Sulphinates 103 Vitamin

Allyl sulphones can be converted to dienes by alkylation and elimination of sulphinic acid under basic conditions (equation 64)105. Several vitamin A related polyenes have been synthesized following this two-step protocol (Table 10)106. The poor leaving-group ability of the arylsulphonyl group requires treatment with strong base for elimination. However, elimination of the allylsulphonyl group takes place readily under palladium catalysis (equation 65)107. Vinyl sulphones can be converted to dienes via Michael addition, alkylation with allyl halides and elimination of sulphinic acid sequence (equation 66)108. 

Retinol Derivatives. Aryl sulphones have been used in two new syntheses in the vitamin A series. Reaction of /8-cyclocitryl phenyl sulphone (102) with the bromo-compound (103) gives the intermediate sulphone (104), which on base-catalysed elimination affords methyl retinoate (98). Alternatively retinol (99) has been prepared in high yield by condensation of the C15 bromide (105) with the C5 hydroxy-sulphone (106), followed by elimination of sulphinic acid. The syntheses... 

After the elimination, water-soluble sulphinates can be readily recovered, in shcirp contrast to the alternative Wittig reaction which inevitably suffers from difficulty in recycling phosphine oxide. The sulphone methodology was applied for the first time to the synthesis of vitamin A derivatives by Julia and has been developed as the Rhone-Poulenc process [1-3]. The initial design to prepare retinoic acid (1) involves coupling between the C 15-bromide 2 and the C5-sulphone 3, followed by treatment of the resulting carboxy sulphone 4 with base (Scheme 1) [1]. 

The alkylation/elimination methodology is also applicable to synthesis of carotenoids. The basic strategies for the apo-8 -p-carotenoids [ 12] and for p,p-carotene (3) [ 13] are depicted in Schemes 10 and 11. Vitamin A acetate (10) was reacted with sodium /7-phenoxybenzene-sulphinate to give the sulphone 31. The reaction of 31 with the bromo compounds 32 and 33, respectively gave the apocarotenoic acid ester 34 and the corresponding aldehyde 482. 

Thiols can be oxidised further using more forcing conditions. For example, MBT above with excess H2O2 gives a sulphinic acid, which can eliminate SO2 in acid to give benzothiazole [230]. A reaction analogous to this is used to make clomethiazole, an intermediate in vitamin Bi manufacture [231]. In alkali, sulphinic acids are oxidised further by H2O2 to sulphonic acids [232]. 

A synthesis of 95% pure all-rran5 vitamin A has been achieved by the ir-allylpalladium complex coupling of appropriate Cs + Cis units in 41% yield. The reaction is accomplished when a stoicheiometric amount of the crystalline Pd chloride complex of prenyl acetate is coupled to the sulphinate of vinyl-/8-ionol. All five possible nor-analogues of all-rran5-geranylgeraniol have now been prepared by conventional procedures. The n.m.r. data are usefully... 

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