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Isodesmic and homodesmic equations at the B3LYP/6-311+G(d,p)+ZPVE level of theory have been used to estimate strain for the homologous series of cyclic allenes and cyclic butatrienes. A simple fragment deformation approach also has been applied and appears to work better for the larger rings. For the cyclic allene series, estimates for allene functional group strain (kcal/mol) include: 1,2-cyclobutadiene, 65; 1,2-cyclopentadiene, 51; 1,2-cyclohexadiene, 32; 1,2-cycloheptadiene, 14; 1,2-cyclooctadiene, 5; 1,2-cyclononadiene, 2; 1,2,4-cyclohexatriene, 34; and bicyclo[3.2.1]octa-2,3-diene, 39. For cyclic butatrienes, functional group strain estimates include: 1,2,3-cyclobutatriene, >100; 1,2,3-cyclopentatriene, 80; 1,2,3-cyclohexatriene, 50; 1,2,3-cycloheptatriene, 26; 1,2,3-cyclooctatriene, 17; and 1,2,3-cyclononatriene, 4. Barriers to interconversion of enantiomers in cyclic allenes are reduced with increasing strain. Newly predicted values include: 1,2-cyclopentadiene <1 kcal/mol and bicyclo[3.2.1]octa-2,3-diene, 7.4 kcal/mol. Estimated levels of strain parallel the known reactivity of these substances.

An asymmetric synthesis of the quinone epoxide dimer (+)-torreyanic acid (48) has been accomplished employing [4 + 2] dimerization of diastereomeric 2H-pyran monomers. Synthesis of the related monomeric natural product (+)-ambuic acid (2) has also been achieved which establishes the biosynthetic relationship between these two natural products. A tartrate-mediated nucleophilic epoxidation involving hydroxyl group direction facilitated the asymmetric synthesis of a key chiral quinone monoepoxide intermediate. Thermolysis experiments have also been conducted on a model dimer based on the torreyanic acid core structure and facile retro Diels-Alder reaction processes and equilibration of diastereomeric 2H-pyrans have been observed. Theoretical calculations of Diels-Alder transition states have been performed to evaluate alternative transition states for Diels-Alder dimerization of 2H-pyran quinone epoxide monomers and provide insight into the stereocontrol elements for these reactions.

A concise approach to the tetrahydroxanthone natural products has been developed employing vinylogous addition of siloxyfurans to benzopyryliums and a late stage Dieckmann cyclization. Using this methodology, chiral, racemic forms of the natural products blennolides B and C have been synthesized in a maximum of four steps from a 5-hydroxychromone substrate. The regio-and diastereoselectivity of vinylogous additions was probed using computational studies which suggest involvement of Diels-Alder-like transition states.Tetrahydroxanthones are a class of mycotoxins 1 bearing both monomeric and dimeric frameworks. The recently isolated tetrahydroxanthones blennolides A (1) and B (2) ( Figure 1) 2 are monomer units of the antitumor agents secalonic acids B (3) and D (4), 3 the latter which exhibits antibacterial, cytostatic, and anti-HIV properties. 4 Blennolide C (5), the methyl isomer of 1, and the antifungal agent parnafungin A (6) 5 also possess the characteristic dihydro-2H-xanthenone framework found in many tetrahydroxanthones. Related, isomeric natural products including paecilin B (7) (stereochemistry unassigned) containing the isomeric chromone lactone moiety have also been reported. 6 Recently, Bräse and Nicolaou have reported elegant approaches to blennolide C (5) and the related natural product diversonol employing biomimetic construction of the tetrahydroxanthone core. 7 Herein, we describe a concise approach to racemic blennolides and related tetrahydroxanthones employing a "retrobiomimetic" process 8 involving vinylogous addition of siloxyfurans to benzopyryliums.Biosynthetically, the blennolides appear to be derived from a sequence involving oxidation of benzophenone ester 8, oxa-Michael addition, and reduction to dihydro-2H-xanthenone 9 (Figure 2, (a)). 9 The chromone lactone structure 10 found in paecilin B (7) 6 appears to be derived from hydrolysis/lactonization of the tetrahydroxanthone framework. 6b,c We envisioned that precursor 11 may be obtained by vinylogous addition of siloxyfurans 10 to activated benzopyrylium salts 12. 11 Conjugate reduction of butenolide 11 should afford chromone lactone 10. The last step in the sequence entails a "retrobiomimetic" transformation 8 in which tetrahydroxanthones 9 may be produced by Dieckmann cyclization 7k of chromone lactones 10. We initiated our study by treating the readily available 5-hydroxychromone 13 12,13 with a number of Lewis acids in an effort to promote vinylogous addition of 2-trimethylsilyloxy furan (Scheme 1). Unfortunately, in our initial experiments we did not observe substantial adduct formation. In light of the high reactivity of 4-siloxy-1-benzopyrylium salts towards carbon nucleophiles, 11a,b we focused our efforts on silyl triflate activation of chromone 13.In particular, we reasoned that dialkylsilyl ditriflate reagents, generally used to protect diols as silylenes, 14 may directly afford activated siloxybenzopyrylium species. In the event, treatment of 13 with diisopropyl silyl ditriflate in the presence of 2,6-lutidin...