Pyrroles propargylic ketones

Dake extended this approach to the synthesis of pyrroles 293 from monocarbonyl-containing skipped propargylic ketones 290 catalyzed by Ag- or Au(I)-triflates... 

Yet another method has been described (162) (Scheme 50) for the preparation of the tricyclic enamine (225). /V-Alkylation of ethyl pyrrole-2-carbox-ylate with 242 in the presence of sodium hydride gave, after hydrolysis, the amino acid (243). This was cyclized to 244, reduced to 238, then oxidized to 225. Alkylation of 225 with propargyl bromide, followed by hydration with a mercuric salt gave the ketone (227), but this could not be cyclized, thus confirming the observation made by Weinreb and Auerbach (156) but contrasting with the report of Dolby et al. (160). 

A ruthenium-catalyzed three-component reaction between propargylic alcohols, 1,3-dicarbonyl compounds, and primary amines leading to fully substituted pyrroles was developed <07CEJ9973>. Cyclohexa[a]pyrroles ( azabicyclo[4.3.0] systems ) were formed by a three-component sequence involving allenic ketones, primary amines, and acryloyl chloride <07SL431>. An oxidative dimerization sequence involving arylpyruvates in the presence of ammonia was the key step in an approach to the pyrrole natural product, lukianol A <07S608>. 

Scheme 13 shows additional examples of constructions of four-carbon chains functionalized appropriately for condensation to pyrroles. Af,Af-bis(trimethylsilyl)propargyl amines can be converted to ketones or esters by lithiation and acylation. These compounds then undergo cuprate addition. The resulting allenyl silyl ethers cyclize to pyrroles on treatment with acid <93T4603). 

A recent report from Kirsch s group illustrated that vinyl propargyl ethers 36, as surrogates of skipped allenyl ketones 37, could be employed in a very efficient synthesis of densely substituted pyrroles 29S via the Ag/Au(I)-catalyzed... 

Hidai and Uemura reported that the bimetallic Ru and Pt(II) two-catalyst system could be applied to the 2 + 2 + 1 synthesis of pyrroles 364 from propargylic alcohols 195, enolizable ketones 196, and anilines 363 (Scheme 8.126) [143]. Moderate yields of up-to-fully substituted pyrroles 364 could be achieved via this approach, though a large excess of carbonyl compound and aniline were required to achieve full conversion. This transformation is believed to proceed via the Ru-catalyzed propargylic substitution of 195 with 196 (vide infra) to give doubly skipped alkynyl ketone... 

The reaction of the oxazolone 142 (bearing two substituents at C-2 atom) with DMAD led to the nonaromatic pyrroline 143, which after passing through a column with active AI2O3 gave the pyrrole 144 by elimination of methyl vinyl ketone with aromatization. Treatment of 142 with methyl propargylate produced a 3 2 mixture of the regioisomers 145 and 146, while the reaction with acrylonitrile led to the pyrroline 147 in 25 % yield [62],... 

The classic Hantzsch pyrrole synthesis is based on the reaction of ketones bearing electron-withdrawing group in a-position with a-haloketones or aldehydes in the presence of amine or ammonia. For example, the condensation of the masked bromoacetaldehyde 278 with ethyl 4,4,4-trifluoroacetoacetate (279) and propargyl amine gave the pyrrole 280 [95], The yield of pyrrole 280 was not given. 

In 2003, the Uemura group reported a diversity-oriented approach to highly substituted furans based on ruthenium- and platinum-catalyzed intramolecular annulation of propargylic alcohols 59 and ketones 60 (Scheme 19.28) [22]. This reaction is related to the aforementioned pyrrole synthesis (Scheme 19.13). Based on the time profile of the reaction, in which rapid formation/consumption of the alk-4-yn-l-one 63 was seen but only gradual formation/consumption of the diketone 122 was observed, they proposed a mechanism including alkyne hydration and subsequent cyclization of the resulting diketones. However, this reaction can be considered as a furan synthesis by formal reaction between the C=0 and alkyne groups. 

The iron(III) chloride-catalyzed ring expansion reaction of 2-azetidinone-tethered alkynols and allenols provides pyrroles or y-lactones, respectively (Scheme 4-351). The proposed mechanism for the pyrrole formation includes a Meyer-Schuster rearrangement of the propargyl alcohol to the corresponding allenyl alcohol, P-lactam ring opening, tautomerization of the allenyl alcohol to the a,P-unsaturated carbonyl compound, and cyclization by attack of the amino group to the ketone under dehydration. ... 

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