A highly effective synthesis of haloalkylidene-substituted heterocycles by copper(II)-catalyzed cyclization of alkynyl ureas and secondary amides has been developed. The reaction, which involves a catalytic amount of CuCl2 and a stoichiometric amount of N-halosuccinimide, occurs selectively through an alkoxyhalogenation process. Alternatively, alkoxychlorination and alkoxybromination reactions can be performed working solely with stoichiometric CuCl2 and CuBr2, respectively.

Intramolecular palladium-catalyzed amination reactions are becoming important tools for the synthesis of various nitrogen-containing­ heterocycles. This account highlights the developments achieved in this field by domino processes in oxidative conditions using unactivated olefins, due to their advantages in terms of step economy and efficiency. These reactions involve the change of oxidation state in the palladium intermediate, requiring the presence of an oxidizing agent to regenerate the catalytic cycle. This kind of additive is essential for the success of the reaction and it can also furnish nucleophilic species that are incorporated into the final product. Reactions can occur at either the intra/intra- or intra/intermolecular level, providing valuable methodologies for the preparation of (poly)heterocyclic scaffolds. Besides, procedures based on the use of strengthened catalytic systems, more recently, disclosed intriguing conditions have enlarged the possibility to modulate the substrate reactivity. Perspectives in this field are directed to the discovery of new reaction conditions, focusing on the employment of oxidatively stable ligands useful for the asymmetric catalysis­.1 Introduction2 Carboamination Reactions2.1 Pd(0)/Pd(II)2.2 Pd(II)/Pd(IV)3 Aminooxygenation Reactions3.1 Pd(0)/Pd(II)3.2 Pd(II)/Pd(IV)4 Diamination Reactions4.1 Pd(0)/Pd(II)4.2 Pd(II)/Pd(IV)5 Aminohalogenation Reactions5.1 Pd(0)/Pd(II)5.2 Pd(II)/Pd(IV)6 Conclusions

The Pd-catalysed reactions of allenyl ethers and allenylamines derived from commercially available o-aminophenols and o-nitroaniline have been studied. Using a wide variety of aryl- and heteroaryl halides, carboamination of the allenes led to sequential C–C and C–N bond formation. Both carbo- and hydroamination processes resulted in the formation of nitrogen-containing benzo-fused rings. In the case of aminoallenes arising from o-phenylenediamine, the regioselectivity of the cyclization step was strongly dependent on the protecting group tethered to the nitrogen atoms, allowing the formation of five- and seven-membered rings

Easily accessible N-tosylglycine allylamides have been converted into diversely functionalized piperazinone derivatives by inter-intramolecular oxidative domino palladium-catalyzed reactions. Aminochlorination and aminoacetoxylation processes were achieved by employing CuCl2 and PhI(OAc)2 as the oxidizing agents to give 5-chloromethyl- and 5-acetoxymethyl-substituted piperazinones, respectively. Inter-intramolecular domino palladium-catalyzed reactions of N-tosylglycine allylamides were used to access piperazinones with functional groups that can undergo further transformations. Aminochlorination and aminoacetoxylation processes were achieved by using CuCl2 and PhI(OAc)2 as oxidizing agents to give 5-chloromethyl- and 5-acetoxymethyl-substituted piperazinones, respectively

As tudy of the palladium(II)-catalyzed cyclizationo fu nsaturated N-sulfonylamides was undertaken, using (diacyloxyiodo)benzenes as terminal oxidizing agents.D ifferent reactivities were observed as af unction of the nature of the unsaturation (terminal vs. internal), or of the hypervalent iodine compound used (diacetoxyiodobenzene vs. bistrifluoroacetoxyiodobenzene). Proper parameter selection allowst he direction of the cyclization to be chosent owards either ag lobal aminoacetoxylation, an allylic amination via aminopalladation, or an allylic amination via allylic C-H activation.Thel iterature devoted to the oxidative Pd(II)-catalyzed addition of nucleophilest oo lefins is very extensive andt he method allows the construction of an umber of synthetically useful compounds starting from simple unsaturated substrates. [1] Although different terminal oxidants have been used for this purpose, the attention was recently directed toward hypervalent iodine reagents. [2,3] In particular,P hI(O 2 CCH 3 ) 2 , alias PIDA, hasb een efficiently usedt op romote 1,2aminoacetoxylations of unsaturated amine derivatives. In this context, some of us recently described the intra-intermolecular conversion of glycine allylamides into acetoxymethyl-substituted piperazinones [Scheme 1, Eq. (1)]. [4] In this contribution, we show that slight modificationso ft he substrate and/or the oxidizing system can trigger alternative mechanisms [Scheme 1, Eqs. ( 2) and (3)].I nt he frame of our con-stant interest in the mechanismso fP d-catalyzed nucleophilic additionst oa lkenes, [5,6] we envisioned an extensiono ft he above initial studyt on itrogen-based substrates bearing terminal as wella si nternal unsaturations,a nd to the testing of newr eactionc onditions. Our new study started with N-tosylglycine N'-crotyl-N'-benzylamide 1b as the model substrate,u sing the reactionc onditions optimized in our previous study [Pd(OAc) 2 5mol%, PhI(O 2 CCH 3 ) 2 (2.0 equiv.), AcONa (1.0equiv.) and Bu 4 NHSO 4 (1.0 equiv.)].No reaction occurred when working with CH 2 Cl 2 as solvent,e ither at room temperature or at reflux. However, on changingt oD CE at reflux (conditions 1), we obtainedt he 5-vinylpiperazinone 3b in 50% yield (Scheme 2, andT able 1, entry 1), insteado ft he anticipated corresponding aminoacetoxylated product. [4] Performing the cyclization in MeCN at room Scheme1.Previous and present studies on Pd(II)-catalyzed cyclizations using PhI(O 2 CR) 2 .