Metal-free pyrrole synthesis

Oxidation reactions were used in the synthesis of porphyrin d, the metal-free ligand system of naturally occurring heme d,. In a total synthesis of porphyrin d,12d oxo functions were introduced into isobacteriochlorin 3 by selenium dioxide oxidation to yield 4. The selenium dioxide selectively attacks the 3- and 8-positions of the partially reduced pyrrole rings of the chromophore. In another synthesis23a c of porphyrin d, an isobacteriochlorin 5, derived by... 

Another group reported the synthesis of iV-alkenyl pyrroles 47 through transition metal-free conditions by stirring pyrrole 45 with alkyne 46 and adding potassium phosphate to facilitate the reaction. In this case, the ratio of Z/E isomers was 99 1 (14CAJ75). 

Maulide et al. developed a unified method for the direct transfer of ylides and the metal-free arylation of carbonyl compounds. This was applied in the synthesis of pyrrole 76 from 75 upon treatment with Martin s sulfurane in toluene at room temperature. The dearomatization of both indole and pyrrole could be effected with a variety of electron-donating or -withdrawing groups in good to excellent yields (13JA7312). 

Pal et al. [26] reported an iodine-catalyzed four-component reaction of 1,3-dicar-bonyl compounds, amines, aldehydes, and nitroalkanes affording polysubstituted pyrroles 3 under a metal-free condition. This is the first example of Grob and Ca-menisch s pyrrole synthesis [27] catalyzed by iodine via one-pot four-component reaction (Scheme 10.2). 

Das et al. [29] developed a simple, efficient, cost-effective, and metal-free four-component coupling reaction of aldehydes, amines, dialkyl acetylenedicaiboxyl-ates, and nitromethane for the synthesis of corresponding 1,2,3,4-tetra-substituted pyrroles 6 using molecular iodine as a catalyst (Scheme 10.4). 

Bandyopadhyay D, Cruz J, Yadav RN, Banik BK (2012) An expeditious iodine-catalyzed synthesis of 3-pyrrole-substituted 2-azetidinones. Molecules 17 11570-11584 Reddy GR, Reddy TR, Joseph SC, Reddy KS, Pal M (2012) Iodine catalyzed four-component reaction a straightforward one-pot synthesis of functionalized pyrroles under metal-free conditions. RSCAdv 2 3387 3395... 

Das B, Bhunia N, Lingaiah MA (2011) Simple and elficient metal-free synthesis of tetra-substituted pyrroles by iodine-catalyzed four-component coupling reaction of aldehydes, amines, dialkyl acetylenedicarboxylates, and nitromethane. Synthesis 2011 3471-3474 Khan AT, Ghosh A, Khan MM (2012) One-pot four-component domino reaction for the synthesis of substituted dihydro-2-oxypyrrole catalyzed by molecular iodine. Tetrahedron Lett 53 2622-2626... 

The synthesis has been modified to produce a series of porphyrin octaethanol derivatives (ethers) [162]. Pyrrole trimethyl ester (37) is selectively hydrolysed with sodium methoxide in methanol to give the diacid monoester (38), which is reduced (BH3/THF) and tosylated. The ditosylate was heated with the appropriate alcohol to afford the diether (with concommital transesterification of the pyrrolic a-ester). Oxidation with lead tetra-acetate gave compound 39, which was converted to the metal-free porphyrin in one pot by treatment with potassium hydroxide to hydrolyse the ester, hydrobromic acid to decarboxylate and cyclize, and chloranil to oxidize the macrocycle to the porphyrin (Scheme 44). 

Radha Krishna Murthi [53] accessed to a faster and efficient metal-free synthesis of polysubstituted pyrroles (23) in good yields under ultrasoxmd assistance. Starting materials were p-keto esters (19), benzylamines (20), aromatic aldehydes (21), and nitromethane (22) in the presence of amberlyst-15 as a reusable catalyst via a four-component reaction (Scheme 7). 

This section covers cyclizations to the pyrrole nucleus catalyzed by other metals (Ti, Mn, Ru, Pd, Pt, Zn, In). Dembinski and co-workers used zinc(II) chloride as ligand-free catalyst for the microwave-assisted cyclization of homopropargyl azides 26 to afford substituted pyrroles 27 (Scheme 8) [62]. A similar methodology for the synthesis of 2,4,5-trisubstituted pyrroles was described by Driver et al. employing substituted 1-azidobuta-l,3-dienes in a cyclization reaction using catalytic amounts of zinc(ll) iodide [63]. A three-component zinc-catalyzed one-pot cyclization of aromatic and aliphatic propargylic acetates, silyl enol ethers, and primary amines to substituted pyrroles has been described by Zhan et al. The reaction sequence includes propargylation of the silyl enol ether, amination, 5-exo-(7ig-cyclization, and isomerization [64]. Hiroya and co-workers have shown... 

Anion displacement of halides with azolyl anions is one common route to azolyl complexes. One example of such a synthesis is shown in Equation 4.21. In other cases, azolyl complexes have been prepared by proton transfer between the free azole and a metal alkox-ide or hydroxide. An example involving the synthesis of palladium-azolyl complexes is shown in Equation 4.22. In some rare cases, reactions of pyrrole and d early metal alkyls also lead to the formation of a metal-nitrogen bond via o-bond metathesis, as shown in Equation 4.23. Finally, several late-transition-metal-azolyl complexes possessing accompanying hydride Hgands have been prepared by N-H activation of pyrrole and other azoles. 

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