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A broad range of functionalized 5-alkylidenecyclopentene derivatives are synthesized by the rhodium(I)-catalyzed [3+2]-cyclization reaction of chromium alkenyl(methoxy)carbene complexes and activated allenes. A tentative reaction pathway is proposed that involves the rhodium(I) carbene complexes as the species responsible for the [3+2]-cyclization.

A diastereo- and enantiospecific formation of tetrasubstituted cyclopropane carbene complexes and cyclopropanecarboxylates from lithiated aryloxiranes and alpha,beta-unsaturated Fischer carbene complex is described. The results revealed that lithiated styrene, phenypropylene, and stilbene oxides react diastereo- and when, optically active, enantiospecifically with alpha,beta-unsaturated Fischer carbene complexes to give stereodefined tetrasubstituted cyclopropane carbenes and cyclopropanecarboxylates.

A highly stereoselective preparation of cyclopropane-fused bicyclic and cyclopropyl carbene tungsten complexes using a synthetic procedure that combines the chemistry of lithiated oxazolinyloxiranes with that of some Fischer-type carbene complexes are reported. A mechanism for the formation of pentacarbonyl(cyclopropylmethoxymethylene)tungsten compounds is reported and their oxidation to cyclopropane-gamma-lactone and -carboxylate.

A straightforward route to 1-azabicyclo alkaloid scaffolds with several ring sizes is reported. Various polysubstituted azabicyclic ring skeletons, including several examples of the quinolizidine alkaloids are presented and their relative stereochemistry is adequately discussed.

The potential of Fischer-type carbene complexes for accessing different types of heterocycles are reviewed for the attention of people involved in organic synthesis mediated or catalyzed by organometallic reagents. The review shows that, metal carbene complexes of group 6 are reactive toward a wide array of heteroatom-containing substrates, allowing access to a great variety of mono- and polyheterocyclic compounds.

The reaction of carbene complex 1a with alkynyl methyl ketone lithium enolates can be directed to the formal [3+2] or [4+1] cyclization products by a slight variation of the reaction conditions. Consecutive three-component coupling reactions with carbene complex, lithium enolates, and aldehydes to give, in a diastereoselective way, hydroxy carbonyl compounds and tricyclic polyethers are presented.

Cyclization reactions of group 6 Fischer carbene complexes with cyclopentanone and cyclohexanone enamines are described. The novel alpha,beta,beta'-anulation reaction of cyclopentanone enamines and alkenylcarbene complexes represents the shortest thermal access to tricyclo octanes.

Research has been conducted on the N-alkylidene glycine ester enolates produced from glycine asters aldimines. The reaction carried out between these enolates and chiral alkoxyalkenylcarbene complexes of chromium is described.

The cyclopropanation reaction of chromium Fischer carbene complexes with alkenyl oxazolines are studied in both racemic and enantioselective methods. The results show that alkenyl oxazolines are excellent electron-poor alkene surrogates for the cyclopropanation reaction with many Fischer carbene complexes.

In-situ generated dialkylboroxy and diaminoboroxy Fischer carbene complexes lead to oxaborolane or oxazaborolidine derivatives through the use of an intramolecular C-H insertion reaction. Further oxidation of these intermediates produces 1,3-diol or 1,2-amino alcohol derivatives. Diastereoselectivities as high as 99% are attained when starting from boroxy Fischer carbene complexes derived from terpenes, which represents a regio- and diastereoselective modification of this type of natural product.

Enantiomerically pure alpha'-amino alpha,beta-epoxy ketones (2) were prepared in an efficient synthesis starting from alpha'-amino bromomethyl ketones and the further transformation of compound 2 into an amino diepoxide as a synthetic application. The synthetic procedure for the synthesis of enantiopure alpha'-amino alpha,beta-epoxy ketones is based on the Darzens reaction which is one of the more reliable methods for the construction of alpha,beta-epoxy ketones.

The enantioselective synthesis of (-)-(5S,8R,9S)-5-(3-furyl)-8-methyloctahydroindolizine alkaloid and the total synthesis of (-)nupharamine was described. The approach demonstrated that 4-piperidones derived from chiral 2-aminodienes were useful precursors of piperidine alkaloids. In addition, the enantiomers of these alkaloids were equally approachable in optically pure form by this synthetic approach by employing the chiral 2-aminodiene derived from (R)-2-methoxymethylpyrrolidine.

Halomethyllithium and 1-aminoalkyl halomethyl ketones were used in the synthesis of enantiomerically pure (2S,3S) and its diastereoisomer (2R,3S)-2-halomethyl-1,2-epoxyalkan-3-amine. The latter compounds were generated by treating the ketones with (iodomethyl)lithium at -78 degrees C. Epibromohydrins or 2-(1-aminoalkyl)epichlorohydrins were obtained when the mixture was allowed to cool at room temperature. The amines were used in deriving chiral 2-(halomethylidene)-3-(dibenzylamino)-alkan-1-ol or unsaturated 1,3-aminoalcohols through halogeno-lithium or hydrogen-lithium exchange.

