Unexpected reaction pathways in the reaction of alkoxyalkynylchromium(0) carbenes with aromatic dinucleophiles

Thermal- or SiO(2)-induced reactions of the Michael adducts of 1,2-aromatic dinucleophiles and alkynylchromium(0) carbene complexes, compounds 7-10, form different products in good yields depending on the nature of the aromatic dinucleophile used. Thus, 1,2-diaminobenzene derivatives 7 and 8 rearrange to pentacarbonylchromium(0) isocyanide complexes 11, 12, 14, and 15 in a process that occurs through bicyclic intermediates 24. Adducts 9 derived from o-aminophenol give 2,3-dihydro-1,5-benzoxazepine derivatives 17 by intramolecular 1,2-addition, followed by protonation at the chromium center and reductive elimination. In contrast, base-promoted addition of the phenolic hydroxy group in compound 9 a affords 3-ethoxy-5-phenyl-5,6-dihydro-2H-1,6-benzoxazocin-2-one (18), together with the expected adduct 17 a. Compound 18 is formed by a nucleophilic addition to a CO ligand in a preformed carbene complex. This is a new example of the rare attack of a nucleophile on a CO ligand in a Fischer carbene complex. Adducts 10 form seven-membered-ring carbene complexes 19 and 20 by intramolecular aminolysis. In contrast, reaction of alkynyl carbene complexes with 1,8-diaminonaphthalene under very mild conditions leads to 2-substituted perimidines 33 together with the corresponding ethoxymethylmetal carbene complex 32 through an unprecedented fragmentation process in a formal retro-Aumann reaction.     

Diastereoselective synthesis of three-, five-, six-, and seven-membered rings from Fischer carbene complexes and 4-unsubstituted 1-amino-1,3-dienes

Fischer carbene complexes react with 4-unsubstituted 1-amino-1,3-dienes to give different carbocyclization products depending on the nature of the carbene complex and on the substitution pattern of the aminodiene. Thus, the reaction of arylcarbene chromium complexes and 1-aminodienes diastereoselectively affords cyclopropane derivatives by means of a formal [2+1] carbocyclization reaction. In particular, pentacarbonyl[(2-furyl)(methoxy)methylene]chromium complex furnishes formal [4+1] carbocyclization products. Starting from beta-substituted alkenylcarbene complexes, formal [4+1] reactions occur and cyclopentenamine derivatives are diastereoselectively formed. However, when the alpha,beta-disubstituted alkenylcarbene complex pentacarbonyl[(5,6-dihydro-2H-pyran-2-yl)(methoxy)methylene]tungsten is used, the outcome of the reaction depends on the substitution on the carbon atom at the 3-position of the aminodiene, generating the [3+2] or [4+3]-cyclization products if the substituent is or is not a hydrogen atom, respectively. Finally, when the reaction is performed with alkynylcarbene complexes, benzaldehyde derivatives are obtained if the triple-bond substituent is a phenyl group or indene derivatives if the group is an alkenyl moiety.     

Rhodium(I)-catalyzed [3+2+2]-cyclization of alkenyl Fischer carbene complexes with methyl buta-2,3-dienoate

A variety of alkenyl chromium Fischer carbene complexes react with methyl buta-2,3-dienoate in the presence of a rhodium catalyst to afford substituted cycloheptene derivatives 7, along with minor amounts of cyclopentene derivatives 6. Through this [3+2+2]-cyclization two allene units and one alkenyl carbene ligand are assembled in a selective manner.     

Photolytic reaction of chromium and molybdenum carbene complexes with imines : Synthesis of cepham, oxapenam, and oxacepham derivatives

A variety of substituted β-lactams, including a cepham analog, were synthesized by the photochemical reaction of [(methoxy)(methyl)carbene]chromium complexes with substituted imines. Oxazines and oxazolines were inert towards chromium carbene complexes. Oxazines were converted to bicyclic β-lactams by the photolytic reaction of molybdenum carbene complexes. Oxazolines were considerably less reactive and produced only low yields of β-lactam product and an equivalent amount of the corresponding oxazinone, incorporating two (MeO)(Me)C(CO) groups.     

