Hydrogenation, catalytic pyrroles

Many synthetic methods have been reported for the pyrrolidine alkaloids, including procedures based on the Hofmann-Loffler reaction 132,412), the metal hydride reduction of pyrrolines 413,414), the a-alkylation of N-nitro-sopyrrolidine 412,415), the catalytic hydrogenation of pyrroles 133), the reductive amination of 1,4-diketones 25,138), the direct alkylation of 1-methoxy-carbonyl-3-pyrroline 416), the versatile synthesis from the Lukes-Sorm dilac-... 

The susceptibility of pyrroles to acid-catalyzed polymerization is a distinct disadvantage in the catalytic hydrogenation of pyrroles in acidic media and, similarly, the oligomerization of indoles by acids can also be a problem under such hydrogenation conditions. 

The catalytic hydrogenation of pyrroles to pyrrolidines (2,3,4,5-tetrahydropyrroles), although an old transformation (equation has not been heavily exploited as a preparative route to pyrrolidines. Nevertheless, sufficient examples exist so as to illustrate the importance of this method. As would be expected, the hydrogenation of 2,5-disubstituted pyrroles proceeds with cis stereoselectivity (equation 2). - ... 

The use of rhodium-amino acid complexes in catalytic hydrogenation has been reported by Rajca to be capable of reducing a wide variety of aromatic and heteroaromatic compounds under mild conditions (1 atm, 22 °C, DMF 1 atm = 101 kPa). Thus, the rhodium-anthranilic acid catalyzed hydrogenation of pyrrole under these mild conditions yields a 2 1 mixture of pyrrolidine and 2,5-dihydropyrrole (53% conversion after 8 h)." Recently, Lunn found that the hydrogenation of pyrrole can be carried out with a nickel-aluminum alloy, as generated with aqueous KOH, to give pyrrolidine in 58% yield, albeit relatively slowly (4 d, r.t.)."... 

Catalytic hydrogenation converts pyrrole and furan into the corresponding saturated heterocycles, pyrrolidine and tetrahydrofuran. Since thiophene poisons most catalysts, tetrahydrothiophene is synthesized instead from open-chain compounds. 

The asymmetric hydrogenation of pyrroles is a useful method to optically active pyrrolidines that are building blocks of pyrroline based alkaloids and otlier biolog ically active compounds. It was not until very recently that the catalytic asymmetric hydrogenation of pyrroles has become the truth. 

A claim has been made in patents issued to Auzies (374) that nicotine can be prepared on an industrial scale from ammonia and butadiene. This process is reported to involve the production of pyrrole by the catalytic interaction of ammonia and butadiene, the methylation and hydrogenation of pyrrole, the conversion of ZV-methylpyrrolidine to 8-chloropyridine by heating over a thorium catalyst with chloroform, and the interaction of /8-chloropyridine with A-methylpyrrolidine over the same catalyst. The process, however, does not seem to have been put into practice and the reactions described have never been confirmed by a precise chemical investigation. 

Halogen atoms in general have been replaced by hydrogen in pyrroles by zinc and alkalior catalytically , 352-3, xhe same replacement, brought about by boiling halogen hydracids, is discussed below. 

Reduction of isoindoles with dissolving metals or catalytically occurs in the pyrrole ring. Reduction of indolizine with hydrogen and a platinum catalyst gives an octahydro derivative. With a palladium catalyst in neutral solution, reduction occurs in the pyridine ring but in the presence of acid, reduction occurs in the five-membered ring (Scheme 38). Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cw-1,3-dihydro derivative (Scheme 39) (80JOC3982). 

A zinc-free alternative to the Knorr pyrrole synthesis employs catalytic hydrogenation, as for 17 + 18 to 19. Oximes such as 17 are readily prepared by nitrosation (NaNOa, HO Ac) of the active methylene group. 

The synthesis is straightforward because for the preparation of the tetrapyrranc a bipyrrole can also be used as a central unit to which a benzyl 5-(acetoxymethyl)pyrrole-2-carboxylate can be attached as the terminal pyrrole rings. Debenzylation by catalytic hydrogenation then gives the desired tetrapyrrane building block 68. 

Pyrrole itself is an obvious precursor of pyrrolidine by catalytic hydrogenation. One example of construction of an ant pyrrolidine analog from a pyrrole has been published (Scheme 24) (169). 

Miscellaneous Reactions Berkessel " has identified peptide-like urea-based bifiinctional organocatalysts for the highly efficient dynamic kinetic resolution of azalactones (Scheme 11.14a). Another selective hydrogen-bonding activation mechanism that enables the addition of pyrroles to ketenes using catalytic quantities of azaferrocene 36 has been introduced by Fu and coworkers (Scheme 11.14b). ° ... 

The. -methylpyrrole ring in nicotyrine—l-methyl-2-(3 -pyridyl)pyrrole— was reduced to nicotine both by catalytic hydrogenation [454] and by zinc [ 55] in 40% and 12% yield, respectively. 

Catalytic hydrogenation may selectively reduce the double bond, or reduce the aromatic ring as well depending on the reaction conditions used [430,463, 464]. Only exceptionally has the benzene ring been hydrogenated in preference to the pyrrole ring [463,46S. ... 

In indole s isomer pyrrocoline (l-azabicyclo[4,3,0]nonatetraene) catalytic hydrogenation over palladium in acidic medium reduced the pyrrole ring [466, in neutral medium the pyridine ring [467],... 

Catalytic hydrogenation of the unstable pyrroles (281a-c), which are prepared by heating the 1,4-diketones (280a-c) with an excess of ammonium carbonate at 120°C, gives 2,5-dialkylpyrrolidines (lOa-c) (cis trans = 85 15, 85% conversion) (Scheme 25) 133). Reductive amination of 1,4-diketones (282b,f,h,i) with ammonium acetate and sodium cyanoborohydride produces 2,5-dialkylpyr-rolidines (10b,f,h,i) identical to natural products in 50-90% yields. Each pyrrolidine is an approximately 1 1 mixture of cis and trans isomers (Scheme 26) 25,138). 

Catalytic hydrogenation of 2-alkyl-2,5-dihydro-l//-pyrrole with 5% rhodium on carbon gave 2-substituted pyrrolidines in 95-96% ee (Pirkle analysis42) without attendant racemization. 

Problem 20.13 Name the products formed when ( ) furan, (b) pyrrole are catalytically hydrogenated. 

Catalytic reduction of pyrroles gives successively A3-pyrroles and pyrrolidines. Tetrahydrofurans are formed by the catalytic reduction of furans with Raney nickel and hydrogen ring cleavage products... 

Halogen can be removed by catalytic hydrogenation and so it is possible to use halogen as a blocking group in pyrrole chemistry. In the thiophene and selenophene series, a-halogens are preferentially removed by reduction with zinc and acetic acid, as illustrated by the preparation of 3-bromothiophene (390) from 2,3,5-tribromothiophene (389) (81SC25). 

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