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Notizen: 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.

Notizen: The structures of the norbornenyl and norbornyl sulfones exo-5, endo-5 and endo-6 have been determined experimentally, by X-ray analysis, and theoretically by ab initio calculations (HF/6-31+G*). X-ray crystal structure analyses of the lithiated allylic norbornenyl and norbornyl sulfones endo-3/ent-endo-3·2diglyme and endo-4/ent-endo-4·2diglyme revealed dimeric O-Li contact ion pairs devoid of C-Li bonds. The anions of endo-3/ent-endo-3·2diglyme and endo-4/ent-endo-4·2diglyme adopt both the endo conformation (C2-S) and are characterized by in the exo direction pyramidalized anionic C atoms. The degree of pyramidalization of the C2 atom of 3 is higher than that of 4. Ab initio optimizations (HF/6-31+G*) of the structures of the anions of methylenenorbornene I and methylenenorbornane II resulted in local minima featuring non-planar C2 atoms which are pyramidalized in the exo direction in both cases, but to different degrees. In both cases cryoscopy of 3 and 4 in THF at -108.5 °C revealed approximately 1:1 mixtures of monomers and dimers. The sulfones exo-5, endo-5, exo-6 and endo-6 as well as the lithiosulfones 3 and 4 were studied by NMR spectroscopy. 1H-NMR (400 MHz), 13C-NMR (100 MHz) and 6Li-NMR (44 MHz) spectroscopy of 3 and 4 at -100 °C in [D]8THF revealed in each case only one set of signals, independent of the configuration of the starting sulfones. This indicates in both cases that attainment of both the monomer-dimer and the endo/exo equilibria of 3 and 4 is fast on the NMR time scale. According to 6Li{1H}- and 1H{1H}-NOE experiments of 3 and 4 the monomeric and dimeric species endo-3 and endo-4, having endo anions, seem to be preferred in THF solution. Ab initio calculations of the anions of 3 and 4 resulted in structures endo-3(-Li+), exo-3(-Li+), endo-4(-Li+) and exo-4(-Li+) (HF/6-31+G*), whose atomic point charges were calculated by the method of Kollman et al. The C2 atoms of endo-3(-Li+) and endo-4(-Li+) are pyramidalized in the exo direction whereas the C2 atoms of exo-3(-Li+) and exo-4(-Li+) are pyramidalized in the endo direction. According to the calculations, the endo anions are more stable than the exo anions. There is good agreement between the optimized structures of the free anions and the experimentally determined structures of the anions of the contact ion pairs in the crystal. Reactions of 3 and 4 with DX, MeI, EtI, nPrI and nHeI occurred at the C2 atom under the selective formation of the corresponding endosulfones endo-8a-e and endo-9a-e, respectively, in all cases. Thus, an earlier report on the selective formation of the exosulfone exo-9b in the reaction of 4 with MeI has to be revised. Product ratios were independent of the configuration of the starting sulfones and varied with the nature of the electrophile. Selectivities were highest in the case of the norbornyl species 4. Reaction of 3 with PhCHO occurred at the α position (C2) to afford the alcohols endo-8f and exo-8f (88:12) as single diastereomers and at higher temperatures at the γ position (C8), whereas reaction of 4 with PhCHO took place at the γ position even at low temperatures. Methylation of endo-5 and exo-5 at -105 °C by both the stepwise method and by the in situ method gave different ratios of exo- and endo-methylation products. The selectivities of reaction of 3 and 4 with electrophiles have been rationalized by the Curtin-Hammett/Winstein-Holness concepts. It is proposed that endo-3 (endo-4) and exo-3 (exo-4) are conformationally labile on the time scale defined by the rate of their reactions with electrophiles, and are attacked by electrophiles with high selectivities from the exo and the endo face, respectively, because of the shielding by the phenyl group and the direction of the pyramidalization of the anionic C atom. Preferential formation of the endosulfones is thus ascribed to exo attack of electrophiles on endo-3 (endo-4) being faster than endo attack on exo-3 (exo-4) because of Houk's staggering effect. Methylation of 3 and 4 by the in situ method showed 3, whose C2 atom is stronger pyramidalized, to be more reactive than 4. The base-catalyzed H/D exchange of sulfones endo-5, exo-5, endo-6 and exo-6 with NaOCD3 in CD3OD proceeded in all cases with a high degree of retention of configuration.