Pyrrolidine and piperidine formation via copper(II) carboxylate-promoted intramolecular carboamination of unactivated olefins: diastereoselectivity and mechanism

An expanded substrate scope and in-depth analysis of the reaction mechanism of the copper(II) carboxylate-promoted intramolecular carboamination of unactivated alkenes is described. This method provides access to N-functionalized pyrrolidines and piperidines. Both aromatic and aliphatic gamma- and delta-alkenyl N-arylsulfonamides undergo the oxidative cyclization reaction efficiently. N-Benzoyl-2-allylaniline also underwent the oxidative cyclization. The terminal olefin substrates examined were more reactive than those with internal olefins, and the latter terminated in elimination rather than carbon-carbon bond formation. The efficiency of the reaction was enhanced by the use of more organic soluble copper(II) carboxylate salts, copper(II) neodecanoate in particular. The reaction times were reduced by the use of microwave heating. High levels of diastereoselectivity were observed in the synthesis of 2,5-disubstituted pyrrolidines, wherein the cis substitution pattern predominates. The mechanism of the reaction is discussed in the context of the observed reactivity and in comparison to analogous reactions promoted by other reagents and conditions. Our evidence supports a mechanism wherein the N-C bond is formed via intramolecular syn aminocupration and the C-C bond is formed via intramolecular addition of a primary carbon radical to an aromatic ring.     

Palladium(II)-catalyzed intramolecular diamination of unfunctionalized alkenes

Intramolecular diamination reactions are described which yield cyclic ureas as direct products of an oxidative alkene transformation in the presence of palladium acetate and iodosobenzene diacetate as terminal oxidant. The reaction is truly catalytic in metal catalyst and represents the proof of principle for this elusive type of alkene oxidation.     

Total synthesis of (S)-(+)-tylophorine via enantioselective intramolecular alkene carboamination

The enantioselective synthesis of (S)-(+)-tylophorine, a potent cancer cell growth inhibitor, has been accomplished in eight steps from commercially available 3,4-dimethoxybenzyl alcohol. A copper (II)-catalyzed enantioselective intramolecular alkene carboamination was employed as the key step to construct the chiral indolizidine ring.     

NHC-catalyzed intramolecular redox amidation for the synthesis of functionalized lactams

A very efficient NHC-catalyzed lactamization reaction is reported. For most cases, the ring expansion reaction proceeds to cleanly furnish five- and six-membered N-Ts and N-Bn lactams, without the need for further purification. Evidence is presented suggesting a dual role for the stoichiometric base: (1) deprotonation of the triazolium precatalyst and (2) activation of the nitrogen leaving group through hydrogen bonding.     

Copper(II) carboxylate promoted intramolecular diamination of terminal alkenes: improved reaction conditions and expanded substrate scope

The copper(II) carboxylate promoted diamination reaction has been improved by the use of the organic soluble copper(II) neodecanoate [Cu(ND)2]. Cu(ND)2 allowed the less-polar solvent dichloroethane (DCE) to be used, and as a consequence, decomposition of less-reactive substrates could be avoided. High diastereoselectivity was observed in the synthesis of 2,5-disubstituted pyrrolidines. Ureas, bis(anilines), and alpha-amido pyrroles derived from 2-allylaniline could also participate in the diamination reaction.     

Copper(II) acetate promoted intramolecular diamination of unactivated olefins

A concise method for the synthesis of cyclic sulfamides and vicinal diamines is presented. This method is enabled by Cu(OAc)2 and demonstrates a new transformation for this metal. Both five- and six-membered vicinal diamine-containing heterocycles have been synthesized in good to excellent yields, and substrate-based asymmetric induction has been achieved. This is the first reported example of intramolecular diamination of olefins.     

Z-Selective intramolecular Horner-Wadsworth-Emmons reaction for the synthesis of macrocyclic alkenes

The Z-selective intramolecular Horner-Wadsworth-Emmons reaction of the substrates 7-12 (RO)₂P(O)CHR′CO₂Et (R′ = (CH₂)_nCHO) (R = Ph or o-tBuC₆H₄) gives the 13-18-membered cyclic alkenes selectively (up to Z:E = 97:3) in good yields using NaH in THF under high dilution conditions.     

Pd(II)-catalyzed intramolecular amidoarylation of alkenes with molecular oxygen as sole oxidant

Stereoselective palladium-catalyzed synthesis of structurally versatile indoline derivatives, using molecular oxygen as the sole oxidant, is described. New C-N and C-C bonds form across an alkene in an intramolecular manner. The C-N bond-forming step proceeds via a syn-amidopalladation pathway. The moderate kinetic isotope effects (intramolecular KIE = 3.56) suggest that electrophilic aromatic substitution occurs in the arylation step.     

The first enantioselective intramolecular aminocarbonylation of alkenes promoted by Pd(II)-spiro bis(isoxazoline) catalyst

The highly ligand acceleration effect of spiro bis(isoxazoline) ligand (SPRIX) on the Pd(II)-catalyzed intramolecular aminocarbonylation of alkenyl amine derivatives was realized. Furthermore, the chiral Pd(II)-SPRIX catalyst accomplished the first enantioselective intramolecular aminocarbonylation. The reaction of N-(2,2-dimethyl-pent-4-enyl)-p-toluenesulfonamide in the presence of Pd(II)-SPRIX catalyst and p-benzoquinone in methanol under a carbon monoxide atmosphere afforded [4,4-dimethyl-1-(p-toluene-sulfonyl)-pyrrolidin-2-yl]-acetic acid methyl ester in good yield with moderate enantioselectivity.     

