1,3-Diphenylisobenzofuran1

[5471-63-6]  · C20H14O  · 1,3-Diphenylisobenzofuran  · (MW 270.34)

(highly reactive diene,1 suitable for the trapping of unstable or transient dienophiles as their Diels-Alder adducts; standard reagent for the determination of singlet oxygen; useful reagent in the synthesis of polyaromatic species)

Physical Data: yellow crystalline needles, mp 128-130 °C.

Solubility: sol acetonitrile, benzene, chloroform, dichloromethane, DMSO, THF, toluene.

Handling, Storage, and Precautions: air sensitive; light sensitive.

Properties.

The majority of isobenzofurans should only be viewed as reactive intermediates. 1,3-Diphenylisobenzofuran (1) is a moderately stable compound and is commercially available. On the other hand, isobenzofuran (2) has only been isolated at low temperatures.2 The reactivity of these species is confined to the furanoid ring. Isobenzofurans have been described as the most reactive Diels-Alder dienes known.3 The reactivity is attributable to the extra resonance energy gained by formation of an aromatic ring during the cycloaddition.

Synthesis.

Owing to the extensive interest in isobenzofurans in recent years, numerous technologies for their preparation have been forwarded, and these have been amply reviewed.4 Synthesis from phthalan precursors is most popular and useful (eq 1).5

In a convenient protocol, 3,6-di-2-pyridyl-s-tetrazine and 1,4-dihydro-1,4-endoxynaphthalene react in two steps to yield isobenzofuran, which can subsequently react with the dienophile of interest (eq 2).6

Trapping of Unstable Dienophiles as Diels-Alder Adducts.

Cycloaddition reactions of 1,3-diphenylisobenzofuran have been extensively exploited for trapping unstable dienophiles. The Diels-Alder cycloaddition of the parent isobenzofuran is some 11 times faster than of the 1,3-diphenyl analog,7 and hence this species is often used in instances where the highest level of reactivity is required. Exceedingly unstable species, such as Dewar furan, can be generated and trapped in this manner (eq 3).8

The isobenzofuran must, however, itself be generated immediately prior to carrying out the reaction.9 The more stable 1,3-diphenylisobenzofuran is an excellent trapping agent for reactive or unstable alkenes and alkynes and has extensively been exploited in this application. Adducts with species such as arynes, cycloalkenes, and cycloalkynes are commonly prepared. For example, 3,4-pyridynes readily form cycloadducts with 1,3-diphenylisobenzofuran (eq 4).10

A highly strained polycyclic alkyne, 4-homoadamantyne, has been generated and trapped as a cycloadduct with 1,3-diphenylisobenzofuran (eq 5).11 Similarly, a highly strained cyclopropene, tricyclo[3.2.1.02,4]oct-2(4)-ene, has been synthesized and trapped in this manner (eq 6).12 The related species 5,6-dimethyl-1,3-diphenylisobenzofuran is purported to be more stable and yield more easily characterized adducts.13

The Diels-Alder reaction of 1,3-diphenylisobenzofuran can be accelerated by catalysis with Lewis acids, such as Boron Trifluoride Etherate. Cycloaddition with diethyl vinylphosphonate yields a mixture of two isomers in high yields (75%) (eq 7).14

Diels-Alder additions of isobenzofurans with alkenic dienophiles normally yield mixtures of exo and endo adducts. Reversible cycloadditions tend to favour exo isomers, presumably on thermodynamic grounds.

Higher Order Cycloadditions.

Isobenzofurans are frequently utilized as 4p components in cycloaddition reactions. These can be Diels-Alder [4p + 2p] or higher order [4p + 4p] and [4p + 6p] cycloadditions. Tropone yields the [p4 + p6] thermal cycloadduct (eq 8).15

Synthesis of Polyaryl Systems.

Cycloaddition of isobenzofurans followed by deoxygenation of the cycloadducts constitutes a powerful methodology for the synthesis of polyaromatic species (eq 9).16

Reaction with Singlet Oxygen.

1,3-Diphenylisobenzofuran reacts rapidly with singlet oxygen to yield an unstable endoperoxide17 which subsequently decomposes to o-dibenzoylbenzene (eq 10), although the details of this reaction are controversial.18 The quenching reaction has become a standard in the field of singlet oxygen chemistry.19 Disappearance of 1,3-diphenylisobenzofuran can be monitored by measurement of absorbance at 415 nm or by loss of fluorescence emission at 458 nm.20

Lithiation of Isobenzofuran.

