A successful new strategy for the asymmetric synthesis of pentalenolactone E (2a) and pentalenolactone F (2b) has been developed. This strategy involves the assembly of ring A of 2a and 2b through a Binger‐type Pd‐catalyzed [3 + 2]‐cycloaddition reaction of diquinene 7 with the diphenyl‐substituted methylenecyclopropane 18. Diquinene 7 is available in an enantiomerically pure state in 8 steps from diester 8 by using a pig liver esterase catalyzed enantioselective hydrolysis as the key step. Unexpected facial selectivities of 1,3‐dipolar and Pd‐catalyzed [3 + 2]‐cycloaddition reactions as well Michael reactions of 7 have been observed. Thus, 7 reacted with CH2N2 with a stereoselectivity of 98% or greater in favour of reaction at the concave side, with formation of the cisoid triquinane 27. A Trost‐type Pd‐catalyzed reaction of 7 with 11 gave the transoid triquinane 6 and the cisoid triquinane 12 in ratios of 1:1.7 to 1:5.3 depending on the polarity of the solvent. Binger‐type Pd‐catalyzed cycloaddition reactions of 7 with methylenecyclopropane (13) in toluene afforded a mixture of 6 and 12 in a ratio of 1:7. In the Pd‐catalyzed reaction of 7 with the phenyl‐substituted methylenecyclopropanes 14a/b the cisoid triquinane 15 was obtained with a selectivity of 6.7:1 or above. Pd‐catalyzed reactions of 7 with the disubstituted methylenecyclopropanes 16 and 18 gave, however, the transoid triquinanes 17 and 19, respectively, with selectivities of 23:1 and 7:1, respectively. Nakamura‐type cycloaddition of 7 to the methylenecyclopropanone ketal 20 led to the quantitative formation of the transoid triquinane 21a and the cisoid triquinane 22a in a ratio of 1:2. The structures of cycloadducts 12, 15, 19 and 27 were determined by X‐ray analyses. The π‐facial differentiation may be ascribed mainly to a stabilization of the concave transition states by an electrostatic interaction between the lactone carbonyl group and the nucleophilic reagents. The stereoselectivity model proposed has been substantiated by a study of the analogous cycloaddition reactions of diquinenes 29a−c, which exhibited only a low π‐facial stereoselectivity, and by an X‐ray structure analysis of 7, which revealed a slight concave pyramidalization of the double bond. X‐ray structure analysis and NMR spectroscopy of diquinane 28a showed the 5E‐conformation, in which the hydroxy group occupies the pseudoaxial position, to be the more stable one. According to force‐field calculations, the 5E‐conformation seems to be stabilized by an intramolecular electrostatic interaction between the hydroxylic oxygen atom and the lactone carbonyl group, corresponding to the initial step of an intermolecular nucleophilic attack at the carbonyl group. The O−C1 distance and the O−C1−O angle found in the crystal structure of 28a support this notion.

A formal asymmetric synthesis of pentalenolactone E (1b) and pentalenolactone F (1a) has been accomplished. Ozonolysis of the diphenyl‐substituted triquinane 3 and Kauffmann methylenation of ketone 5 with WOCl3‐2 MeLi yielded the unsubstituted triquinane 9. The crucial rearrangement of the linear triquinanoid lactone 11 to the angular triquinanoid lactone 14a was accomplished using orthoformate and acid in methanol. Subjecting triquinanes 14a/b to the selenoxide method gave triquinene 15. Homologation of γ‐lactone 15 to the angular diquinanoid δ‐lactone 2 via a Horner‐Wadsworth‐Emmons or Peterson reaction of hemiacetals 16a/b was, however, not successful. Chemoselective reduction of 14a afforded hemiacetals 21a/b, reaction of which with the phosphonate salt 17a ultimately led to the ketene dithioacetal 22. The angular intermediates 25a/b were obtained from 22 by reduction to give the linear hemiacetals 24a/b, which rearranged to the dithio ortholactones 25a/b in the presence of acid. Introduction of the double bond and deprotection were accomplished via selenation of 25a/b with N,N‐diethylbenzeneselenylamide and treatment of selenides 30a/b with silver nitrate. The unsaturated aldehydes 28 and 29 thus obtained were converted to 2 and 31, respectively, by oxidation with manganese dioxide in the presence of sodium cyanide, methanol and acetic acid. Alkene 2 was isolated by crystallization.

Formal Asymmetric Synthesis of Pentalenolactone E and Pentalenolactone F. Part 2. Construction of the Angular Diquinanoid δ-Lactone.-An asymmetric synthesis of the diquinanoid δ-lactone (XI), a known precursor of pentalenolactones E and F, starts from (I). The latter was prepared in the preceding paper.-(HERRMANN, E.; GAIS, H.-J.; ROSENSTOCK, B.; RAABE, G.; LINDNER, H. J.; Eur.

Formal Asymmetric Synthesis of Pentalenolactone E and Pentalenolactone F. Part 1. Retrosynthesis and π-Facial Differentiation in Palladium-Catalyzed and Dipolar [3 + 2]-Cycloaddition Reactions of Bicyclic Alkenes: Evidence for Electrostatic Control of Stereoselectivity.-A new strategy for the formal asymmetric synthesis of the title sesquiterpenoids (I) and (II) with a Pd-catalyzed [3 + 2]-cycloaddition for the construction of the diquinane skeleton as the key step is developed. Several [3 + 2]-cycloadditions of the diquinene (V) with e.g. (VI), (IX), or (XI) lead to the formation of the adducts with unexpected facial selectivities. Michael reactions of (V) take an expected steric course, too. The practically exclusive formation of the cisoid triquinane (XV) in the 1,3-dipolar cycloaddition of (V) with CH 2 N 2 represents an exceptional example of the electrostatic control of the stereoselectivity by a functional group. The linear triquinane (X) would be a suitable precursor for the key intermediate (III). -(ROSENSTOCK, B.; GAIS, H.-J.; HERRMANN, E.; RAABE, G.; BINGER, P.; FREUND, A.; WEDEMANN, P.; KRUEGER, C.; LINDNER, H. J.; Eur.