Metal-catalyzed enantioselective conjugate additions are highly reliable methods for stereoselective synthesis; however, multicomponent reactions that are initiated by conjugate arylation of acyclic π-systems are rare. These reactions generally proceed with poor diastereoselectivity while requiring basic, moisture sensitive organometallic nucleophiles. Here, we show that Rh-catalysts supported by a tetrafluorobenzobarrelene ligand (Ph-tfb) enable the enantio-, diastereo-, and Z-selective α,δ-difunctionalization of electron-deficient 1,3-dienes with organoboronic acid nucleophiles and aldehyde electrophiles to generate Z-homoallylic alcohols with three stereocenters. The reaction accommodates diene substrates activated by ester, amide, ketone, or aromatic groups and can be used to couple aryl, alkenyl, or alkyl aldehydes. Diastereoselective functionalization of the Z-olefin unit in the addition products allows for the generation of compounds with five stereocenters in high dr and ee. Mechanistic studies suggest aldehyde allylrhodation is the rate-determining step, and unlike reactions of analogous Rh-enolates, the Rh-allyl species generated by δ-arylation undergoes aldehyde trapping rather than protonolysis, even when water is present as a cosolvent. These findings should have broader implications in the use of privileged metal-catalyzed conjugate addition reactions as entry points toward the preparation of acyclic molecules containing nonadjacent stereocenters.

Metal-catalyzed enantioselective conjugate additions are highly reliable methods for stereoselective synthesis, however multi-component reactions that are initiated by conjugate arylation of acyclic p-systems are rare. These processes generally proceed with poor diastereoselectivity while requiring basic, moisture sensitive organometallic nucleophiles. Here we show that Rh-catalysts supported by a tetrafluorobenzobarrelene ligand (Ph-tfb) enable the enantio-, diastereo-, and Z-selective a,d-difunctionalization of electron-deficient 1,3-dienes with organoboronic acid nucleophiles and aldehyde electrophiles to generate Z-homoallylic alcohols with three stereocenters. The reaction accommodates diene substrates activated by ester, amide, ketone, or aromatic groups and can be used to couple aryl, alkenyl, or alkyl aldehydes. Diastereoselective functionalization of the Z-olefin unit in the addition products allow for the generation of compounds with five stereocenters in high dr and ee. Mechanistic studies suggest aldehyde allylrhodation is the rate determining step, and unlike reactions of analogous Rh-enolates, the Rh-allyl species generated by d-arylation undergoes aldehyde trapping rather than protonolysis, even when water is present as a co-solvent. These findings should have broader implications in the use of privileged metal-catalyzed conjugate addition reactions as entry points towards the preparation of acyclic molecules containing non-adjacent stereocenters.

Metal-catalyzed enantioselective conjugate additions are highly reliable methods for stereoselective synthesis, however multi-component reactions that are initiated by conjugate arylation of acyclic p-systems are rare. These processes generally proceed with poor diastereoselectivity while requiring basic, moisture sensitive organometallic nucleophiles. Here we show that Rh-catalysts supported by a tetrafluorobenzobarrelene ligand (Ph-tfb) enable the enantio-, diastereo-, and Z-selective a,d-difunctionalization of electron-deficient 1,3-dienes with organoboronic acid nucleophiles and aldehyde electrophiles to generate Z-homoallylic alcohols with three stereocenters. The reaction accommodates diene substrates activated by ester, amide, ketone, or aromatic groups and can be used to couple aryl, alkenyl, or alkyl aldehydes. Diastereoselective functionalization of the Z-olefin unit in the addition products allow for the generation of compounds with five stereocenters in high dr and ee. Mechanistic studies suggest aldehyde allylrhodation is the rate determining step, and unlike reactions of analogous Rh-enolates, the Rh-allyl species generated by d-arylation undergoes aldehyde trapping rather than protonolysis, even when water is present as a co-solvent. These findings should have broader implications in the use of privileged metal-catalyzed conjugate addition reactions as entry points towards the preparation of acyclic molecules containing non-adjacent stereocenters.

The efficiency of an amino imidate organocatalyst was evaluated in the Michael reaction of ketones with nitroalkenes. tert-Butyl L-proline imidate was found to be a syn-selective catalyst generating products with moderate to good enantioselectivities, of up to 84% e.e. The best substrates were found to be cyclic ketones and -nitrostyrenes. The catalytic efficiency and enantioselectivity was enhanced by the addition of 10 mol% of benzoic acid.