Efficient Synthesis of Polycyclic γ‐Lactams by Catalytic Carbonylation of Ene‐Imines via Nickelacycle Intermediates

Abstract

The nickel(0)-catalyzed carbonylative cycloaddition of 1,5-and 1,6-ene-imines with carbon monoxide (CO) is reported. Keytothis reaction is the efficient regeneration of the catalytically active nickel(0) species from nickel carbonyl complexes such as [Ni(CO) 3 L].Avariety of tri-and tetracyclic g-lactams were thus prepared in excellent yields with 100 % atom efficiency.Preliminary results on asymmetric derivatives promise potential in the synthesis of enantioenriched polycyclic g-lactams.

Enantioselective Synthesis of Polycyclic γ-Lactams with Multiple Chiral Carbon Centers via Ni(0)-Catalyzed Asymmetric Carbonylative Cycloadditions without Stirring

“…In our previous work, we preliminarily examined the asymmetric carbonylative cycloaddition of 1a in the presence of a catalytic amount of a chiral nickel complex, which revealed that the use of the chiral phosphoramidite (S,S,S)-L1 afforded a better reaction efficiency and enantioselectivity than that of a chiral monodentate phosphine (MOP) and chiral bisphosphines (Scheme 2, entry 1). 11,17,18 Thus, the reaction between 1a and CO gas (0.5 atm, ca. 7 equiv.…”

“…9b,c Recently, we have developed a nickel-catalyzed carbonylative cycloaddition between ene-imines and CO, which diastereoselectively yielded a variety of tricyclic γ-lactams that include two contiguous stereogenic carbon centers at the C4,C5 positions. 10,11 The diastereoselectivity of this nickel-catalyzed process is determined during the oxidative cyclization of the ene-imines on a nickel(0) complex. 12 We thus envisioned the development of the corresponding enantioselective variant, in which the overall enantioselectivity on those two neighboring carbon centers is determined simultaneously during the oxidative cyclization on a nickel(0) complex that bears a chiral ligand.…”

Ni-catalyzed hydroalkylation of olefins with N-sulfonyl amines

“…When tetrafluoroethene bearing no hydrogen atom was subjected together with silane, alkylation of imines took place 47 . Moreover, Ogoshi's group recently used carbonyl insertion to interrupt the facile β-H elimination; displacement of the nickel from the nickellacycle intermediate provides saturated γ-lactams 59,60 .…”

Reductive Coupling of Acrylates with Ketones and Ketimines by a Nickel‐Catalyzed Transfer‐Hydrogenative Strategy

“…Although further expansion of the strategy will require the identification of new catalysts and/or fragment coupling steps,w ew ere keen to uncover additional processes which might be achieved using the nickel(0) system presented here.S pecifically,w ee nvisaged that a-oxo imines might couple with acrylates to provide lactams.T his proposition was appealing because only sparse reports document the use of stoichiometric metallic reductants to achieve this seemingly simple process,a nd no catalytic approaches are available. [7] Pleasingly,w hen the Np-methoxyphenyl imine 10 a was exposed to the reaction conditions optimized for lactonization, spirocycliclactam 11 a was generated in 68 %y ield (Table 3). Further evaluation revealed that this lactamization process has similar scope to the lactonization methodology.Indeed, electronically diverse isatin-based imines (10 b-e)a ll engaged in smooth reductive coupling to provide lactam targets 11 b-e in good to excellent yield.…”

“…Our studies in this area were initiated by considering synthetic entries to g-butyrolactones and lactams, [4][5][6][7] which are versatile intermediates as well as core motifs in an array of natural products.A na ppealing,y et unrealized approach to these compounds resides in metal-catalyzed reductive coupling of either ac arbonyl or imine with an acrylate to afford a g-amino or g-hydroxy ester,w hich upon cyclization would provide the target (Scheme 1d). This disconnection requires the identification of as trategy which enables reductive CÀC bond formation, but avoids nonproductive reduction of the starting materials.W er easoned that these criteria might be fulfilled by coupling the release of the reductant to the formation of either the lactone or lactam, thereby minimizing nonproductive background reduction events.Such aproposition appears practically challenging,h owever,asimple solution is availed by harnessing the native reducing power of the alcohol released upon cyclization to drive turnover.…”