Nickel-catalyzed couplings and cyclizations involving allenes, aldehydes, and organozincs

Cyclizations of allenyl aldehydes and intermolecular couplings of allenes and aldehydes provide a direct procedure for the preparation of homoallylic alcohols. The couplings and cyclizations involve the use of diorganozinc reagents as reducing agents and Ni(COD)₂ as the catalyst.     

Nickel-catalyzed reductive cyclizations and couplings

For over 50 years, nickel catalysis has been applied in cycloaddition processes. Nickel-catalyzed reductive couplings and cyclizations, however, have only recently attracted a high level of interest. This group of new reactions allows a broad range of multicomponent couplings involving two or more pi components with a main-group or transition-metal reagent. These processes allow the assembly of important organic substructures from widely available reaction components. Multiple contiguous stereocenters, polycyclic ring systems, and novel arrays of complex functionality may often be prepared from simple, achiral, acyclic precursors. With three or more reactive functional groups participating in the catalytic processes, many mechanistic questions abound, including the precise timing of bond constructions and the nature of reactive intermediates. This Review is thus aimed at providing a critical evaluation of recent progress in this rapidly developing field.     

Nickel-catalyzed cyclizations and couplings with vinylzirconium reagents

[reaction: see text] 1,3-Dienes were prepared by a variety of nickel-catalyzed couplings and cyclization processes. Intermolecular or partially intramolecular couplings of alkynes, vinylzirconium reagents, and either aldehydes or enones efficiently proceeded to generate a broad range of functionalized dienes.     

Pathways for cyclizations of hydrazine-derived 2-(2-cyanovinyl)-3-oxo-cyclohex-1-ene enolates

The introduction of a hydrazine functionality into 2-(2-cyanovinyl)-3-oxo-cyclohex-1-ene enolates results in their spontaneous cyclizations with participation of the hydrazine moiety. Depending on the reaction conditions used, the hydrazine-derived enolates are transformed into derivatives of 1-arylpyridine-2-one-3-carbonitriles or pyrazoloquinolinones in a one-pot synthesis. They also react with anilines to give the corresponding N1-substituted pyridine-2-one-3-carboxamides. Product characterization was performed by means of spectroscopic and X-ray diffraction studies. In addition, for structure elucidation purposes, a counter synthesis of 1-arylaminopyridine-2-one-3-carboxamide was also carried out.     

Efficient oxidative radical cyclizations of ester enolates with carbocation desilylation as termination: synthesis of cyclopentanoid monoterpenes and analogues

[reaction: see text] An efficient oxidative radical cyclization approach for the synthesis of 2-alkenyl cyclopentane or cyclohexane carboxylates from omega-silylallyl ester enolates induced by recyclable SET oxidant ferrocenium hexafluorophosphate has been developed. A new tandem alkoxycarbonylation/oxidative radical cyclization/cationic termination process forms the basis for a five-step synthesis of the cyclopentanoid monoterpene dihydronepetalactone and analogues.     

One-step deprotonation route to zinc amide and ester enolates for use in aldol reactions and Negishi couplings

Simple amides and esters are conveniently deprotonated by Zn(tmp)₂ (tmp = 2,2,6,6-tetramethylpiperidinyl anion) to generate Zn enolates. Enolates formed by this method are suitable for use in aldol reactions that tolerate base-sensitive functional groups. Additionally, the Zn enolates are readily coupled with aryl bromides using typical Pd-catalyzed coupling methods.     

Conjugate additions of cyclic oxygen-bound nickel enolates to alpha,beta-unsaturated ketones

The reaction of nickel enolates displaying a metallacyclic structure with the alpha,beta-unsaturated ketones methyl vinyl ketone (MVK) or methyl propenyl ketone (MPK) takes place in two stages, affording initially bicyclic adducts, which subsequently isomerize to the corresponding open-chain products. The former are generated with high stereoselectivity and can be considered as the products of the [2+4] cycloaddition of the enolate to the enone. The ring opening process involves a prototropic rearrangement that can be catalyzed by water. In the case of the reaction of the parent nickel enolate complex 1 (which displays an unsubstituted Ni-O=C(R)CH2 arrangement) with MVK, a double-addition process has been observed, consisting of two successive cycloaddition/isomerization reactions. The carbonylation of the different cyclic and noncyclic products affords the corresponding lactones that retain the stereochemistry of the organometallic precursors. This methodology allowed trapping the primary product of the reaction of 1 with MPK as the corresponding organic lactone, demonstrating that the cycloaddition process takes place with exo selectivity. DFT modeling of the latter reaction provides further support for a quasi-concerted cycloaddition mechanism, displaying a nonsymmetric transition state in which the C-C and the C-O bond are formed in an asynchronous manner.     

