General base-catalysed cyclization

With the exception of the parent compounds, where the Michael adducts are isolated, acrylic esters [see, e.g. 6,7,31,105,111 ] and nitriles [6,7], and vinyl ketones [26, 113, 115] generally yield the cyclopropanes (Table 7.6) under the standard Makosza conditions with chloroform. Mesityl oxide produces a trichlorocyclopropy-lpropyne in low yield (10%) [7]. When there is no substituent, other than the electron-withdrawing group at the a-position of the alkene, further reaction occurs with the trichloromethyl anion to produce spiro systems (35-48%) (Scheme 7.12) [7, 31]. Under analogous conditions, similar spiro systems are formed with a,p-unsaturated steroidal ketones [39]. Generally, bromoform produces cyclo adducts with all alkenes. Vinyl sulphones are converted into the dichlorocyclopropane derivatives either directly or via the base-catalysed cyclization of intermediate trichloromethyl deriva-... 

Base-catalysed cyclization of halogeno-acid amides (88) to give lactams has been carried out using t-butoxide in DMSO, but the yields are generally lower than for other bases. The same author has suggested that the nature of the product, /S-lactam (89) or 3-oxomorphoIine (90), from the reaction of the chloro-keto-amide (91) with base is controlled by the d acceptor abilities of the aromatic halogen substituent X. ... 

More classical approaches to the 2-benzazepine system, in particular the 2-benzazepinone 23, have been reported by Le Digueiher et al. The first was based on (5)-phenylalanine carboxamide 20 via the protected acetoxy compound 21 and acid-catalysed cyclization to 22 A-alkylation and carbamate deprotection then afforded 23. The second, more general route, was based on N-Boc aminomalonate 25 and 2,2 -dibromo-o-xylene, and then steps via 26 and 27. Yields were fair to moderate. The benzazepinone 23 was converted into the N-substituted derivatives 24, which were potent and specific farnesyl transferase inhibitors such compounds are of interest as potential anti-tumour agents <04BMCL767>. 

Pyrroles.—Formation. A general synthesis of 2-aryl-pyrroles (112) is by cycliz-ation of the esters (111), which are obtained from unsaturated aldehydes and methyl azidoacetate. Thermolysis of the acetylene (113 Ar = p-MeC6H4) gives Al-(p-tolyl)pyrrole with the elimination of p-thiocresol. The pyrrole derivative (115) is the product of the action of benzylamine on tri-(t-butylthio)cyclopropenylium perchlorate (114). Azoalkenes combine with fi-dicarbonyl compounds or with enamines to yield derivatives of Al-aminopyrrole thus the ester (116) and ethyl acetoacetate form (117). The base-catalysed addition of methyl propiolate to toluene-p-sulphonylmethyl isocyanide, T0SCH2NC, gives the ester (118). The dipolar cyclo-adduct (120) of piperidinocyclopentene to the azo-compound (119) forms the A-(tosyl-amino)pyrrole derivative (121) and piperidine on heating. ... 

Internal aldol cyclization of compounds (805) is greatly enhanced by the presence of a trans (but not a cis) methyl group at C-10 (i.e. R = Me instead of H), and leads to the predominance of the twistanone (806 R = Me) in the base-catalysed equili-brium. The trans-methyl group is likely to destabilize conformation (807) relative to (808) which is more suited to the condensation, requiring relatively minor rotational motion to give the necessary boat-form. A general review of twistane chemistry has appeared. 

A general route to 3-substituted butenolides (72), which could have considerable potential, is the cyclization of phosphonium salts (71), simply by treatment with triethylamine in methylene chloride. The salts are easily obtained from a-bromo-ketones and bromoacetic acid and, in the examples quoted in this preliminary study, overall yields are high except when 2-bromocyclohexanone was used as the ketonic component (c/. 3, 133). The 3-substituted butenolide group present in naturally occurring cardenolides can be built up from an a-methylthioketone residue by a Reformatsky reaction, followed by acid- and base-catalysed rearrangements. ... 

In general, the main synthetic approaches to five- and six-membered 1,2-oxaphos-phacyclanes are based on intramolecular cyclizations in a series of co-halogenalkyl-, co-hydroxyalkyl-, and co-acetyloxyalkyl-substituted phosphorus compounds proceeding via different reaction mechanisms along with metal-catalysed transformations. As... 

The catalytic system proved not only applicable to alkyl hahdes, but also allowed for the intramolecular conversion of aryl halides. Interestingly, the corresponding Mizoroki-Heck-type cyclization products were formed selectively, without traces of reduced side-products (Scheme 10.27) [55]. Therefore, a radical reaction via a single electron-transfer process was generally disregarded for cobalt-catalysed Mizoroki-Heck-type reactions of aromatic hahdes. Instead, a mechanism based on oxidative addition to yield an aryl-cobalt complex was suggested [51]. 

The first general method of transforming a penicillin into a cephalosporin, the acid-catalysed rearrangement of penicillin sulphoxides, continues to receive attention. That this rearrangement proceeds via a sulphenic acid derivative has been further confirmed by isolation of the crystalline sulphenic acid (74 f, y) from the thermal rearrangement of the penicillin sulphoxide (27 f, y). This intermediate slowly reverts to the penicillin at 38 0, and, on treatment with methanesulphonic acid in dimethylacetamide, cyclizes to cephalosporin (75 f, y). Trapping of (74) by oxidation to the sulphinyl chloride (76 f, y) has been reported cyclization to a cephalosporin sulphoxide was accomplished under base catalysis/ Treatment of penicillin sulphoxides with azo-compounds also effects rearrangement to... 

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