Phenanthridine quaternary salts

The suggestion5 that phenanthridine can probably be alkylated directly under suitably vigorous Friedel-Crafts conditions does not appear to have been tested experimentally. It receives support, however, from the successful conversion of the quaternary salts (220) (R1 = Me, R2 = H) and (220) (R1 = H, R2 = Ph) into the corresponding 221 by heating with polyphosphoric acid.287 Not surprisingly, however, the related salt (220) (R1 = H, R2 = m-methoxy-phenyl) forms 222 under similar conditions.17 Direct alkylation of phenanthridine has been achieved photochemically (see p. 400). 

A photochemical ring construction similar to that described in Scheme 5 was used in the synthesis of the aromatic lycorine alkaloid ungeremine (51) (Scheme 6). Photocyclization of the somewhat inaccessible imine (48) gave the phenanthridine derivative (49) in 21 % yield which upon metal hydride reduction and cyclization with phosphorus tribromide afforded the quaternary salt (50) which was shown to be identical with the methyl ether of ungeremine (51) obtained as shown. 

Although phenanthridine was discovered in the late nineteenth century1, 2 neither the parent base nor its derivatives attracted attention until useful therapeutic activity was established in certain quaternary phenanthridinium compounds.3 A substantial number of substituted phenanthridines (and many phenanthridinium salts) have now been described and lists of compounds appearing in the literature from 1884 until 1955 are available.4, 6 Phenanthridines have attracted surprisingly little systematic attention, although the system is of considerable theoretical interest and, with its nine nonequivalent carbon atoms, may be expected to provide a rigorous test of molecular orbital reactivity correlations. Naturally occurring derivatives include several Amaryllidaceae and Papaveraceae alkaloids, notably, lycorine, haemanthamine, and chelidonine the chemistry of the phenanthridine alkaloids has been reviewed.6... 

Further examples of the reduction of the carbon-nitrogen link by means of lithium aluminum hydride have been reported,90, 332 and sodium borohydride has been used for the same purpose in the reduction of a number of 6-alkyl-l,2,3,4,4a,10b-hexahydrophenanthri-dines.42 Quaternary phenanthridinium salts form IV-alkyldihydro-phenanthridines on treatment with lithium aluminum hydride.333... 

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