Cycloadditions and annulations of transition metal carbene complexes

The synthetic aspects of several reactions from the multifaceted chemistry of Fischer carbene complexes are examined. Their benzannulation reactions with acetylenes are utilized in the synthesis of anthracyclinones via two approaches which differ by beginning at opposite ends of the molecule with either an aryl or an alkenyl substituted chromium carbene complex. The latter has been employed in a formal synthesis of daunomycinone. The Diels-Alder reactions of ,β-acetylenic chromium carbene complexes provide for a facile entry into substituted cyclohexenyl chromium carbene complexes that are subsequently employed in benzannulation reactions. These tandem cycloaddition/annulation reactions are incorporated into model studies for the synthesis of anthracyclinones and wentilactone A. Their potential is also demonstrated for coupling to yet a third reaction of organochromium compounds ; aromatic nucleophilic substitutions on arene chromium tricarbonyl complexes. The annulations of β,β-disubstituted alkenyl complexes provides for a regio- and stereoselective synthesis of 2,4-cyclohexadienones under neutral conditions at near ambient temperatures.     

Iron in the service of chromium: the ortho-benzannulation of trans,trans-dienyl Fischer carbene complexes

Chromium Fischer carbene complexes with trans,trans-dienyl substituents on the carbene carbon will react with diiron nonacarbonyl to give 2-alkoxycyclohexa-2,4-dienone iron tricarbonyl complexes and/or 2-alkoxyphenols in excellent yields. In the presence of silica gel or base, the cyclohexadienone complex will suffer loss of the iron and aromatization to give 2-alkoxyphenols. The formation of 2-alkoxyphenols from dienyl chromium carbene complexes is a known process (ortho-benzannulation) that only occurs with certain cis,trans-dienyl complexes. Control experiments show that trans,trans-dienyl chromium carbene complexes do not undergo conversion to 2-alkoxyphenols in the absence of an iron source. The process most likely occurs either via coordination of the dienyl unit in the chromium carbene complex to an iron tricarbonyl group and then loss of the chromium or via direct trans-metalation of the carbene ligand to give an iron carbene complex and then internal coordination to the dienyl unit such that cis to trans isomerization of the alpha,beta-double bond occurs.     

Microwave-assisted solid-phase Dötz benzannulation reaction: a facile synthesis of 2,3-disubstituted-1,4-naphthoquinones

A microwave-assisted solid-supported Dötz benzannulation of chromium carbene complexes with various alkynes has been developed. The oxidative cleavage of the resulting resin-bound 1,4-naphthols affords 2,3-disubstituted-1,4-naphthoquinone derivatives in good to moderate yields with high purities.     

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.     

Electrospray mass spectra of group 6 (Fischer) carbenes in the presence of electron-donor compounds

Fischer carbene complexes 1-7 are not ionized under standard electrospray ionization (ESI) conditions. We report here that unsaturated chromium and tungsten (Fischer) carbene complexes can be ionized in an electrospray ion source in the presence of electron-donor compounds such as hydroquinone (HQ) or tetrathiafulvalene (TTF). The addition of these compounds, which seem to act as electron transfer agents, permits the recording and study of their ESI mass spectra in the negative mode of detection. Both chromium and tungsten(0) carbene complexes undergo in the first fragmentation stage a double simultaneous decarbonylation process.     

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.     

Synthesis and cyclic voltammetry of some new metal carbene substituted cyclopentadienyliron half sandwich complexes

The syntheses of a number of cyclopentadienylcarbene iron half sandwich complexes are described. In addition to their spectroscopic characterization an X-ray crystal structure analysis is provided. The complexes prepared include chromium, molybdenum, and tungsten carbene complexes. The dicarbonyliron unit is substituted by benzyl, butyl or trimethylsilylmethyl groups. In two cases tetrametallic dimeric complexes connected by a propyl chain are presented. The reaction of the formylcyclopentadienyliron complex with a chromium carbene complex provided a vinylogous representative. Cyclic voltammetry was performed, and the data obtained are discussed in comparison to similar ferrocene based complexes.     

Reactions of Complex Ligands. Part 107 Densely Substituted Hydroquinoid Phenanthrene and Triphenylene Cr(CO)3 Complexes: Chromium‐Templated Synthesis and Molecular Structure

