Synthesis of vitamin A derivatives

An olefinic bond can be produced by alkylation of the a-carbanion of a sulphone followed by base-promoted elimination (Equation 1). This process is attractive practically in view of recovery of the reagent. 

Better stereoselectivity for the (all- )-geometry is attained under such heterogeneous conditions in comparison with the homogeneous reaction in methanol or pyridine. This is ascribed to i-yw-elimination in a concerted manner on the surface of the solid base (Fig. 1). 

Alkylation takes place cleanly at the a-carbon, presumably because of the biased equilibrium between dianion 14 and 75 in favour of the charge-separated dianion 14 (Equation 2). 

The elimination is effected by treatment of 16 with an excess of sodium amide in liquid ammonia containing r-BuOH to give vitamin A (17). Again, this protic reagent is crucial for the successful elimination. The content of the (all- )-isomer in the product thus obtained is 67% at best. 

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Tanaka et al. reported a synthesis of vitamin A derivatives from C15 phosphonates [85]. Vitamin A acetate was prepared in 92% yield by reaction of the C15 phosphonate with 2-methyl-4-acetoxy-2-butenal, Fig. (47). 

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]. 

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