Lactones, from

FUJIMOTO - BELLEAU Cyclohexenone Synthesis Synthesis of fused cyclohexenones from lactones (an alternative to the Robinson annulation). 

General synthetic routes to spiroketals 189 from lactones and lithiomethoxy-butenyne 184 have been described (83TL5303 88JOC652 89JOC1157 90JOC5894). Three synthetic schemes have been realized. 

By analogy, thermal cyclization was described also for 6-nitro-2 -hydroxy-biphenyl-2-carboxylic acids, e.g. 14, obtained by other methods. The same product 15 was also formed from lactone 17, prepared by oxidation of fluorenone 16 (Scheme 2). If the reaction was performed in DMF, the corresponding dimethylamide was isolated (82KGS703, 86KGS852, 87KGS314, 89MI1). 

Vinyl triflates derived from lactone enolates are also viable coupling partners In Ni(ll)/Cr(ll)-mediated carbon-carbon bond forming reactions... 

Indole-2,3-quinodimethanes [44] 44 are bicyclic outer-ring dienes that are widely used to prepare a variety of heterocyclic polycyclic compounds. These dienes, generated by extrusion of CO2 from lactones, are then trapped by dienophiles. Some examples of Diels Alder reactions of the dienes 44 are reported in Scheme 2.19. 

Ketone (16) can be made by the cyclisatlon route" as the y-chloroketone (17) comes from lactone (18)... 

Pipecolic acids substituted at the 2-position were obtained from lactones by simultaneous 0- and N-deprotection on 10% Pd/C (0.08 mol Pd/mol) in EtOH-AcOH (2 1) for 1 hour (Scheme 4.75).318... 

Scheme 6.177 a-Methylenation of ketones [335], lactam formation from lactones [336], urea formation [337], and Knoevenagel condensation [338, 478]. 

The procedure was proved to be general for the preparation of protected hydroxy acids from lactones (121). This apparently trivial process is often difficult to carry out, as the attempted derivatization of y or J-hydroxyacids frequently results in relactonization rather than hydroxyl protection. The method was applied to several aldonolactones to produce the corresponding intermediate hydroxyamides. Protection using [(2-trimethylsilyl)-ethoxy]methyl chloride, methoxymethyl chloride, ter/-butylchlorodimeth-ylsilane, or zm-butylchlorodiphenylsilane followed by ozonolysis gave the protected N-(y- or <5-hydroxyacyl)indole derivatives. Mild saponification gave indole and the acetal- or silyl-protected hydroxy acids. 

Another interesting approach was developed by Ikegami and coworkers, who used an anomeric orthoester as the key intermediate (Scheme 7.14).59 Formation of orthoester 16 from lactone was effected by TMSOTf and TMSOMe. Subsequent Lewis acid mediated reduction afforded p-mannoside in high selectivity, presumably because of the stereoelectronically controlled hydride delivery from the a face. 

Reduction of lactones leads to cyclic bemiacetals of aldehydes. With a stoichiometric amount of lithium aluminum hydride in tetrahydrofuran at —10° to —15° and using the inverse technique, y-valerolactone was converted in 58% yield to 2-hydroxy-5-methyl tetrahydrofuran, and a-methyl-5-caprolac-tone in 64.5-84% yield to 3,6-dimethyl-2-hydroxytetrahydropyran [1028]. Also diisobutylaluminum hydride in tetrahydrofuran solutions at subzero temperatures afforded high yields of lactols from lactones [7024]. 

Silyloxypropanols (314) derived from lactones undergo oxidative ring expansion to afford higher homologous o ,/3-unsaturated lactones (316) (90TL197). The reaction proceeds through the fluoride ion assisted formation of intermediate 315, which on reductive elimination of F " species yields the product (Scheme 80). 

What kind of polymers are made from lactones ... 

Synthesis of Heterocyclic Compounds Starting from Lactones, Lactams, and Thiollactones ... 

M. Lakhrissi and Y. Chapleur, Efficient synthesis of dichloroolefins from lactones and acetates, J. Org. Chem., 59 (1994) 5752-5757. 

Esters are prepared by reaction of aldonic acids or lactones with an alcohol in the presence of hydrogen chloride 80 the reaction is slower with 1,4-lactones. Amides are readily formed from lactones by reaction with liquid ammonia followed by evaporation of the solvent.81 D-Gluconamide has also been prepared by treatment of D-glucono-1,5-lactone with concentrated ammonium hydroxide and subsequent precipitation with ethanol.82 A-Substituted aldonamides may be obtained by reaction of the aldono-lactones with ethanolamine, diethanolamine, and related species.83... 

Instead of enol triflate, the enol phosphate 334, derived from lactone 333, is used for the coupling to afford the cyclic enol ether 335. No coupling of phenyl phosphate... 

Figures for the dissociation constant and relative affinity have no theoretical significance, but they provide a useful measure of the inhibitory power (of the solution) resulting from lactonization. 

Spiroketals and oxaspirolactones.1 An improved route to spiroketals from lactones involves use of cerium 3- or 4-cerioalkoxides such as 1, prepared from 3,3-dimethyloxetane by reductive cleavage with lithium di-r-butylbiphenylide (LDBB) followed by transmetallation. Use of the intermediate lithium 3-lithioalkoxide as the... 

Cyclic ethers from lactones. The ready addition of RLi to the C=S group of thionolactones (14, 9) has been used to prepare functionalized cyclic ethers from lactones of the same ring size. The first step involves Lawesson thionation of lactone... 

Polyesters from Lactones Deriving from 1,3-Propanediol.149... 

The production of polyesters from lactones (cyclic esters) avoids the problems usually encountered in traditional polyester synthesis due to esterification equilibrium and water production. In fact, they yield in a single step, in the presence of ROP catalysts, high molecular weight polymers endowed with optimum mechanical properties. This is particularly true when large lactones are used as starting monomers. On the other hand, one of the main drawbacks connected with their use lies in their high cost. 

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