Chromium Tricarbonyl Research Articles

Solution phase peptide synthesis with ferrocenyl amino acid derivatives

We report the successful stepwise synthesis of di- and tripeptides starting from ferrocenyl amino acids in solution. This methodology is extended to the synthesis of homo- and hetero-bimetallic peptides. Using the fluorenyl-methoxy-carbonyl (Fmoc) protecting group, the ferrocenyl methyl leucine derivative 2 is obtained quantitatively as a starting material. Coupling to PG-Ala-OH (PG=protecting group, tert-butoxy-carbonyl (Boc) or Fmoc) and Boc-Met-Phe-OH yields dipeptides 3a, b and the tripeptide 5 in very good yield. The Fmoc derivative 3b can be used for further deprotection/coupling cycles and serves as a precursor for the bis(ferrocenyl) tripeptide 7 after deprotection and coupling to Fc-CH 2-Phe-OH. Coupling of Fmoc deprotected 3b to benzoic acid chromium tricarbonyl yields the hetero-bimetallic dipeptide 8 in good yield. In addition to reversible electrochemistry of the ferrocenyl group, compound 8 shows characteristic IR bands around 2000 cm −1 which enable its sensitive detection. All new compounds are completely characterized. Their constitution is established by MS and characteristic NMR spectra. Two isomers are observed at room temperature because rotation about the tertiary amide bond is slow on the NMR time scale (Δ G ‡=70±1 kJ mol −1 by VT 1H-NMR). Cyclic and square wave voltammetry experiments on the bis(ferrocenyl) tripeptide 7 do not indicate an electronic interaction between the two ferrocenyl moieties. Molecular modelling and NMR investigations do not give any indication of a rigid structure in solution but suggest a through-space distance of about 10 Å between the metal centres.

Synthesis of 1,2-Dihydro-1,2-azaborines and Their Conversion to Tricarbonyl Chromium and Molybdenum Complexes

1,2-Dihydro-1,2-azaborines (1c, 1d, and 1e) have been prepared by the reaction of the corresponding 2,3-dihydro-1H-1,2-azaborol-3-yllithium reagents (1c, 1d, and 1e). The reaction of 1e with Py3Mo(CO)3 and BF3·OEt2 affords Mo(CO)3 complex 5e, while the reaction of 1c with Cr(CH3CN)3(CO)3 affords Cr(CO)3 complex 6c. X-ray structures of 5e and 6c show that the metals are η6-bound to the 1,2-dihydro-1,2-azaborine rings.

Synthesis of (R)-{η6-[O-methyl-N-(α-methylbenzyl)hydroxyamino]benzene} chromium tricarbonyl via nucleophilic aromatic substitution of (η6-fluorobenzene) chromium tricarbonyl

Chiral hydroxylamine chromium tricarbonyl complexes may be prepared in satisfactory to reasonable yield via nucleophilic aromatic substitution of the anion derived from N,O-substituted hydroxylamines and (η6-fluorobenzene) chromium tricarbonyl. The enantiomerically pure complex (R)-{η6-[O-methyl-N-(α-methylbenzyl)hydroxyamino]benzene} chromium tricarbonyl 6a was characterised by X-ray crystallography.

Unexpected endo selectivity of conjugate nucleophilic addition to an arene-Cr(CO)3 complex: enantioselective synthesis of the diterpene 11-epi-helioporin B.

[reaction: see text]. Starting from a nonracemic planar-chiral arene tricarbonyl chromium complex, an epimer of the bioactive marine diterpene helioporin B was synthesized in a highly stereoselective fashion. The stereostructure of the product (11-epi-helioporin B) corresponds to that of other serrulatane-type natural products. In a key step of the synthesis, 2-lithioacetonitrile undergoes conjugate nucleophilic addition to an unsaturated complex. Remarkably, this addition occurs in an endo mode, i.e., from the complexed face of the pi-ligand.

Donor and acceptor properties of the chromium tricarbonyl substituent in benzylic and homobenzylic anions, cations, and radicals.

Both benzylic cations and anions are strongly stabilized by chromium tricarbonyl complexation, while benzylic radicals are largely unaffected. Density functional theory calculations were performed on primary, secondary, and tertiary benzylic species to explore the effect of substitution on the stabilizing ability of the chromium tricarbonyl moiety. Complexed 1-indanyl species were also examined to elucidate the effect of conformational restraint. It was found that the strong stabilization of benzylic anions and the slight destabilization of benzylic radicals by chromium tricarbonyl are insensitive to skeletal changes. Chromium-complexed benzylic cations, however, are highly sensitive to changes in the organic framework, with increased substitution or constriction of conformational mobility eroding the effect of the metal. 2-Indanyl species were also examined to study the effect of the chromium tricarbonyl fragment on homobenzylic species. It was found that the metal fragment stabilizes distant anions by field and inductive effects and cations by a direct interaction of the metal with the cationic carbon. Homobenzylic radicals, however, do not interact with the chromium tricarbonyl moiety and suffer a slight inductive destabilization.

