Studies Asymmetric Reactions Of α-dialkyl Diazomethylphosphonates With Para-quinone Methides And γ-Methylidene-δ-valerolactones

Phosphonates as structural motifs are widely existed in pharmaceutical and natural products.Owing to the promising biological activities to phosphonates derivatives,the development of new strategies to these special units have drawn synthetic chemist’s extensive attention.α-Diazophosphonates are particularly useful in the preparation of phosphonatefunctionalized molecules.The first chapter shown that α-diazophosphonates as carbene intermediates can undergo a wide variety of chemcial transformations in modern organic synthesis.α-Diazophosphonates,as nucleophiles,which have been successfully employed in common addition reactions with the carbonyl compounds and imines.α-Diazophosphonates as a class of1,3-dipoles can be used to participate in cycloaddition reactions.α-Diazophosphonates as an unprecedent class of synthons are extensively employed in modern organic synthesis.At present,the study of the asymmetric addition to α-diazophosphonates as nucleophiles are rarely reported.The first part: the phase-transfer catalysts derived from cinchona alkaloid were selected as the organic catalysts.The asymmetric addition reaction of α-diazomethylphosphonates and para-quinone methides provided a series of chiral diaryl-methylated diazomethylphosphonates(60-85% yield,73-99% ee).The transition state model was proposed.The absolute configuration of desired products was determined by X-ray crystallographic analysis.The resulting products were further transformed into bioactive compounds,namely,chiral dihydrocinnoline phosphonate and α-aminophosphonate.α-Diazophosphonates as important class of 1,3-dipoles are extensively employed in modern organic synthesis,which can be used to construct various nitrogen heterocycles compounds by cycloaddition reaction.At present,the study of the asymmetric cycloaddition reaction to α-diazophosphonates as electrophiles have not been reported.The second part: the asymmetric[4+1] cycloaddition reaction of dialkyl diazomethyl phosphonates and γ-methylidene-δ-valerolactones provided various 2-phenylpyrrolidine-phosphonates(54-90% yield,42-93% ee).The probable mechanism was proposed.The absolute configuration of desired products was determined by X-ray crystallographic analysis.The reaction substrate has a widely range of application and mild conditions,offering a simple and highly efficient tool for constructing chiral2-phenylpyrrolidine-phosphonate derivatives with a quaternary carbon stereocenter.