1. Einleitung. -Im Rahmen unserer Untersuchungen uber das photochemische Verhalten von Indazolen [ 11, Anthranilen [2], Benzisoxazolen [3] und 2,l-Benzisothiazolen [4] in saurem Milieu bzw. protischen Losungsmitteln [4] interessierten wir uns auch fur die Photoreaktionen von 1-substituierten Benztriazolen in protischen und aprotischen, aromatischen Losungsmitteln, woruber wir vor langerer Zeit I)
Heptalenecarbaldehydes 1/1′ as well as aromatic aldehydes react with 3‐(dicyanomethylidene)‐indan‐1‐one in boiling EtOH and in the presence of secondary amines to yield 3‐(dialkylamino)‐1,2‐dihydro‐9‐oxo‐9H‐indeno[2,1‐c]pyridine‐4‐carbonitriles (Schemes 2 and 4, and Fig. 1). The 1,2‐dihydro forms can be dehydrogenated easily with KMnO4 in acetone at 0° (Scheme 3) or chloranil (=2,3,5,6‐tetrachlorocyclohexa‐2,5‐diene‐1,4‐dione) in a ‘one‐pot’ reaction in dioxane at ambient temperature (Table 1). The structures of the indeno[2,1‐c]pyridine‐4‐carbonitriles 5′ and 6a have been verified by X‐ray crystal‐structure analyses (Fig. 2 and 4). The inherent merocyanine system of the dihydro forms results in a broad absorption band in the range of 515–530 nm in their UV/VIS spectra (Table 2 and Fig. 3). The dehydrogenated compounds 5, 5′, and 7a–7f exhibit their longest‐wavelength absorption maximum at ca. 380 nm (Table 2). In contrast to 5 and 5′, 7a–7f in solution exhibit a blue‐green fluorescence with emission bands at around 460 and 480 nm (Table 4 and Fig. 5).
A method for the synthesis of allocolchicinoids is explored that involves the benzannulation reaction of Fischer chromium carbene complexes with alkynes. The benzannulation reaction is employed to install the aromatic C-ring via the reaction of an alpha,beta-unsaturated carbene complex in which the carbene complex is attached to a seven-membered ring that is to become the B-ring of the allocolchicinoids. Two different regioisomeric series can be accessed depending on which position the carbene complex is on the seven membered ring. A key issue that is addressed is the stereochemistry of the newly formed axis of chirality that results from a stereo-relay from an existing chiral center on the seven membered ring at the position destined to be C(7) in the allocolchicinoids. The level of stereochemistry is dependent on the position of the carbene complex on the seven membered ring. A mechanism is proposed to account for this stereochemical dependence and to account for the observed effects of temperature and solvent on the stereoselectivity. Finally, the benzannulation reactions of optically pure complexes are examined and quite surprisingly one, but not both, of the diastereomeric products is racemized. The racemization can be prevented with the proper choice of solvent and temperature. A mechanism is proposed to account for the racemization of only one of the diastereomers of the product that involves the intermediacy of an ortho-quinone methide chromium tricarbonyl complex.
Steric vs hydrogen-bonding atropisomerization control of configurationally stable analogues of the biaryl natural product allocolchicine is described. Intramolecular hydrogen bonding between the C8 hydroxy group and the C7 oxygen functionality in (aR,7R)-diastereomer II of 2 and 4 leads to its thermodynamic stabilization relative to the opposite diastereomer (aR,7S)-I, which is manifested by the strong preference toward II under thermal equilibration conditions (>94% de). Protection of C8-OH removes the H-bonding and results in repulsive interaction between C7 and C8 functionalities, which destabilizes II. Steric tuning of the C8 protecting group in 7-12 allows for almost complete inversion of the axial configuration in 2 under thermal equilibration conditions (>96% de toward I). Previously unavailable phenolic allocolchicinoids (aR,7S)-2,I are subsequently released by deprotection.
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