Lactones methylene compound

The Tebbe reagent [//-chloro-bis(cyclopentadienylXdimethylalumin-ium)-/r-methylenetitanium] in its pure, crystalline (70,71) or crude (72) forms has been employed for the methylenation of aldonolactones. Thus, D-ribono- 1,4-lactone derivatives 71a and 71b reacted with Tebbe s reagent to give (70,71) the exo-methylene compounds 72a and 72b. 

The electrogenerated Mn(lll)-assisted coupling of various olefins with active methylene compounds proceeds by indirect electrooxidation with a small amount of Mn(OAc)2 in the presence or absence of Cu(OAc)2 [196]. The Mn(Ill)-assisted carboxymethylation of styrenes (142) affords y-aryl-y-lactones (143) in good current yields (Scheme 57) [194, 195, 206, 207], (Table 9). 

The preparation of protected (/ )-2-methyl-cysteine by Fukuyama starts with the enantio-selective discrimination of the prochiral ester groups in 6 with pig liver esterase (Scheme 3) [5]. The ester function of the resulting product 7 is selectively reduced (7 16). Cyclization to the )9-lactone gives compound 17. Attack of the thioacetate at the )9-lactone methylene carbon atom provides the (/f)-compound 18. Selective reduction of the carboxylic acid function in 7 gives the (S)-compound 19 in an analogous fashion. 

Hesse has described an exaltolide (cyclopentadecanolide) (134 Scheme 42) synthesis starting from the readily available 2-cyanocyclododecanone (130). The latter is converted to the quaternary ammonium salt (131), which undergoes fragmentation under mild conditions to provide the lactone (133) via the lactole anion (132). The methylene compound (133) exhibits similar musk odor, as does (134). 

A characteristic part of the molecule of these substances is the a-methylene lactone ring. Compounds possessing this moiety are of great interest also as fungicidal, bactericidal and cytostatic agents. 

Activated methylene compounds such as dimethyl malonate have found substantial utility in palladium catalyzed allylic substitution reactions. Accordingly, the Krapcho decarboxylation is often used in conjunction with these reactions. As an example, the first total synthesis of enantiomerically pure (-)-wine lactone has utilized the sequence of reactions.27 First, the allylic substitution reaction of 2-cyclohexen-l-yl acetate (49) with alkali sodium dimethylmalonate yielded 51 with high enantioselectivity, as a result of the use of chiral phosphine ligand 50. The malonate was then subjected to Krapcho decarbomethoxylation using NaCl, H2O, and DMSO at 160 °C to yield 52. This reaction has been used similarly following the allylic substitution reaction with other malonate derivatives.28-30... 

The branched-3-C-methyl derivative 32 was formed stereoselectivity and in high yield when dimethylcopper lithium in the presence of TmsCl added 1,4-fashion to the corresponding 2,3-unsaturated lactone. Several similar examples were also described including addition of active methylene compounds e.g. diethyl malonate under basic conditions). ... 

A few examples of base promoted domino ring opening lactonization of epoxides with active methylene compounds (malonate, cyanoacetate, acetoacetates) are known earlier in the literature [42]. Pizzo s group has recently described domino nucleophilic ring opening of epoxides by active methylenes, catalyzed by polymer-supported bases, under solvent-free conditions (SolFCs) (Scheme 4.24)... 

Cyclocondensation of 2-hydroxybenzaldehydes (saHcylaldehydes) with reactive methylene compounds (malonic esters, cyanoacetic esters, malononitrile) in the presence of pyridine and other bases also leads - via lactonization of the primary condensation product 19 - to derivatives of coumarin-2-carboxylic acid 20 (Knoevenagel synthesis) ... 

A further small tweaking of the reaction conditions involves great changes a further new cascade channel is breaking. This is accomplished by modulation of the nucleophilicity of the activated methylene compounds applied. When used with isocyanoacetate 87 instead of cyanoacetates 86 as a methylene-activated component, an Ugi-like multicomponent cascade reaction is observed. This reaction was first detected by deployment of ethyl isocyanoacetate 87 in reactions of ribose and proline. In these experiments, proline—once the catalyst in the Knoevenagel condensation/ketalization/oxa-Michael cascade reactions—is directly incorporated into the product. As a result of that, seven-membered lactone 89 is formed. This sharp difference is demonstrated in Scheme 2.18 [40]. 

Boron fluoride Methylene compounds from ketones via / -lactones... 

An important side reaction observed during methylenation of 17a-acetoxy 20-ketones (4) is the formation of the unsaturated lactones (6) in high yield. These compounds arise by aldol condensation and dehydration. 

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