Lactones, preparation from anhydrides

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Lithium 2-thiophenethiolate, readily prepared from thiophene, -butyllithium, and sulfur, reacts with / -butryo-lactone to give carboxylate derivative 98 which can be readily acidified to the free acid. Cyclization in the presence of trifluoroacetic anhydride gives thieno[2,3-3]thiopyran (Scheme 27) <1996TA2721>. 

Fleet and co-workers (75a) synthesized various tetrazoles from manno- and rhamnopyranoses, as well as furanoses, based on the intramolecular 1,3-dipolar cycloadditions of azides with nitriles (Scheme 9.75). All of these tetrazoles were tested for their inhibitory activities toward both glycosidases and other sugarprocessing enzymes. D-Mannopyranotetrazole (397) was prepared from L-gluono-lactone (393). Azide 394 on ring opening with ammonia followed by dehydration with trifluoroacetic anhydride gave the azido nitrile 395. Intramolecular 1,3-dipolar cycloaddition of 395 in refluxing toluene followed by deprotection produced the D-mannopyranotetrazole 397 in 86% overall yield. 

Albertsson and coworkers [240-244] carried out extensive research to develop polymers in which the polymer properties are altered for different applications. The predominant procedure is ring-opening polymerization which provides a way to achieve pure and well defined structures. They have utilized cyclic monomers such as lactones, anhydrides, carbonates, ether-lactones. The work involved the synthesis of monomers not commercially available, studies of polymerization to form homopolymers, random and block copolymers, development of cross-linked polymers and polymer blends, surface modification in some cases, and characterization of the materials formed. The characterization is carried out with respect to the chemical composition and both chemical and physical structures, the degradation behavior in vitro and in vivo, and in some cases the ability to release drug components from microspheres prepared from the polymers. 

The photochemistry summarized in Scheme I at the beginning of this review is that observed in the absence of oxygen. It has been known for many years 7) that preparative reactions of a-diketones should be performed in an inert atmosphere and that reproducible results in mechanistic studies can only be obtained if careful degassing procedures are employed. The products formed in the presence of oxygen are anhydrides (or the derived carboxylic acids) and, in special cases, lactones derived from de-carbonylated intermediates. An obvious explanation for this behaviour was that triplet states of diketones act as sensitizers for formation of singlet oxygen which then reacts with ground state diketone. 

The dihydroxy lactone from L-threonic acid is prepared from L-dibenzoyl tartaric anhydride by catalytic hydrogenation over palladium. The substituted anhydride is formed from tartaric acid and benzoyl chloride. 

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

The preparation of the lactone 291 (R = H) has already been described (Vol. 4, p. 486, Ref. 243), and this route to chrysanthemic acid has now been improved by making the optically active lactone, starting from commercially available optically active phenylglycinol (reduction of a-phenylglycine) and the anhydride... 

In a second synthesis of 8-deoxyvemolepin, described by Yoshikoshi (Scheme 33) [43], ozonolysis of compound 264, prepared from compound 247 (see Scheme 31), followed by treatment with acetic anhydride provided the formyl lactone 265 in moderate yield. Since this product was unstable it was immediately reduced with sodium borohydride to give the corresponding alcohol 266. After protection of the hydroxyl group the... 

Racemic Malolactonate. The first cyclic monomer prepared was the benzyl ester of the 3-lactone of malic acid. Initial attempts to make the lactone directly from malic acid itself were unsuccessful, so bromosuccinic acid was chosen as the starting material. This compound was converted to its anhydride by refluxing in acetyl chloride, and the anhydride was reacted with benzyl alcohol to yield a mixture of the two bromosuccinic acid monobenzyl ester isomers. Only one of these esters, IIIB, is capable of being converted to the lactone by... 

Isobenzofuran, MA Diels-Alder adduct, 127, 129 Isobenzothiophene, MA Diels-Alder adducts, 129 Isobutene, MA copolymerization, 338, 339, 402, 522, 524, 533, 539, 586 Isobutenylsuccinic anhydride hydrolysis to lactone, 176 MA copolymerization, 342 maleimide copolymerization, 342 preparation from MA, 14 Isobutoxysuccinic acid, preparation, 46 Isobutyl acrylate, MA copolymerization, 530, 532 Isobutylene... 

Phthalides.—Substituted bromobenzenes (96 R = Br) can be carbonylated in the presence of catalytic amounts of Pd(OAc)2 to give phthalides (97 n = 1) and other lactones (97 n = 2, 3) in yields ranging from 42— 70%. (For much the same reaction, see ref. 94). Alternatively, a sequence of thallation [T1(02CCF3)3] and Pd"-catalysed carbonylation can be used to convert benzyl alcohols (96 R = H) into lactones (97). ° The latter method can also be used to prepare phthalic anhydrides from benzoic acids. Presumably both methods will be largely restricted to symmetrical substrates. The dianions (98) can be obtained from the parent benzyl alcohols using Bu"Li in hexane at 0 C they react with CO2 to give good yields of 7-methoxyphthalides. ... 

Other reagents used for the preparation of lactones from acid anhydrides are lithium borohydride [1019], lithium triethylborohydride (Superhydride ) [1019] and lithium tris sec-butyl)borohydride (L-Selectride ) [1019]. Of the three complex borohydrides the last one is most stereoselective in the reduction of 3-methylphthalic anhydride, 3-methoxyphthalic anhydride, and 1-methoxynaphthalene-2,3-dicarboxylic anhydride. It reduces the less sterically hindered carbonyl group with 85-90% stereoselectivity and is 83-91% yield [1019]. 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

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