Synthesis of isoquinolines through the coupling of Fischer carbene complexes with o-alkynylpyridine carbonyl derivatives

The reaction of Fischer carbene complex with o-alkynylpyridine carbonyl derivatives has been investigated. This involves the generation of furo[3,4-c]pyridine as transient intermediates through the coupling of o-alkynylpyridine carbonyl derivatives with carbene complex and subsequent Diels–Alder trapping with suitable dienophiles resulted in the formation of isoquinoline derivatives and the entire sequence can be run in one pot. When an olefinic tether was present, intramolecular Diels–Alder cycloaddition occurred followed by ring opening to yield tricyclic alcohols.     

Synthesis of naphthalenes through three-component coupling of alkynes, Fischer carbene complexes, and benzaldehyde hydrazones via isoindole intermediates

The synthesis of naphthalene derivatives through three-component coupling of 2-alkynylbenzaldehyde hydrazones with carbene complexes and electron-deficient alkynes has been examined. The reaction involves formation of an isoindole derivative, followed by intramolecular Diels-Alder reaction, followed by nitrene extrusion. The reaction was highly regioselective using unsymmetrical alkynes.     

Synthesis of pyrroles through coupling of enyne-hydrazones with Fischer carbene complexes

[reaction: see text] The coupling of enyne-imines with Fischer carbene complexes leads to the formation of alkenylpyrrole derivatives. Maximum yields of pyrrole adducts were obtained using N,N-dimethylhydrazones. A mechanism involving alkyne insertion followed by nucleophilic attack of the imine nitrogen at the intermediate alkenylcarbene complex was proposed.     

Benzannulation of heterocyclic ring systems through coupling of Fischer carbene complexes and heterocycle-bridged enynes

An efficient annulation process resulting in heterocyclic rings fused to benzene rings has been discovered. The reaction is highly tolerant of numerous functional groups.     

Fischer type carbene ligands in dinuclear complexes

A large number of iron and ruthenium dinuclear complexes containing heteroatom substituted carbene ligands have been obtained by two different synthetic routes. The first method consists in reacting heteroatom substituted -carbyne cationic complexes with CN^– ion. The second involves the displacement of the SMe₂ molecule in the sulfonium [Fe₂{-C(CN)(SMe₂)}(-CO)(CO)₂CP₂]SO₃CF₃ by appropriate nucleophilesX ^– (X=OR, SR, NR₂, PR₂). Spectroscopic (IR, NMR) and structural investigations together with reactivity studies on these complexes have greatly contributed to better understanding the factors which favor bridging vs. terminal coordination of heteroatom substituted carbene ligands.     

Difluoroboroxymolybdenum Fischer carbene complexes as precursors of acyl radicals: dimerization and trapping with electron-deficient alkenes

Pentacarbonyl acyl molybdates 1 react with boron trifluoride to give difluoroboroxy Fischer carbene complexes 2, which undergo loss of the metal fragment at room temperature to form 1,2-diketones 3, 1,2-hydroxy ketones 4, or dimers 5 through a dimerization or decarbonylation-dimerization process of acyl radicals. Decomposition of 2 in the presence of electron-deficient alkenes 11 and 18 furnishes the two-, three-, and four-component coupling products 12, 13, 19, 20, and 21.     

Synthetic approach to substituted cyclopropanes based on the coupling reaction of lithiated chloroalkyloxazolines with Fischer carbene complexes

Regioselective addition of lithiated oxazoline 2a, easily available from 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline 1a (LDA, THF, -98 degrees C), to alpha,beta-unsaturated Fischer carbene complexes 3 afforded cyclopropylcarbene complexes 4 as sole diastereoisomers. Exposure of carbene complexes 4a-c (M = Cr) to air and sunlight gave cyclopropane carboxylate derivatives 5a-c. A plausible mechanistic explanation is proposed. Moreover, when lithiated oxazoline 2b was generated from 1b in the presence of the carbene complex 3a,b, the oxazolinylcyclopropane carboxylates 6a,b formed as a 1:1 mixture of diastereoisomers. Chiral lithiated oxazoline 2c added regioselectively and diastereoselectively to chromium complexes 3a,b and to tungsten complexes 3d,e, leading, after oxidation of the metal fragment, to esters 7a,b with good diastereoselectivity (dr = 4:1). The reaction of lithiated oxazoline 2d with chromium complex 3b and tungsten complex 3e proceeded less diastereoselectively, furnishing, in both cases, after oxidation, the ester 7c as a 3:2 diastereoselective mixture.     

