Copper-Catalyzed Cross-Coupling Reaction With Alkyl Halides And Tosylates

Transition metal-catalyzed C-C cross-coupling of non-activated alkyl halides or pseudohalides has emerged as an important method in modern organic synthesis. In chapter one, we first summarized the history and current situation of Cu-catalyzed cross-coupling of alkyl halides and sulfonate, then we briefly introduced the latest achievements of other transition metal-catalyzed this type reaction. We compared the characteristics and mechanism of Cu and other transition metal-catalyzed reaction, leading to the conclusion: the mechanism of Cu-catalyzed reaction is different from other transition metal-catalyzed such reaction, the development of a new Cu catalyst system can be a good complement of the existing catalytic system, overcome difficulties of other transition metal-catalyzed reaction.In chapter two, We find that by using LiO’Bu as base, CuI can efficiently catalyze the cross-coupling reaction of aryl boronate esters or alkyl9-BBN reagents (9-BBN=9-borabicyclo[3.3.1] nonane) with primary halides and pseudo-halides. To our best knowledge, this is the first example of Cu-catalyzed Suzuki-Miyaura couplings of non-activated alkyl halides. The advantages of replacing the Grignard reagents with organoborons are well known, including the higher functional group tolerance and the better commercial availability of the reagents. These experimental data rule out the possible involvement of a radical mechanism. This new transformation not only expands the concept and utility of Copper-catalyzed alkylation reactions in a fundamental sense, but also provides practically useful reactivities that may complement Ni and Pd-catalyzed Suzuki-Miyaura reaction of alkyl halides.In chapter three, we report the cross-coupling reaction of non-activated secondary alkyl halides and tosylates with secondary alkyl Grignard reagents under copper catalysis (CuI/TMEDA/LiOMe). To our best knowledge, this reaction presents the first example of transition metal-catalyzed cross-coupling reactions of secondary alkyl electrophiles with secondary alkyl nucleophiles. This catalyst expands the synthetic toolbox for the construction of C-C bonds between two tertiary carbons through transition metal-catalyzed cross-coupling. Moreover, because this Cu-catalyzed cross-coupling reaction proceeds by an Sn2mechanism, it provides a general approach for the making C-C bonds with stereocontrol from chiral secondary alcohols.In chapter four, we report a new and general method for the synthesis of primary and secondary alkylboronic esters via Cu-catalyzed borylation of the corresponding alkyl halides and pseudo-halides, providing a practical method for the preparation of alkylboronic esters with diverse skeletons and functional groups. This reaction also presents, to our best knowledge, the first example of transition metal catalyzed borylation of non-activated alkyl halides or pseudohalides. We also report a mild protocol for the Suzuki-Miyaura coupling of alkylboronic esters with aryl halides. Moreover, this reaction doesn’t proceed by an Sn2mechanism, so this method expands the concept and scope of Cu-catalyzed cross-coupling reactions in a fundamental sense.