Spiro{bicyclo[4.2.0]octa-1,3,5-triene-7,2-[1,3]-dioxolan}-8-one1

[6383-64-8]  · C10H8O3  · Spiro{bicyclo[4.2.0]octa-1,3,5-triene-7,2-[1,3]-dioxolan}-8-one  · (MW 176.18)

(serves as a 1,4-dipole synthon for synthesis of anthraquinone-related ring systems2)

Physical Data: mp 109-112 °C.

Preparative Methods: this simple monoethylene acetal of benzocyclobutenedione3 may be prepared by reaction of the parent dione with Ethylene Glycol in benzene with a trace of p-Toluenesulfonic Acid and azeotropic removal of water,1 or by a three-step method that is essentially a silicon analog of the Kornblum oxidation (eq 1).4 The latter approach affords control over acetal regiochemistry in systems with unsymmetrical substitution on the aromatic ring.

Purification: crystallizes from benzene-hexane; slightly yellow needles.

Annulation Reactions.

Reaction with lithiated quinone bisacetals affords anthraquinone-related structures (eq 2).2 Studies support a stepwise rather than a concerted mechanism for this 1,4-dipole-type annulation.5 Thus reaction with a highly functionalized lithioquinone bisacetal followed by hydrolysis and demethylation steps gave the 7-O-methyl epimer of the anthracycline aglycons 4-demethoxydaunomycinone (R = H) or daunomycinone (R = OMe) (eq 3).4 A related strategy was used in a synthesis of a-citromycinone,6 although the annulation yield was only 30%.

This method has also been used in an approach to the tetracycline antibiotics,7 giving an annulation adduct which, after addition of Methyllithium, showed the correct relative configuration at key eventual positions of the tetracycline ring system (eq 4).

Ring Expansion.

Reaction with 1-lithioalkynes affords 1,2-adducts which undergo palladium triflate-catalyzed ring expansion to (Z)-2-alkylideneindan-1,3-dione monoacetals (eq 5),8 a methodology that has been used in the synthesis of a benzo analog of the antiviral agent abikoviromycin.9


1. Cava, M. P.; Stein, R. P. JOC 1966, 31, 1866.
2. Jackson, D. K.; Narasimhan, L.; Swenton, J. S. JACS 1979, 101, 3989.
3. (a) Cava, M. P.; Napier, D. R.; Pohl, R. J. JACS 1963, 85, 2076. (b) South, M. S.; Liebeskind, L. S. JOC 1982, 47, 3815.
4. Swenton, J. S.; Anderson, D. K.; Jackson, D. K.; Narasimhan, L. JOC 1981, 46, 4825.
5. Spangler, L. A.; Swenton, J. S. JOC 1984, 49, 1800.
6. Swenton, J. S.; Anderson, D. K.; Coburn, C. E.; Haag, A. P. T 1984, 40, 4633.
7. Spangler, L. A.; Swenton, J. S. CC 1986, 828.
8. (a) Liebeskind, L. S.; Mitchell, D.; Foster, B. S. JACS 1987, 109, 7908. (b) Liebeskind, L. S.; Chidambaram, R.; Mitchell, D.; Foster, B. S. PAC 1988, 60, 2734.
9. Mitchell, D.; Liebeskind, L. S. JACS 1990, 112, 291.

Gary W. Morrow

The University of Dayton, OH, USA



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