Rh-Catalyzed Asymmetric Hydroformylation Of Disubstituted Alkenes

Owing to the perfect atom economy,asymmetric hydroformylation(AHF)of alkenes represents one of the most efficient routes for the preparation of chiral aldehydes.In the past decades,intensive research efforts have been made in this area,and a range of chiral phosphorus ligand systems have been developed for AHF reactions.To date,many simple terminal alkenes have been converted into chiral aldehydes with practical levels of regio-and enantioselectivity by asymmetric hydroformylation,but only very limited examples have been reported in asymmetric hydroformylation of 1,2-disubstituted and 1,1-disubstituted alkenes.In this asymmetric transformation,the development of chiral ligands is a key issue.Therefore,it is very necessary to broaden the type of substrates and develop new chiral phosphine ligands in the AHF area.In this thesis,we documented the development and application of phosphorus ligands for Rh-catalyzed asymmetric hydroformylation.Our work focused on the development of new substrates and new chiral phosphine ligands,and we achieved the asymmetric hydroformylation of a series of disubstituted alkenes.The detailed content is as follows:(1)We developed an efficient approach for synthesizing chiral cyclopentane carboxaldehydes by a catalytic desymmetrizing hydroformylation of cyclopentenes.This transformation exhibits excellent enantioselectivities(up to 97%ee)and high diastereoselectivities(up to>99:1 dr)under mild reaction conditions.The key intermediate,(1S,3S)-(3-hydroxymethyl)cyclopentanol,for the synthesis of carbocyclic-ddA was obtained in an efficient way.(2)We developed an efficient approach for synthesizing valuable chiral ?-aldehydesilanes by a catalytic asymmetric hydroformylation of Z-alkenylsilanes.Because of the hindered silicon groups,this transformation exhibits excellent regioselectivities(?/? up to>99),and respectively,the corresponding ?-aldehydesilanes are obtained with excellent enatioselectivities(up to 97%ee).In a synthetic sense,we achieve the asymmetric hydroformylation on the ? position of the oxygen atom indirectly by using the silicon group as a surrogate for the hydroxyl.Moreover,experiment results and DFT calculations indicate that the silicon group are primary factors of the regiocontrol and substrates' reactivity in this asymmetric transformation.(3)We developed a novel hybrid phosphorus ligand and applied it to the Rh-catalyzed enantioselective anti-Markovnikov hydroformylation of unfunctionalized 1,1-disubstituted alkenes.By employing the new catalyst,linear aldehydes with ?-chirality can be prepared with high yields(up to 96%)and enantioselectivities(up to 93%ee).Furthermore,catalyst loading as low as 0.05 mol%furnished the desired product in good yield and undiminished selectivity,demonstrating the efficiency of this transformation in large-scale synthesis.