Oxydative Aryl‐Aryl‐Verknüpfung von 6,6′,7,7′‐Tetramethoxy‐1,1′,2,2′,3,3′,4,4′‐octahydro‐1,1′‐biisochinolin‐Derivaten

Abstract

We describe the synthesis of 2 by intramolecular oxidative coupling of 1, 1'-biisoquinoline derivatives 1 (Scheme 1). This heterocyclic system can be considered as a union of two apomorphine molecules and may thus exhibit dopaminergic activity. -The readily available tetrahydrobiisoquinoline 6 was methylated to 11 (Scheme 4) and reduced (with NaBH3CN) to ruc-7 and (catalytically) to meso-7 (Scheme 3). Reduction of 11 with NaBH, and of the biurethane ruc-9 with LiA1H4/A1Cl3 afforded mesoand ruc-10, respectively (Scheme 4). Demethylation of 6, meso-10, mesoand rac-7 led to 12, meso-14, meso-and ruc-13, respectively (Scheme 5). The latter two phenols were converted with chloroformic ester to the hexaethoxycarbonyl derivatives mesoand ruc-15 and subsequently saponified to the biurethanes mesoand ruc-16, respectively (Scheme 5). -In order to assure proximity of the two aromatic rings, the ethano-bridged derivatives meso-and ruc-18 were prepared by condensing mesoand ruc-7 with oxalic ester and reducing the oxalyl derivatives mesoand ruc-17 with LiAlH,/AlCl,, respectively (Scheme 6). The 'H-NMR. spectra at different temperatures showed that ruc-18 populated two conformers but ruc-17 only one, all with C,-symmetry, and that meso-17 as well as meso-18 populated two enantiomeric conformers with C,-symmetry. Whereas both oxalyl derivatives 17 were fairly rigid due to the two amide groupings, the ethano derivatives 18 exhibited coalescence temperatures of -20 and 30". -The intramolecular coupling of the two aromatic rings was successful under 'non-phenolic oxidative' conditions with the tetramethoxy derivatives 7 , 10 and 18, the ruc-isomers leading to the desired dibenzophenanthrolines, the meso-isomers, however, mostly to dienones (Scheme 9): With VOF, and FS0,H in CF3COOH /CH2C12 ruc-7 was converted to ruc-19, ruc-18 to ruc-21 and ruc-10 to a mixture of ruc-20 and the dienone 23b of the morphinane type. Under the same conditions meso-10 was transformed to the dienone 23 a of the morphinane type, whereas meso-18 yielded the dienone 24 of the neospirine type, both in lower yields. The analysis of the spectral data of the six coupling products offers ') Aus der Dissertation von M.-A. Siegfried, Universitat Zurich, 1978. evidence for their structures. With the demethylation of rac-20 and ruc-21 to rac-25 and rac-26, respectively, the synthetic goal of the work was reached, but only in the rac-series (Scheme 10). -In the course of this work two cleavages of octahydro-1, 1'-biisoquinolines at the C ( l), C (1')-bond were observed: 1) The biurethanes 9 and 16 in both the meso-and rac-series reacted with oxygen in CF,COOH solution to give the 3,4-dihydroisoquinolinium salts 27 and 28; the latter was deprotonated to the quinomethide 30 (Scheme 11). 2) Under the Clarke-Eschweiler reductive-methylation conditions meso-and rac-I were cleaved to the tetrahydroisoquinoline derivative 32.

Efficient Copper-bisisoquinoline-based Catalysts for Selective Aerobic Oxidation of Alcohols to Aldehydes and Ketones

“…The preparation of bisisoquinoline ligands were reported elsewhere [ 23 ]. The structure of the bisisoquinoline ligands (L 1 and L 2 ) were shown in Figure 2 .…”

Trifluoromethanesulfonic anhydride–4-(N,N-dimethylamino)pyridine as a reagent combination for effecting Bischler–Napieraiski cyclisation under mild conditions: application to total syntheses of the Amaryllidaceae alkaloids N-methylcrinasiadine, anhydrolycorinone, hippadine and oxoassoanine

“…Thus, the bisamide 1316 is readily converted into the tetracycle 14 (78%) (mp 199-201 "C; lit.16 mp 198-202 "C) on treatment with Tf20-DMAP and the structure of the product has been confirmed by X-ray analysis.1 While the same conversion can be effected with POC13 a lower yield (60%) of an impure product is obtained. 16 We acknowledge financial support from the Australian Research Council in the form of a research grant to M. G. B. and an APRA Scholarship to C. J. C; A. W. is the grateful recipient of a University of Melbourne Post-Graduate Scholarship.…”

Diasteroselektive Hydroxyalkylierungen in 1‐Stellung von Tetrahydroisochinolinen und Synthese von Aporphin‐, Protoberberin‐ und Phthalid‐Alkaloider

“…H); 5,88 (s, OCH20); 4,63 (s, ArCH,N); 3,78 (I, J = 6, CH,N); 2,76 (t, J = 6, ArCH,); 1,30 (.T, t-Bu). MS: 261 (100, M+'), 246 (42,2), 204 (56,7), 176 (37,6), 161 (65,8), 148 (63,6), 57 (69,5). Anal.…”