Pyrroles with ketones

The synthesis will therefore normally produce a 2,4-substituted pyrrole, with in addition an ester group or an acyl group at the 3-position, if a keto ster or a diketone respectively has been employed, and an ester group or an alkyl (aryl) group at the 5-position, according to the nature of the amino-ketone. 

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

Synthesis ol 2-aminofurans (thiophenes, pyrroles) by cortdensation of malononitnles with ketones. 

Pyrrole forms weaker NH-0 hydrogen-bonded complexes with ethers.106,1 6,157,163 The dipole moment of the pyrrole-1,4-dioxane complex shows it to be predominantly a binary system in which the pyrrole molecule occupies an axial position to the dioxane ring163 (see Section III, A, 2). Particularly strongly hydrogen-bonded NH-0=C complexes are formed between pyrrole and ketones.147,149,156 IR studies of the effect of the complex formation upon both the NH- and the C=0 stretching frequencies have been made. 

Halo ketones react with enamines 177 to form pyrroles (the Hantzsch pyrrole synthesis, ) and with -keto esters 179 under basic conditions to give furans 180 (the FeistBenary furan synthesis, ). The orientation in the Hantzsch pyrrole synthesis 177 178 differs from that in the FeistBenary furan synthesis 179 180 (Scheme 99). In an example of a modified Hantzsch synthesis, the -aminoacrylonitrile 182 reacts with ketone 181 to give pyrrole 183 in a moderate yield (Scheme 100) a series of similar compounds can be synthesized using this approach <1997S530>. A solid-phase extension of the Hantzsch synthesis has also been reported <1998BML2381>. 

Quaternary anilinium salts (240), obtained from reaction of (pyrrol-l-yl)methanol and the appropriate aniline with trioctylphosphine, react in polar solvents via the azonia-fulvene ion (241) with enamines through a Mannich-type reaction followed by cyclization to give pyrrolizidines 242 and 243124. The ratio between the pyrrolizidines formed varies considerably with ring size of the enamine employed (equation 50). Pyrrolizines have also been obtained by reaction of pyrrole with two equivalents of enamine125 or condensation of some ketones with L-sodium or L-ethyl prolinate126. 

In contrast to pyrrole 136, benzotriazol-l-yl(17/-indol-2-yl)methanone 138, under the same reaction conditions, reacted sluggishly with ketones and aldehydes to afford compounds 139 in lower yields (16-83%) sometimes together with side products (Scheme 29) <2004JOC9313>. For example, reaction of indole 138 with /i-tolualdehyde produced compounds 140 and 141 in 30% and 23% yields, respectively. 

Cyclization of intermediates derived by addition of lithium enolates to BOC-protected aminoaldehydes or ketones has been used as a route to a set of pyrroles with interesting substitution patterns (Equation 4). For example, treatment of the rf/ -generated precursor 22 with hydrochloric acid gave the fused system 23. However, a drawback... 

In principle, the synthesis can be realized as a one-pot process treatment of ketones with hydroxylamine in KOH-DMSO following interaction of the formed ketoximes with acetylene. Various pyrroles with alkyl, cycloalkyl, aryl and hetaryl substituents, as well as pyrroles condensed with aliphatic macrocycles, terpenic and steroid structures, together with their vinyl derivatives now become available. 

Under harsher conditions, oxime 15 reacted with acetylene to furnish pyrrole 17, ketone 18, 1-vinyl adamantane (20) and adamantane (19) (6 7 3 1 mass ratio), the isolated yield of pyrrole 17 reaching 34% (Equation (6)). 

Although not formally classified as calixarenes, compounds closely related in architecture to the calix[4jarenes have been prepared by the condensation of furans, thiophenes, and pyrroles with aldehydes and ketones. Furan undergoes acid-catalyzed condensation with aldehydes and ketones to give 15 76-79), as shown in Fig. 9. 

Fig. 9. Acid-catalyzed formation of cyclic tetramers from furan, thiophene, and pyrrole with aldehydes and ketones...