Deprotonation of isobenzofuran occurs readily to yield the 1-lithio species. In practice, the phthalan precursor is lithiated (0.05 equiv diisopropylamine/2.1 equiv MeLi/0 °C), yielding 1-lithioisobenzofuran, which reacts smoothly with electrophiles (eq 11).21

Photochemistry.

1,3-Diphenylisobenzofuran22 and isobenzofuran23 photodimerize to form head-to-head [8p + 8p] adducts (eq 12). The latter adduct has been determined to have anti stereochemistry. The reaction is reversible for the 1,3-diphenylisobenzofuran adduct. Thermolysis returns the starting material.24 This head-to-head dimer can also be generated thermally25 and is encountered in the product mixture of cycloaddition reactions.26


1. (a) Rodrigo, R. T 1988, 44, 2093. (b) Friedrichsen W. Adv. Heterocycl. Chem. 1980, 26, 135.
2. (a) Warrener, R. N. JACS 1971, 93, 2346. (b) Wege, D. TL 1971, 2337. (c) Wiersum, U. E.; Mijs, W. J. CC 1972, 347.
3. Tobia, D.; Rickborn, B. JOC 1987, 52, 2611.
4. (a) Rodrigo, R. T 1988, 44, 2093. (b) Friedrichsen W. Adv. Heterocycl. Chem. 1980, 26, 135.
5. Newman, M. S. JOC 1961, 26, 2630.
6. Warrener, R. N. JACS 1971, 93, 2346.
7. Tobia, D.; Rickborn, B. JOC 1987, 52, 2611.
8. (a) Warrener, R. N.; Pitt, I. G.; Russell, R. A. AJC 1991, 44, 1275. (b) Pitt, I. G.; Russel, R. A.; Warrener, R. N. JACS 1985, 107, 7176.
9. Warrener, R. N. JACS 1971, 93, 2346.
10. Tsukazaki, M.; Snieckus, V. H 1992, 33, 533.
11. Komatsu, K.; Kamo, H.; Tsuji, R.; Masuda, H.; Takeuchi, K. CC 1991, 71.
12. Chenier, P. J.; Bauer, M. J.; Hodge, C. L. JOC 1992, 57, 5959.
13. (a) Kim, M. White, J. D. JACS 1977, 99, 1172. (b) White, J. D.; Mann, M. E.; Kirshenbaum, H. D.; Mitra, A. JOC 1971, 36, 1048.
14. Lasne, M.-C.; Ripoll, J.-L.; Thuillier, A. JCS(P1) 1988, 99.
15. Takeshita, H.; Wada, Y.; Mori, A.; Hatsui, T. CL 1973, 335.
16. (a) Wong, H. N. C.; Man, Y.-M.; Mak, T. C. W. TL 1987, 6359. (b) Man, Y.-M.; Mak, T. C. W.; Wong, H. N. C. JOC 1990, 55, 3214.
17. Rio, G.; Scholl, M.-J. CC 1975, 474.
18. Friedrichsen, W. Adv. Heterocycl. Chem. 1980, 26, 135.
19. (a) Haugen, C. M.; Bergmark, W. R.; Whitten, D. G. JACS 1992, 114, 10293. (b) Matheson, I. B. C.; Lee, J.; Yamanashi, B. S.; Wolbarsht, M. L. JACS 1974, 96, 3343. (c) Manring, L. E.; Gu, C.-L.; Foote, C. S. J. Phys. Chem. 1983, 87, 40. (d) Rodgers, M. A. J.; Peteres, J. Biochem. Biophys. Res. Commun. 1980, 96, 770.
20. Young, R. H.; Wehrly, K.; Martin, R. L. JACS 1971, 93, 5774.
21. Crump, S. L.; Rickborn, B. JOC 1984, 49, 304.
22. Schönberg, A.; Mustafa, A.; Aziz, G. JACS 1954, 76, 4576.
23. Warrener, R. N.; Pitt, I. G.; Russell, R. A. CC 1982, 1195.
24. (a) Courtot, P.; Sachs, D. H. BCF 1965, 2259. (b) Le Berre, A.; Lonchambon, G. BCF 1967, 4328. (c) Haupp, G.; Teufel, E. JCR(M) 1978, 1301.
25. Schönberg, A.; Mustafa, A.; Barakat, M. Z.; Latif, N.; Moubasher, R.; Mustafa, A. JCS 1948, 2126.
26. (a) Pitt, I. G.; Russell, R. A.; Warrener, R. N. JACS 1985, 107, 7176.

Paul Ch. Kierkus

BASF Corporation, Wyandotte, MI, USA



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