Further Ring Closures

The thermolysis of diethylaminomethylenemalonate (1302) in mesity-lene at 160°C for 6 hr yielded anthranilate (1303), but when the reaction was carried out in heptanol, only reesterified aminomethylenemalonate was obtained (88JOC880). 

Heating /V-methyl-yV-phenylaminomethylenemalonate (1304) in a distillation apparatus at 240°C for about 20 min afforded anthranilate (1305) in 56% yield (88JOC880). 

The reaction of diaminomethylenemalonate (1306) and benzoyl chloride in the presence of triethylamine in boiling chlorobenzene for 6 hr afforded 2-azetin-4-ones (1307) in 48-73% yields (77ZOR954). 

The Dieckmann cyclization of aminomethylenemalonates (1308) in boiling ethanol for 45 min, by the action of alkoxide, gave pyrrole-2,4-dicar-boxylates (1309) in 24-86% yields (77HI821 78CPB2224). Pyrrole-2,4-dicarboxylate (1309, R = H,R = Et) was also prepared in 71% yield from 1308 (R = H, R1 = Et) by reaction with sodium hydride in boiling benzene for 4 hr (78CPB2224). The 1-phenyl derivative (1309, R = Ph, R1 = Et) was prepared in 52% yield in an exothermic reaction of 1308 (R = Ph, 

3-Hydroxypyrrole-2,4-dicarboxylate (1309, R = H, R1 = Et) could be prepared in 30% yield in the reaction of ethyl JV-ethoxycarbonylglycinate and EMME in the presence of sodium sand in a mixture of benzene and xylene at reflux temperature for 3 hr (62JA635). 

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Ring opening and further ring closure of 2-imino-oxythiolan-l,3 derivatives (32) by water and/or methanol lead to the corresponding A-4-thiazoline-2-one (26) (Scheme 14) (30-32). 

The reaction of amines with the 4-phenylazo derivative (228) results in their rearrangement into triazolines. Depending on the basicity of the amines and the size of the alkoxy group, three different triazolines (229. 230, and 231) are obtained (Scheme 117) (454. 459, 472). In all cases, the first step involves nucleophilic addition of the amine to the carbonyl group followed by ring opening and further ring closure. 

In Scheme 7, the peroxidic 0-0 bond of the hydroperoxyl group is broken together with /1-scission of the formed alkoxyl radical, and, further, ring closure of alkyl peroxyl diradical may occur. The process generates a hydroxyl radical, methylcarbonyl terminal groups (-CH2-CO-CH3) and dioxetane. The latter is unstable and decomposes into an excited triplet state of formaldehyde and/or excited triplet state of methylcarbonyls (Scheme 8). 

Photocycloaddition of l,2-dichloro-l,2-difluoroethene to hexafluoroben-zene produces an unstable ortho adduct that during the irradiation undergoes further ring closure, yielding 3,4-dichloro-l,2,3,4,5,6,7,8-octafluorotricy-clo[4.2.0.02,5]oct-7-ene [156,157], This was further elaborated into perfluorocy-clooctatetraene [156] and into its valence isomer, perfluorobicyclo[4.2.0] octa-2,4,7-triene [157],... 

Dienes also can alkylate arenes to give products which are generally cyclic. For example, isoprene reacts with 1,2,4-trimethylbenzene in the presence of H2SO4 to give an indane derivative (equation 91). A large number of phenols have been used for alkylations with dienes. The products are either allylated phenols, or products derived by further ring closure of the phenolic oxygen with the side chain derived from the diene. 

As expected, the influence of the halogen in a-halo ketones strongly influences the course of the reaction. At — 10°C, 2-chlorocyclohexanone reacted with pyrrolidine to give the isolable intermediate amino-substituted allylic chloride 6 (X = Cl) in 85% yield, along with 15% of bicyclic aminal. The corresponding a-bromo ketone showed the expected tendency for further ring closure into the cyclopropanone aminal 7, while a-fluorocyclohexanone was completely transformed into the allylic fluoride 6 (X = F). ... 

It is well known that the most direct access to 4-acetoxy-P-lactams is the addition of CSI to the corresponding vinyl acetate [17]. Kametani and coworkers [18] were the first to accomplish the total synthesis of antibiotic ( ) PS-5 by reaction between 3-ethyl-4-acetoxyazetidin-2-one 12 and the lithium enolate of r-butyl a-diazoacetylacetate and further ring closure in the resulting p-lactam 15 by the carbene insertion reaction developed by Merck (Scheme 2). The same authors [19] reported the synthesis of antibiotic ( ) PS-6 starting from the corresponding 4-acetoxyazetidin-2-one 13. 

Recent methods for the synthesis of optically active p-amino acids [115] and further ring closure [116] have also been developed. For instance, the P-amino acid 294 (Fig. 12), has been prepared by reductive amination of 295 [117]. Conversion of 294 to the PS-5 intermediate 293 has been previously reviewed [5f]. 

At the same time, the adjacent SiOH groups on the polymers condense wherever further ring closures are possible, leading to more compact, three-dimensional species, the precursors of colloidal particles. 

It has been shown in previous studies by several fast reaction techniques that the complexation reaction between a metal ion and a bidentate ligand involves several discrete steps (5). As shown in figure 2, step 1 represents rapid (diffusion controlled) formation of an outer-sphere complex and step 2 the formation of a monodentate complex for which the forward rate constant can be identified with that for water exchange (kex) measured by n.m.r. methods. Since PADA is a bidentate ligand, a further ring closure step (3) takes place in which the final product is formed. The rate of ring closure is generally assumed to be rapid compared with the rate of dissociation of the monodentate complex (i.e. kj k 2) ... 

Ortho-para oxidative coupling of the diphenol, reticuline (6.148), can be conceived of as giving the dienone (6.149) which could afibrd thebaine (6.151) as shown [101]. This hypothesis is strongly supported by the observation that this dienone, (6.149), called salutaridine, is a constituent of opium poppies, is formed from radioactive tyrosine (6.94) and norlaudanosoline (6.123), and is a highly efficient and specific precursor for the opium alkaloids. The transformation of salutaridine (6.149) into thebaine (6.151) requires a further ring-closure, which occurs chemically when the two epimeric alcohols (6.150) are treated with acid. In contrast to the purely chemical reaction, only one of the alcohols was efficiently converted into thebaine in vivo, indicating that the reaction is enzyme mediated (and therefore part of normal biosynthesis). 

The emerging addition product is not applicable to further ring closure, because no Si-functional groups exist in the compound. Reactions of derivatives containing several Si—H groups, for example (MeHSi— 112)3 HC = C—... 

As shown in Chart 5.1, a wide variety of alkaloid skeleta are derivable from Type I precursor and tryptamine by further ring closures. It is worth pointing out that in so far as they have been investigated, they all have had the same stereochemistry for the carbon equivalent to C-15 of yohimbine. In this chapter, certain tetrahydro-j8-carboline alkaloids, viz., the yohimbines, their ring E seco equivalents and ring E oxygen heterocycles will be discussed since they show much chemistry in common. Over the years most of their degradation products have been synthesized, they have been interrelated, their absolute stereochemistries derived, and some have been synthesized. For these reasons they have become valuable reference compounds. 

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