Iron Porphyrin Catalyzed N−H Insertion Reactions with Ethyl Diazoacetate

Abstract

A series of metalloporphyrin complexes were surveyed as catalysts for carbene insertion from ethyl diazoacetate into the N−H bonds of amines. Iron(III) tetraphenylporphyrin chloride, Fe(TPP)Cl, was found to be an efficient catalyst for N−H insertion reactions with a variety of aliphatic and aromatic amines, with yields ranging from 68 to 97%. Primary amines were able to undergo a second insertion when another equiv of EDA was added by slow addition. N-Heterocyclic compounds were poor substrates, giving low yields or no N−H insertion products. Competition reactions and linear free energy relationships provided mechanistic insights for the insertion reaction. The relative rates for N−H insertion into para-substituted aniline derivatives correlated with Hammett σ+ parameters. Electron-donating groups enhanced the reaction, as indicated by the negative value of ρ (ρ = −0.66 ± 0.05, R2 = 0.93). These results are consistent with a ratedetermining nucleophilic attack of the amine on an iron carbene complex. In addition, the decomposition of EDA catalyzed by FeII(TPP) or FeIII(TPP)Cl was examined with various amounts of added pyridine. The Fe(II) catalyst is strongly inhibited by the presence of pyridine. In contrast, catalysis by the Fe(III) porphyrin is accelerated by amines. These experiments suggested that an iron(III) porphyrin carbene complex is the active catalyst.

The nature of chemical innovation: new enzymes by evolution

“…A particularly interesting set of reactions proceeds through metal-carbenoid intermediates that had never been exploited for catalysis by heme proteins. The synthetic porphyrin systems relied on synthetic activated reagents such as ethyldiazoacetate (EDA) to generate the metal carbenoid, which could then react with olefins or insert the carbene into various N-H, C-H, or O-H bonds (Baumann et al 2007;Chen et al 2004;Wolf et al 1995). That the metal-carbenoid intermediate resembles compound I in the native P450 catalytic cycle (Fig.…”

Bulk gold catalyzed oxidation reactions of amines and isocyanides and iron porphyrin catalyzed N-H and O-H bond insertion/cyclization reactions of diamines and aminoalcohols

“…61 Recently, iron(III) tetraphenylporphyrin chloride (Fe(TPP)Cl) was found to be a robust catalyst in N-H insertion reactions of amines with ethyl diazoacetate. 56 A very low catalyst loading (<1 mol%) led to high yielding (68-97%) reactions within ten minutes for both aryl and alkyl amines. It was found that in addition to glycine ethyl ester derivatives, tertiary amines could be prepared from primary amines when treated with two equivalents of EDA.…”

“…N-H bond insertion reactions utilizing diazo compounds and amines provide a simple route for the formation of important products and synthetic intermediates, such as glycine ethyl ester derivatives, 55 tertiary amines, 56,57 and nitrogen heterocycles. 50 Several metal complexes are reported to catalyze N-H bond insertion reactions.…”

Synthesis and chemical reactivity of new zinc porphyrin diazoacetates catalyzed by ruthenium and iron porphyrins

“…22 The insertion of electrophilic carbenes in the N-H bonds of protected -amino esters or amides is a powerful method for N-alkylating this class of compounds. 23 Since we 7,8 and others [24][25][26][27] previously reported N-H insertion of diazoesters catalyzed by metalloporphyrins (Fe, Ru), N-H insertion with a diazo porphyrin ester was also investigated (Scheme 2). The results presented in Scheme 2 show that the iron complex is a good catalyst for the transformation of tryptophan methyl ester into the expected N-H inserted products with 69%…”

“…Treatment of thiophenol with diazoporphyrin ester catalyzed by complex 1a gave insertion of the diazo derivative into the S-H bond with 85 % yield. The mechanisms of the cyclopropanation reaction, N-H insertion and S-H insertion, catalyzed by metalloporphyrins, have been previously discussed by us 8 and others [25][26][27] several times, and will not be presented herein. All the new derivatives were identified by NMR and mass spectral analysis.…”