Lactones, alcoholysis

Asymmetric alcoholyses catalyzed by lipases have been employed for the resolution of lactones with high enantioselectivity. The racemic P-lactone (oxetan-2-one) illustrated in Figure 6.21 was resolved by a lipase-catalyzed alcoholysis to give the corresponding (2S,3 S)-hydroxy benzyl ester and the remaining (3R,4R)-lactone [68]. Tropic acid lactone was resolved by a similar procedure [69]. These reactions are promoted by releasing the strain in the four-membered ring. 

Because of the particular structural features of compound 4, pointed out in Section I, the D-glucofuranosyluronic halide anomers not only have inverse thermodynamic stabilities with respect to those of D-glucopyranosyl halides but also show a different behavior towards alcohols. For instance, 2,5-di-O-acyl-a-D-gluco-furanosylurono-6,3-lactone halides, which are difficult to prepare, do not react with alcohols, inasmuch as an endo approach of the reagent is inhibited.14 The /3-bromides and -chlorides, however, just like /3-D-glucopyranosyl chlorides, are subject to alcoholysis, with formation of /3-D-glucofuranosidurono-6,3-lactones.16... 

A recent review has been published on this important topic Except for the method which consists of the alcoholysis in the presence of mercury salts of aldose dialkyldithioacetals, most of the available procedures have been referred to earlier in this Chapter. Glycofuranosyl halides prepared from y-lactones offer a potentially valuable route (p. 410). 

Although the intramolecular aminocarbonylation described above is an extension of the standard amide-forming reaction, a different type of intramolecular aminocarbonylation has been studied, wherein the amine moiety adds across the olefin moiety activated by a Pd catalyst to generate /3-aminoalkyl-Pd species, followed by CO insertion and alcoholysis, forming a lactone or an ester. ... 

On irradiation of 86 (n = 2 and 3) in alcoholic solutions, methyl- (86%), ethyl- (74%), and isopropyl- (52%) esters of the corresponding j-(2-hydroxy-phenyl)-alkane carboxylic acids are formed.40,54 tert-Butanol, however, fails to yield any alcoholysis product whatsoever. A considerable influence of ring substituents on the quantum yield of ethanolysis of the lactones 86 and the... 

Addition to carbonyl group by a nucleophile is commonplace. However, a-lactones undergo alcoholysis with formation of a-alkoxy carboxylic acids [144]. The acceptor role of the carbonyl is restored in the bistrifluoromethyl-a-lactone [145]. It may also be considered that the a-carbon is reluctant to become an acceptor because of the fluorine atoms. 

In an intramolecular variation [57], the acid-promoted alcoholysis of the (3-lactam ring in 10, Scheme 3, produced 2,3-aziridino-y-lactones 11, which are intermediates of glutamic acid derivatives with potential activity as excitatory neurotransmitter of the central nervous system. 

Scheme 3 Intramolecular acid alcoholysis of P-lactams leading to y-lactones...

Esterification of carboxylic acids with alcohols, including bulky secondary ones, by equimolar di-2-thienyl carbonate (2-DTC) in the presence of a catalytic amount of 4-(dimethylamino)pyridine in toluene solvent at room temperature followed by addition of a catalytic amount of hafnium(IV) trifluoromethanesulfonate, Hf(OTf)4, afforded the corresponding esters in good to high yields. In step 1 (Scheme 1), interaction of the acid and 2-DTC (1) produces the thienyl ester (2) with evolution of CO2 and formation of 2(5H)-thiophenone (3). In step 2, the added Hf(OTf)4 forms with (2) an activated complex (4), alcoholysis of which yields the ester (5) and a further molecule of 2(5H)-thiophenone.1 The procedure was also effective for converting [Pg.48]

Chelation with copper(ll) Lewis acids has been used to change the reactivity of bis ketenes toward alcohols. The alcoholysis of 52 in the presence of copper acetylaceto-nate derivatives afforded the cyclic lactones 54 (Sch. 14) [35]. The addition of alcohols to 52 without the Lewis acid led to the formation of ketene esters 53 which would not undergo cyclization upon treatment with the copper(ll) complexes. It is suggested that chelation of the bis-ketene in a jr-fashion accounts for the lactone products. Although chiral Lewis acids were used, the products were obtained as racemates probably because of very facile epimerization. 