An early approach to the synthesis of cephalotaxine (Scheme 32) was reported by Dolby et al. (64) in 1972, shortly before Auerbach s and Wein-reb s report (22). The Vilsmeier-Haack condensation of piperonylamide 187 with pyrrole yielded ketone 188, which was successively reduced with sodium borohydride, hydrogenated, and acylated to give the precursory chloro amide 189. The photocyclization of 189 produced lactam 190, which, after reduction of the carbonyl with lithium aluminum hydride and subsequent oxidation with mercuric acetate, yielded the enamine 43. This mate-... 

A modestly enantioselective pyrrole carbinol formation has been investigated <05SL2420>. Treatment of lithium pyrrolate with a ketoaldehyde in the presence of a chiral ligand preferentially led to the formation of pyrrole carbinol 49 (50% ee). A hydroxy-directed reduction of the ketone in the side chain by the addition of zinc borohydride provided 50 (88% de). Pyrrole carbinols serve as convenient precursors to aldehydes. A subsequent deprotective Horner-Wadsworth-Emmons reaction involving 50 and phosphonate ester 51 gave unsaturated ester 52. 

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. ... 

These are stable compounds which do not polymerise or autoxidise. For the most part, pyrrole-aldehydes and -ketones are typical aryl-ketones, though less reactive - such ketones can be viewed as vinylogous amides. They can be reduced to alkyl-pyrroles by the Wolff-Kishner method, or by sodium borohydride via elimination from the initial alcoholic product (cf. 16.11). Treatment of acyl-l-phenylsulfonyl-pyrroles with f-butylamine-borane also effects conversion to the corresponding alkyl derivatives. ... 

A process that produces pyrroles, from ketones and hydroxyproline, works well with isatins. ... 

Hydrazonium salts (117) with sodium hydride in DMSO give azirines (118), which react further with ketones to give 2f/-pyrroles (119) benzyl cyanide similarly gives 120 (Scheme 43).114-116 This reaction is claimed to be the most convenient general route to 2H-pyrroles (yields 20-80%).114... 

The pivotal step associated with our approach to compounds 31-34 was an organocatalysed, enantioselective and intramolecular Michael addition reaction of the nucleophilic C-2 carbon of a pyrrole to an iV-tethered a,p-unsaturated aldehyde residue and thereby estabhshing the required CD-ring system. Full details of the reaction sequence are shown in Scheme 4 and this involves initial reaction of the potassium salt, 35, of pyrrole with butyrolactone (36) to give, after acidic workup, compound 37 (60-90%). Conversion of this last species into the corresponding Weinreb amide 38 (87%) followed by its reaction with ethylmagnesium bromide then afforded the ethyl ketone 39 (95%) that was subjected to standard Homer-Wadsworth-Emmons (HWE) conditions and thereby generating the... 

Hybrid linear tri- and tetra-oligomers possessing combinations of furan, thiophene or pyrrole have been obtained (2000TL2919, 2001T7323) by BFs-catalysed reactions of diols 18, and 22 with pyrrole, etc. The diols are obtained from reactions of bisanions of the parent heterocycles or their dimers with ketones. 

Volatile components of natural and roasted hazelnuts have been investigated by several researchers [7,88,90-98]. Among several volatile aroma-active compounds detected in roasted hazelnut, 5-methyl-( )-2-hepten-4-one (fllbertone) has been reported as the primary odorant (nutty-roasty and hazelnutlike) [88,93,94,96]. Alasalvar et al. [98] studied the comparison of natural and roasted Turkish Tombul hazelnuts and found a total of 39 compounds in natural hazelnut and 79 compounds in roasted hazelnut. These included ketones, aldehydes, alcohols, aromatic hydrocarbons, terpenes, furans, pyrroles, pyrazines, and acids. Pyrazines, pyrroles, terpenes, and acids are detected in roasted hazelnut only. The combination of several volatile aroma-active components that increases upon roasting may contribute to the distinctive and unique flavor of roasted hazelnut. Pyrazines together with ketones, aldehydes, furans, and pyrroles may contribute to the characteristic roasted aroma of hazelnut. Detail information about flavor and volatile compounds in major tree nuts are detailed in Chapter 7. 

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