Studies On Cobalt-Catalyzed Asymmetric Sequential Hydrofunctionalization Of Alkyynes

Chiral molecules are widely present in nature and have been found broad applications in asymmetric synthesis,functional materials,and medicinal chemistry.Concise construction of chiral compounds with high optical activity is one of the hot reseach fields of synthetic chemistry.Asymmetric noble metal catalysis is one of the powerful,economically feasible tools for the synthesis of valuable chiral molecules for drugs and fine chemicals.Compared to well-defined platinum group metals,earth-abundant transition metals show unique advantageous features,such as large reserve,good biocompatibility and environment benign.In regard to green and sustainable chemistry,earth-abundant transition metals such as iron and cobalt can be alternative to the rare precious one.Nowadays,due to the absence of reliable rules for the chiral ligand design for cobalt catalysis,asymmetric transformation enabled by cobalt still have huge challenges which largely limited their synthetic utility.Easily availability,versatile reactivity and other features make alkynes become one of the most useful chemical motifs.Asymmetric sequential reaction provides a possibility in transforming alkyne to chiral alkyl compound.Developing a protocol using alkynes to construct more valuable products with excellent chemo-,regio-and enantioselectivity enabled by cobalt catalysis is highly desirable.However,to realize the above transformation,there lie several challenges:1)how to ensure the catalytic activity of earth-abundant metal catalysts for the sequential reaction,2)how to achieve the high chemo-,regio-and enantioselectivity in one pot sequence synchronously,3)how to make multi reaction processes be compatible in one pot sequence.The core of this dissertation is achieving highly selective sequential hydrofunctionalization of alkynes enabled by cobalt catalysis.Part Ⅰ:Highly chemo-and regioselective cobalt-catalyzed Markovnikov hydrosilylation of alkynes.A highly selective cobalt-catalyzed Markovnikov hydrosilylation of alkynes was developed for the first time by using oxazoline-imino-pyridine(OIP)as ligand.Various functionalized groups,such as halide,free alcohol,free aniline,ketone,aldehyde,ester,amide,and nitrile are well tolerated.To date,this is the most efficient cobalt catalytic system(TOF＝65520 h-1)for hydrosilylation of alkynes.Part Ⅱ:Regio-and enantioselective cobalt-catalyzed sequential hydrosilylation/hydrogenation of terminal alkynes.Based on OIP ligand,cobalt-catalyzed regio-and enantioselective sequential hydrosilylation/hydrogenation reaction of terminal alkynes in one pot to prepare chiral organosilanes was developed for the first time.This one-pot protocol was operationally simple and atom-economic using relatively simple and readily available starting materials,such as alkynes,silanes and hydrogen gas,to construct more valuable chiral silanesPart Ⅲ:Cobalt-catalyzed asymmetric sequential hydroboration/hydrogenation of internal alkynes.By using electron-rich imidazoline-imino-pyridine(IIP)ligand,we developed a highly regio-and enantioselective cobalt-catalyzed sequential hydroboration/hydrogenation of internal alkynes to afforcd the chiral secondary organoboronates for the first time.Through mechanistic studies,it was found that HBpin could efficiently promote the asymmetric hydrogenation process of tri-substituted alkenyl boronates.Part Ⅳ:Cobalt-catalyzed sequential asymmetric double hydrosilylation of aliphatic terminal alkynes for the synthesis of chiral gem-bis(silyl)alkanes.Compared with single silyl compounds,bis(silyl)ones are few studied due to the lack of the efficient synthetic protocols.Here,using relay catalytic strategy,a novel highly enantioselective synthesis of gem-bis(silyl)alkanes enabled by cobalt-catalyzed sequential asymmetric double 1.1-hydrosilylation of aliphatic alkynes was developed for the first time.The synthetic utilities of gem-bis(silyl)alkanes were demonstrated by diverse downstream transformations.Based on control experiments and qualitative and quantitative kinetic studies,a possible mechanism was proposed.In summary,using chiral cobalt complexes as catalysts,highly chemo-,regio-and enantioselective sequential hydrofunctionalizations of alkynes were achieved for the synthesis of valuable chiral boronyl and silyl-based compounds.