Chem. SCI.: 1,2-benzylboronization of 1,2-disubstituted non activated olefins catalyzed by nickel

The functional group reaction of olefins has been one of the research hotspots in the field of organic synthesis There are more studies on the homodifunctionalization (epoxidation, dihydroxylation, bromination, etc.) of olefins, but less on the different difunctionalization In addition to C-C bond, 1,2-carboboration of alkenes can also be used to construct general C-B bond, which is an important intermediate for the synthesis of many bioactive compounds and / or natural products At present, researchers have developed the 1,2-benzyl boration of activated olefins, but there are few reports on the 1,2-benzyl boration of non activated olefins Yoshida reported the method of building internal borate by copper catalyzed 1,2-benzyl boronization of monosubstituted olefins Later, Fu Yao's group reported a method of constructing terminal borate by allyl ether (scheme 1a) However, the 1,2-benzyl boronization of non activated olefins is still difficult to achieve Recently, the M Kevin Brown team of Indiana University developed a nickel catalyzed stereoselective 1,2-benzyl boration method for 1,2-disubstituted alkenes (scheme 1b), which was recently published in Chem SCI (DOI: 10.1039 / c9sc04199k) (photo source: chem SCI.) recently, the author catalysed the 1,2,3,4,5,6,6,6,7,7,7,9,9,10,10,10,10,10,10,10,10,10,10,10,10,10,10,10,10,10,10,10,10, 2-aryl boration is of interest The reaction may be carried out by the addition of alkene and [Ni] - bpin, and then by using the alkyl - [Ni] complex captured by aryl bromide (scheme 2); subsequently, the resulting alkyl aryl - [Ni] complex is reduced to produce a csp3-csp2 bond Since the formation of csp3-csp3 bond can be realized by reducing and eliminating the dialkyl - [Ni] complex with nickel catalyst, the author thinks that if the alkyl - [Ni] complex can be captured by benzyl electrophilic reagent, the benzyl boration reaction can proceed smoothly (picture source: chem SCI.) firstly, the author has made a preliminary study on aryl boration with cyclopentene and benzyl chloride (bncl) as substrates, and successfully obtained the target product 3 (DR > 20:1) It was found that DMA was the best solvent and Ni (COD) 2 was the best pre catalyst In addition, bnbr or bnoco2t Bu, as well as other primary and secondary alkyl halides, could not be obtained (picture source: chem SCI.) under the best reaction conditions, the author discussed the substrate range of the reaction (scheme 3) When cyclopentene is substituted, benzyl boration takes place on the opposite side of alkene substituent Pyrrolidine and furan heterocycles are also suitable for this reaction Alkenes with larger carbon rings or fatty carbon chains can also participate in the reaction, but the yield is reduced, mainly due to incomplete transformation The reaction of e-4-octene and z-4-octene produced two kinds of enantiomers, which indicated that the reaction was stereospecific However, 1,1-disubstituted olefins, terminal olefins and alkenyl aromatics have poor reactivity and low yield In addition, only homodimerization of electrophilic reagents occurred in the reaction of 1-phenylethyl chloride (picture source: chem SCI.) structural fragments produced by benzyl boration of cyclopentene and related heterocycles are often found in natural products and drug like molecules (scheme 4) For example, the intermediate 27 obtained from the benzyl boronization of ene 25 is an important structural fragment of PPAR α / γ agonist 28 In addition, 30 and 32 tricyclic structures can be obtained by intramolecular cross coupling (picture source: chem SCI.) by studying the mechanism of related nickel catalyzed aryl boration, the author proposed a scheme 5A for the reaction of alkyl - [Ni] complex 34 with benzyl chloride: the reaction of alkyl - [Ni] complex 34 with benzyl chloride can be eliminated by substitution (path a) or oxidation addition / reduction (pathb ）The oxidation addition of the latter can be carried out by double electron or single electron processes In order to determine which way the reaction is more likely to be carried out, Hammett analysis was carried out If the reaction is carried out by substitution, a "U" curve will appear, in which the benzyl chloride reaction with electron donor and electron acceptor is faster than that without substitution If the reaction is carried out by oxidation addition (path B), Hammett analysis cannot be used to compare the two electron or single electron processes For the nickel catalyzed 1,2-benzyl boration, a linear relationship of R = 1.68 (R 2 = 0.973) was observed, indicating that the substitution may not be feasible (scheme 5b) However, the author believes that this analysis can not exclude the alternative approach (picture source: chem SCI.) conclusion: M Kevin Brown research group has developed a nickel catalyzed stereoselective 1,2-benzyl boration method for non activated olefins, which can effectively convert a variety of olefins and benzyl chlorine into interesting products or related skeletons of bioactive molecules In addition, the study will be helpful to broaden the scope of Ni catalyzed CBB reaction.