release of carboxylic acids from 3 were initially investigated with a benzoate leaving group (LG ) PhCO2-). Irradiation of 0.02 M solutions in 30% D2O in CD3CN with a 120 W sunlamp produced benzoic acid in 58% yield at 100% conversion. An additional product was isolated as a ca. 1:1 mixture of diastereomers in 36% yield by column chromatography. Its structure, which was assigned as 6 (LG ) PhCO2-),8 suggested that it was produced via cycloaddition of an o-quinone methide intermediate 5 with unreacted starting material (Scheme 3), which would account for the low yields of photoreleased benzoic acid. Similar results were obtained upon photolysis of 3 (LG ) PhCO2-) at 542 nm with light passed through a monochromator. (3) (a) Bochet, C. G. Tetrahedron Lett. 2000, 41, 6341-6346. (b) Bochet, C. G. Angew. Chem., Int. Ed. 2001, 40, 2071-2073. (4) Furuta, T.; Wang, S. S.-H.; Dantzker, J. L.; Dore, T. M.; Bybee, W. J.; Callaway, E. M.; Denk, W.; Tsien, R. Y. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 1193-1200. (5) Banerjee, A.; Grewer, C.; Ramakrishnan, L.; Jager, J.; Gameiro, A.; Breitinger, H.-G. A.; Gee, K. R.; Carpenter, B. K.; Hess, G. P. J. Org. Chem. 2003, 68, 8361-8367. (6) Herre, W.; Wunderer, H. Tetrahedron 1972, 28, 5433-5443. (7) (a) Quantum yield determinations were performed at 458 nm. The ferrioxalate actinometer concentration was increased to ensure that all of the long-wavelength light was absorbed, as prescribed in ref 7b. (b) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photochemistry, 2nd ed.; Marcel Dekker: New York, 1993; pp 301, 303. (8) The spectral data for the ca. 1:1 diastereomeric mixture of 6 (LG ) PhCO2-) were as follows (minor diastereomer carbons are in parentheses): 1H NMR (CDCl ) δ 1.40 (s, 3 H), 1.44 (s, 3 H), 1.68 (m, 8 H), 1.86 (s, 6 3 H), 1.85 (m, 4 H), 2.13 (s, 3 H), 2.15 (s, 3 H), 2.17 (m, 4 H), 2.19 (s, 3 H), 2.20 (s, 3 H), 2.45 (m, 2 H), 2.73 (m, 6 H), 2.88 (m, 4 H), 2.99 (m, 2 H), 3.34 (m, 2 H), 5.23 (d, J ) 12 Hz, 2 H), 5.32 (d, J ) 12 Hz, 2 H), 5.76 (m, 2 H), 7.41 (t, J ) 7.8 Hz, 4 H), 7.54 (t, J ) 7.8 Hz, 2 H), 7.95 (d, J ) 7.8 Hz, 4 H); 13C NMR (CDCl3) δ 10.7 (10.6), 11.6, 13.2 (13.1), 17.9 (17.8), 24.1, 25.0 (24.9), 32.61 (32.58), 36.6, 48.0 (47.9), 52.3 (52.0), 55.9 (55.8), 58.6, 94.94 (94.92), 102.6, 110.9 (110.8), 112.0 (111.8), 112.5, 128.7, 129.8, 133.5, 138.98 (138.96), 139.3, 145.0 (144.8), 145.6 (145.5), 146.9 (146.7), 166.2, 193.8 (193.4), 199.1. Anal. Calcd for C33H36N2O6: C, 71.15; H, 6.52; N, 5.03. Found: C, 70.76; H, 6.58; N, 4.99. 3730
Scheme 3
The intermediacy of o-quinone methide 5 was probed by photolyzing the benzoate derivative of 3 (LG ) PhCO2-) with 0.1 M 3-(dimethylamino)cyclohexen-1-one 7 as a trapping reagent (Scheme 3). In addition to 92% yield of benzoic acid, a cycloadduct was obtained in 87% yield, which was identified as 8 after chromatographic isolation.9 With other carboxylate leaving groups (LG ) PhCH2CO2or LG ) 4-CNC6H4CO2-), the cycloadduct 8 was obtained in 79% and 82% yields, along with 92% and 89% yields of the corresponding carboxylic acids. Evidently, the presence of the electron-releasing pyrrolidino and the dimethyl groups in 5 reduces its reactivity compared to other o-quinone methides,10 since attempts to trap 5 with various electronrich alkenes (ethyl vinyl ether, vinylene carbonate, methyl trimethylsilyldimethylketene acetal) failed to produce the corresponding cycloadducts. The intermediacy of o-quinone methide 5 could account for new absorption bands that were observed at 339 and 455 nm after 30 min of photolysis of 5 × 10-4 M aminoquinone 3 (LG ) PhCO2-) at 2 °C in 30% aq CH3CN with a sunlamp (Figure 1) or at 542 nm. Upon warming to 20 °C, the new absorptions disappeared, and the rate of disappearance was strongly accelerated by adding 8 × 10-3 M dimethylaminocyclohexenone 7.11a In 30% phosphate buffer in CH3CN at (9) Compound 8, mp 194-196 °C. The spectral data were as follows: NMR (CDCl3) δ 1.08 (s, 3 H) 1.09 (s, 3 H) 1.86 (m, 2 H) 2.05 (s, 3 H) 2.16 (s, 3 H) 2.21 (m, 2 H) 2.29 (s, 2 H) 2.39 (s, 2 H) 2.93 (m, 1 H) 3.24 (m, 2 H) 3.34 (m, 1 H) 5.79 (m, 1 H); 13C NMR (CDCl3) δ 10.8, 11.7, 20.1, 24.1, 28.6, 32.4, 32.7, 41.6, 50.9, 56.0, 102.9, 107.7, 111.5, 113.9, 114.4, 138.8. Anal. Calcd for C21H25NO3: C, 74.31; H, 7.42; N, 4.13. Found: C, 74.28; H, 7.56; N, 4.20. (10) Wan, P.; Barker, B.; Diao, L.; Fischer, M.; Shi, Y.; Yang, C. Can. J. Chem. 1996, 74, 465-475. (11) (a) The 550 nm band in Figure 1 is due to unreacted starting material. At low concentrations (
