Ring under high pressure

Success of the reactions depends considerably on the substrates and reaction Conditions. Rate enhancement in the coupling reaction was observed under high pressure (10 kbar)[l 1[. The oxidative addition of aryl halides to Pd(0) is a highly disfavored step when powerful electron donors such as OH and NHt reside on aromatic rings. Iodides react smoothly even in the absence of a... 

Cyclohexanedimethanol (47) starts from dimethyl terephthalate. The aromatic ring is hydrogenated in methanol to dimethyl cyclohexane-l,4-dicarboxylate (hexahydro-DMT) and the ester groups are further reduced under high pressure to the bis primary alcohol, usually as a 68/32 mixture of trans and cis forms. The mixed diol is a sticky low melting soHd, mp 45—50°C. It is of interest that waste PET polymer maybe direcdy hydrogenated in methanol to cyclohexanedimethanol (48). 

Other examples of nucleophilic attack on the oxirane ring include the formation of (3-halohydrins with silica-gel supported lithium halides <96TL1845>, the addition of amines catalyzed by lithium triflate, an ersatz for lithium perchlorate <96TL7715>, and the addition of pyrroles, indoles and imidazoles under high pressure i.e., 91 —> 93) <96JOC984>. 

Kinetic studies of various systems have been carried out as follows the reaction of 2,2 -dichlorodiethyl sulfide and of 2-chloroethyl ethyl sulfide with diethylenetriamine and triethylamine in 2-methoxyethanol ° the catalysed reactions of substituted phenols with epichlorohydrin the reactions of para-substituted benzyl bromides with isoquinoline under high pressure the reactions of O-alkylisoureas with OH-acidic compounds [the actual system was N, N -dicyclohexyl-0-(l-methylheptyl)isourea with acetic acid] and tlie ring opening of isatin in aqueous binary mixtures of methanol and acetonitrile cosol vents. 

Imidazole was converted by hydrogenation over platinum oxide in acetic anhydride to 1,3-diacetylimidazolidine in 80% yield, and benzimidazole similarly to 1,3-diacetylbenzimidazoline in 86% yield [480. While benzimidazole is very resistant to hydrogenation over platinum at 100° and over nickel at 200° and under high pressure, 2-alkyl- or 2-aryl-substituted imidazoles are reduced in the benzene ring rather easily. 2-Methylbenzimidazole was hydrogenated over platinum oxide in acetic acid at 80-90° to 2-methyl-... 

Pyrrole and its simple derivatives do not react easily as dienes. Pyrrole itself only combines with dimethyl acetylenedicarboxylate (DMAD, dimethyl but-2-ynedicarboxylate) under high pressure and then it is by C-2 substitution. However, A-acylpyrroles, such as A-acetyl- and N- tert-butoxycarbonyl)pyrrole, do undergo Diels-AIder addition reactions. Here, internal resonance within the acyl group reduces the availability of the lone-pair electrons, formally on nitrogen, to delocalize into the ring, thus making the carbon unit more diene-like (Scheme 6.12). 

Only a few papers on the formation of compounds with small rings have been published. One example is the [2 + 2]-cycloaddition of electron-rich enamines to Schiff bases under high pressure (1.4 GPa) (87JOC365). The reaction leads to substituted azetidines (1). Four-membered ring heterocycles, thietane derivatives (4), are formed by interaction of sulfene (2) with enamines (3) (86CB257 93JOC3429). 

The method is a modification of one used by Barton and McCombie.8 Reduction of ketones.9 Ketones can be reduced to alcohols by Bu3SnH in the presence of either AIBN or a Lewis acid, but this reaction is limited to unhindered ketones. However, even sterically hindered ketones, such as f-butyl methyl ketone, can be reduced under high pressure (10 kbar) in the absence of a catalyst. This method is particularly useful in the case of cyclopropyl and a,p-epoxy ketones, which are reduced to the corresponding alcohols. Reduction of these ketones with Bu3SnH under radical conditions results in ring-opened products. 

In a manifestation of the reaction shown above, quinoline rings have also been formed by the cycloaddition of /V-arylketenimines 543 with 3,4-dihydro-2//-pyran 455 under high-pressure conditions (Scheme 100) <2001H(55)1971>. The reaction is proposed to proceed via the initial formation of 544 by attack of the enol ether on the protonated ketenimine subsequent electrophilic aromatic substitution gives 545. Protonation of the enamine to give 546 is followed by elimination to produce 547. Protection of the alcohol with 455 gives 548. 

A synthesis by Elati et al.51 involved condensation of 4-pyridinecarboxaldehyde (35) with 25 in the presence of /Moluenesulfonic acid (TsOH) to give the enone 36 in 96% yield. Global hydrogenation of the alkene and pyridine ring in the presence of Pd/C under high-pressure hydrogen gas gave piperidine 37 in 90% yield. Finally, N-benzylation with benzyl bromide provided 3 in 65% yield (Scheme 6). 

Impressive yields of large rings (up to 95% for an 18-membered ring) may be realized by reaction of tosyl-protected primary amines with a,co-dibromides in DMF in the presence of cesium carbonate (equation 177)954"956. The same reaction has also been performed successfully under high-pressure conditions. 

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