Hydrogenation cyclization

The direct cyclization of 5-styrylpyrazole-4-carboxylic acids can be accomplished only if N-1 is substituted by methyl [83H(20)1581]. Otherwise, the three-step route (hydrogenation, cyclization, and dehydrogenation) remains an alternative (Section II,A,l,a). An exception is the cyclization of phenylbenzofuranpropionic acids which forms dibenzofurotropone systems this reaction is accompanied by spontaneous dehydrogenation [78IJC(B)567],... 

On the other hand, imidazoquinoxalines 94 or pyrazoloquinoxalines 95 have been built starting from orf/ o-fluoroanilines 91 and imidazol- or pyrazol-carboxylic acids 92 and 93. Interestingly, the presence of an electron-withdrawing group as the substituent is not needed in most entries was just hydrogen. Cyclization by... 

A one-pot cross-metathesis/hydrogenation/cyclization protocol allows for the synthesis of 6-disubstituted tetrahy-dropyran-2-ones 1001 from homoallylic alcohols 1000 and acrylic acid (Equation 393, Table 47) <20030L459>. This methodology is invaluable during the total synthesis of (—)-centrolobine <2004TL6603>. 

With adiponitrile, an open-chain dinitrile, however, such cyclization leading to a seven-membered cyclic imine occurs to a much lesser extent (see, e.g., eq. 7.25). The hydrogenative cyclizations have been utilized for the synthesis of pyrrolidine and piperidine derivatives from 1,2- and 1,3-dicyano compounds.118,119... 

Hydrogenative cyclization of aromatic nitro compounds at the amino group has been described in a number of examples and widely utilized in the synthesis of five- and six-membered /V-heterocyclic compounds. Walker synthesized 5,6-dimethoxyoxin-dole and 5,6-dimethoxyindole by hydrogenative cyclization of ethyl 4,5-dimethoxy-... 

Scheme 9.17 Intennediates of the hydrogenative cyclization of nitro nitriles leading to indoles.

Tandem hydroformylatlon - Michael addition - hydrogenation - cyclization... 

After y-alkylation of 116 with methyl bromoacetate and subsequent condensation with (R)-phenethylamine, the resulting imine 117 was dia-stereoselectively hydrogenated, cyclized, and deprotected to give lactam 118. The cw-tricyclic triazolium salt 119 was then obtained as a solid in 24% yield by a modified three-step procedure reported by Knight and Leeper (1998). 

Cossy et al. demonstrated that, in the presence of the ruthenium catalyst 10 and Pt02, the tandem cross-metathesis—hydrogenation—cyclization reactions of the alkenol 19 with acrylic acid 20 or acrolein 21 under H2 atmosphere gave the lactone 22 or lactol 23, respectively (Scheme 8).89 The ruthenium catalyst 10 and Pt02 are compatible under the reaction conditions. 

Especially noteworthy is the field of asymmetric catalysis. Asymmetric catalytic reactions with transition metal complexes are used advantageously for hydrogenation, cyclization, codimerization, alkylation, epoxidation, hydroformylation, hydroesterification, hydrosilylation, hydrocyanation, and isomerization. In many cases, even higher regio- and stereoselectivities are required. Fundamental investigations of the mechanism of chirality transfer are also of interest. New chiral ligands that are suitable for catalytic processes are needed. 

Table 16 illustrates the i oduct distribution with temperature for the reaction of ethylene with REX. These data reveal a complex series of reacticms initially involving add catalysed polymerization of ethylene to low molecular weight aliphatic pdynar. Subsequent intermolecular hydt ygen transfer and de-hydrogenation-cyclization reactions followed by isomerization and cracking reactions account for the formation of the other products. 

The VNS cyanomethylation of 2-chloro-5-nitropyridine affords the corresponding nitropyridyl-substituted acetonitrile that undergoes hydrogenative cyclization into 5-chloro-6-azaindole (Scheme 68), a key starting material for the synthesis of potential Xa factor inhibitor [186]. 

The synthetic practicality of the Meyer-Schuster rearrangement was demonstrated in the synthesis of ( )-virantmycin, a metabolite of Streptomyces nitrosporeus, which has been shown to possess antiviral activity. When the attempted conversion of 17 to 19 via a hydrogenation/cyclization sequence was unsuccessful, an alternate pathway utilizing the Meyer-Schuster reaction was explored. Treatment of 17 with acid was presumed to give the a,P-unsaturated ketone which underwent a spontaneous Michael reaction to give 18. Reduction of the resulting ketone 18 was followed by dehydration to provide 19. 

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