Palladium catalyzed nucleophilic addition reactions of allylic phosphonates and their application to the preparation of natural products.

摘要

Racemic and non-racemic alpha-hydroxy phosphonates were prepared via the Pudovik reaction. Cinnamyl hydroxy phosphonate is a solid and can be purified to >98% e.e. by recrystallization. Cross metathesis between hydroxy phosphonates or their carbonate derivatives and alkene provided a new way to access a variety of racemic and non-racemic phosphonates.; Vinyl phosphonates were prepared via palladium catalyzed intermolecular rearrangement of acetoacetoxy phosphonates or intermolecular nucleophilic addition to phosphono allylic carbonates. Reactions proceeded with complete transfer of chirality. Vinyl phosphonates also were obtained via the Claisen rearrangement.; Wacker oxidation of the vinyl phosphonates proceeded with high regioselectivity and only the beta-carbon was oxidized to form 1,4-diketo phosphonates in high yields. Diketo phosphonates underwent the Horner-Wadsworth-Emmons reaction in the presence of base to provide cyclopentenones. Using K2CO 3/18-crown-6 as the base gave cyclopentenones in high chemical yields. However, erosion (racemization) occurred at the chiral center of cyclopentenones. Using Ba(OH)2 as the base prevented racemization at the chiral center.; Palladium catalyzed nucleophilic addition was successfully applied to the total synthesis of the natural (-)-enterolactone. tert-Butyl methyl malonate was reacted with phosphono carbonate to give the vinyl phosphonate. Ozonolysis of the vinyl phosphonate followed by decarboxylation provided a lactone, precursor of enterolactone. The optical rotation of the lactone confirmed the absolute configuration. Sibi et al. reported the conversion of lactone to enterolactone. Thus synthesis of the lactone represents a formal synthesis of (-)-enterolactone.; 5-Isobutyl-3-methylcyclopent-2-enone was used as the intermediate for the total synthesis of natural product, (+)-myomontanone. Reduction of cyclopentenone with PtO2 under hydrogen atmosphere followed by base and triflate source yielded vinyl triflate. Attempts to synthesize myomontanone via Stille carbonylative coupling of vinyl triflate and 3-furyl stannane failed to give satisfactory result. Alternatively, insertion of CO into the triflate followed by trapping with MeOH and reduction-oxidation provided aldehyde. The aldehyde was used to access myomontanone by reacting with 3-furyl lithium followed by oxidation. Both 1H NMR spectroscopy and IR showed that the addition of 3-furyl lithium to the aldehyde gave the desired alcohol. However, oxidation of the alcohol to myomontanone using Swern oxidation or magtrieve was unsuccessful.