Cy‐SaBOX/Copper(II)‐Catalyzed Highly Diastereo‐ and Enantioselective Synthesis of Bicyclic N,O Acetals

Abstract

Facile and effective access for the asymmetric construction of the useful and important skeleton of the bicyclic N,O-acetals is described. Cu(II) /SaBOX could catalyze the reaction of β,γ-unsaturated α-ketoesters with cyclic enamines efficiently, thus affording the desired products in excellent yields with excellent stereoselectivities (21 examples; up to 99 % yields; up to >95:5 d.r.; and 95-99 % ee). This reaction can be well performed on gram scale, even with only 1 mol % catalyst loading. The single-crystal structures of the copper complexes lead to a good understanding of the stereo-synergistic effects of the sidearm.

Cy‐SaBOX/Copper(II)‐Catalyzed Highly Diastereo‐ and Enantioselective Synthesis of Bicyclic N,O Acetals

“…[8] Combining these results with the stereoinduction model of hetero-DAr eaction of b,g-unsaturated a-ketoester 2b with enol ethers,a sr eported by the groups of Evans,[4d] Jørgensen, and Houk independently, [4a-f,13] an enantioinduction model of the current reaction is proposed as shown in Figure 2. [12] In conclusion, an efficient Cu II /SaBOX-catalyzed hetero-DA reaction of b,g-unsaturated a-ketoesters with cyclic enamines has been developed. [12] In conclusion, an efficient Cu II /SaBOX-catalyzed hetero-DA reaction of b,g-unsaturated a-ketoesters with cyclic enamines has been developed.…”

“…[12] To understand the synergistic effect of the sidearm, the single crystals of the complexes CuBr 2 /L2 and CuBr 2 /L8 were prepared and analyzed by X-ray crystallography. The gram-scale reaction of 1a with 2b proceeded well, even with only 1mol %catalyst loading, thus providing 1.3 grams of the desired product 3b in 74 %y ield with 92 % ee and 92:8 d.r.…”

Sidearm Modified Bisoxazoline Ligands and Their Applications

“…[32] Moreover, PhBn-diPh-SaBOX gives the best results in the copper(II)-catalyzed diastereo-and enantioselective synthesis of bicyclic N,O-acetals (Scheme 14d). [33]…”

Unexpected Cascade Reactions of Ortho‐Hydroxyenaminones and β,γ‐Unsaturated α‐Ketoesters to Access Hydrogenated Benzoxazolepolycycles and Pyrrole−Phenol Atropisomers

“…[1] In addition, they also constitute the key intermediates for the construction of biologically interesting molecules. [2] In view of the synthetic importance and medicinal relevance, not surprisingly, considerable attention has been devoted to the assembly of such useful skeletons and some elegant approaches have been achieved, including C3-functionalization/cyclization sequence of tryptophols and indole derivatives, [3] [3 + 2] cycloaddition of indoles with phenols [4] and oxaziridines, [5] cascade cyclization of β,γ-unsaturated α-ketoesters with alkyl amides [6] and cyclic enamines, [7] N,O-acetalization of 2-hydroxybenzamide with aldehydes, [8] and others. [9] Although substantial advances have been made, some of them still suffer from limitations of multistep procedures, substrate availability and expensive metal catalysts and are often unsatisfactory in yield and generality.…”