Sequenced cyclizations involving intramolecular capture of alkyl-oxyaminyl radicals. Synthesis of heterocyclic compounds

A cascade radical cyclization process involving oxime ethers tethered to a brominated phenyl and an activated olefin moiety is described. The generated aryl radicals using tri-n-butyltin hydride react with the CN bond to yield neutral alkyl-oxyaminyl radicals, which were then simultaneously captured by the activated double bond to provide heterocyclic systems with a pyrrolidinic nucleus.     

Synthesis of new thieno[3,2-b]pyridine derivatives by palladium-catalyzed couplings and intramolecular cyclizations

Two methyl 3-aminothieno[3,2-b]pyridine-2-carboxylates were prepared from 3-fluoro or 3-nitropicolinonitriles and methyl thioglycolate in DMF/KOH(aq). From the unsubstituted precursor in the pyridine ring, di(hetero)arylamines were obtained by C-N Buchwald-Hartwig coupling with bromonitrobenzenes and with 2-bromopyridine. In the latter case a tetracyclic compound was formed by intramolecular cyclization. Using a brominated derivative in the pyridine ring as a coupling component, it was possible to synthesize C-C (Suzuki and Sonogashira) and C-N (Buchwald-Hartwig) coupling products and a tetracyclic compound obtained by bifunctionalization of the thienopyridine system.     

NMR spin-spin couplings involving nuclei in the neighborhood of a carbonyl group. 3JCH couplings in alpha-substituted acetamides

In this work 3JCH spin-spin coupling constants (SSCCs) for the cis- and trans-conformers for alpha-X-acetamides (X = F, Cl, Br and CN) (1-4) were studied in detail since they were found to be notably different for both conformers. These differences are rationalized as originating in the changes of the strong negative hyperconjugative interactions that take place within the carbonyl group. Such changes are found to depend not only on conformation, but also on solvent. For the cis-conformers there is a close proximity between the X-substituent and the in-plane oxygen lone pair of pure p character, which affects notably their respective negative hyperconjugative interactions. Both the efficiency for transmitting the Fermi contact (FC) term through the coupling pathway of 3JCH SSCCs and its potential as a probe to study the stereochemical properties of the XH2C group are discussed.     

Synthesis, structure, and olefin polymerization with nickel(II) N-heterocyclic carbene enolates

Two novel N-heterocylic carbene enolate nickel complexes have been prepared and shown to be active for ethylene and propylene polymerization to yield linear polymers.     

Novel cyclizations involving vinyl sulfones: Stereoselective construction of perhydroazulenes and trans-hydrindanes.

Anionic species formed by treatment of vinyl sulfones with hydridoaluminates were trapped intramolecularly by esters to provide six- and seven-membered cyclic ketosulfones, exemplified by the stereoselective construction of trans-hydrindanes and of perhydroazulenes. This led to formal syntheses of confertin and damsinic acid.     

Diastereoselective multicomponent cyclizations of Fischer carbene complexes, lithium enolates, and allylmagnesium bromide leading to highly substituted five- and six-membered carbocycles

The one-pot sequential reaction of a chromium alkoxycarbene complex, a ketone or ester lithium enolate, and allylmagnesium bromide enabled the selective synthesis of novel diastereomerically pure pentasubstituted cyclopentanols or tetrasubstituted 1,4-cyclohexanediols, depending on the degree of substitution at the Cbeta position of the enolate anion. A few exceptions have been encountered in which tetrasubstituted cyclopentanols or pentasubstituted 1,4-cyclohexanediols were selectively formed. The use of 2-iodoethoxycarbene complexes gave access to 1,2,4-cyclohexanetriols. These multicomponent-coupling reactions involved the formation of lithium alkylpentacarbonylchromates as key intermediates, which further evolved through intramolecular processes, such as insertion of an alkene, CO insertion or addition to a carbonyl group, and, moreover, could be trapped in intermolecular reactions with different electrophiles and styrene. The substitution pattern of the alkylchromate carbon chain has been proposed to control the nature of the annulation process.     

New oscillating chemical reactions involving copper and nickel tetraazamacrocyclic complexes

Copper and nickel complexes with tetraazamacrocyclic ligands are shown to act as catalysts in Belousov-Zhabotinskii oscillating reactions. New oscillating reactions, viz. the oxidation of unsaturated macrocyclic complexes of copper and nickel by bromate-ions, have been discovered.