Bidentate planar chiral η 6-arene tricarbonyl chromium(0) complexes: ligands for catalytic asymmetric alkene hydrosilylation

S EAr-type reactions of various heterocycles with ortho-substituted (1′ S, P)-tricarbonyl[(1-chloroethyl)-η 6-benzene]chromium(0) derivatives lead to a family of novel planar chiral bidentate and pseudo-bidentate ligands. Two members of this family (1′ S, P)-2-[1′-tricarbonyl-η 6-((2″- P, P-diphenylphosphino)phenyl)-chromium(0))ethyl] furan and thiophene show high activity and enantioselectivity in the Pd-catalyzed hydrosilylation of styrenes.

Stereoselective synthesis of the axially chiral A-B ring system of vancomycin utilizing a planar chiral arene chromium complex.

[reaction: see text] The axial biaryl ring system of vancomycin was stereoselectively synthesized by utilizing a planar chiral tricarbonyl(arylhalide)chromium complex. Both enantiomers of the planar chiral (arylbromide)chromium complexes, (+)-9 and ent-(-)-9, can be stereoselectively transferred to an absolutely identical key intermediate 23 for the vancomycin A-B ring system by the diastereoselective Suzuki-Miyaura cross-coupling reaction as key step.

Synthesis of benzocyclobutadiene trimers and all- Z-tribenzo[12]annulene. A new family of concave π-systems

Nickel-catalyzed oligomerization of trans-1,2-dibromobenzocyclobutene formed cyclic dimers and trimers. Upon heating, the major anti-cyclic trimer afforded a cage compound, whereas the minor syn-trimer produced all- Z-tribenzo[12]annulene. Dehydrogenation of the anti-trimer with DDQ resulted in the formation of an indenoazulene derivative, and a similar reaction of the syn-trimer yielded a bowl-shaped system. All- Z-tribenzo[12]annulene was also synthesized using a stepwise route starting from o-diiodobenzene and o-ethynylbenzyl alcohol, the overall yield being 22%. All- Z-tribenzo[12]annulene behaved like π-prismand and formed chromium(0) tricarbonyl and silver(I) complexes.

The tricarbonylchromium template for stereocontrol in radical reactions of arenes.

Chromium tricarbonyl complexed aryl aldeyhydes and ketones underwent Sm(II)-promoted radical lactone formation in the presence of alpha,beta-unsaturated esters to produce diastereomerically pure lactones in good yields. The completely diastereoselective lactone formation involves capture of the benzylic ketyl radical by the ester anti to the chromium tricarbonyl moiety. The relative stereochemistry of the lactone and chromium tricarbonyl moieties was proven by X-ray crystallography and supports the proposed mechanism. Enantiopure chromium tricarbonyl complexed arenes afforded single enantiomers when subjected to Sm(II)-promoted radical lactone formation condiditions. The enantio- and diastereomerically pure chromium tricarbonyl complexed lactones were subsequently treated with BF3.OEt2 to generate a mixture of diastereomers via Lewis acid promoted chromium tricabonyl directed cationic rearrangement. The diastereomers were separated and individually decomplexed with I2 to afford both of the corresponding chromium-free enantiomerically pure lactones starting from a single enantiomerically pure chromium tricarbonyl complex.

Intramolecular Pd-catalyzed carbocyclization, Heck reactions, and aryl-radical cyclizations with planar chiral arene tricarbonyl chromium complexes.

(o-butenylhalobenzene)Cr(CO)(3) complexes were synthesized by diastereoselectve allylmetal additions to o-halo benzaldehyde complexes. The addition of allylZnBr proved particularly convenient and clean. The complexes undergo intramolecular Pd-catalyzed cyclizations (Heck reactions) without decomplexation and/or alkene isomerization. In complexes with a benzylic stereogenic center, the diastereoselectivity of the alkene carbopalladation is governed by the planar chirality of the complex rather than by the benzylic stereogenic center in the side chain. This reaction outcome can be rationalized by the geometry of the arene plane vs that of the Pd coordination plane in the transition step of the alkene carbopalladation step. An alternative cyclization procedure involves the generation of a Cr(CO)(3)-coordinated arene radical from the bromo and iodo complexes. Intramolecular aryl-radical cyclization affords indan complexes. The transition metal arene pi-bond remains intact during this process.

