Cyclisation/rearrangement

Stannous chloride-mediated reductive cyclisation-rearrangement of the nitro-ketone 269 (obtained from the nitro-acid, 268) gave the dibenzothiazepine derivative 270 in good overall yield mechanistically it was proposed that a hydroxylamine intermediate leads to the rearrangement after intramolecular nucleophilic addition to the ketone [02JOC8662]. 

Oxazole formation can be envisaged as proceeding by three possible pathways 1,3-dipolar cycloaddition of a free ketocarbene to the nitiile (Path A), the formation and subsequent 1,5-cyclisation of a nitrile ylide (Path B) or the formation and subsequent rearrangement of a 2-acyl-2//-azirine (Path C) (Scheme 9). 

The cyclisation of naphthyl propargyl ethers occurs efficiently under microwave irradiation leading to naphthopyrans, but naphthofurans are formed in the presence of base <96JCR(S)338>. The thermal rearrangement of naphthyl 3-trimethylsilylprop-2-ynyl ethers yields the 4-trimethylsilyl derivatives of naphthopyrans <96H(43)751>. 

Even if organocatalysis is a common activation process in biological transformations, this concept has only recently been developed for chemical applications. During the last decade, achiral ureas and thioureas have been used in allylation reactions [146], the Bayhs-Hillman reaction [147] and the Claisen rearrangement [148]. Chiral organocatalysis can be achieved with optically active ureas and thioureas for asymmetric C - C bond-forming reactions such as the Strecker reaction (Sect. 5.1), Mannich reactions (Sect. 5.2), phosphorylation reactions (Sect. 5.3), Michael reactions (Sect. 5.4) and Diels-Alder cyclisations (Sect. 5.6). Finally, deprotonated chiral thioureas were used as chiral bases (Sect. 5.7). 

As mentioned in CHEC-II(1996), three main routes have been reported for the formation of furazan rings (1) the dehydrative cyclisation of 1,2-dioxims (2) the deoxygenation of furoxans and (3) the Boulton-Katritzky rearrangement of other five-membered heterocyclic systems <1996CHEC-II(4)229>. In this section the recent publications on the synthesis of furazans published after 1996 are discussed. 

Cyclopenta-l,4-dioxanes 95 are formed in high yields through the acid-catalysed rearrangement of the dioxolanes 94 in which electrocyclisation of a hydroxypentadienyl carbocation, akin to a Nazarov cyclisation, is involved (Scheme 62) <00CEJ4021>. 

If so, is it then not likely that both mechanisms could operate, possibly with cross-over routes between one another, during the course of a reaction Such a concept would go a long way towards explaining the many rearrangements, cyclisations, etc. characteristic of the process. 

Dienes, 11 addition to, 194-198 cisoid conformation, 197, 350 conjugated, 11 Cope rearrangement, 354 cyclisation, 346 cycloaddition to, 348 Diels-Alder reaction, 197, 349 excited state, 13 heat of hydrogenation, 16,194 isolated, 11 m.o.s of, 12 polymerisation, 323 Dienone intermediates, 356 Dienone/phenol rearrangement, 115 Dienophiles, 198, 350 Digonal hybridisation, 5 Dimedone, 202 Dimroth s Ej- parameter, 391 solvatochromic shifts, 391 solvent polarity, 391 Y and,392 Dinitrofluorobenzene proteins and, 172... 

Under the same conditions of NaH/THF, the ester 3 gave ltf-2-benzopyran derivative 5 in 60% yield, apparently by 6-endo-dig ring closure. Closer study of this latter transformation, however, revealed that the initial product of base-induced cyclisation was in fact the isobenzofuran 4, which was extremely labile, and that 5 was formed from 4 by acid-catalysed rearrangement during work-up of the reaction mixture. 

The propargyl ether 1 was heated in refluxing dimethylaniline for 5 hours in the expectation that Claisen rearrangement followed by cyclisation would lead to the linear tricyclic system. The only product - isolated in only 12.5% yield - was, however, the angular tricyclic ketone 2. 

The reaction proceeds by way of the imine (109) which is converted into the enamine (110) by proto tropic rearrangement before being cyclised with concentrated sulphuric acid. 

In practice the cyclisation of (122) takes place in two stages. Initially a base-catalysed rearrangement converts (122) into o-hydroxydibenzoylmethane (123) which may be isolated, and then cyclised in the presence of acid to flavone (118) (Expt 8.46). 

A syn displacement of the bromine by benzylamine in the presence of triethylamine led, by a Sn2 reaction, to the a and p amino compounds which were separated into 326 (18%) and 327 (81%) respectively. The dichloroacetamide 328 derived from the latter, when subjected to the action of tri-n-butyltinhydride (2eq) and 2,2 -azobisisobutyronitrile underwent a 5-ero ring closure to furnish via the radical 329, the hydrooxindole 330 (51%) and significant amount of the rearrangement product 331 (30%). The latter is believed to be formed by fragmentation of the cyclohexadienyl radical 332 generated from the cyclohexyl radical 329. On diborane reduction, 330 provided the cis hydroindole 333, which on 0,N-debenzylation afforded ( )-c -fused bicyclic aminoalcohol 334, a compound that had been previously cyclised with formaldehyde to ( )-elwesine (320) by Stevens et al [85]. 

Tazettine. The elegant method [99] for the construction of cis-arylhydroindoles B (X = H) (Scheme 55) involving tandem azaCope rearrangement - Mannich cyclisation from appropriate cyclopentane A (X = H) was examined for the substrate A (X = SiR3 X/Ar Irons) as means of possible entiy into cis -arylhydroindole B (X = SiR3 X/Ar irons) potentially capable of subsequent direct conversion into pretazettine. 

Conversion of the trimer (80) to the seven-membered ring system (81) occurs readily with cesium fluoride [3,75], whereas in the presence of TAS fluoride, the di-anion (82) is trapped. These observations lead to the most likely mechanism for rearrangement as that in Scheme 37 [3]. The cyclisation step shown in Scheme 37 is made more easily accepted by the fact that the diene (83) (Scheme 38), undergoes rapid rearrangement in the presence of fluoride ion, giving the cyclic system (86) [77]. The ready cyclisation of a crowded anion (84) to give what appears to be a sterically unfavourable intermediate (85) would not be easily predictable ... 

C. Booma and K. K. Balasubramanian, A novel tandem Ferrier rearrangement cyclisation, Tetrahedron Lett., 34 (1993) 6757-6760. 

---