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Development of useful reactions involving tandem cyclizations based on the novel reactivities of allenic compounds

This review highlights author's recent study on allenic compounds. In the first section, organocopper-mediated ring-opening reaction of ethynylaziridines and palladium-catalyzed reductive synthesis of allenes including those which are not accessible by other means, are described. In the second section, palladium-catalyzed stereoselective cyclization of allenes and tandem reaction leading to aziridines, pyrrolidines, benzoisoindoles, and cyclopropanes are presented. The final section presents aziridination and medium-ring formation by intramolecular reaction of bromoallenes, which are scarcely investigated until quite recently. The latter reaction is based on our recent discovery that bromoallenes can act as allylic dication equivalents in the presence of a palladium catalyst and alcohol.     

Cascade cyclizations via N,4-didehydro-2-(phenylamino)pyridine biradicals/zwitterions generated from enyne-carbodiimides

Thermolysis of the enyne-carbodiimides 7 having the central carbon-carbon double bond incorporated as part of the cyclopentene ring favors the formation of the corresponding N,4-didehydro-2-(phenylamino)pyridine intermediates, either as the sigma,pi-biradicals 8 or as the zwitterions 8', for subsequent synthetic elaborations. By placing appropriate substituents at the acetylenic terminus, a variety of the intramolecular decay routes are available for the initially formed sigma,pi-biradicals/zwitterions, leading to the 5,6-dihydrobenzo[c][1,8]naphthyridine 21, the 1,2,3,4-tetrahydro[1,8]naphthyridine 24 and related compounds 25 and 26, the 5,6-dihydrobenz[f]isoquinoline 28, and the benzofuro[3,2-c]pyridine 30. Surprisingly, the use of the dimethylamino group of the 2-(dimethylamino)phenyl substituent to capture the carbocationic center in the zwitterion 8e' furnished the 5H-pyrido[4,3-b]indole 32 in only 14% yield. The majority of the products were the 1H-pyrrolo[2,3-b]quinolines 34 and 35, isolated in 48 and 7% yields, respectively. However, it was possible to redirect the reaction toward 32 by conducting thermolysis of the enyne-carbodiimide 7e in the presence of 5 equiv of dimethylphenylsilyl chloride. Under this reaction condition, the 2-pyridone imine 37 was isolated in 86% yield, which on exposure to silica gel was converted to 32 in essentially quantitative yield. Thermolysis of the enyne-carbodiimide 42 having a methoxymethyl substituent at the acetylenic terminus led to the formation of 46' as a pyridine analogue of ortho-quinone methide imine. An intramolecular hetero-Diels-Alder reaction of 46' then furnished the tetrahydro[1,8]naphthyridino[2,1-c][1,4]benzoxazine 47.     

Mixed-ligand complexes of nickel(II) involving sulphur-containing ligands and diaminocarboxylic acids

Summary Stability constants for mixed-ligand complexes of the types [NiABH₂], [NiABH] and [NiAB] formed by Ni^II with l-cysteine (cys), d-penicillamine (pen) or l-cysteic acid (cya) as ligand A and dl-2,3-diaminopropionic acid (dapa), dl-2,4-diaminobutyric acid (daba) or dl-ornithine (orn) as ligand B have been determined by the computerbased analysis of pH titration data obtained at 37 °C and I = 0.15 mol dm^–3 (NaClO₄). In the [NiABH] species, for all three secondary ligands (B), when A = pen or cya the labile proton appears to be attached to the terminal amino group of ligand B, whereas when A = cys it is not clear where the proton is located. In all the systems in the [NiABH₂] species, one proton resides with the primary ligand (A) and the other with the secondary ligand (B). In the [NiAB]-type complexes, cys and pen chelate through the amino and thiolato groups, while cya binds in a glycine-like mode and the secondary ligands (B) coordinate in a terdentate manner.Author to whom all correspondence should be directed.     

Knorr cyclizations and distonic superelectrophiles

The acid-catalyzed Knorr cyclization has been studied by experimental and theoretical methods. The results of these studies indicate that beta-ketoamides such as acetoacetanilide undergo diprotonation at the two carbonyl oxygen atoms to form distonic superelectrophiles. Direct observation of a dicationic superelectrophile was achieved by low-temperature 1H, 15N, and 13C NMR from FSO3H-SbF5-SO2ClF solutions. In synthetic studies, the Br?nsted superacid CF3SO3H is found to be an effective acid catalyst for the Knorr cyclization.