Nicolaou Taxol Total Synthesis - C Ring Synthesis

C Ring Synthesis

As shown in Scheme 1, the ring synthesis of ring C began with a Diels-Alder reaction between diene 1.3 and dienophile 1.1 in the presence of phenylboronic acid (1.2), which, after addition of 2,2-dimethyl-1,3-propanediol, gave five-membered lactone 1.8 in 62% yield. Boron served as a molecular tether and aligned both diene and dienophile for this endo Diels-Alder cycloaddition. After protection of the hydroxyl groups as tert-butyldimethylsilyl ethers, reduction of the ester with lithium aluminium hydride and selective deprotection of the secondary hydroxyl group gave lactone diol 1.11. The unusual lactone hydrates 1.9 and 1.10 were isolated as synthetic intermediates in this process.

Lactone diol 2.1, after selective protection, was reduced with lithium aluminium hydride to give triol 2.4. This triol, after protection as the 5-membered ring acetonide, was selectively oxidized to the aldehyde using tetrapropylammonium perruthenate (TPAP) and N-methylmorpholine N-oxide. Aldehyde 2.6 served as a starting point for the construction of ring B (Scheme 4, compound 4.2).