Lactones, hydrolysis Wittig reaction

Reformatsky reaction between either methyl (Z)- or ( )-4-bromo-3-methylbut-2-enoate and /3-cyclocitral (158) gives the 5-lactone (161) as the main product, indicating an E to Z inversion during the reaction. Alkaline hydrolysis of (161) then gave (Z)-/S-ionylideneacetic acid (162), which was also prepared by Wittig reaction.66... 

However, the addition of isoprene (entry 4) reveals a serious lack of regiochemical control under these noncatalyzed reaction conditions. Removal of menthol by methanolysis or hydrolysis (Si02> H2O) afforded enantiomerically pure methoxy- or hydroxy-substituted lactones (424) or (425). Wittig reaction of (425a) provided carboxylic acid (426), a key intermediate for a synthesis of 6,7-dehydroaspidosper-midine. 

In a stereocontrolled route to thromboxane B2, Corey and coworkers used the Eschenmoser rearrangement for the preparation of lactone (91 Scheme 14). The product of the 3,3-sigmatropic shift, amide (90), is directly iodolactonized, thus avoiding often troublesome amide hydrolysis conditions. Another application involving a carbohydrate derivative was demonstrated by Fraser-Reid and coworkers (Scheme 15). Reductive elimination of benzylidene (92), followed by in situ alkylation, Wittig reaction, DIBAL-H reduction and rearrangement, led to amide (94), which was transformed into the corresponding pyranoside diquinane by double radical cyclization. 

A protected version of the aldehyde 174 comes from acetal formation and reduction of the remaining C02H group. Acid catalysed hydrolysis of the acetal gives the lactone 177 that is protected as 178. Hydrolysis and oxidation give 179 ready for the Wittig reaction. 

Conversion of 393 to L-daunosamine (386) is accomplished by reduction of the lactone to lactol 394 followed by a Wittig reaction and acid hydrolysis with 20% HCl—THF (1 1.7)... 

In the synthesis of D-ristosamine (388), all that is required is inversion of the 5-methyl group of lactone 393. This is readily accomplished by opening the lactone ring with potassium superoxide, acidification to pH 4, and a Mitsunobu reaction. Once again, reduction of the lactone to lactol (71% yield) followed by Wittig reaction and acid hydrolysis (HCl, methanol) affords the desired sugar 388, isolated as the diacetate in 23% yield [124]. 

Accordingly, aldehyde 112 and phosphonium salt 113 on Wittig reaction gave alkene 114 (Scheme 6.21) as a single diastereomer, which on spontaneous lac-tonization of C5 alcohol furnished lactone 115. Lactone in 115 was opened under lithium aniline amide conditions to afford the aniline amide, which on protection and Moffat oxidation furnished activated imide 116. Hydrolysis of 116 using... 

Danishefsky has reported a modified route to /ra 5-fused butyrolactones (53) involving attack on a c/j-epoxide (51) by the acetylenic alane (52), followed by acid catalysed hydrolysis and lactonization other anions were found to be unsuitable. Similar fused lactones are available from a -epoxycyclohexanones by sequential Wittig-Horner reaction and acid-catalysed cyclization. 

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