Transition metal mediated asymmetric synthesis VIII. Preparation of tricarbonyl(cyclohexadienyl)iron(1 +) cations with oxygenated side-chains

Tricarbonyl(cyclohexadiene)iron complexes bearing side-chain oxygen functionality and have been prepared and their reactions with triplenylcarbenium ion reagents examined. In the case of ethers, no hybride abstraction was observed and deoxygenation was completely dominant. An acyl-substituted complex also proved unsatisfactory as a substrate for hydride abstraction. Thallium oxidation was found to provide a successful alternative, affording the expected alkoxyethyl-substituted dienyl cations. The reaction of the acyl-substituted complex with thallium tristrifluoroacetate was less efficient, but also produced the acyl cation in a better. though still low, yield.     

Synthetic studies relating to acetylergosterol-(tricarbonyl)iron

Acetylergosterol(tricarbonyl)iron has been prepared in good yield using benzylideneacetone(tricarbonyl)iron. The steroidal complex may be hydroborated or subject to osmolysis, to yield potential vitamin D precursors.     

Reactivity of acyclic (pentadienyl)iron(1+) cations: synthetic studies directed toward the frondosins

A short, 4-step route to the scaffold of frondosin A and B is reported. The [1-methoxycarbonyl-5-(2',5'-dimethoxyphenyl)pentadienyl]Fe(CO)(3)(+) cation was prepared in two steps from (methyl 6-oxo-2,4-hexadienoate)Fe(CO)(3). Reaction of this cation with isopropenyl Grignard or cyclohexenyllithium reagents affords (2-alkenyl-5-aryl-1-methoxycarbonyl-3-pentene-1,5-diyl)Fe(CO)(3) along with other addition products. Oxidative decomplexation of these (pentenediyl)iron complexes, utilizing CuCl(2), affords 6-aryl-3-methoxycarbonyl-1,4-cycloheptadienes via the presumed intermediacy of a cis-divinylcyclopropane.     

Stereochemical leakage mechanisms for tricarbonyl(dienyl)iron cations

ψ-Endo to ψ-exo leakage during solvolysis of a ψ-endo-dienol—Fe(CO)₃ dinitrobenzoate ester does not proceed via a syn, syn-cis-dienyl—Fe(CO)₃ cation. The most probable leakage mechanism involves non-stereospecific ionization of the dinitrobenzoate ester. syn,syn-cis-Dienyl—Fe(CO)₃ cations are formed from ψ-exo-dienol—Fe(CO)₃ complex during chromatography on grade I neutral alumina.     

Synthesis and reactivity of tricarbonyl(1-methoxycarbonyl-5-phenylpentadienyl)iron(1+) cation

Tricarbonyl(1-methoxycarbonyl-5-phenylpentadienyl)iron(1+) hexafluorophosphate (7) was prepared in two steps from tricarbonyl(methyl 6-oxo-2,4-hexadienoate)iron. While addition of carbon and heteroatom nucleophiles to 7 generally occurs at the phenyl-substituted dienyl carbon to afford (2,4-dienoate)iron products, the addition of phthalimide proceeded at C2 to afford a (pentenediyl)iron product (18). Complex 18 was structurally characterized by X-ray diffraction analysis.     

Synthetic studies with iron carbonyl complexes. Versatile synthesis of olefinic side-chains to a tricarbonyl(cyclohexadiene)iron(0) ring

Tricarbonyl(cyclohexadiene)iron(0) complexes bearing olefinic side-chains at the 2- or the 5-position have been prepared by a versatile route. Terminal olefins are isomerised to internal isomers. The presence of a methoxy substituent at the 2-position prevents isomerisation of the coordinated diene into conjugation with the olefin, so locking the side-chain at the 5-exo-position.     

Generation of trans-π-pentadienyliron tricarbonyl cations from protonation of (trans,trans-2,4-hexadienal)iron tricarbonyl

Protonation of (trans,trans-2,4-hexadienal)iron tricarbonyl, (V) has been shown to yield two trans-pentadienyliron cations, an s-cis form, (VIa) and an s-trans form (VIb), in an approximately equal ratio. This ratio represents a kinetically controlled product distribution and indicates that the original unprotonated aldehyde complex was present in equally populated s-cis and s-trans forms. Both trans ions, (VIa) and (VIb) isomerize to the cis ion (VIIb), ΔF^ne = 18.5 kcal/mol. From an analysis of the kinetics and NMR line widths it is clear that the barrier to rotation about the C₁C₂ bond in (VI) is at least 15 kcal/mol and probably considerably exceeds this number. At temperatures below −100° the OH protons of (VIa) and (VIb) can be observed owing to slow exchange at this temperature. Chemical shifts of these protons indicate extensive charge delocalization.     

Optically active 1-Alkoxy-2,2-bis(trifluoromethyl)aziridines

1-Alkoxy-2,2-bis(trifluoromethyl)aziridines containing an ester group in the position of the alkoxy substituent undergo nucleophilic substitution (ammonolysis and hydrolysis) with retention of the aziridine ring. The corresponding carboxylic acids, which were separated to give the antipodes with an optical purity of 95% through the diastereomeric salts with R- and S--phenylethylamine, were obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1495–1500, November, 1980.     

