Synthesis of Secondary Unsaturated Lactams via an Aza-Heck Reaction

Abstract

The preparation of unsaturated secondary lactams via the palladium-catalyzed cyclization of O-phenyl hydroxamates onto a pendent alkene is reported. This method provides rapid access to a broad range of lactams that are widely useful building blocks in alkaloid synthesis. Mechanistic studies support an aza-Heck-type pathway.

Synthesis of N−H Bearing Imidazolidinones and Dihydroimidazolones Using Aza‐Heck Cyclizations

“…[17] Urea-forming aza-Heck reactions can also be sequenced with our earlier aza-Heck protocol to rapidly build up complex nitrogen-containing polycycles.F or example,a za-Heck cyclization of O-phenyl hydroxamate 36 using the previously reported aza-Heck strategy results in spirocyclic lactam 37 in good yield. [12] Tw osteps covert 37 to N-phenoxy urea 38,w hich can then be converted to fused tricyclic product 39 in 93 %isolated yield as single diastereomer using the urea-forming protocol (Scheme 3).…”

Heck‐Like Reactions Involving Heteroatomic Electrophiles

“…[48] We identified O -phenyl hydroxamates as the best nitrogen electrophiles for this transformations. Other more reactive (electron-deficient) hydroxamate esters as O -benzoyl and O -pentafluorobenzoyl were inferior substrates, giving rise to undesired products: primary amide (presumably through protodepalladation of aza-Pd II intermediate) and urea derivatives (formed via Lossen rearrangement).…”

Synthesis of Indolines and Derivatives by Aza‐Heck Cyclization

“…These include both trisubstituted alkenes (10)(11)(12), tetrasubstituted alkenes (13), and those bearing ar ange of groups,i ncluding alkyl, aryl, ester,a nd nitrile moieties (5)(6)(7)(8). Them odel product 3b was isolated in 84 %y ield.…”