A-hydroxy-y-lactone

In addition, Cushman and co-workers121 reported the synthesis of a 1-hydroxyethylene dipeptide with a Pro moiety at the C-terminus using the reaction between an a-amino aldehyde and a lithium cyclopentanone enolate. Matternich and Liidi 22 described the synthesis of a y-(aminoalkyl)-a-hydroxy-y-lactone starting from the addition of an a-amino aldehyde to a pyruvate enolate. 

Garcia et alf have described the synthesis of a-hydroxy- y-lactones by the alkylation of protected cyanohydrin anions with epoxides. 

The catalytic system has been efficiently applied to the sequential [4 + 2] cycloaddition/ring opening reaction to afford highly enantioenriched a-hydroxylated carbonyl derivatives in excellent yields (Scheme 10.7). A variety of important classes of compounds, such as a-hydroxy-y-lactone, a-hydroxy-y-lactam, factor Xa inhibitor,... 

An aqueous solution of glyoxylic acid reacts with cyclopentadiene to provide a-hydroxy-y-lactones the more acidic the solution, the faster the reaction (Scheme 13) [68]. Thus at pH 0.9 (2.25 M glyoxylic acid solution in water) the reaction is complete after 90 min at 40 °C providing a 83 % yield of a-hydroxy-y-lactones. In the case of cyclohexadiene, the reaction is complete after 2 days at 90 °C in water, compared to 21 h at 120 °C for the reaction with butyl glyoxylate in neat conditions (Scheme 13). These results show that it is possible to exploit the die-nophilic character of a carbonyl group in water in spite of its quasi total hydration. Pyruvaldehyde, glyoxal, and even ketones like pyruvic acid, also react with dienes in water [69]. 

An aqueous solution of glyoxylic acid reacts with cydopentadiene to provide a-hydroxy-y-lactones (Eq. 4) the more acidic the solution, the faster the reaction [41]. 

Calcium chloride a-Hydroxy-y-lactones from / -hydroxy aldehydes... 

Finally, the a-hydroxy-y-lactones could be obtained optically pure, by esterification with acetyllactyl chloride and the resulting acetyllactyl derivatives were separated. Recently, a kinetic resolution of the a-hydro) -y-lactones has been described by Shiina, using an asymmetric acyl-transfert catalyst ((R)-BTM) in the presence of an acetylating agent. 

Synthesis of a-Hydroxy-y-lactones by Addition of a-Hydroxy Carbon Radicals to Unsaturated Esters... 

This new method for the construction of a-hydroxy-y-lactones is quite general for a variety of alcohols and a,P-unsaturated esters (Figure 6.9). The preparation of a-hydroxy-y-spirolactones from cyclic alcohols is especially notable, because these spirolactones have been very difficult to synthesize until now. The reaction can be explained by Scheme 6.18 (i) in situ generation of an a-hydroxy carbon radical from an alcohol assisted by NHPI/Co(II)/02, (ii) the addition of the radical to methyl acrylate, (iii) trapping of the adduct radical by O2, and (iv) intramolecular cydization to give a-hydroxy-y-butyrolactone. Considering the low-cost material, reaction efficiency, and reaction simplicity, this method provides an innovative approach to a-hydroxy-y-lactones which has considerable industrial potential. 

Ring contraction of mesylates of a-hydroxy-y-lactones provides a route to 3 -0-methyloxetanocins. The synthesis of oxetanocin emd oxetanose chemistry has been reviewed (in Japanese). ... 

The initial studies of Lubineau et al. [41] focused on reacting cyclopentadiene with aqueous glyoxylic acid at different pH levels. The reaction rate increased substantially at lower pH. At pH 0.9, the reaction of cyclopentadiene in aqueous glyoxylic acid provides a-hydroxy-y-lactones 128 and 129 in 83% yield (73/27 ratio) after stirring the heterogeneous mixture for 1.5 h at 40°C ... 

The reaction of cyclohexadiene with aqueous glyoxyhc acid at pH 1 is complete after 2 days at 90°C, providing a-hydroxy-y-lactones 131 and 132 (60/40 ratio) in 85% yield [41] ... 

The development of efficient and practical aqueous 0x0 Diels-Alder methodology allowing for convenient access to substituted dihydropyrans and a-hydroxy-y-lactones set the stage for further synthetic exploitation. The following is a brief account of synthetic applications of the aqueous 0x0 Diels-Alder reaction. 

T. Iwahama, S. Sakaguchi, Y. Ishii, Catalytic a-hydroxy carbon radical generation and addition. Synthesis of a-hydroxy-y-lactones from alcohols, a,p-unsaturated esters and dioxygen, Chem. Commun. (2000) 613-614. 

The structure of the non-nitrogenous part of pantothenic acid was re-poited as an a-hydroxy-y-lactone (247) and finally found to be a-hy-droxy-/3,j3-dimethyl-7-butyrolactone (pantoic lactone) (372, 427). Synthe-... 

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