Phosphine‐Free Palladium‐Catalyzed Allene Carbopalladation/Allylic Alkylation Domino Sequence: A New Route to 4‐(α‐Styryl) γ‐Lactams

Abstract

Free to decide: Various 4-(alpha-styryl) gamma-lactams are synthesized in 61-88% yield by a phosphine-free palladium-catalyzed carbopalladation/allylic alkylation domino sequence (see scheme). The cyclization is totally regio- and diastereoselective in favor of the 3,4-trans-disubstituted gamma-lactam. The process is successfully applied to the synthesis of a new aza analogue of the naturally occurring lignan (+)-oxo-parabenzlactone.

Dual reactivity of O-α-allenyl esters under palladium(0) catalysis: From carbopalladation/allylic alkylation domino sequence to decarboxylative allenylation

“…Indeed, in the presence of the more electron-rich 4-iodotoluene, the reaction gave only traces of the corresponding lactone 5 (entry 4). Coming back to 1-iodo-4-nitrobenzene, use of phosphine-free conditions (Method C), previously developed by us for the cyclization of the related N-aallenyl malonamides [8], led to the best reaction yield with 1b (53%) (entry 5). Interestingly, although the catalytic systems involved in Method A and C are of extremely different natures, they are both equally effective.…”

“…The above study shows that the carbopalladation/allylation sequence of O-a-allenyl malonates has a much more limited efficiency and scope than that of the corresponding malonamides [8]. This is likely due to the high propensity of O-aallenyl esters to suffer competitive oxidative addition onto the palladium(0) catalyst [12].…”

“…Such an allene carbopalladation/allylation domino sequence was exploited by some of us, as part of our research dedicated to the synthesis of pyrrolidin-2-ones via transition-metal-catalyzed processes [7]. Indeed, a family of trans 4-(a-styryl) g-lactams was recently prepared in high yields, using a readily accessible N-a-allenyl malonamide precursor and various aryl iodides under palladium(0) catalysis (Scheme 1) [8].…”

Recent progress towards transition metal-catalyzed synthesis of γ-lactams

“…As outlined in Scheme 20, the linear allenyl amide precursor 44 reacted with a variety of aryl iodides (electron-rich or electron-poor) to furnish the corresponding γ-lactams 45 in moderate to good yields (61-88%). 32 This methodology was readily used in the facile synthesis of γ-lactam 46, a racemic aza analogue of the naturally occurring lignan (+)-oxo-parabenzlactone 47.…”

The Heck Reaction Applied to 1,3- and 1,2-Unsaturated Derivatives, a Way towards Molecular Complexity

“…A phosphine-free Pd-catalyzed allene carbopalladation/allylic alkylation sequence was exploited by Poli and coworkers to get 4-(α-styryl) γ-lactams 62 from β-aminoallene 61 ( Scheme 32 ) [ 37 ]. High yields were obtained for electron-rich as well as electron-poor aryl iodides.…”