Study On Catalytic Borylation Reactions Of Unsaturated Hydrocarbons

Organoboron compounds are often stable to air and moisture,easy to store and low toxicity,in which C–B bonds can be converted into C–C and C–X bonds stereospecifically(X: nitrogen,oxygen,halogens,etc.).Based on the above outstanding advantages,organoboronates have become one of the most important intermediates in organic synthetic chemistry.Organoboron compounds have become an indispensable tool in synthetic chemistry which was widely used in the fields of drugs and materials on account of the traditional transformation(e.g.,Suzukicoupling reaction).Therefore,the development of novel and efficient methods for the synthesis of organoboron compounds has been one of the most active research fields in organic synthesis.The borylation/functionalization of unsaturated hydrocarbons has attracted the attention of synthetic chemists among the many syntheses,mainly due to: 1)Unsaturated hydrocarbons(e.g.,olefins,alkynes)are important bulk products in petroleum and coal chemical industry,and can be obtained directly from the petroleum cracking process or prepared quickly by a simple chemical conversion.2)Another functional group could also be introduced when constructing C–B bonds,which could increase the complexity of moleculars,and the C–B bonds could also realize subsequent transformation efficiently,providing potential for further transformation of molecules.Since Brown’s pioneering work in organoborane chemistry in 1956,the borylation/functionalization of unsaturated hydrocarbons catalyzed by transition metals(e.g.,Rh,Ir,Ru,Fe,Co,Ni,Cu,etc.)and non-transition metals(e.g.,organic phosphine,carbene and inorganic bases,etc.)of unsaturated hydrocarbons have been developed greatly.There are still some unsolved challenges,such as: 1)The realization of controllable and divergent borylation/functionalization of unsaturated hydrocarbons(i.e.,precise acquisition of a range of different types of monoborylation and polyborylation products)has hardly been explored,with only a few cases of transition metal-based conversion so far,and the more challenging nontransition metal-catalyzed transformation is still an unknown field.2)The dearomative borylation/functiona-lization of unsaturated hydrocarbons is still a hard challenge,primarily due to the need to overcome the above thermodynamically adverse dearomatization,where the more challenging asymmetric transformation has not been reported to date.In view of the above challenges,we developed the controllable and divergent hydroboration of unsaturated hydrocarbons catalyzed by alkali metal borohydride innovatively,and realized the efficient preparation of a series of different organoboron compounds.The copper-catalyzed borylation/cyclization of alkenes was achieved with excellent chemoselectivity,enantio-and diastereoselectivity,acquiring chiral indolines containing four continuous stereocenters.The specific research contents are as follows:1)The development of controlled,divergent borylation/functionalization of unsaturated hydrocarbons and the preparation of many different types of boron-containing compounds remain challenging in numerous borylation/functionalization of unsaturated hydrocarbons,that is mainly attributable to the different types of multiple bonds(e.g.,C–C triple bond and different types of C–C double bonds)have different spatial and electronic structures,and the catalytic system needs to overcome the above differences to achieve the corresponding borylation/functionalization.To our knowledge,only a few cases of divergent borylation of unsaturated hydrocarbons catalyzed by transition metals have been reported to date,while corresponding transformations catalyzed by non-transition metals have not been achieved.In this chapter,we have developed a catalytic system of alkali metal borohydride,a nucleophilic tetracoordinate alkylboron intermediate was generated through efficient hydroborylation of alkali metal borohydride with π bond,and then performs the transborylation with HBpin to achieve the controllable and divergent monoboration,bisboration and triboration between 1,3-enynes and HBpin successfully,affording borylated libraries—allenylboronates,(Z)-2,4-diborylatedalkenes,(E)-2,4-diborylatedalkenes and 2,4,4-triborylatedalkanes with 50%-95%yield.This strategy has the advantages of simple catalytic system,controllable amount of boron groups introduced and excellent regional selectivity.It is the first case of precise and controllable divergent borylation of unsaturated hydrocarbons catalyzed by non-transition metals.The successful development of this catalytic system also provides a solid foundation for the subsequent development of novel non-transition metal-catalyzed borylation.2)In recent years,transition metal-catalyzed borylation of allenes has attracted great attention,but it is still a huge problem to develop the E-selective functionalization of allenes and realize the controllable and divergent borylation/functionalization of allenes.This is mainly due to the fact that allenes contain two adjacent orthogonal π bonds,and the hydrometallation or borylmetallation requires from the side of the C=C double bond with less hindrance overcoming spatial differences.To our knowledge,only one transition metal-catalyzed stereodivergent borylation of allenes has been reported,while the corresponding transformation catalyzed by non-transition metal is still unknown.In this chapter,on the basis of the previous work of alkali metal borohydride catalytic system,we also generate the nucleophilic tetracoordinate alkylboron intermediates through the efficient hydroborylation of alkali metal borohydride with π bond,and then transborylation with HBpin,achieving controllable and divergent Z-selective borylation and E-selective borylation of allenes and HBpin,acquiring Eallylborates and Z-allylborates stereospecifically with 45%-95% yield.This strategy is the first case of non-transition metal-catalyzed stereodivergent borylation of allenes,which has the advantages of simple catalytic system,transition metal-free,excellent regio-and stereoselectivity.The catalytic system also provides a new idea for the challenging E-selective other functionalization of allenes.3)The dearomative borylation/functionalization of unsaturated hydrocarbons remains a difficult challenge,despite the extensive development of borylation/functionalization(e.g.,hydroborylation,carboboration,aminoboration,etc.)of unsaturated hydrocarbons catalyzed by transition metals,that is mainly due to the need for catalytic systems to overcome the above thermodynamically adverse dearomatization.The more challenging asymmetric dearomative borylation/cyclization has not yet been reported.In this chapter,we develop a cheap metal copper-catalyzed system,which generates nucleophilic alkylcopper intermediates through selective borylcupration of Cu–B active species with π bond,and then performs intramolecular Michael addition on indoles,achieving the dearomative borylation/cyclization of indoles with excellent chemoselectivity,enantio-and diastereoselectivity to synthesize indoline derivatives containing four continuous chiral centers(up to 86% yield and up to 98% ee).This strategy is the first case to realize the copper-catalyzed asymmetric borylation/cyclization of alkenes.It has the advantages of mild reaction conditions,wide functional group compatibility,and excellent enantio-and diastereoselectivity.It provides an efficient and simple means for the synthesis of chiral indoline skeletons which are widely existed in bioactive molecules.The asymmetric dearomative borylation/functionalization also provides a new strategy for the development of challenging asymmetric dearomative borylation/functionalization.