Tricarbonyl(h6-Arene)Chromium(0) Complexes as Chiral Auxiliaries: Asymmetric Synthesis of b-Lactones

The optically pure tricarbonyl(η6-2-substituted benzaldehydes)chromium are used as chiral auxiliaries in the condensation with a series of doubly lithiated carboxylic acids. The intramolecular ring closure of the obtained Cr(CO)3 complexed β-hydroxyacids affords the optically pure β-lactones in satisfactory yield.

Chiral Ancillaries in the Benzannulations of Alkoxy and Amino Carbene Complexes with Alkynes

The asymmetric benzannulation of chiral Fischer car- bene complexes were investigated with a series of complexes bear- ing either chiral alcohols or chiral amines at the heteroatom stabilizing substituent. A set of seven alkenyl complexes and one aryl complex were prepared from five chiral alcohols; (1S,2R,5S)- (+)-menthol, (1R,2S)-(−)-trans-2-phenylcyclohexanol, (±)-trans-2- methylcyclopentanol, (±)-isoborneol, and (−)-8-phenylmenthol. The reaction of all seven of the alkenyl complexes with pent-1-yne and 3,3-dimethylbut-1-yne gave (arene)chromium tricarbonyl com- plexes with very low asymmetric inductions (0−20% de). The phe- nyl carbene complex derived from (+)-menthol gave good asymmetric induction with 3,3-dimethylbut-1-yne as had been pre- viously reported, but the reaction with pent-1-yne gave lower induc- tion and a much lower chemical yield. Alkenyl complexes bearing prolinol derivatives as the heteroatom stabilizing substituent also gave very low induction in reactions with pent-1-yne and this held true for both E- and Z-isomers of these complexes. An alkenyl car- bene complex derived from the C-2 symmetrical amine, 3,5-dime- thylmorpholine, reacted with pent-1-yne to give moderate yields of the (arene)chromium tricarbonyl complex but only in 10% de. High asymmetric inductions were observed for the cyclohexadienone an- nulation of atropisomeric 2-(N-methyl-3-methylindolyl) carbene complexes prepared from the chiral auxiliary, (4R,5S)-5-phenyl-4- methylimidazolidinone. Each atropisomer gives a single and differ- ent diastereomer of the same 4H-carbazol-4-one where it is the chiral axis of each atropisomer that controls the sense of induction and not the chirality of the auxiliary. Thus it is likely that these com- plexes, unlike all of the others examined in this work, react with acetylenes in a process in which the chiral auxiliary is not free to ro- tate about the carbene carbon in any of the reaction intermediates leading to product formation.

Molecular design using electrostatic interactions. Part 3: Synthesis and properties of chromium tricarbonyl complexes of cationic mono-, di- and tripodands

Water soluble polycationic arene host systems have been prepared, using DABCO as the source of the cationic charge, in which the arene group is complexed to chromium tricarbonyl. Association constants for two salts were determined by NMR methods and the role of IR carbonyl band of the Cr(CO) 3 moeity as reporter group explored. The different properties of the salts in the solid state, in water and, where possible, organic solvents were examined and it was found that the nature of the anion had no effect on the carbonyl IR band in water, although it did in the solid state.

Diastereoselective Transformation of Arenes into Highly Enantiomerically Enriched Substituted Cyclohexadienes

Sequential addition of a C-nucleophile and a C-electrophile to enantiomerically pure arene tricarbonyl chromium complexes 3a,b, 6, and 8b, containing aryl bound chiral oxazoline, SAMP-hydrazone and chiral imine auxiliaries affording substituted cyclohexadienes. C-Nucleophiles included alkyl-, vinyl-, and phenyl-lithium reagents. C-Electrophiles included methyl iodide, allyl bromide, benzyl bromide, and propargyl bromides. The 1,3-cylohexadienes were obtained with a 1,5,6-substitution pattern. The results are consistent with a diastereoselective exo-nucleophilic addition to an ortho position of the complexed arene, followed by addition of the electrophile to the metal center. With allyl, ben-zyl, and propargyl groups, direct reductive elimination then yielded trans-5,6-substituted products. With methyl iodide, reductive elimination was preceded by CO insertion and acetyl cyclohexadienes were formed exclusively whose in situ deprotonation/alkylation gave products in which three C-substituents had been added across an arene double bond with complete regio- and stereocontrol. The two path-ways reflect migratory aptitude to carbonylation. An X-ray structure determination of the phenyl oxazoline complex 3a allowed a rationalization of observed diastereoselectivity. Asymmetric induction was very high with the oxazoline and the SAMP-hydrazone complexes (>90% de) whereas the chiral benzaldehyde imine complex 8b afforded the substituted diene aldehydes in moderate enantiomeric purity (34-58% ee). Changing the reaction medium from THF to toluene in reactions with 8b resulted in products of the opposite chirality.