Reactivity of (bicyclo[5.1.0]octadienyl)iron(1+) cations: application to the synthesis of cis-2-(2'-carboxycyclopropyl)glycines

The addition of carbon and heteroatom nucleophiles to (bicyclo[5.1.0]octadienyl)Fe(CO)(2)L(+) cations 5 or 8 (L = CO, PPh(3)) generally proceeds via attack at the dienyl terminus on the face of the ligand opposite to iron to generate 6-substituted (bicyclo[5.1.0]octa-2,4-diene)iron complexes (11 or 13). In certain cases, these products are unstable with respect to elimination of a proton and the nucleophilic substituent to afford (cyclooctatetraene)Fe(CO)(2)L (4 or 7). Decomplexation of 13f, arising from addition of phthalimide to 8, gave N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (19). Oxidative cleavage of 19 (RuCl(3)/NaIO(4)) followed by esterification gave the cyclopropane diester 22, which upon hydrolysis gave cis-2-(2'-carboxycyclopropyl)glycine (CCG-III, 18) (eight steps from 4, 43% overall yield). This methodology was also utilized for preparation of stereospecifically deuterated CCG-III (d-18) and optically enriched (-)-18. Deprotonation of 22 resulted in cyclopropane ring opening to afford the benzoindolizidine (23).     

Nucleophilic addition to (3-methylpentadienyl)iron(1+) cations: counterion control of regioselectivity; application to the enantioselective synthesis of 4,5-disubstituted cyclohexenones

The regioselectivity of malonate addition to (3-methylpentadienyl)Fe(CO)3+ is controlled by the malonate-counterion association. The Li+ salt of malonate proceeds via C1 nucleophilic attack to afford the 1,3Z-diene complex 4a, while reaction of highly dissociated ion pair (i.e., Na+ or Li+/12-crown-4) salt proceeds at the C2 internal carbon to eventually afford cyclohexenone products 6. Reaction of 1a with the sodium salt of bis(8-phenylmenthyl)malonate proceeds with excellent diastereocontrol to afford a single diastereomeric cyclohexenone.     

Synthesis and structural characterization of tricarbonyl 1-azahexa-1,3,5-triene iron(0) complexes

Transition Metal Chemistry -     

Diastereoselective spiroketalization: stereocontrol using an iron(0) tricarbonyl diene complex

It has been demonstrated that an element of planar chirality can influence the formation of an adjacent spiroketal stereocenter. Appropriately functionalized enantiomerically pure 1- and 2-sulfinyl 1,3-dien-5-ones and their corresponding iron(0) tricarbonyl complexes (7, 17) have been prepared, and the derived spiroketals (8, 18) are made in good to excellent diastereoselectivity. A preliminary exploration of the combined effects of planar and central chirality upon the diastereoselectivity revealed matched and mismatched combinations (14).     

Optically active N-(α-phenylethyl) amides of isomeric 1-phenylpyrazolecarboxylic acids

The rotatory dispersion of the (–)-N-(-phenylethyl)amides of the isomeric 1-phenylpyrazolecarboxylic acids depends on the position of the amido group in the pyrazole ring. The difference in the spectropolarimetric behavior of the isomers can be used to determine the position of a substituent in the pyrazole ring. The phenylpyrazole group induces a pronounced Cotton effect in the region of its absorption if there is conjugation between the benzene and pyrazole rings. The analogy in the spectropolarimetric behavior of the (–)-N-(-phenylethyl)amides of 1-phenylpyrazole-4-carboxylic and benzoic acids attests to the aromatic character of the 4 position in the pyrazole ring, which is also well known from its chemical properties.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1569–1572, November, 1970.     

Diene(tricarbonyl)iron complexes linked to spirooxazolones for the synthesis of cyclopropyldihydroxyphenylalanine

Complexed cyclopropyl-3,4-dihydroxyphenylalanine (∇ DOPA) were synthesized by diazomethane cyclopropanation of the appropriate diene(tricarbonyl)iron complexes linked to azlactones. Opening of the oxazolone ring by treatment with MeOH and DMAP gave the corresponding methyl esters. Introduction of the Boc group, cleavage of the carbamate with hydrazine provided Boc-protected cyclopropylogs of dl-dihydroxyphenylalanine.     

Synthesis of phospholipids by means of cyclic enediol pyrophosphates : Optically active monovalent and divalent cation salts of diphosphatidylglycerol (Cardiolipin)

A new method for the synthesis of the cardiolipin family of phospholipids which are characteristically located at the inner membrane of mitochondria, and particularly abundant in the heart, is described in this paper. A 1,2-diacyl-sn-glycerol, derived from stearic, palmitic, or myristic acid, is converted into the corresponding 1',3'-diphosphatidylglycerol (DPG), by means of the phosphorylating reagent di(1,2-dimethylethenylene) pyrophosphate in 29%, 23% and 25% overall yields, respectively. The synthesis involves four steps, two of which are carried out in one-flask; only one intermediate and the final product, DPG·2NH₄⁺·2H₂O, are purified, the former by silica gel, and the latter by DEAE-cellulose column chromatography. The ammonium salts are converted into metal ion salts, DPG·2Na⁺· 2H₂O, DPG·Mg²⁺ 2H₂O and DPG·Ca²⁺·2H₂O by metathesis with NaCl, MgCl₂ and CaCl₂, respectively.     

Mass spectrometry of transition metal π-complexes : VI. π-cyclopentadienyl(cyclohexadienyl)iron derivatives

Mass spectra of exo-R-cyclohexadienyl(cyclopentadienyl)iron derivatives have been studied to show that the main fragmentation routes involve stereo-selective migration of the endo-hydrogen of the cyclohexadienyl ring to the iron.