Reactions of lactones

Lipases have also been used as initiators for the polymerization of lactones such as /3-bu tyro lac tone, <5-valerolactone, e-caprolactone, and macrolides.341,352-357 In this case, the key step is the reaction of lactone with die serine residue at the catalytically active site to form an acyl-enzyme hydroxy-terminated activated intermediate. This intermediate then reacts with the terminal hydroxyl group of a n-mer chain to produce an (n + i)-mer.325,355,358,359 Enzymatic lactone polymerization follows a conventional Michaelis-Menten enzymatic kinetics353 and presents a controlled character, without termination and chain transfer,355 although more or less controlled factors, such as water content of the enzyme, may affect polymerization rate and the nature of endgroups.360... 

The reaction of lactones of benzyl alcohols with Et3SiH/TFA results in complete reduction of the alcohol part of the lactone to the methylene group while preserving the carboxylate function (Eq. 148).305... 

Addition of alcohols to lactones results in the formation of orthoacid or orthoester derivatives. Thus, reaction of lactone 95a with potassium cyanide in ethanol led to displacement of the tosyl group by cyanide and addition of ethanol to the lactone carbonyl group, to give the orthoacid derivative 95b, which was isolated as its acetate 95c. Mild deacylation of 95c led back to 95b, but under more vigorous reaction conditions the open-chain methyl aldon-ate was obtained (90). 

Aldonamides are readily prepared by reaction of lactones with liquid ammonia (86,99,100), with ammonium hydroxide (101,102), or by bubbling ammonia gas into alcoholic solutions of the sugar lactones (103-104). Aldonamides of the tetronic adds are stable in aqueous solution (105), but penton- or hexon-amides are hydrolyzed, as shown by the change of the optical rotation of the amide solutions (106). The hydrolysis is catalyzed by acids and bases, and the product was the ammonium salt of the aldonic acid. 

The reverse reaction of lactonization of pilocarpic acid is proton-catalyzed and, hence, favored at low pH. Thus, the pilocarpine/pilocarpic acid ratio was 1.0, 1.6, 2.7, 4.0, 5.1, and 6.7 at pH values of 6.0, 5.6, 5.2, 4.8, 4.4, and 4.0, respectively [161]. Interestingly, the lactonization of isopilocarpic acid is ca. 17-fold faster than the lactonization of pilocarpic acid, since the second-order rate constants of proton-catalyzed lactonization at 25° were 0.96 and 0.055 M-1 min-1 for isopilocarpine and pilocarpine, respectively [162], A lack of planarity in the lactone ring of pilocarpine, and a more lac-tone-like planarity in isopilocarpine, appear to account for this difference in reactivity between the two epimers. 

A three-component reaction of lactone 178 with cyanoacetic derivatives in ethanol or ionic liquid (bmimlPFg proceeds smoothly with formation of 2-aminopyrans 221 in high yields (04RCB724, 08JCO741, 08RCB2373), while kojic acid 181 acts in the same manner (04RCB724) (Scheme 83). 

The enolate generated by reaction of lactone 88 with lithium diisopropylamide (LDA) is quenched with an excess of methyl iodide to give methyl lactone 89 in excellent yield. As expected, the electrophilic attack is stereoselective for the less sterically hindered convex face of the lactone enolate, giving the product with the desired 7iJ-stereochemistry with greater than 95 5 selectivity (Equation 22) <1997TL3817>. 

The photoalkylation reactions of lactones, lactams and keto-ethers seem to be free radical reactions. It would be too early to draw a final conclusion about the detailed mechanism of these reactions however, the fact that they can also be induced with peroxides at elevated temperatures provides a good indication as far as the nature of these reactions is concerned. 

With more complicated structures such as lactones the identification problems become more complex as the reaction of lactones in water result in the formation of a carboxylic acid group and a neighbouring phenol... 

Few chemical reactions of lactone-carbonylcobalt complexes have been reported. Hydrogenation 24) of butenolactone-heptacarbonyldi-cobalt, Co2(CO)g(HC2H), gives y-butyrolactone, butyric acid, and dodecacarbonyltetracobalt. Treatment of the same lactone complex with sulfuric acid in warm acetone 50, 125) gives a cobalt cluster compound of formula Co3(CO)gCCH=CHCOOH. The use of methyl alcohol in place of acetone in the latter reaction yields Cog(CO)gCCH=CHCOOMe. 

