Studies on Diastereo- and Enantioselective 1,2-Addition of 1,1-Diborylalkanes to Imines

Abstract

Chiral b-aminoboron compounds are very important in organic synthesis because such compounds are potentially versatile building blocks that can be easily transformed into various pharmaceuticals, natural products, and bioactive molecules. Although several methods have been developed for synthesizing chiral b-aminoboron compounds over the past decades, the development of efficient protocols is still required. Herein, we developed a copper-catalyzed stereoselective 1,2-addition of 1,1-diborylalkanes to imines to afford synthetically valuable chiral b-aminoboron compounds. In chapter 1, the successful development of a Cu(I)/(R)-monophos catalytic system for the diastereo- and enantioselective 1,2-addition of 1,1-diborylalkanes to cyclic aldimines was reported, furnishing synthetically useful enantioenriched b-aminoboronate esters containing adjacent stereocenters. The obtained chiral b-aminoboronate esters were afforded in good yield with excellent stereoselectivity; their synthetic utility was demonstrated through the formation of new C–O and C–C bonds upon transformation of the boron group. However, the limitation remained that 1,2-addition of 1,1-diborylalkanes to N-tosyl-protected aldimines afforded products with low diastereoselectivity. In chapter 2, an improved and scalable procedure to achieve the copper-catalyzed diastereo- and enantioselective 1,2-addition of 1,1-diborylalkanes to N-protected acyclic aldimines was described. We found that the installation of an N,N-dimethylsulfamoyl-group as N-protecting group in acyclic aldimines allows the 1,2-addition reaction to proceed with good-to-excellent diastereoselectivity and enantioselectivity, thus providing b-aminoboronate esters bearing vicinal chiral secondary amines and secondary boronate esters in good yields. The reaction can provid the products on the gram scale, and their synthetic usefulness was demonstrated via additional functionalization. In chapter 3, a broadly applicable copper catalytic conditions for the diastereo- and enantioselective 1,2-addition of 1,1-diborylalkanes to cyclic ketimines and a-imino esters were diclosed. The developed method provided a broad range of chiral b-aminoboronate esters bearing adjacent a-tertiary amines and secondary boronate esters in good yield with high diastereo- and enantioselectivity. Synthetic applications of the obtained b-aminoboronate esters were demonstrated via further manipulations.