Rh(III)-Catalyzed Intra- and Intermolecular 3,4-Difunctionalization of 1,3-Dienes via Rh(III)-π-Allyl Amidation with 1,4,2-Dioxazolones

Abstract

We herein report a modular strategy, which enables Rh­(III)-catalyzed diastereoselective 3,4-amino oxygenation and diamination of 1,3-dienes using different O- and N-nucleophiles in combination with readily available 3-substituted 1,4,2-dioxazolones (78 examples, 37–91% yield). Previous attempts to functionalize the internal double bond rested on the use of plain alcoholic solvents as nucleophilic coupling partners thus dramatically limiting the scope of this transformation. We have now identified hexafluoroisopropanol as a non-nucleophilic solvent that allows the use of diverse nucleophiles and greatly expands the scope, including an unprecedented amino hydroxylation to selectively install valuable, unprotected β-amino alcohols across 1,3-dienes. Moreover, various elaborate alcohols prove to be compatible providing unique access to complex organic molecules. Finally, this method is employed in a series of intramolecular reactions to deliver valuable nitrogen heterocycles as well as γ- and δ-lactones.

Rhodium‐Catalyzed Enantioselective 1,4‐Oxyamination of Conjugated gem‐Difluorodienes via Coupling with Carboxylic Acids and Dioxazolones

“…[8] Although directing group-assisted [9] or oxygen-and nitrogen-tethered strategies [10] have been established in (twocomponent) couplings that circumvented the distinctive challenges in regio-and enantioselective difunctionalization of conjugated dienes, the modular and selective threecomponent N-and O-difunctionalization of conjugated dienes remains rare and challenging. Very recently, Rovis reported a Rh III -catalyzed three-component approach to achieve diastereoselective vicinal oxyamination of conjugated dienes, [11] while Wang developed a site-selective 1,2amino oxygenation of 1,3-diene via copper-mediated Ncentered radical addition (scheme 1a, right). [12] However, these systems are limited to racemic synthesis, and com-pared with the exhaustively explored asymmetric carbonbased functionalization of conjugated dienes, regio-and enantioselective installation of both N-and O-functional groups across conjugated dienes is less explored.…”

Aminoalcohol Synthesis through Nonprecious Metal Catalysis: Enantioselective Cu-Catalyzed Reductive Coupling of Aldehydes and Allenamides

“…Our group has been interested in developing reductive allylation reactions utilizing allenamides ( 4 ) as a tool to access important chiral 1,2-aminoalcohol motifs through aminoallylation , (Scheme C). We have strategically focused on Cu-catalyzed processes due to the improved sustainability of Cu over catalysts derived from precious metals. ,, Ketone electrophiles can be employed to provide 1,2-aminoalcohols 5 bearing a tertiary alcohol motif under either chiral catalyst control , or through auxiliary control. − …”

Three-component regioselective carboamidation of 1,3-enynes via rhodium(iii)-catalyzed C–H activation

“…4 In 2019, Ellman elegantly reported Rh( iii )-catalyzed 1,1-carboamination of terminal alkenes using dioxazalone as the amidating reagent. 5 Subsequently, Ellman 6 and Rovis 7 independently reported 1,2-carboamination of bridged bicyclic alkenes or acrylates. Recently, Glorius reported 1,4-carboamidation of conjugated dienes, 8 and our group realized the related enantioselective version with the complementary 1,2-regioselectivity.…”