Synthesis Of Chiral Heterocycles By Palladium-Catalyzed Asymmetric Hydrocarbonylation

Chiral heterocycles are widely present in various natural products,drugs,pesticides,herbicides and dyes.Therefore,developing the methods of synthesizing chiral heterocycles has important research significance.Asymmetric hydrocarbonylation has many advantages,such as mild reaction conditions,high efficiency,good stereoselectivity,and wide application range of substrates,which is one of the most effective methods of synthesizing chiral carbonyl compounds.In this dissertation,three items of research works were conducted to apply the palladiumcatalyzed asymmetric hydrocarbonylation in the synthesis of chiral heterocycles:1.Synthesis of chiral γ-butyrolactone by palladium catalyzed asymmetric hydrocarbonylationIn this chapter,we firstly synthesized chiral 4-hydroxy-2-methylene-1-butyric acid and acetyl-protected homopropargyl alcohol substrates.Chiral γ-butyrolactones with different substitutions were synthesized by asymmetric hydrocarbonylation(32examples,60-99% yield,84:16 – 98:2 dr).In the palladium-catalyzed asymmetric hydrocarbonylation of alkenes,we investigated the effect of different configurations between substrates and chiral ligands and the results of control experiments also revealed that the hydroxyl group in alkene substrate played a vital role in the proceeding of asymmetric hydrocarbonylation.In addition,in the palladium-catalyzed asymmetric dihydrocarboxylation of alkynes,we developed a consecutive catalytic system with one achiral palladium catalyst and a chiral palladium catalyst.The results of control experiments verified that the achiral monophosphine ligand and chiral bisphosphine ligand couldn’t coordinate onto one palladium center,they do not interfere with each other in the catalytic system and perform their respective functions.Lastly,the synthesized chiral γ-butyrolactones were subjected to a simple two-step reaction to synthesize tetrahydrofuran fused-ring compounds containing three chiral centers,achieving moderate yields and excellent diastereoselectivity.The absolute configurations of products were determined by X-ray crystallographic analysis.2.Synthesis of chiral succinimides by palladium-catalyzed asymmetric hydroamidocarbonylationIn this chapter,we successfully synthesized a series of chiral succinimides in moderate to good yields and enantioselectivities via palladium-catalyzed asymmetric hydroamidation(20 examples,57-91% yield,66:34 – 96:4 er).Acrylamides bearing aryl and alkyl substituent and N-substituted acrylamide were well tolerated.The target product was directly generated through intramolecular hydroamidocarbonylation.The method was also successfully applied in the asymmetric hydroamidation of acrylamide substrates bearing thioether group.3.Synthesis of chiral δ-valerolactone by palladium catalyzed asymmetric hydroesterificationIn this chapter,asymmetric hydroesterification of 3-phenyl-3-ene-1-butanol,3-diphenylphosphine oxide-3-ene-1-butanol,and 3-toluenesulfonyl-3-ene-1-butanol was investigated.For the asymmetric hydroesterification of 3-phenyl-3-ene-1-butanol,good reactivity was achieved.But the enantioselectivity is relatively low.The highest yield can reach 78% and the highest enantioselectivity can reach 33% ee.Better results were obtained in the asymmetric hydroesterification of 3-diphenylphosphine oxide-3-ene-1-butanol(87% yield and 42% ee value).95% yield and 93% ee were achieved in the asymmetric hydroesterification of 3-toluenesulfonyl-3-ene-1-butanol.In addition,asymmetric hydroesterification of homoallyl thioether was attempted and 42-82% yield with 12-93% ee was obtained.