Valuable New Cyclohexadiene Building Blocks from Cationic η⁵‐Iron–Carbonyl Complexes Derived from a Microbial Arene Oxidation Product

Abstract

Biooxidation of benzoic acid by Ralstonia eutropha B9 provides an unusual cyclohexadiene carboxy diol that contains a quaternary stereocentre. Tricarbonyliron derivatives of this chiron, on treatment with acid, give two isomeric η(5)-cyclohexadienyl complexes as observed by NMR spectroscopy. Both of these can be subjected to the addition of nucleophiles to provide isomeric cyclohexadiene complexes with new substituent patterns, several of which have been characterised crystallographically. De-metallation of these provides a versatile library of cyclohexadiene building blocks, the utility of which is demonstrated by formal syntheses of oseltamivir. The mechanism of product formation and its stereochemical implications are discussed, as are the procedures undertaken to establish the enantiopurity of a representative cyclohexadiene product.

Selective Iron-Mediated C- and O-Addition of Phenolic Nucleophiles to a Cyclohexadiene Scaffold Using Renewable Precursors

“…We opted for the second of these strategies in the preparation of the initial cationic iron complex. Once formed, the complex can react with a wide range of nucleophiles, including alcohols, amines, amides, azide, hydride, carbamate, thiols, enolates and malonates, allyl silanes, electron rich aromatics and heterocycles, organocuprates, organolithium reagents, organozinc reagents, Grignard reagents, phosphines, phosphites, and halides …”

“…The precursor for complex 1 , diene 2 , could be synthesized via a cycloaddition reaction between an acrylate ester and furan, both available from biorenewable sources (Scheme ). − Alternatively, structurally similar dienes can also be made via biocatalytic cis -dihydroxylation of aromatic molecules, and these have been exploited using iron carbonyl chemistry. ,− …”

“…Subsequent nucleophilic addition then takes place stereoselectively, to the opposite face of the coordinated iron carbonyl moiety. , Other advantages of this methodology are the mild reaction conditions used, and the fact that the tailoring of reaction conditions for each class of nucleophile is generally not required. Applications of this method include the synthesis of natural products, such as siculinine and clausine K; antiviral compounds, such as oseltamivir phosphate (Tamiflu); , probes for infrared spectroscopy; as well as parallel synthesis applications . While anilines have been widely shown to react as nucleophiles via selective C - or N -addition, − the analogous reactivity of phenols has not been examined to the same extent. , Considering also that phenols can potentially be sourced from lignin or other biomass sources, we have investigated their application as nucleophiles using the cationic iron carbonyl methodology.…”

Palladium Catalyzed Stereoselective Arylation of Biocatalytically Derived Cyclic 1,3-Dienes: Chirality Transfer via a Heck-Type Mechanism

“…However, benzoate dioxygenase (BZDO), expressed by R. eutropha B9, transforms benzoic acid with complementary selectivity, affording ipso / ortho dihydroxylated product 1 as a single enantiomer (Scheme a). Compound 1 has been subjected to various transformations such as oxidations and acetalization and been used for preparing natural products and pharmaceuticals . One diversification approach could involve metal-catalyzed cross-coupling of the diene sp 2 -carbons .…”