Homer reaction, building block

Dimethyl (2/ ,3 )-tartrate provides the central C4 building block. Homer olefination is used to attach the C2 building block at one end. Asymmetric Sharpless epoxidation converts the resulting olefin to the Cg epoxide. The Cn chain, produced from the Cg and C3 building blocks, is attached at the other end. The missing Ci atom is provided by CH2N2 an Arndt-Eistert reaction leads, via the Cxg diazo ketone, to the Cjg hydroxycarboxylic acid. Cycliza-tion of the seco-isomer gives enf-100 Scheme 52). 

The analogous Homer variation of the Wittig reaction was shown to provide high (Ej-selectivity (>98%) for the new carbon-carbon double bond and to preserve the (Zj-configuration in the building blocks [10,11] (Scheme 3). A major drawback, however, is the low yield (10-30%). 

Starting from L-ascorbic acid, a chiral building block from nature, 2,3-isopro-pylidene-L-glyceraldehide 21 was obtained and subjected to an il-selective Homer-Wadsworth-Emmons-type reaction [38] with phosphonate 22 to give -alkene 23. Two-step manipulation of the diol unit in 23 afforded 24 which underwent y-allylic coupling to (R)-25 with 97% e.e. and 77% yield. In the last three steps, cyclic ketone (45)-4 was obtained, with approximately 65% yield. This can be converted to sertraline by one of the routes described above. 

Example 9.8 This is an example of the creative use of a chiral building block from nature in the synthesis of (+)-sertraline (15,46 )-TM 9.3. Asymmetric synthesis starts from D-glyceraldehyde available by oxidative splitting of maimose or ascorbic acid [23]. Protected as acetal 17, this aldehyde is coupled to -alkene 19 with phosphonate 18, a reagent in the Homer-Wads worth-Emmons reaction (Scheme 9.13). 

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