The Betzer and Ardisson Synthesis of -Discodermolide

The first use of 5 was the addition to the aldehyde 4. The product 6 was ozonized, and the resulting aldehyde was earned on to the cc,P-uiisatuiated ester. Exposure of the hydroxy ester to benzaldehyde under basic conditions delivered, by intramolecular Michael addition, the 

The next addition of the reagent 5 was to the aldehyde 10. The adduct 11 was deproto-nated with -Btii to effect a limination, providing, after protection of the alcohol, the aU e. up g of 12 with the amide 7 gave a ketone, enantioselective reduction of which under Itsnno-Corey conditions led, again after protection of the alcohol, to the alkyne 13. 

Oxidation followed by selective hydrogenation and iodine-tin exchange then completed the assembly of 1. Note that PtOj, not typically used for partial hydrogenation, was the catalyst of choice for this congested alkyne. 

The third application of the enantiomerically-pure reagent 5 was addition to the aldehyde that had been prepared by ozonolysis of 15. Advantage was then taken of another property of the alkenyl carbamate, Ni-mediated Grignard coupling, to form the next carbon-carbon bond with high geometric control. Deprotection of the diene 17 so prepared followed by iodination then completed the synthesis of 2. 

The convergent coupling of 1 with 2 was carried out imder Suzuki conditions. Reduction of the iodide of 2 to the corresponding alkyl Uthium followed by exchange with B-OMe-9-BBN gave an intermediate organoborane, that smoothly coupled with 1 imder Pd catalysis to give 18. Deprotection and carbamate formation then led to (+)-discodermolide 3. 

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