Phenanthridines rearrangement

The first successful transformation of protoberberines to benzo[c]-phenanthridines was reported by Onda et al. (122,123). Irradiation of the enamines 200 and 195, the Hofmann degradation products of the corresponding protoberberines, in benzene afforded the initial photoproducts 201, which immediately rearranged to the tetrahydrobenzo[c]phenanthridines 202 in 70% yield (Scheme 37). Dehydrogenation of 202 afforded dihydro-chelerythrine (203) and dihydrosanguinarine (204), which were further oxidized with dichlorodicyanobenzoquinone (DDQ) to yield chelerythrine (205) and sanguinarine (206), respectively. 

Dihydropyridines have also been starting points for stereospecific syntheses of hydro-phenanthridines and isoquinolines. Interest exists in these compounds because of the occurrence of this structural feature in alkaloids. For example, isoquinuclidine (263), derived from JV-alkoxycarbonyl-l,2-dihydropyridine, undergoes a Cope rearrangement to give the isoquinoline derivative (264) (80JA6157). Further chemical transformations of (264) provided a formal total synthesis of reserpine (Scheme 50). 

By suitable substitution the enaminones can often serve as precursors for heterocycles and preparation of indoles, carbazoles, quinolines, acridines and phenaNthridines can be achieved easily. However, this part of enaminone chemistry can lead to surprising and unexpected reactions if the multifunctional properties of the enaminones are ignored, e.g. ring contraction, ring expansion and other rearrangements are observed. In some cases jft-ketoenamines react as the ene-component in cycloaddition. Enaminones are even suitable synthones for building aromatic rings. 

Intramolecular reaction involving attack of an electrophilic orf/w-position of aryl groups on the enaminone carbonyl is shown by the ring closure of anilinomethylenecy-clohexanones to tetrahydro phenanthridines (equation 185). Including rearrangement, the reaction leads to acridines (equation 185). The course of the reaction depends on the conditions255. ... 

On the route to benzo[c]phenanthridine alkaloids [37], naphthol 51 (Scheme 20) was 0-alkylated with 2-bromo-2-methylpropionoamide under forcing conditions to give 52 in 93% yield. The rearrangement of 52 was executed with sodium hydride in DMF-DMPU and the hydroxy-amide 53 was hydrolyzed to give the aminonaphthyl derivative 54. 

P450 enzyme, protopine 6-hydroxylase, to yield an intermediate that rearranges to dihydrosanguinarine (40). This intermediate also serves as the precursor to the benzo(c)phenanthridine alkaloid macarpine (Fig. la). The copper-dependent oxidase dihy-drobenzophenanthridine oxidase, which has been purified (41, 42), then catalyzes the formation of sanguinarine from dihydrosanguinarine. 

Cyclization to the benzo[c]phenanthridine (127) competes with rearrangement to the ring-expanded product (128) on irradiation of the amine oxide (129). A practical synthesis of the chlorin macrocycle (130) has been developed by irradiation of the seco-compound (131) in tetrahydrofuran containing TFA and Hiinig s base this is thought to take place by photocyc-lization of the ISrr-tautomer (132), followed by elimination of methanol. Analogous approaches have been employed in the syntheses of ( )-bonellin dimethyl ester and 20-methyl- and 20-cyano-isobacteriochlorins. " ... 

The mechanism of the related photorearrangement of heterocyclic N-oxides is still a matter for debate. Evidence that rearrangement of the phenanthridine N-oxides (48) to the N-substituted phenanthridones (49) and the dibenzo[d,f]-1,3-oxazepines (50) proceeds by way of biradical intermediates rather... 

Five-membered ring aizides can rearrange upon decomposition to form 6-membered ones. Acid decomposition of 9-azidofluorene (298) yielded in this manner phenanthridine (299) Unsym-metrical fluorenes produce mixtures, thus both 301 and 302 have been obtained from 300 . 

When thebenine is distilled with zinc-dust, in addition to pyrene a phenanthridine-like base, stable to chromic acid, is obtained. This substance, thebenidine, has the structure [xvn] [19] and has recently been synthesized by the action of phosphorus pentoxide on 4-formami-dophenanthrene [20]. During the dehydration of the oxime [xn] a quantity of a basic substance was obtained. It is believed to be [xvm] or the isomeric [xix] [11] (cf. the rearrangement of C and N during the preparation of isoquinoline by the dehydration of cinnamaldoxime [21]). 

The benzo[k]phenanthridine system is accessible by the rearrangement of dihydrofuro[2,3-b]quinolines brought about by anhydrous altiminium chloride. The... 

The intramolecular Diels-Alder reaction of 5-(3-butynyl)-3//-pyran[2,3-c]isoquinoline-3,6-dione (132) in boiling benzene afforded a pyrrolophe-nanthridone, which yielded 2-methoxy-anhydrolycorin-7-one (136). Hippadine (44) was synthesized by means of l-aza-T-oxa[3.3]sigmatropic rearrangement of A-(2-methoxycarbonylvinyloxy)-8,9-methylenedioxy-phenanthridin-6-one (133) (137) or by palladium-mediated intramolecular cyclization of 7-bromo-A-[(6-bromo-3,4-methylenedioxy)benzoyl]indoline (134) (138) (Fig. 10). 

Details have appeared of the earlier very interesting report which showed that tazettine (3 R = OMe, = H) is an artifact produced from pretazettine (2 R = OMe, R = H) during isolation. This type of rearrangement can be carried out with basic reagents also and applies with identical implications to the criwelline (3 R = H, R = OMe) -precriwelline (2 R = H,R = OMe) relationship. The interconversion of alkaloids possessing a 5,10h-ethano-phenanthridine nucleus (4) with those of the aforementioned [2]benzopyrano-[3,4-c]indole type (3) has been reported. Carefully executed experiments show that variation in temperature, solvent, or pH is sufficient to alter the ring systems... 

Reaction of 2-acetyl-5,5-dimethyl-cyclohexandione 169 (R1 = Ac) with enaminone 31 (R = H) in refluxing ethanol afforded the phenanthridine-1,7-dione 383 (90KGS66). Alternatively, 383 was obtained from bicyclic tetraketone 384 on treatment with ammonia (83ZOR2322). The 9,10-dihydrophenanthridine 386 rather than the rearranged product 387 was obtained by thermolysis of 2-arylaminomethylene derivative 385, obtained from the reaction of dimedone and arylamine in the presence of triethyl orthoformate and polyphosphoric acid (77S723, 96JHC905) (Scheme 79). 

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