Pyrrole ketones, bicyclic

In a related reaction, heating ketones in the presence of TlClsOTf leads to 1,3,5-trisubstituted arenes. " Nitriles react with 2 mol of acetylene, in the presence of a cobalt catalyst, to give 2-substituted pyridines. " Triketones fix nitrogen gas in the presence of TiCU and lithium metal to form bicyclic pyrrole derivatives. " ... 

A new synthesis of pyrroles generates a 1,3-diketone by reacting a lithium enolate of a ketone with an acid chloride in situ addition of a hydrazine yields, potentially, a tetrasubstituted pyrazole.297 Tolerant of a wide range of functional groups, it is also easily adapted to rapid preparation of fused bicyclic pyrazole systems. 

Intramolecular radical substitution of pyrroles and indoles has been well studied this is exemplified in Schemes 90 <1997TL7937> and 91 <2000TL10181>. Intramolecular radical acylation of l-(-halogenoalkyl)-2-methylsulfonyl-5-substituted pyrroles leads to bicyclic ketones with displacement of the sulfonyl moiety <2000TL3035>. Similar cyclizations can be achieved using acyl selenide precursors to generate an acyl radical... 

Intramolecular radical acylation of l-(co-halogenoalkyl)-2-methylsulfonylpyrroles led to bicyclic ketones with retention or loss of the sulfonyl moiety (Scheme 189, Equations 232-234) <2000TL3035>. Under standard conditions, l-(2-bromoethyl)-2-(methylsulfonyl)-l/7-pyrroles 980 gave the expected 2,3-dihydro-177-pyrrolizin-l-ones 981 in moderate to good yields, and a small amount of the reductive dehalogenation products 982 (Equation 232). 

In addition to furan, other heterocycles have been examined." Thiophene undergoes efficient photocycloaddition with benzaldehyde to afford a single exo photoproduct (183) in 60% yield. As reported by Jones and coworkers,the photolysis of IV-methylpyrrole in the presence of aldehydes or ketones yields the corresponding 3-hydroxyalkyl derivative (184), even when the reaction mixture is free from any trace of acid. In order to use the pyrrole nucleus for stereoselective alkaloid synthesis (cf. caesalpinine, 185) in the fashion developed with the furan nucleus, pyrrole substituents that stabilize the presumed intermediate bicyclic oxetane must be discovered. 

Other uses of cobalt(I) catalysts include the reductive intramolecular cyclization of bromocyclohexenones to form bicyclic ketones [391] and the radical cyclization of bro-moacetals [392,393]. Krautler and coworkers [394] found that 1,4-dibromobutane interacts with electrogenerated cob(I)alamin to afford a tetramethylene-l,4-di = Co -cobalamin species. In a recent study of the reactions of cobalt(I) tetraphenyl porphyrin with benzyl chloride or 1-chlorobutane, Zheng and coworkers [395] reported that alkyl radicals are transferred from the cobalt center to a nitrogen of a pyrrole ring, leading to formation of an A-alkyl cobalt porphyrin complex. 

An alternative synthetic route to (bicyclic) pyrroles 41 involves the coupling of a cyclic ketone with an amine and an a,/i-unsaturated nitroalkene on the surface of alumina (Scheme 17.30) [14]. After MW irradiation for 13-15 min the product 41 was obtained in 71-86% yield. In this synthesis, substitution on the a-position of... 

More recently (2004), Joule proposed a novel synthetic route to access the akuammiline scaffold with reports from his group s synthetic efforts toward realizing this plan. Retrosynthetically, they envisioned akuammiline (1) to result from late stage imine formation of ketone 247 (Scheme 32). The functionality at position 16 would then be elaborated from a carbonyl contained in diketone 248, which in turn was planned to be obtained via an intramolecular Claisen condensation and double bond isomerization of enamine 249, the latter the product of an aza-Diels—Alder cycloaddition involving cyclic 1-aza-1,3-diene 250 and an acrylate 251. To access azadiene 250 they planned an oxidative ring opening of bicyclic pyrrole 252. 

In the forward direction, they first focused on accessing a bicyclic pyrrole scaffold such as 252. Toward this end, 2-phenyl-4H-benzoxazin-4-one (254) was treated with the Grignard derivative of pyrrole in THF to provide (pyrrolyl)ketone 255 (Scheme 33). Pyrrole 255 was next acylated at the... 

The first total synthesis of the intricate Stemona alkaloid (+ /—)-isostemofoline (224) was reported by Kende and coworkers 81) starting from 1,2-hexanediol (225) which was straightforwardly converted to 227 (Scheme 22) 82). Reductive cycUzation with sodium hydrosulfite in refluxing aqueous ethanol, and protection of the unstable pyrrole as tert-butyl carbamate, afforded 228 in five steps with 12% overall )deld. The key bicyclic ketone 231 was assembled by [4 + 3] cycloaddition of pyrrole 228 and diazoester 229 promoted by rhodium octanoate dimer, followed by enol silane deprotection, exo-specific hydrogenation, and nucleophilic decarboxylation (47% overall yield). Sodium methoxide-catalyzed aldol condensation of ketone 231 and furfural provided the Q-j/i-unsaturated ketone 232 whose olefin configuration was established by nOe studies. Allylation of 232 provided a 2.4 1 mixture of ketone 234 and the corresponding allylic enol ether 233, which could be converted to the former via a stereoselective Claisen rearrangement. 

The reaction of alkyl aryl(hetaryl) ketoximes with acetylene in the system KOH/ DMSO (80°C, 5-60 min), when conducted in the presence of a third component, aliphatic ketone, furnishes, along with the anticipated products (O-vinyl oximes, pyrroles, and N-vinylpyrroles), the unexpected complex bicyclic systans, 4-methylene-3-oxa-l-azabicyclo[3.1.0]hexanes (Scheme 1.177) [361], In the super-base system LiOH/CsF/DMSO, the reaction proceeds selectively, that is, bicyclohexanes are formed in up to 75% yield without O-vinyl oximes or pyrroles. 

The Ga(III)-catalysed three-component 4 -I- 3-cycloaddition reactions of indoles (128), ketones (129), and cyclohexadienes (130) produced cyclohepta[h]indole derivatives (131) in a single step at room temperature (Scheme 40). The 4-i-3-cycloaddition reactions of pyrroles with stabilized 2-(silyloxy)allyl cations formed tropinones in high yields (85%)4 The intramolecular 4-t-3-cycloaddition reaction of diaza-oxyallyl cationic intermediates and cyclic dienes yielded bicyclic ureas in good to excellent yields. ... 

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