SN2″-Selective and Enantioselective Substitution with Unsaturated Organoboron Compounds and Catalyzed by a Sulfonate-Containing NHC-Cu Complex

The first broadly applicable strategy for SN2″-selective and enantio­selective catalytic substitution is disclosed. Transformations are promoted by 5.0 mol% of a sulfonate-containing NHC-Cu complex (NHC = N-heterocyclic carbene), and are carried out in the presence of commercially available allenyl-B­(pin) (pin = pinacolato) or a readily accessible silyl-protected propargyl-B­(pin). Acyclic, or aryl-, heteroaryl-, and alkyl-substituted penta-2,4-dienyl phosphates, as well as those bearing either only 1,2-disubstituted olefins or a 1,2-disubstituted and a trisubstituted alkene were found to be suitable starting materials. Cyclic dienyl phosphates may also serve as substrates. The products containing, in addition to a 1,3-dienyl group, a readily functionalizable propargyl moiety (from reactions with allenyl-B­(pin)) were obtained in 51–82% yield, 84–97% SN2″ selectivity, 89:11–97:3 E:Z ratio, and 86:14–98:2 enantiomeric ratio (er). Reactions with a silyl-protected propargyl-B­(pin) compound led to the formation of the corresponding silyl-allenyl products in 53–89% yield, 69–96% SN2″ selectivity, 98:2 to >98:2 E:Z ratio, and 94:6–98:2 er. Insight regarding several of the unique mechanistic attributes of the catalytic process was obtained on the basis of kinetic isotope effect measurements and DFT studies. These investigations indicate that cationic π-allyl-Cu complexes are likely intermediates, clarifying the role of the s-cis and s-trans conformers of the intermediate organocopper species and their impact on E:Z selectivity and enantio­selectivity. The utility of the approach is demonstrated by chemo­selective functionalization of various product types, through which the propargyl, allenyl, or 1,3-dienyl sites within the products have been converted catalytically and chemo­selectively to several useful derivatives.