Pyrrolyl aldehydes

Substituted Indoles from Pyrrolyl Aldehydes J. Prakt. Chem. 315,295(1973)... 

As in the example shown below, the Vilsmeier-Haack reaction was performed on 2-benzoyl-1-methyl-lf/-pyrrole to afford the C2 formylation product in 44% yield and the C3 ketone affords the C2 formylation product in 44% yield in 56% yield The two pyrrolyl aldehydes, in turn, were converted into the corresponding hydroxamates, which are a new class of histone deacetylase (HDAC) inhibitors. 

A mixture of 9.5 g pyrrolyl-2-aldehyde, 29.2 g dimethyl-succinate and NaH (9.6 g of 50% suspension in oil) in 100 ml benzene is stirred at room temperature 6 hours, cooled and carefully acidified with glacial acetic acid. Add water and ether and dry, evaporate in vacuum or work up (JACS 72,501 (1950), JCS 1025(1959)) to get ca. 17 g (80%) 3-methoxycarbonyl-4-(2 -pyrrolyl)-3-butenoic acid (I) (recrystallize-acetone-benzene). A mixture of 12 g (I), 7 g sodium acetate and 70 ml acetic anhydride is left overnight at room temperature with occasional shaking. Then gradually raise the temperature to 70-75° over 2 hours, maintain for 4 hours and work up (see JCS 1714(1955), 986( 1958)) to get ca. 8 g (60%) methyl-4-acetoxy-indole-6-carboxylate (II) (recrystallize-petroleum ether). If desired, this can be converted to 4-OH-indole-6-COOH and 4-methoxyindole-COOH as described in the ref. or decarboxylated as described elsewhere here. If the 1-methyl cpd. is used, 1-Me-indole results. 

The formation of 3-pyrrolylcarbinols (280) from the photochemically induced reaction of pyrrole, or its 1-alkyl derivatives, with aliphatic aldehydes and ketones is thought to proceed via an oxetane intermediate (279) (79JOC2949). In contrast, the analogous reaction of 1 -phenylpyrrole with benzophenone leads to the formation of the diphenyl(2-pyrrolyl)car-binol, whilst the oxetane (281) has been isolated from the photoaddition of 1-benzoylpyrrole and benzophenone (76JHC1037, B-77MI30500). 2-Benzoyl-1-methylpyrrole undergoes a normal Paterno-Buchi photocyclization with 2,3-dimethylbut-2-ene, via the n -> v triplet... 

An enantioselective organocatalytic (with tetrahydro-47/-imidazol-4-one-based catalysts of type 456-HX) Friedel-Crafts alkylation of pyrroles 455 by ot, 3-unsaturated aldehydes generates 3-pyrrolyl carbonyls 457, useful synthons for the construction of a variety of biomedical agents (Equation 108) <2001JA4370, 2002JA1172, 2004ASC1175, 2005JA15051 and references therein>. 

A partially related reaction is the photochemical synthesis of bis(pyrrolyl)- and bis(indolyl)methanes by irradiation of (hetero)aryl aldehydes in the presence of the... 

Analogous pyrrolyl derivatives are also found as furan metabolites. Furans are oxidized by CYP to reactive furan-epoxides, which rearrange to ene-dial or ene-keto-aldehyde metabolites (Figure 33.20). After... 

Condensations of pyrroles with aldehydes and ketones oceur easily by acid catalysis, but the resulting pyrrolyl-carbinols cannot usually be isolated, for under the reaction conditions proton-catalysed loss of water produces 2-alkylidene-pyrrolium cations that are themselves reactive electrophiles. Thus, in the case of pyrrole itself, reaction with aliphatic aldehydes in acid inevitably leads to resins, probably linear polymers. Reductive trapping of these cationic intermediates, producing alkylated pyrroles, can be synthetically useful, however all free positions react acyl and alkoxycarbonyl-substituents are unaffected. ... 

The reaction of N-aminoazonium salts with aliphatic and aromatic aldehydes in the absence of base gives the Schiff base type compounds 28.151,153-156 Some aliphatic ketones also react with N-aminoazonium salts.40,155 Hexane-2,5-dione reacts with N-aminopyridinium perchlorate to give l-(l -pyrrolyl)pyridinium cation 29 together with some of the bisper-chlorate 30.157 Certain esters such as diethyl malonate and ethyl cyano-acetate react with N-aminopyridinium salts in the presence of base to give the corresponding N-acylimines 31.48 However, the reaction of ethyl aceto-acetate and acetylacetone with N-aminoazonium salts in the presence of base gives 1,3-dipolar cycloaddition products (Section IV,C,1).36,154,158 The reaction of ethyl acetoacetate with 1-alkyl-l,2,4-triazole 4-imine affords zwitterionic triazolo[4,3-/>]pyridazines 32.139,159... 

A mixture of 9.5 g pyrrolyl-2-aldehyde, 29.2 g dimethyl-succinate and NaH (9.6 g of 50% suspension in oil) in 100 ml benzene is stirred at room temperature 6 hours, cooled and carefully acidified with glacial acetic acid. Add water and ether and dry, evaporate in vacuum or work up (JACS 72,501(1950), JCS 1025(1959)) to get ca. 17 g (80%) 3-methoxycarbonyl-4-(2 -pyrrolyl)-3-butenoic acid... 

In 1998, Du Pont claimed the synthesis of bis(pyrrolyl) and bis(indolyl) ligands 1-3 characterized by a binaphthol backbone (Scheme 2.124) [10]. Unfortunately, the synthesis was detailed only for ligand 1. It was tested in the hydroformylation of methyl 3-pentenoate at 5 bar syngas pressure, where almost perfect selectivity for the formation of the terminal aldehyde was observed. The ligand was also used to convert 1- and 2-hexene. In comparison to a corresponding diphosphite with electron-withdrawing 3,5-CFg-phenyl groups, improved 1-heptanal selectivity was achieved. In the reaction with 1,3-butadiene, mainly pentenal was formed. 

Also, palladium-catalyzed hydroformylation of alkynes is known [98]. Particularly, Beller s group showed that a wide range of symmetrically and unsymmet-rically substituted alkynes can be converted into the unsaturated aldehydes by the effect of a palladium complex modified with a bidentate 2-pyrrolyl phosphine (Scheme 4.20) [103]. 

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