Diversification of Unprotected Alicyclic Amines by C−H Bond Functionalization: Decarboxylative Alkylation of Transient Imines

Abstract

Despite extensive efforts by many practitioners in the field, methods for the direct a-C À H bond functionalization of unprotected alicyclic amines remain rare. A new advance in this area utilizes N-lithiated alicyclic amines. These readily accessible intermediates are converted to transient imines through the action of a simple ketone oxidant, followed by alkylation with a b-ketoacid under mild conditions to provide valuable b-amino ketones with unprecedented ease. Regioselective a'-alkylation is achieved for substrates with existing asubstituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a S N Ar step.

FeCl2 Catalyzed Three-Component Reactions of Phospholes, Pyrrolidine, and Ketones (Aldehydes): Chemoselective Synthesis of 1-Phosphafulvenes

“…A common feature of these reactions is that they involve an intermediate iminium ion, which is formed by condensation of a secondary amine with an aldehyde (or ketone) (Scheme a). Seidel et al recently developed a new strategy for the redox-neutral α-C–H functionalization of simple secondary amines (e.g., pyrrolidine) . These redox-neutral transformations combine a reductive N-alkylation with an oxidative α-functionalization.…”

“…On the basis of the above experiments and reported mechanisms involving intermediate iminium ions and intermediate azomethine ylides through internal redox isomerization of iminium ion, we proposed a possible mechanism for the chemoselective formation of [6 + 4] products 3 and biphospholes 9 (Scheme b).…”

Norhygrine Alkaloid and Its Derivatives: Synthetic Approaches and Applications to the Natural Products Synthesis

“…[40] The synthesis of d). [41] Decarboxylation of acid 30 followed by reaction with benzaldehyde at boiling in toluene for one day in the presence of Cu 2 (OH) 2 CO 3 catalyst, leads to the formation of ketone 31 (Scheme 7,a). [42] Reaction of the proline derivative 32 with trimethyl[(1phenylethenyl)oxy]silane in the presence of (diacetoxyiodo)benzene and molecular iodine, which resulted in the formation of a ketone 33 (Scheme 7,b).…”

Breaking the tert-Butyllithium Contact Ion Pair: A Gateway to Alternate Selectivity in Lithiation Reactions

“…Although each of the unique activation modes outlined above allow for high site selectivity to be achieved, in most cases the heteroatom controls the reactivity patterns of the heterocycle substrate and often precludes remote positions from being functionalized. 5,6 Therefore, the ability to override embedded heteroatoms and selectively convert remote C-H bonds within oxygen heterocycles into carbon-carbon bonds without directing groups is highly desirable because it would allow for typically inaccessible carbon centers to be functionalized in a single step (Figure 1B). 7,8 Although contemporary undirected C-H functionalization reactions have gained momentum and provided elegant avenues for the installation of halogens, 9,10 oxygen, 11 nitrogen, 12 or boron 13 subunits at various locations, the development of intermolecular carbon-carbon bond forming processes has been challenging and slow to develop.…”