An efficient method to synthesize the β-lactams with high regioselectivity via Pd-catalyzed C(sp(3))-H bond activation and intramolecular amination of simple and readily available aminoquinoline carboxamides was demonstrated. C6F5I plays a significant role in the formation of the C-N bond of the four-membered ring β-lactams. High yield along with wide substrate scope and functional group tolerance makes this reaction applicable to build natural-product-derived β-lactams. This method has been applied to the efficient synthesis of the β-lactamase inhibitor MK-8712.

Mild, metal-free, highly regioselective hypervalent-iodine mediated C-2 acetoxylation and C-3 oxidations of N-substituted indoles with (diacetoxyiodo)benzene [PhI(OAc)] have been reported. The reaction involves three cascade steps. The quantity of PhI(OAc) employed in this reaction plays a key role in the outcome of three types of products (2a-4a). Furthermore, the mild and highly regioselective C-2 oxidation and C-3 dichlorination of N-substituted indoles with PhICl have been developed. Extensive studies including in situ IR techniques and HO-labeling experiment were performed to gain insight into the possible reaction mechanism.

The study of Pd-catalyzed arylation,alkoxylation, and acyloxylation reactions at the C3 positiono fl-pipecolinic acid derivatives to afford cis-disubstituted piperidines as single stereoisomers was performed. To demonstrate the utility of the reaction, compound 10,a na nalogueo f (À)-3S-3-PPP (9)t hat is used as an euroleptic drugf or the treatment of schizophrenia, was synthesized featuring the arylation and radical decarboxylation reactions as key steps.Piperidines bearings ubstituents at the C3 positiona re important structuralm otifs that are widespread amongb iologicallyactive natural products and pharmaceuticals. For example, (À)-veratramine (1)a nd IPI-926 (2), [1] isolated from plants of the genus Veratrum,h ave anticancer activity (Figure 1). (À)-Prosopinine (3), (+ +)-prosophylline (4), and their respective deoxo analogues 5 and 6, [2] as well as (+ +)-febrifugine (7)a nd its diastereoisomer 8, [3] all contain chiral core structurest hat are 3-hydroxy-substituted piperidines and have antibiotic, anesthetic, analgesic, and central nervouss ystem-stimulating properties. (À)-3S-3-PPP (9) [4] and, in particular,i ts analogue 10[5] act as dopaminergic autoreceptor agonists that can be used as neurolepticd rugs for the treatment of schizophrenia. Duet ot heir important biological activities, ag reat many methodsf or the stereoselective formation of piperidines based on chiral-poolderived routes, auxiliary-controlled methods, andc atalytic, asymmetricr eactions have been reported.[6] However,m ethods for the direct CÀHf unctionalization of piperidine derivatives selectively at the C3 positionare scarce. [7] Complementary to traditional synthetic routes, we envisionedt hat the aforementioned types of molecules could be efficiently accessed via the functionalization of methylene CÀH bondsa tt he C3 positiono fp iperidine derivatives. Transitionmetal-catalyzed CÀHb ond functionalization with the assistance of auxiliary groups has become one of the more important protocols for construction of carbon-carbona nd carbonheteroatom bonds overthe past few decades. [8] The Daugulisg roup was the first to describe the Pd-catalyzed arylationr eaction of b-C(sp 3 )ÀHb onds in carboxamides with 8-aminoquinoline (AQ) providing the auxiliary assistance. [9] Several other groups have also reported CÀCb ond forming reactions via Pd, Ni, or Fe catalysis, relying on the same AQ directingg roup. [10,11] Moreover,C ÀOb ondf ormation was achieved through Pd or Cu catalysis together with the use of high-valent iodine derivatives as oxidants. [12] Recently,w ep ublished ap aper on the Pd-catalyzedi ntramolecular amination reaction of the b-C(sp 3 )ÀHb onds in carboxamides with AQ as the directing group.[13] We subsequently expanded the scope Figure 1. Biologically active compounds with aC 3f unctionalized piperidine skeleton.Ms= methanesulfonyl.[