Either (3+3) or (4+3) carbo- and/or heterocyclizations of alkenyl and alkynyl (methoxy)carbene complexes were effected in a study of the cycloaddition reactions of a variety of C-heteroarylimines with alpha,beta-unsaturated Fischer carbene complexes. The cyclization pattern was dependent on both the nature of the imine and the type of unsaturation of the carbene complex. These transformations were found to be initiated by a 1,2- or 1,4-addition to the electrophilic carbene complex. The carbene complex ligand acts as a C(sub 3) unit in all the processes.

The synthesis of functionalized enantiomerically pure cis- and trans-2-aminocyclohexanecarboxylic acid derivatives from 4-nitrocyclohexanes has been undertaken. These compounds have the beta-amino ester moiety in a conformationally restricted environment which is a distinct characteristic of peptidomimetics and beta-peptides. The synthetic procedure allows for the derivation of a large variety of cyclic beta-amino acid derivatives with different substituents.

A study was conducted to analyze the synthesis of various derivatives of pipeocolic acids using enantiomerically pure 4-piperidones determined by the asymmetric (4+2) Diels-Alder cycloaddition of chiral 2-aminodienes with imines. The reactions were performed under N2 employing solvents which were dried following conventional procedures. Results showed that cis and trans-6-(hydroxymethyl)pipecolic acids can be determined by a stereoselective epimerization of the alpha-carbon of a particular pipecolate.

The synthesis of novel boroxyvinylcarbene complexes with a cyclic chelate structure has been undertaken. This fixes the s-cis conformation of the exocyclic carbon-carbon and carbon-chromium double bonds temporarily. The Diels-Alder type reactions of the boron difluoride complexes with 2-amino 1,3-dienes are described, as well as a Diels-Alder reaction with chiral 2-amino 1,3-dienes.

A study was conducted to analyze the cycoaddition reaction of Fischer carbene complexes with 2-aza-1,3-butadienes. A number of carbene complexes were utilized in the study, including aryl, alkynyl and alkenyl. Results indicated that the reactions produced 5 to 7-membered nitrogen-membered heterocycles in a selective fashion. Findings also showed that the cycloaddition reactions generated a 1:1 mixture of diastereoisomers.

A novel method of synthesizing azetidines was developed through employing iodine-treated azazirconacyclopentanes. The design featured the formal {2 + 2} cycloaddition between alkenes and imines. It was revealed that the outcome of the process was determined by the relative position of the carbon-carbon multiple bond with respect to the imine complex. Ring closure of the corresponding diiodide resulted in the formation of the four-membered ring in lieu of a corresponding azepine derivative.

A novel method of synthesizing alpha-amino epoxides was designed through the use of the reaction of chiral 1-aminoalkyl chloromethyl ketones with organometallic compounds. The reaction resulted in enantiomerically pure 3-azetidinols and alpha-amino epoxides with high yield and diastereoselectivity. The mechanism underlying this reaction depended on the presence of the hydroxyl and alkyl groups at C2 and by the bulky groups attached to the nitrogen.

Optically active 2,3,4-substituted azetidines were synthesized as N-mesylated derivatives from 1,3-amino alcohols containing three chiral centers via cyclization. The alcohols were prepared via the diastereoselective reduction of enantiomerically pure beta-amino ketones. The reaction, which proceeded via an S(N)2 mechanism, afforded all possible diastereoisomers of the azetidines.

The thermal stability of vinylic organolithium compounds obtained from secondary aliphatic allylamines was investigated. The results revealed that when such complexes are subjected to heating at reflux of tetrahydrofuran, dimerization or cyclodimerization occurs to yield diamino 1,4-dienes or cis-2,3-disubstituted 4-methylenepyrrolidines, respectively. In contrast, the corresponding 1,3-dilithio derivatives prepared from aromatic allylamines undergo solvent-induced protonation.

Two pathways for the cleavage of the C propargylic-C acetylenic bond in propargylamides using organolithium complexes are examined. Both generate lithium propargylamides, the first by reacting secondary aliphatic 2-bromoallylamines with an excess of alkyllithiums and the second, by reacting the precursor with BuLi and t-BuLi, successively. In both cases, the product undergoes Calpha-Cbeta cleavage to saturated secondary amines and hexahydropyrimidines, respectively.