Inversion of the direction of stereoinduction in the coupling of chiral gamma,delta-unsaturated Fischer carbene complexes with o-ethynylbenzaldehyde

[reaction: see text] A variety of gamma,delta-unsaturated carbene complexes that feature a stereogenic center at the beta-carbon couple with 2-ethynylbenzaldehyde to afford hydrophenanthrene derivatives with a high degree of stereoinduction. The direction of stereoinduction is opposite for examples where the stereogenic center is acyclic vs examples where it is within a ring.     

Synthesis, structure and benzannulation of chalcogen-tethered Fischer carbene complexes

Addition of PhSH-NEt₃ or PhSeNa to PhCCC(OC₂H₅)M(CO)₅ [M = Cr or W] afforded stable, β-chalcogenide tethered conjugated carbene complexes 3-6 as a mixture of E,Z-isomers. The Z-configuration was ascribed to those isomers that readily yield cyclometallated complexes. Aminolysis with methylamine yielded corresponding amino carbene complexes as mixtures of E,Z-isomers. Alkylation by methyl iodide afforded separable E,Z-isomers of dimethylamino complexes. One-step aminolysis of ethoxy carbene complexes with dimethylamine furnished only the Z-isomer of the dimethylamino complex. The Z-isomer of dimethylamino carbene complexes yielded cyclometallated products on warming. Representative crystal structures of these complexes confirm isomer assignments. Only E-isomers of the S or Se-tethered ethoxy complexes undergo benzannulation reaction with alkynes, with loss of chalcogenide atom.     

Synthesis of nitrogen-containing compounds using chromium Fischer carbene complexes

Synthetic utility of the Fischer-type carbene complexes of chromium for the preparation of nitrogen-containing compounds is demonstrated. Alkoxy carbene complexes reacted with imines to give (optically active) 3-pyrrolines and beta-methoxy allylic amine derivatives in good yields. The amino carbene complexes reacted with alpha,beta-unsaturated aldehydes to give substituted pyrroles in good yields.     

Diastereoselective cyclopropanation of ketone enols with Fischer carbene complexes

Treatment of aryl/heteroaryl methoxycarbene complexes of chromium with -substituted ketone lithium enolates between -78 degrees C and room temperature resulted in the diastereoselective synthesis of 1,2,2,3-tetrasubstituted cyclopropanols. An exception has been observed in the reaction with cyclohexanone lithium enolate that yielded a bicyclic 2-buten-4-olide. 1,2-Dimethoxycyclopropanes and 1-methoxy-2-trimethylsilyloxycyclopropanes were isolated by quenching the reactions with MeOTf or Me3SiCl, respectively. This novel cyclopropanation process involves formation of lithium (3-oxoalkyl)pentacarbonylchromate intermediates which on warming undergo intramolecular addition to the carbonyl group. This cyclization is equivalent to the cyclopropanation in smooth conditions of electron-rich alkenes with Fischer carbene complexes.     

Amine-catalyzed coupling of aldehydes and ketenes derived from Fischer carbene complexes: formation of beta-lactones and enol ethers

Aldehydes react with ketenes generated from photolysis of Fischer chromium carbene complexes to generate either beta-lactones or enol ethers resulting from decarboxylation of beta-lactones. The reaction is catalyzed by tertiary amines and can occur with diastereoselectivity greater than 20:1 with DMAP as the catalyst.     

