Methyl lactones, transesterification

Fig. 11 Enantioselectivity in the CALB-catalyzed transesterification of co-methyl lactones [75]...

Based on these reactivities various derivatives of carbenes, such as the aminocarbene 238, are prepared by displacement of the OR group in 237 with amine via addition elimination, analogous to transesterification [74,75], As an example the carbanion 240, generated by deprotonation of 239, attacks ethylene oxide to give the lactone equivalent 241, which is further alkylated by chloromethyl methyl ether, again at the -position. Finally the oc-methylene-y-lactone 242 is obtained by oxidative demetallation with a Ce(TV) salt [76],... 

Lanthanide-based initiator systems offer a fourth possibility, permitting the block copolymerization of lactones with compounds such as ethylene,tetrahy-drofuran, l-LA, trimethylene carbonate, and methyl methacrylate. Detrimental side reactions such as macrocyclic formation, transesterification, and racemiza-tion are absent and the reactions are extremely fast. 

Transesterification of the /erf-butyl ester 29.1 to the corresponding methyl ester 29 2 [Scheme 6.29] is not straightforward. Typical acid-catalysed cleavage of the tm-butyl ester is precluded by the acid-sensitivity of the fiiran. whereas basic methanolysis suffers from the electrophilicity of the unsaturated lactone. However, brief immersion of a thin layer of 29.1 in a round bottom flask in an oil bath pre-heated to 210 °C, followed by treatment of the crude product with (trimethylsi)y])diazomethane afforded the methyl ester 29.2 in near-quantitative yield.76 The elimination did not proceed in refluxing decalin (190 °C). 

While the polymerization of optically inactive AA-BB and AB monomers under DKR conditions leads to chiral polyesters, these approaches always result in limited molecular weights since a condensation product is formed that needs to be effectively removed. A solution for this would be to use the eROP of lactones, where no condensation products are formed during polymerization. In principle, the eROP of lactones can lead to very high MW polyesters (>80kgmol 1) [57]. Addition of a methyl substituent at the ro-position of the lactone introduces a chiral center. Peeters et al. conducted a systematic study of substituted e-caprolactones which revealed that monomers with a methyl at the 3-, 4-, or 5-position could be polymerized enantioselectively while a methyl at the 6-position (a-methyl-e-caprolactone, 6-MeCL) could not [58]. The lack of reactivity of the latter monomer in a Novozym 435-catalyzed polymerization reaction was attributed to the formation of S-secondary alcohol end-groups. These cannot act as a nucleophile in the propagation reaction since the lipase-catalyzed transesterification is highly R-selective for secondary alcohols. 

In order to prepare the cyclohexenaldehyde 8, 3-hydroxy-2-pyrone 14 and ethyl 4-hydroxy-2-methyl-2-butenoate 15 are subjected to a Diels-Alder reaction in the presence of phenylboronic acid which arranges both reactants to the mixed boro-nate ester 19 as a template to enable a more efficient intramolecular Diels-Alder reaction with optimal control of the regiochemical course of the reaction. Refluxing in benzene affords the tricyclic boronate 20 as primary product. This liberates the intermediate cycloadduct 21 upon transesterification with 2,2-dimethylpropane-l,3-diol which, on its part, relaxes to the lactone 22. Excessive i-butyldimethyl-silyltriflate (TBSTf) in dichloromethane with 2,6-lutidine and 4-7V,A-dimethyl-aminopyridine (DMAP) as acylation catalysts protects both OH goups so that the primary alcohol 23 is obtained by subsequent reduction with lithiumaluminum-hydride in ether. 

A very different route used an unusual lactone (7.262) in a Mitsunobu type transesterification reaction with methanol to give 7.263. Reduction of the ester to an aldehyde with diisobutylaluminum hydride and Wittig olefination gave methyl 3-(N-trityl-4-hydroxy-2-pyrrolidino)prop-2E-enoate, 7.264. 

A range of carboxylic esters undergo mild and neutral transesterification when treated with iodotrimethylsilane followed by an alcohol. The reaction is limited to primary and secondary aliphatic alcohols, and yields between 40 and 98% are obtained. Another non protic trans-esterification method involves treatment of the methyl esters of various carboxylic acids with tetra-n-alkylammonium halide at 140 °C, leading to the production of the corresponding n-alkyl esters. The generality of this method clearly depends on the availability of the required tetra-n-alkylammonium halide. Lactones react with iodotrimethylsilane in the presence of an alcohol to provide a convenient route to iodoalkyl esters in good yield. ... 

The protection of quinic acid was accomplished by T lactone formation, benzyl ether formation at the least hindered secondary equatorial alcohol, and methylation of the remaining two alcohols. The secondary alcohol of the resulting 167 was deprotected (hydrogenolysis) and the alcohol was oxidized to provide ketone 168. A transesterification followed by a )3-elimination provided 169. Protection of the secondary alcohol provided intermediate... 

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