Protoberberines Hofmann degradation

Scheme 3. Hofmann degradation of protoberberines. Reagents a, Mel b. Amberlite IRA-400 c, 20% KOH, MeOH d, B2H6 e, H202, NaOH f, LAH, THF g, 10% NaOH.

Scheme 36. Acid-catalyzed cyclization of the Hofmann degradation products of dihydro-protoberberines. Reagents a, cone HC1 b, POCl3 c, H2S04 d, 10% HC1. 

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. 

Lead tetraacetate oxidation was applied to construct a benzo[c]-phenanthridine skeleton. The Hofmann degradation product 224 derived from the phenolic protoberberine 59a was oxidized with lead tetraacetate to afford the p-quinol acetate 225, which was cyclized to the benzo[c]-... 

Hofmann degradation of the nonnatural protoberberine 454 afforded the 10-membered ring base 455 (65%) in addition to the styrene-type compound (13%) (Scheme 92). Dihydroxylation of the former with N-bromosuccinimide in the presence of a large excess of hydrochloric acid and subsequent oxidation of the product diol 456 with periodic acid afforded the dialdehyde 457. On irradiation in tert-butyl alcohol 457 provided ( )-cis-alpinigenine (445) along with ( )-alpinigenine (441) as a result of endo and exo intramolecular cycloaddition, respectively, of the intermediate photodienol (221,222). 

In order to rationalize the IR-spectral differences and the differing course of the Hofmann degradations, the possible conformations of the two configurational isomers of C-13 methyl substituted tetrahydro-protoberberines were considered first by Bersch (104), and later by Jeffs (105), and the conclusions are based upon the following arguments. 

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