Densely substituted hydroquinoid phenanthrene ( 10 – 18 ), acephenanthrene ( 19 ), and triphenylene chromium tricarbonyl complexes ( 20 – 22 ) have been prepared via benzannulation of naphthalenyl ( 1 – 7 ), acenaphthenyl ( 8 ) and phenanthrenyl carbene complexes ( 9 ), respectively. The naphthalenyl, acenaphthenyl and phenanthrenyl carbene complexes 1 – 9 were obtained in 52–88 % yield starting from commercially available bromoarenes by dehalolithiation, addition of hexacarbonyl chromium to the lithioarene and O‐alkylation of the resulting acyl chromates with trimethyloxonium tetrafluoroborate (Fischer route). The benzannulation of the aryl carbene complexes (either with 3‐hexyne / (t‐butyl)dimethylsilyl chloride or with (t‐butyl)dimethylsilylethyne) allowed the regiospecific synthesis of the oligocyclic hydroquinoid arene tricarbonyl chromium complexes 10 – 22 in 44–94 % yield thus providing a two‐step synthesis with overall yields of 18 ‐ 80 %. Under the kinetic reaction conditions used the metal atom is exclusively coordinated to the persubstituted terminal hydroquinoid ring. The molecular structures of phenanthrene complexes 10 , 12 – 14 , and 16 , acephenanthrene complex 19 , and triphenylene complexes 20 and 21 in the solid state have been determined by X‐ray crystallography. The carbonyl ligands either adopt an eclipsed ( 10 , 12 , 14 , 16 , 19 , 20 ) or staggered ( 13 , 21 ) exo‐conformation pointing away from the center of the phenanthrene, acephenanthrene and triphenylene ligands, respectively. The coordination of the metal atom to the hydroquinoid ring is unsymmetric with the largest metal‐carbon distances found between the chromium atom and one bridgehead carbon and the ring carbon atom bearing the bulky (t‐butyl)dimethylsilyloxy (TBDMSO) substituent.     

Pd-catalyzed inter- and intramolecular carbene transfer from group 6 metal-carbene complexes.

The use of group 6 metal-carbene complexes in inter- and intramolecular carbene transfer reactions has been studied. Thus, pentacarbonyl[(aryl)(methoxy)carbene]chromium(0) and tungsten complexes, 10, efficiently dimerize at room temperature in the presence of diverse Pd(0) and Pd(II)/Et(3)N catalysts. The effect of additives (PPh(3), AsPh(3), or SbPh(3)) on the nature and the isomeric ratio of the reaction products is negligible. The nature of the reaction products is more catalyst-dependent for metal carbenes 12 bearing alkyl groups attached to the carbene carbon. In these cases, either carbene ligand dimerization or beta-hydrogen elimination reactions are observed, depending on the catalyst. The carbene ligand dimerization reaction can be used to prepare conjugated polyenes, including those having metal moieties at both ends of the polyene system, as well as enediyne derivatives. The intramolecular carbene ligand dimerization of chromium bis-carbene complexes 28 and 30 allows the preparation of mono- and bicyclic derivatives, with ring sizes from six to nine members. For bis-carbene derivatives the beta-hydrogen elimination reaction is inhibited, provided that both metal centers are tethered by an o-xylylene group. Other alkyl complexes 32 form new mononuclear carbene complexes 37 or decompose to complex reaction mixtures. The results obtained in these reactions may be explained by transmetalation from Cr(0) to Pd(0) and the intermediacy of Pd-carbene complexes. Aminocarbene-chromium(0) complexes 15, need harsher reaction conditions to transfer the carbene ligand, and this transfer occurs only in the presence of deactivated olefins. The corresponding insertion/hydrolysis products 48 resulted in these cases. A catalytic cycle involving transmetalation from a chromacyclobutane to a palladacyclobutane is proposed to explain these results.     

New Fischer carbene complexes of rhodium(i): preparation and 2-cyclopentenone ring synthesis by annelation to alkynes

A new type of metal carbene complexes of group 9, specifically a cationic Fischer carbene of rhodium(I), has been synthesized from chromium carbene complexes via double transfer of carbene and CO ligands. These complexes reveal a different reactivity than other transition metal carbenes, including their chromium precursors, toward neutral and electron-poor alkynes, giving selectively polysubstituted cyclopentenones.     

Chromene chromium carbene complexes in the syntheses of naphthopyran and naphthopyrandione units present in photochromic materials and biologically active natural products

The carbene complex 5-(2,2-dimethyl-2H-chromene)methoxylmethylene chromium pentacarbonyl will undergo a benzannulation reaction with phenylacetylene, 1-pentyne, 3-hexyne, and trimethylsilylacetylene to give 7-hydroxy-10-methoxy-3H-naphtho[2.1-b]pyrans as the primary product. These compounds are difficult to obtain pure due to their sensitivity to air. If the benzannulation reaction is performed in conjunction with protection of the phenol function at C-7, then good to excellent yields of 7-alkoxy-10-methoxy-3H-naphtho[2.1-b]pyrans are afforded. If the 7-hydroxy products are captured by triflic anhydride, then the resulting aryl triflate can be used to access 3H-naphtho[2.1-b]pyrans bearing C-7 carbon substituents. The 7-hydroxy products can be oxidized to 3H-naphtho[2,1-b]pyran-7,10-diones which are stable. The chromenyl carbene complex reacts with 1,6-bis(triisopropylsilyl)-1,3,5-hexatriyne to give a 2,3-dihydro-2,2-dimethylbenzo[de]chromene, a product type that has not been seen before in the reaction of Fischer carbene complexes with alkynes. A mechanism is proposed for this process that involves alpha,beta-hydride elimination from a chromacyclobutane intermediate. Chromenyl tungsten complexes react with alkynes to give products that result from cyclization without CO insertion.     