A simple access to 3-functionalized pyrroles and N-bridgehead pyrroles is provided by the cyclization of propargyl-substituted 4-amino-1-azabutadienes. N-bridgehead pyrroles are synthesized from cyclic amines following a series of steps involving metalation of an amine with LDA, addition to a nitrile, propynylation, and cycloamination. Theoretical calculations reinforce the general observation that a more substituted imine nitrogen participates in the cyclization reaction.

Reaction between ethyl N,N-dibenzylated alpha-amino carboxylates with (chloromethyl)lithium in situ at -78 degrees C produces alpha-chloro-alpha'-(dibenzylamino) methylketones (3). The reduction of 3 with NaBH4 or LiAlH4 in the presence of methyllithium generates the threo amino epoxides, whereas the erythro substrate is obtained from amino aldehydes and (halomethyl)lithium. The diastereoisomeric excess purity of threo and erythro is between 94% and 98%. The diastereoselectivity is enhanced by using LiAlH4.

The synthesis of seven-membered carbocycles occurs through the reaction between 2-amino-1,3-butadienes and vinyl chromium Fischer-type carbenes. The hydrolysis product of the initially formed cycloadduct leads to cyclohepta-1,3-diones restoring complete regio- and stereoselectivity. High enantiomeric excesses of the cyclic diketones are obtained when 2-aminobutadienes having a prolinol derivative are used.

The addition of dimethyl acetylenedicarboxylate to (Z)-beta-enamino-lambda (5)-phosphazenes facilitated the synthesis of polyfunctionalized 1-aminobuta-1,3-dienes. This reaction involved a trans addition of the enamine C-H bond to acetylenic triple bond. Enamines are used as starting materials for the preparation of various heterocyclic compounds and as intermediates in the synthesis of biologically-active molecules.

Temporary silylation of the amino group of secondary aliphatic allylamines yields beta-nitrogen functionalized vinylic organolithium compounds through monoanionic intermediates formed by bromine-lithium exchange reaction, or dianionic intermediates from tin-lithium exchange reaction, or dianionic intermediates from tin-lithium transmetalation reaction. These organolithium compounds interact with several electroformites to yield functionalized allylamines.

Nikkomycins B and B(X) reveal an N-terminal amino-acid moiety with four diastereoisomeric lactones which are prepared by employing a new method that allows the synthesis of 1,3-amino alcohols from 4-amino-1-aza dienes. The preparation is done in a diastereo- and enantio-selective fashion. 4-amino-1-aza diene and (R)-O-benzyllactic aldehyde serve as the initial points for the preparation of enantiomerically pure beta-amino ketones. 1, 3-amino alcohol products are used to transform ketones into highly diastereoselective lactones.

Mechanized organolithium compounds containing aryl, heteroaryl or vinyl halides are subjected to an uncatalyzed one-pot pairing interaction to accurately synthesize various N-replaced benzamides and various replaced alcohols. The halide pair reveals various functional groups which are permitted, but unsteady aryl or vinyllithiums in the halogen-metal-exchange step are formed by substrates. This interaction is considered a failure. The pairing interaction reveals the production of alkyl halides as intermediates.

A study was made on the ZnCl2-catalyzed reactions of certain arylimines with 2-amino-1,3-butadienes leading to a stereoselective synthesis of substituted 2-aryl-4-piperidones and 2-aryl-4-aminotetrahydropyridines. The results indicated a smooth chemical reaction and underscored the dependency of the stereochemistry of the cyclization process on the nature of the N-substituent of the imine.

An easy route to biopharmacologically important azaphenanthrenes and azasteroids involves the intramolecular Friedel-Crafts cyclization of heterocycles derived from 4-amino-1-azabutadienes. With pyridones, pyrimidones and pyrimidines, heating with phosphoric acid results in 81-85% yields of benzoquinolones, -quinazolones and -quinazolines. Triflic acid, on the other hand, allows the cyclization of thiazine and thiadiazine dioxides to produce naphthothiazines and -thiadiazines in 89% and 90% yields. The technique is applied to the synthesis of diazasteroids.

The addition of LiAlH4/TiCl4 reducing agent to anti-N-acylamino ketones results in the formation of highly stereoselective syn,anti-N-alkyl-1,3-amino alcohols with three chiral centers. Moreover, replacing the reducing agent with DIBALH/ZnCl2 affords the N-acylamino alcohols. Similarly, the addition of 1N HCl solution to tetrahydropyrimidines in THF results in the stereoselective preparation of syn-1,3-amino ketones. Subsequent introduction of DIBALH/ZnCl2 leads to syn, syn-1,3-amino alcohols.

The utility of fluoride anion as promoter of the oxidation of Fischer carbene complexes is presented. Two different and complementary methods that enable fast and convenient preparation of carbene-derived esters in good yields are developed using stoichiometric or catalytic quantities of fluoride ion.