Carbon−Carbon and Carbon−Heteroatom Bond Formation on Solid Phase Using Cationic Iron Carbonyl Complexes

Abstract

Iron-mediated methodology for the formation of carbon-carbon and carbon-heteroatom sp(3) bonds on solid phase has been developed. Treatment of a polymer-bound cationic iron cyclohexadienyl complex with carbon, oxygen, nitrogen, and phosphorus nucleophiles, followed by cleavage with amines and subsequent decomplexation, yielded 18 different cyclohexadienoic acid amides of high purity. [reaction: see text]

Transition metals in organic synthesis: Highlights for the year 2005

“…Reactions of polymer-bound cationic cyclohexadienyliron tricarbonyl complexes with nucleophiles were described [1554]. Nucleophilic addition of arylamines to cationic 2-methoxy-cyclohexadienyliron tricarbonyl complex followed by oxidative cyclization was used in synthesis of 7-methoxy-Omethylmukonal, clausine H, K, and O [1555].…”

An iron carbonyl approach to the influenza neuraminidase inhibitor oseltamivir

“…2) via (1) employing nucleophiles (Nu) other than BOC-NH 2 for the nucleophilic attack on the iron carbonyl cation; (2) using an activated ester of 3 (e.g., R 1 = p-nitrophenyl), which after oxidative decomplexation can be converted to different esters/amides; (3) using alternate alcohols (R 3 ) or other nucleophiles in the aziridine ring-opening; (4) varying the aziridine acylating reagent (R 2 ). Studies concerning the versatility of the iron carbonyl chemistry to such a diversity oriented approach have been initiated both employing polymer-bound reagents 16a and on solid phase, 22 and results from further investigations toward oseltamivir analogues will be reported in due course.…”

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

“…Once formed, the complex can react with a wide range of nucleophiles, including alcohols, 19 amines, 26 amides, 27 azide, 16 hydride, 16 carbamate, 17 thiols, 28 enolates 26 and malonates, 29 allyl silanes, 30 electron rich aromatics 31 and heterocycles, 30 organocuprates, 26 organolithium reagents, 20 organozinc reagents, 32 Grignard reagents, 26 phosphines, 33 phosphites, 34 and halides. 35 At the outset of our investigation, we aimed to perform the selective C-and O-addition of phenolic nucleophiles to cationic η 5 iron carbonyl cyclohexadienyl complex 1 (Scheme 2).…”

“…Applications of this method include the synthesis of natural products, such as siculinine 14 and clausine K; 15 antiviral compounds, such as oseltamivir phosphate (Tamiflu); 16,17 probes for infrared spectroscopy; 18 as well as parallel synthesis applications. 19 While anilines have been widely shown to react as nucleophiles via selective C-or Naddition, 20−23 the analogous reactivity of phenols has not been examined to the same extent. 18,24 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.…”