The readily available and enantiomerically pure trienes 12 undergo a thermally induced intramolecular Diels-Alder reaction to give the corresponding mixture of compounds 13 and 14. This mixture has been elaborated to an advanced intermediate associated with Nicolaou's recently reported total synthesis of the natural enantiomeric form of the antibiotic platencin (2).
Dedicated to Professor Dieter Hoppe on the occasion of his 70th birthdayAlthough intermolecular [2+2] photocycloadditions of isoquinolones have been studied for some time, [1] the corresponding intramolecular reactions of this substrate class have received little attention. To date, only isoquinolones that carry the olefin for an intramolecular cycloaddition in an N-tethered chain have been examined.[2] Given the prevalence of isoquinoline-derived natural products, [3] the intramolecular [2+2] photocycloaddition of isoquinolones could potentially be very useful, [4] particularly if these reactions could be performed regio-and enantioselectively. We have now studied the photocycloaddition reactions of a selection of 3-and 4-substituted isoquinolones 1-9 (Scheme 1). The various cyclobutane products were formed in high yields and, in the case of 4-substituted isoquinolones, with high enantioselectivities (88-96 % ee) by employing a chiral template. Moreover, it was shown for the first time that kinetic resolution is possible in template-based organic photochemistry.The starting materials for this study were prepared from 4-hydroxyisoquinolone [5] (substrates 1, 4-7), 4-bromoisoquinolone [6] (substrates 2, 8, 9), and 3-hydroxyisoquinolone [7] (substrate 3). Further details on the synthesis of these substrates are found in the Supporting Information. Initial reactions were performed with 4-(but-3-enyloxy)isoquinolone (1). The optimum wavelength for irradiation was found to be around l = 366 nm (fluorescence light tubes), and racemic photocycloaddition products were obtained after 50 min of irradiation at ambient temperature in trifluorotoluene or toluene as the solvent. When performed in the presence of chiral template 10 [8] (2.6 equiv in all experiments), the [2+2] photocycloaddition of isoquinolone 1 (c = 5 mm) was found to occur in a highly enantioselective manner (Scheme 2). [9,10] The best results were achieved at low temperature: the straight photoproduct 11-s was obtained with 93 % ee and the crossed photoproduct 11-c with 96 % ee. The absolute configuration of compound 11-s was proven by conversion into the corresponding N-(À)-menthyloxycarbonyl derivative and subsequent X-ray crystal structure analysis (see the Supporting Information).Based on these results, the mode of action of template 10 is likely effected by hydrogen bonding to substrate 1 and its ability to provide significant enantioface differentiation to the bulky 5,6,7,8-tetrahydronaphtho[2,3-d]oxazole substituent ("steric shield").[11] Still, it is surprising that the enantiomeric excess is so high given the fact that the reactive olefinic carbon-carbon bond of the isoquinolone is located on the periphery [12] of the shielding substituent (vide infra). While the regioselectivity of the intermolecular [2+2] photocycloaddition is significantly influenced by the fact that Scheme 1. Substrates 1-9 employed to probe the selectivity in the intramolecular [2+2] photocycloaddition of isoquinolones. PG = protecting group. Scheme 2. Typical irradiation co...
New and simple protocols are described for the conversion of the enzymatically-derived and enantiomerically pure cis-1,2-dihydrocatechol (X = I) and its 6-methylated derivative into either antipodal form of compounds embodying the tricyclic frameworks of terpenoids . Key steps include intramolecular Diels-Alder (IMDA) and (in some cases) singlet or triplet-based photochemical processes.
A total synthesis of the title natural product, 1, has been achieved using the cis-1,2-dihydrocatechol 7 as starting material. Compound 7 is readily obtained in large quantity and in an enantiomerically pure form through the whole-cell biotransformation of toluene using the genetically engineered microorganism E. coli JM109 (pDTG601) that overexpresses the enzyme toluene dioxygenase (TDO). Three key chemical steps were employed in the synthesis, the first of which was the microwave-promoted Diels-Alder cycloaddition reaction between diene 8 and cyclopent-1-en-2-one to give adduct 9. The second key step was the photochemically promoted oxa-di-π-methane rearrangement of the bicyclo[2.2.2]octenone derivative 15 of 9 to give the epimers 16 and 17, and the third key step was the reductive cleavage of the last pair of compounds so as to afford the linear triquinane 19. Elaboration of compound 19 to target 1 followed established procedures. Single-crystal X-ray analyses were carried out on compounds 11 and 19.
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