Dichloro-2/f-l,4-oxazin-2-one 1513 reacts with a-amino ketones e.g. 1514 to yield bicyclic imidazo-fused intermediates 1516 via an intramolecular cyclization reaction. Reaction of lactones such as 1516 with various nucleophiles generates substituted l//-imidazoles such as 1517 (Scheme 392) <1999T3987>. 

Horton, D, Priebe, W, Synthetic routes to higher-carbon sugars. Reaction of lactones with 2-lithio-l, 3-dithiane, Carbohydr. Res., 94, 27-41, 1981. 

This methodology may be illustrated by the synthesis of exocyclic epoxide 50 (a key compound for the preparation of sugar-lysine chimeras), which was realized by reaction of lactone 49 with methyl bromoacetate (O Scheme 18) [38]. 

Recently, Mudryk and Cohen have found that reactions of lactones with organocerium reagents provide lactols in go yields, as exemplified in Scheme 10. This reactiim leads to an efficient (xie-pot synthesis of spiroketais, as illustrated in Scheme 11. ... 

The reaction of lactone (459) with p-tolylsulfonylmethylmagnesium iodide, followed by reduction of the keto sulfone to the 3-hydroxy sulfone has been studi. ° In this paper, the 3-hydroxy sulfone was reduced to the alkene (460) electrochemically (equation 106). The me c was applied to a wide variety of esters and lactones. The yield of the reduction to the methylene derivative was 70-87%. 

From a mechanistic point of view the first steps of the catalytic cycle should be similar to the telomerization of butadiene itself (Scheme 2). The catalytic precursor generates the Pd(0) species A that reacts to the bis-(ri -allyl) complex C. The C,C bond formation between two C4 units is followed by insertion of carbon dioxide into a Pd,C bond affording the carboxylate intermediate D. Different pathways have been discussed to describe the multiple product formation (refer to ). Interestingly, a bis-(carboxylato) complex may be prepared directly from the reaction of lactone 1, palladium acetate and P(i-Pr)3. This complex was structurally characterized by Behr and co-workers and shows good activity as catalyst. Reviewing the literature, there are some remarkable facts and open questions of theoretical and technical interest ... 

The reaction of lactones with trialkyloxonium salts furnishes lactonium salts, e.g. (404 equation 188), which react with alkoxides to give cyclic orthoesters. - - ... 

Shimizu, T., Osako, K., Nakata, T. Efficient method for preparation of N-methoxy-N-methyl amides by reaction of lactones or esters with MezAICI-MeONHMe HCl. Tetrahedron Lett. 1997, 38, 2685-2688. 

Nucleophilic substitution and electron transfer in the ring-opening reactions of / -lactones 02JHC1249. 

Triethyl phosphite attacks P-propiolactones at the P-carbon at 160°C to give predominantly diethyl 2-(ethoxycarbonyl)ethylphosphonate resulting from a C-0 bond cleavage of the lactone ring. - Bases such as tertiairy amines and sodium alkoxides catalyze the reaction of lactones with phosphites. ... 

Coover, H.W., Jr., and Diekey, J.B., Reaction of lactones with trialkyi phosphite, Eastman Kodak, U.S. Patent Appl. US 2652416, 1953 Chem. Abstr, 48, 10053f, 1954. 

With this new approach in mind, the revised retrosynthetic analysis would utilize two different Wittig reactions to homologate the carbon side chains, providing ketoolefm (+)-16 (Scheme 13). Further disconnection revealed hydroxy aldehyde (+)-27 which could arise from a selective DIBALH reaction of lactone (+)-28. Applying Bringmann s method, lactone (+)-28 would be enantiomerically enriched via a kinetic resolution of a racemic lactone mixture. Racemic lactone ( )-28 could arise from a... 

Reaction of lactones with the Grignard reagent proceeds as follows ... 

The Tebbe reagent is quite useful in that it reacts with the carbonyl of esters to give vinyl ethers. Pine showed that 683 reacted with methyl benzoate to give an 81% yield of 1-methoxy-l-phenylethene. O Similar reaction of lactone 686 with 683 gave the exo-methylene vinyl ether 687 in Holmes synthesis of (+)-laurencin.571 The Tebbe reagent also reacts with conjugated esters via 1,2-addition to give the vinyl ether. ... 

A. P. Tulloch, A. Hill, and J. F. T. Spencer, Fermentation of long-chain compounds by Tor-ulopsis apicola. V. Structure and reactions of lactonic and acidic sophorosides of 17-hydro-xyoctadecanoic acid, Can. J. Chem., 46 (1968) 3337-3351. 

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