Palladium(II)-catalyzed aerobic intramolecular allylic CH activation for the synthesis of indolines

A method for the preparation of indolines via palladium-catalyzed aerobic intramolecular allylic CH activation was developed. Oxygen was successfully used as oxidant with catalytic amount of 1,4-benzoquinone. 16 examples were reported, the majority of substrates gave moderate to good yields.     

Copper(II)-catalyzed amidations of alkynyl bromides as a general synthesis of ynamides and Z-enamides. An intramolecular amidation for the synthesis of macrocyclic ynamides

A general and efficient method for the coupling of a wide range of amides with alkynyl bromides is described here. This novel amidation reaction involves a catalytic protocol using copper(II) sulfate-pentahydrate and 1,10-phenanthroline to direct the sp-C-N bond formation, leading to a structurally diverse array of ynamides including macrocyclic ynamides via an intramolecular amidation. Given the surging interest in ynamide chemistry, this atom economical synthesis of ynamides should invoke further attention from the synthetic organic community.     

Rhodium-catalyzed intramolecular hydroacylation of 1,2-disubstituted alkenes for the synthesis of 2-substituted indanones

The intramolecular hydroacylation of 1,2-disubstituted alkenes was considered to be a challenging task due to the side reactions resulted from the lack of additional substituent at 1-position and the low activity caused by the steric hindrance of substituent at 2-position, and an asymmetric version has not been considered possible due to problems associated with the racemization of the products. We have partially solved these problems. Catalyzed by an activated diphosphine-Rh complex and reacted in a selected dihalogenated solvent, the intramolecular hydroacylation of o-(2-arylvinyl)benzaldehydes provided the corresponding 2-aryl-1-indanones in high yields, and its asymmetric variant using o-(2-alkylvinyl)benzaldehydes afforded chiral 2-alkyl-1-indanones in high yields and with moderate enantioselectivities.     

Cascade intramolecular N-arylation/intermolecular carboamination reactions for the construction of tricyclic heterocycles

A new method for the stereoselective synthesis of tetrahydropyrroloindoles and hexahydropyrroloquinolines of general structure 8 is described. These products are formed through cascade Pd-catalyzed coupling reactions between aryl chlorides and unsaturated amine substrates 5. A single catalyst effects an intramolecular N-arylation reaction followed by an intermolecular alkene carboamination reaction to generate two rings, three bonds, and one stereocenter with good chemoselectivity, diastereoselectivity, and chemical yield.     

Palladium-catalyzed alkene carboamination reactions for the synthesis of substituted piperazines

A strategy for the stereoselective preparation of enantiomerically enriched cis-2,6-disubstituted piperazines from amino acid precursors is described. The target compounds are generated in 95-99% ee with good to excellent levels of diastereoselectivity (usually 14:1 to >20:1) using Pd-catalyzed carboamination reactions between aryl or alkenyl halides and substituted ethylenediamine derivatives to form the heterocyclic rings. The synthesis requires only 4-5 steps from commercially available amino acids, and allows for the modular construction of piperazines bearing different substituents at N¹, N⁴, C², and C⁶. The use of this strategy for the construction of 2,3-disubstituted piperazines, fused bicyclic piperazines, and tetrahydroquinoxalines is also reported. In addition, the mechanism of the key carboamination reactions is discussed, and new models that predict and explain the stereochemical outcome of these transformations are presented.     

Gold(I)-catalyzed intramolecular hydroamination of unactivated alkenes with carboxamides

N-Alkenyl carboxamides undergo gold-catalyzed intramolecular exo-hydroamination to form nitrogen heterocycles in excellent yield.     

Iron(II) triflate as a catalyst for the synthesis of indoles by intramolecular C-H amination

A practical iron-catalyzed intramolecular C-H amination reaction and its application in the synthesis of indole derivatives are presented. As a catalyst, commercially available iron(II) triflate is used.     

One-step synthesis of epoxy(perfluoroalkyl)alkenes

Epoxy(perfluoroalkyl)alkenes were synthesized in one step by reaction of perfluoroalkyl iodides with 2-(allyloxymethyl)oxirane and 2-(oct-7-en-1-yl)oxirane in the presence of sodium dithionite and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) under mild conditions.     

Double Hydrated Cobalt(II) Copper(II) and Nickel(II) Copper(II) Ammine Diphosphates

Synthesis of amorphous and crystalline double hydrated cobalt copper and nickel copper ammine diphosphates with a coordination structure is described.__________Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 3, 2005, pp. 369–372.Original Russian Text Copyright © 2005 by Voitenko, Zhilyak, Kopilevich.     

Cationic Pd(II) catalyzed regioselective intramolecular hydroarylation for the efficient synthesis of 4-aryl-2-quinolones

A divergent regioselective palladium (II) catalyzed approach through post Ugi cyclization is described. The Ugi adduct underwent intramolecular ortho-hydroarylation via 6-endo-dig cyclization for the direct access to 4-aryl-2-quinolones. Incorporation of iodine at the C-3 position of 2-quinolone followed by Suzuki-Miyaura coupling results into the more diversified 3,4-diaryl-2-quinolones.