Lactones and Thiolactones

Macrocyclic 14-membered lactams, lactones, and thiolactones 211 have also been prepared from 3-amino-l,2,5-thiadiazole-4-carboxylic acids 210 (Equation 47) <1996CHE975>. 

Few relevant data are available. Both equilibrium and rate constants have been measured for very few reaction series in solution, but comparisons are possible for lactone and thiolactone formation, and for a few anhydrideforming reactions (Tables 4 and 5). For lactone formation (Table 4) the EM for the rate process is of the same order of magnitude as that derived from the equilibrium constant data, and in some cases actually exceeds it (though only in one case by an amount clearly greater than the estimated uncertainty which is nominally a factor of 4 for these ratios). Lactonization generally involves rate-limiting breakdown of the tetrahedral intermediate, and the transition state is expected to be late and thus close in structure to the conjugate acid of the lactone. 

Comparison of kinetic and thermodynamic EM s for lactonization and thiolactonization reactions"... 

Hydroxy and 7-thiol acids (32 Z = 0, S) usually cyclize spontaneously to give lactones and thiolactones (33). 7-Amino acids (32 Z=NH) require heating to effect lactam formation (33 Z = NH). 

Pyrrolidine (39 Z = NH) and thiolane (39 Z = S) can be prepared from tetramethylene dibromide 38, and tetrahy-drofuran (39 Z = O) is obtained from the diol 40. -Hydroxy and -thiol acids (41 Z = O, S) usually cyclize spontaneously to give lactones and thiolactones 42. -Amino acids (41 Z = NH) require heating to effect lactam formation (42 Z = NH) (Scheme 31). 

These methods parallel the syntheses just described for the five-membered rings. As indicated in structures 5158, standard reactions of aliphatic chemistry can be extended to the preparation of piperidines, tetrahydropyrans, and tetrahydrothiopyrans (53 Z = N, O, S) glutarimides, glutaric anhydrides, and glutaric thioanhydrides (55 Z = N, O, S) and -lactams, -lactones, and -thiolactones (58 Z = N, O, S) (Scheme 37). 

The transition-metal-catalyzed carbonylation reaction has been extensively investigated, and especially the carbonylative ring expansion reaction of strained heterocycles has been shown to be a useful and efficient procedure to synthesize lactams, lactones, and thiolactones.203 The carbonylation of epoxides and aziridines 450 is a powerful tool to construct the /Mactone and /Mactam skeletons 451 (Scheme 142).204 This type of reactions can be regarded as a hetero-[3 + 1]-cycloaddition. 

Occhiato and colleagues published the carbonylative coupling of lactam-, lactone-, and thiolactone-derived enoltrillates with boronic acids [29]. Several asymmetrical dienones were formed in moderate to good yields at room temperature under 1 bar of CO with 1-5 mol% of palladium catalyst (Scheme 4.14). This methodology allows for a convergent and rapid preparation of substrates, which are useful in conjugate additions and Nazarov reactions. 

A variety of thioketones have found applicability in the synthesis of heterocyclic compounds. Chloro-thioacetone reacted with trialkoxy-phosphines to give thiirans. Thiophens have been prepared from mono-thio-j3-diketones, j8-thioketo-esters, > and from a-thioketo-acids. a-Thioacyl-y-lactones and -thiolactones rearrange in acid alcoholic solution to give dihydrofurans and dihydrothiophens, respectively. The simultaneous action of carbon disulphide, sulphur, and triethylamine on aliphatic thioketones gave mixtures of l,2-dithiole-3-thiones and 1,3-dithiole-2-thiones. The formation of thio-ozonides (1,2,4-trithiolans) by... 

Similar views have been expressed by Dafforn and Koshland(4), who found that the rates of formation of some 5-membered ring lactones and thiolactones, although somewhat less spaced in sulpho-lane than in water, follow the same trends in the two basically different solvents (Table II). 

Semi-stabilized arsonium ylides react with lactones and thiolactones to give products of olefination. For example, the ylide from triphenylbenzylarsonium bromide and sodium hydride reacts with benzo-a-pyrone to give the benzylidene (35) as the exclusive product. Carbonyl-stabilized arsonium ylides fail to condense with benzo-a-pyrone. 

Oxazolones (azlactones) are a form of activated lactones, so they are included in this section. CAL-B is an effective catalyst for the DKR of various racemic four-substituted-5 (4H)-oxazolones, in the presence of an alcohol, yielding optically active N-benzoyl amino acid esters as illustrated in Figure 6.24 [40]. Enantioselective biotransformations of lactides [72,73] and thiolactones ]74] have also been reported. 

Korte, F. and Vogel, J., Thin-layer chromatography of lactones, lactams and thiolactones, J. Chromatogr., 9, 381, 1962 Chem. Abs., 58, 9609c, 1963. 

The antibiotic thiolactomycin (43), a fermentation product from a Nocardia species containing an unusual thiolactone moiety was patented as antibiotic no. 2-200 and subsequently reported in the literature in 1982 [73,74]. It resembles a sugar-derived a,/3-unsaturated 4-thioglycono-1,4-lactone and was found to be a broad-spectmm antibiotic [75] by interference with the fatty acid metabolism of bacteria and also inhibited inducible /3-lactamases [76]. A de novo synthesis of the racemate was reported by a Du Pont group in 1984 [77]. Chambers and Thomas [78] reported the synthesis of the (55j-enantiomer in 1989 and concluded from its optical rotation that the natural product is the (5i )-enantiomer. 

Free radical methods for the synthesis of lactones, lactams, and thiolactones 00MI5. 

Korte and Vogel [44] have worked on the TLC of lactones, lactams and thiolactones. They were able to separate a large number of compounds belonging to these groups, using silica gel G and the solvents diisopropyl... 

Several approaches to cyclic thio- and dithio-lactones have been described thus, the reaction of y-oxo-esters with HjS gave 5-mercaptothiolan-2-ones (123) (see Vol. 5, p. 249). A general approach to y- and -thiolactones, e.g. (124), involves the reaction of a bis-metallated thioacid with a- or /6-chloro-ketones and cyclization of the resulting y- or <5-chloro-y6-hydroxy-thioacids. Reactions of cyclic lactones with the dimeric phenylthionophosphine sulphide (125) gave dithiolactones. y-Dithiolactones, e.g. (126), were obtained from 2-alkenyl alkanedithioates, which... 

A simple, well known and inexpensive route to J -oxazolines involves the condensation of an amino alcohol with a carboxylic acid. Replacement of the acid by a lactone (or thiolactone) has led to useful functionalized derivatives (Scheme... 

It has been shown that Lewis acid catalyzed isomerization of thionolactones provides access to thiolactones. For example, exposure of the substrate 22 to catalytic amounts of BF3 OEt2 led to efficient conversion to the thiolactone 23. Such transformations were also found to give minor amounts of lactone or dithiolactone side products <06TL6067>. Substituted tetrahydrothiophene derivatives have also been obtained from 1,4-dithiane-2,5-diol and 2-nitroethyl acetate derivatives by a base induced sequence featuring a Michael addition and a Henry reaction <06TL8087>. 

The cyanobromide (371) was condensed with the bc portion (347) to give the thioether (372) sulfide contraction to give (373) was accomplished using tris(/3-cyanoethyl) phosphine, and with phosphorus pentasulfide the thiolactam-thiolactone (374) was produced. After treatment with Meerwein s salt, reaction with dimethylamine opened the lactone with concomitant formation of an exocyclic methylene group, and subsequent treatment with cobalt chloride or iodide gave the chelate (375) which was reacted with diazabicyclononane to give bisnorcobyrinic add [Pg.435]

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