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Total Synthesis Highlights

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similar ee at 60°C and 60 psi. Brown crotylation of the derived aldehyde 10 delivered 11, that was<br />

homologated to the alkyne 12.<br />

The third fragment 13 was prepared by chiral auxiliary directed aldol condensation. Combination<br />

of 12 with 13 was followed by Au-mediated cyclization, converting the internal alkyne of 14 to<br />

the spiroketal of 15. Pd-catalyzed coupling of 15 with 7 then led to 2 with high diastereocontrol.<br />

The aldol addition of the enolate of 17 to 18 proved elusive under the usual conditions, but with<br />

30 mol % of the Zn catalyst 1 the reaction proceeded smoothly, to deliver 19 with high<br />

diastereocontrol.<br />

To complete the synthesis, hydroboration with 9-BBN was effected on the free carboxylic acid 3,<br />

and Pd-mediated coupling of the derived borane was carried out with the free iodo alcohol 2. As a<br />

result, the product hydroxy acid 20 could be taken directly to the subsequent macrolactonization.

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