The hydrolase-catalyzed reactions utilized most for the selective transformation of such substrates are hydrolysis (Schemes 11.1-1, 11.1-2, 11.1-4, 11.1-5 and 11.1-11), acylation (transesterification) (Schemes 11.1-3, 11.1-6 and 11.1-11) and alcoholysis (transesterification) (Schemes 11.1-7,11.1-8 and 11.1-15). Hydrolase-catalyzed esterification of an alcohol with a carboxylic acid, although highly useful in some casesl6Z, has been utilized to a lesser extent. Catalysis of formation and cleavage of the C-O bond of an ester or lactone by pig liver esterase, most lipases, a-chymotrypsin and subtilisin, which are all serine hydrolases, involves the following steps (Scheme... 

Lipase-catalyzed enantiomer-differentiating inter- and intramolecular alcoholysis of acylated alcohols and lactones in organic solvents may most advantageously be used instead of hydrolysis in aqueous solution in those cases where insufficient stability, high solubility or low functional group selectivity is observed or may be anticipated in the latter case (1-16) (TSble 11.1-22). 

Alcoholysis of y-and P-lactones gives access to enantiomerically pure y-hydrox-yesters and y-lactones (17-24) and P-hydroxyesters and p-lactones (55-63), respectively. Enantiomerically pure enol acetates 67a and the y-acetoxybutenolide 51/ewt-51 have been obtained by hydrolysis of the corresponding racemic substrates. 

As well as the above-described intermolecular alcoholysis of esters, the intramolecular version has been successfully utilized for the synthesis of lactones from racemic hydroxy carboxylic acid esters (25-41, 64—66) (Table 11.1-22). High selectivity in the pig pancreas lipase-catalyzed enantiomer-differentiating lactonization of y-hydroxy carboxylic acid esters with formation of butyrolactones substituted in... 

Table n.1-22. Lipase-catalyzed enantiomer- and enantiotopos-differentiating inter- and intramolecular alcoholysis of esters and lactones in organic solvents (PCL Pseudomonas cepacia lipase, PSL Pseudomonas sp. lipase, PPL pig pancreas lipase, MML Mucor miehei lipase, HLL, Humicola lanuginosa lipase, PFL Pseudomonasfluorescens lipase, CCL Candida cyiindracea lipase, CAL-B Candida antarctica B lipase, CRL Candida rugosa lipase, PRL Penicillium roquefbrti lipase, CAL-A+B Candida antarctica A+B lipase). 

Ring cleavage. Catalyzed hy Sc(OTf)3, alcoholysis of epoxides and aziridines proceeds at room temperature. The ring opening of mei oepoxides is rendered asymmetric if a chiral ligand such as 1 is added to the reaction medium. Lactones give polymers via alcoholysis. ... 

Derivatives of 5-amino-5-deoxy-L-arabinonic (58) and o-xylonic (59) acids were prepared from the respective per-O-methyl aldono-1,5-lactones (56 and 57). Opening of the lactone by alcoholysis followed by tosylation of... 

Alcoholysis of lactones occurs with ring fission analogously to the cleavage of esters to hydroxy carboxylic esters.868-870... 

Alcoholysis of p-lactones provides optically active P-hydroxy esters in one-half of the original quantities."... 

Lactone opening A crucial operation in a synthesis of 12a-deoxytetracycline requires a mild alcoholysis of a lactone under conditions precluding closure of the B-ring, because intermediates with the linear tricarbocyclic array resist further cyclization. After successful lactone opening by treatment with Bu,SnOMe, the a-tetralone unit can be masked as a lactol silyl ether to permit a Dieckmann cyclization to form the A-ring. 

In aqueous acidic media, no appreciable degradation of pristinamycin 1 was observed after 24 hours at room temperature at pH close to 1. In contrast, the macrocycle was very sensitive to basic media at pH above 9 cleavage at the lactone occurs, the rate of reaction depending on the pH value of the medium. The same behavior has been described for virginiamycin [42]. Mild aqueous hydrolysis or alcoholysis under alkaline conditions resulted in formation of the ring-opened hydroxy acid (10) or the corresponding ester, respectively [43]. These ring-opened compounds did not display any antimicrobial activity. 

Scheme 5.5 Alcoholysis of biaryl lactones with metallated (if)-menthoxides.

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