THE TOTAL SYNTHESIS OF RACEMIC LYCORAMINE. THE SYNTHESES AND REACTIONS OF 3-METHOXYALLYLIDENE TRIPHENYLPHOSPHORANE AND DIETHYL 1-METHYLTHIO-1(Z),3-BUTADIENYLPHOSPHONATE.

摘要

The details of the total synthesis of the Amaryllidaceae alkaloid lycoramine (6) from commercially available o-vanillin (53) are disclosed. The 4-aryl-4-alkylcyclohexenone 85, which is the key intermediate, was prepared from either of the two readily accessible aryl alkyl ketones 82 or 52, in a good overall yield by employing a novel procedure for the construction of a quaternary carbon atom via the net geminal acylation-alkylation of a carbonyl group. The synthesis of lycoramine (6) from the cyclohexenone 85 was effected in 49% overall yield by a sequence of reactions, which culminated with the Bischler-Napieralski cyclization of the formamide 100.; During the course of a study by these laboratories into the utilityof heteroatom-substituted allyl and butadienyl phosphoruscompounds as reagents for the annulation of a cyclohexenone ringonto a pre-existing ketone, the chemistry of 3-methoxyallylidenetriphenylphosphorane (204) and diethyl 1-methylthio-1(Z),3-butadienyl phosphonate (221) was investigated.; Details of an efficient synthesis of the phosphorane 204 isreported. In marked contrast to 2-ethoxy allylidene triphenyl-phosphorane 182e, the ylid 204 appears to react in a normal Wittig fashion with an (alpha),(beta)-unsaturated ketone by 1,2 addition at the (alpha) carbon of the allyl moiety to give the 1-methoxy-1,3,5-hexatriene 209. Significantly, the ylid 204 was an effective reagent for the homologation of a variety of ketones and aldehydes by three carbons to the corresponding (alpha),(beta)-unsaturated aldehydes.; A description of the first synthesis of diethyl 1-methylthio-1(Z),3-butadienyl phosphonate (221) is disclosed. Unfortunately, allattempts at forming a six-membered ring with an enone moiety froma ketone or aldehyde using 221 were futile. Upon reaction of 221with either the potassium or lithium enolates of ketones or tertiaryaldehydes, extensive polymerization of 221 was observed. On theother hand, enamines smoothly added to 221 in a 1,4 fashion togive 234b, which could not be cyclized. Other reactions of 221 with nucleophilic partners were also examined.