Dichotomy within 1,4-addition of organolithium and Grignard reagents to α,β-unsaturated Fischer alkoxycarbenes: A new synthesis of Fischer carbenes

The reaction of organolithium and Grignard reagents with pentacarbonyl[(ethoxy)(2-phenylethenyl)carbene]chromium(0) gave, after the quenching of the initially formed product of the 1,4-addition, different products depending on the organometallic and quenching reagents used. The addition of organolithiums, followed by a work-up with acid (AcOH or HCl), afforded the corresponding carbene complexes. In contrast, quenching the reaction mixture with ethanol led to the stereoselective formation of (Z)-enol ethers. The usage of Grignard reagents led to the formation of the carbene complexes regardless of which quenching reagent was used.     

Chromium(0)-rhodium(I) metal exchange: Synthesis and X-ray structure of new Fischer (NHC)carbene complexes of rhodium(I)

An easy approach to Fischer (NHC)carbene complexes of rhodium(I) 3 from methoxy- and aminocarbene complexes of chromium 1 and (NHC)(cod)RhCl (2) is described. The process involves the transfer of the carbene unit and a CO ligand from chromium to rhodium. The X-ray analysis is provided for 3d and the preliminary results on their thermal stability and reactivity toward alkynes and allenes are also reported.     

Reaction of α,β-unsaturated Fischer carbene complexes with allyl alkoxide

Optically enriched homo-binuclear Fischer chromium carbene complexes with planar chiral arene chromium complexes gave α-allyl β-arylpropionates up to 97% ee by reaction with allyl alkoxide and subsequent photo-oxidative demetalation. The chiral hetero-binuclear tungsten carbene complexes afforded anti α-allyl β-hydroxy β-arylpropionates as a major product up to 92/8 dr by the same reaction sequence. High diastereoselectivity in these reactions is contributed to the planar chirality of the arene chromium complex, even though the reaction was carried out under vigorous basic media. The reaction products, α-allyl β-arylpropionates were derived by 1,3-M(CO)₅ shift and subsequent [3,3]-sigmatropic rearrangement. Also, the corresponding chromium-uncomplexed α,β-unsaturated Fischer carbene complexes afforded α-allyl β-arylpropionates under the same conditions. Formation of β-allyl β-arylpropionates via 1,2-M(CO)₅ shift followed by [3,4]-sigmatropic rearrangement was not observed in both reactions of chromium-coordinated and the corresponding chromium-uncoordinated α,β-unsaturated Fischer carbene complexes with allyl alkoxide in the presence of base.     

Efficient synthesis of highly functionalized indazoles and 2,3-dihydro-1,2-benzisoxazoles by reaction of stable Fischer dienyl carbenes and isocyanides

A range of stable chromium and tungsten Fischer dienyl carbenes have been prepared by [3+2] cycloaddition of alkenylethynyl carbene complexes with nitrones or diazoalkanes. Treatment of these systems with isocyanides gives entry to highly functionalized 2,3-dihydro-1,2-benzisoxazoles and indazoles in a completely regioselective fashion, under mild conditions, and with high yields. This methodology can be also applied to the preparation of analogous naphthoisoxazoles starting from arylethynyl Fischer complexes. Reductive cleavage of the isoxazole moiety in the prepared heterocycles also enables the efficient synthesis of highly substituted p-aminophenols.     

Generation of reactive species by one-electron reduction of Fischer-type carbene complexes of group 6 metals and their use for carbon-carbon bond formation

Carbon-carbon bond-forming reactions mediated by one-electron reduction of Fischer-type carbene complexes of Group 6 metals were investigated. In the case of aryl- or silylcarbene complexes of tungsten, the anion radical species generated by one-electron reduction smoothly underwent addition reaction to ethyl acrylate. One-electron reduction of alpha,beta-unsaturated carbene complexes afforded biscarbene complexes by dimerization of the corresponding anion radical species at the position gamma to the metal center. In contrast, one-electron reduction of chromium phenyl- or alkylcarbene complexes gave, via carbonyl insertion, alpha-methoxyacylchromate complexes, which further underwent conjugate addition to various electron-poor olefins to give the corresponding alpha-methoxyketones.