Enantioselective Synthesis of Novel Enantiopure Phosphines via Reaction of a Tricarbonyl(η6-arene)chromium Complex with a Chiral Lithium Amide Base

A range of novel phosphorus-containing tricarbonyl(η6-arene)chromium complexes has been synthesised via the enantioselective ortho-metallation approach using a chiral lithium amide base. Initial asymmetric reaction of a phosphine oxide complex allows the preparation of silyl- or stannyl-substituted products in ca. 73% ee, which then allows the preparation of other phosphine derivatives in very high ee (>95%) following phosphine reduction and enantiomeric enrichment.

Electron Redistribution of Aromatic Ligands in (Arene)Cr(CO)3Complexes. Structural (Bond-Length) Changes as Quantitative Measures

Arene ligands experience significant ring expansion upon coordination with chromium tricarbonyl, as established by precise X-ray crystallographic analyses of various (η6-arene)Cr(CO)3 complexes. Such changes in ligand structures result from the charge (electron) redistribution, Ar+−Cr-, upon arene coordination, since they are closely related to those found in the intermolecular 1:1 complexes of the corresponding series of arenes with nitrosonium cation (NO+). The latter are prototypical examples of charge-transfer complexes as described by Mulliken. As such, they show enhanced degrees of charge (electron) transfer that approach unity, which is confirmed by quantitative comparison with the structural changes measured in the one-electron (oxidative) transformation of electron-rich arene donors (Ar) to the cation-radicals (Ar•+). Such a charge redistribution thus readily accounts for the enhanced reactivity to nucleophilic attack of the arene ligand in various ArCr(CO)3 complexes and related transition-metal/arene analogues.

Free and Cr(CO)3-Complexed Aminophosphine Phosphinite Ligands for Highly Enantioselective Hydrogenation of α-Functionalized Ketones

The synthesis and characterization of a new series of aryl- and cycloalkyl-substituted aminophosphine phosphinites (1−8) obtained from the reaction of the three precursors (S)-2-hydroxymethyl azetidine, (S)-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline, and (S)-2-hydroxymethylindoline and chlorophosphines is described. The aromatic ring in (S)-2-hydroxymethylindoline has allowed the synthesis and isolation of tricarbonyl chromium complexed amino alcohols syn-10 and anti-10, which were similarly converted into the corresponding aminophosphine phosphinites 11−13, presenting a stereogenic center and a planar chirality. Ligand 5 ((S)-Cp,Cp-IndoNOP) revealed an unprecedented 31P NMR fluxional behavior related to a rotation inhibition around the P-heteroatom (N and O) bonds. These new AMPP ligands were used in the enantioselective hydrogenation of various α-functionalized ketones, i.e., dihydro-4,4-dimethyl-2,3−furandione 14, N-benzyl benzoylformamide 15, ethylpyruvate 16, and 2-(N,N-dimethyl)aminoacetophenone hydrochloride 17. The stereoelectronic effects generated by the presence of the tricarbonyl chromium moiety onto the hydrogenations have been assessed. The beneficial effect of the matching chiralities in ligand syn-12 associated with the use of the most appropriate nonchiral ligand Cl has resulted in a win of 13% of ee for the rhodium-based hydrogenation of 15. While using the most suitable new chiral AMPP ligand from this study, the four above-mentioned substrates were converted into the corresponding optically active alcohols in >99% ee (l4/5), >99% ee (15/6), 87% ee (16/5), and >99% ee (17/5), respectively.

ChemInform Abstract: Synthesis of Axially Chiral Anilides by Enantioselective Desymmetrization of Tricarbonyl(N‐methyl, N‐aroyl 2,6‐dimethylaniline)chromium Complexes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective catalysis using planar chiral η 6-arene chromium complexes: 1,2-diols as cycloaddition catalysts

A highly selective Diels–Alder catalyst has been prepared from a commercially available tetrahydronaphthalene diol. Stereocontrol is greatly enhanced by introduction of a planar chiral arene chromium tricarbonyl group, achieved by face selective complexation. The factors influencing stereoselectivity with the catalyst have been investigated and delineated. Under optimal conditions, the catalyst gives >95% e.e. and 98:2 exo: endo ratio in the cycloaddition of methacrolein and cyclopentadiene.

The first examples of ester enolate addition across a chiral (alkoxybenzene)–chromium complex π-bond with a remarkable degree of 1,5-asymmetric induction

The first examples are described wherein addition of an ester enolate to an alkoxy-substituted arene–chromium tricarbonyl complex, to afford a substituted cyclohexenone in high enantiomeric excess.