Regioselective synthesis of substituted o-alkoxyphenol derivatives through thermal benzannulation of Fischer (alkenylcyclobutenyl)carbene complexes

A convenient, regioselective, and general synthetic method for producing highly substituted o-phenol-containing polycycles from Fischer (alkenylcyclobutenyl)carbene complexes has been described. The starting complexes have been synthesized by means of the [2 + 2] cycloaddition reaction of (alkenylethynyl)carbene complexes and a range of enol ethers, and in most cases, they have proven to be stable at room temperature and therefore isolable. The key step of the synthesis consists of the thermal benzannulation reaction of these novel pentacarbonyl dienyl Fischer complexes, which is an unprecedented transformation for these kinds of complexes. The unexpected behavior of (alkenylcyclobutenyl)carbene complexes has been rationalized in terms of their geometries.     

Novel thermal reaction of Fischer carbene complexes with imines: synthesis of beta-methoxy allylic amine derivatives

[formula: see text] Alkyl-substituted chromium Fischer carbene complexes were found to react with various N-tosylimines to give beta-methoxy allylic amine derivatives under thermal conditions. This result is essentially distinct from the photochemical outcome in which beta-lactam derivatives are obtained.     

SET pathway in tributylstannyllithium addition to alkynyl Fischer carbene complexes

The reaction of tributyltin lithium with Fischer type alkynyl carbene complexes has been studied. The reaction proceeds via a nucleophilic pathway to produce the conjugate addition product, and a single electron transfer pathway to afford cyclopentannulated derivatives derived from two units of the alkyne complex. Structure of the latter was confirmed by crystal structure determination of a representative complex.     

Synthesis of hydronaphthalenes through coupling of enyne-carbonyl compounds that contain pendant alkane groups with Fischer carbene complexes

The coupling of enyne-carbonyl compounds that contain pendant alkene groups with Fischer carbene complexes to afford furans that contain pendant alkene groups is described. Subsequent intramolecular Diels-Alder reactions are effective in selected cases, resulting in hydronaphthalene systems after dehydration. Although the Diels-Alder event is thermodynamically unfavorable, the overall transformation of alkene-furans to dihydronaphthalenes is a favorable process.     

Contingency and serendipity in the reactions of Fischer carbene complexes with conjugated triynes

The first examples of reactions of Fischer carbene complexes with triynes are reported. The regioselectivity of the reaction of the two different alkyne functions in the symmetrical triyne depends on the nature of the substituent of the triyne. Bis-silyl-substituted triynes react at the central alkyne unit, whereas bis-aryl- and bis-alkyl-substituted triynes react at the end alkyne unit. The reaction of a Fischer carbene complex with a phenyl substituent also reacts with a bis-silyl-substituted triyne at the central alkyne unit but gives a furan product rather than the normal phenol product. It was also demonstrated that all three of the alkyne units in conjugated triynes could react in turn with a Fischer carbene complex to give access to trisquinones.     

Study of the ESI-mass spectrometry ionization mechanism of Fischer carbene complexes

By means of deuterium-labeling experiments, we have carried out a systematic ESI-MS study to determine the mechanism of ESI ionization of alkenyl and alkynyl group 6 Fischer carbene complexes. These compounds can be ionized under ESI conditions only in the presence of additives such as hydroquinone (HQ) or tetrathiafulvalene (TTF). Our results demonstrate that in the ESI source an anion-radical is formed after the initial HQ- or TTF-mediated electron transfer to the metallic carbene complex. For alkenyl carbene complexes, this species evolves by extrusion of a hydrogen radical to form an allenylchromium anion that is detected as the [M - H](-) ion in the mass spectrum. The preference for this mechanistic pathway could be rationalized by DFT calculations. In the case of alkynyl carbene complexes, experiments combining deuterated substrate, additive, and solvent demonstrate that the previously proposed allene-anion carbene complex is not formed. Instead, the H transfer from the ethoxy group in the anion radical, followed by extrusion of a hydrogen radical, leads to an allenyl anion that is detected in the ESI-MS as [M - H - CO](-).     

Role of imino group in photochemical reactions of Fischer carbene complexes

The photochemical cycloaddition of Fischer iminecarbene complexes bearing two kinds of substituent, imine and alkoxy or amino, has been explored with alkenes and alkynes. It was found that annulated product without CO insertion is formed.