Silyl-Protected Lactaldehydes

TBS-protected lactaldehyde 689 is readily prepared with high enantiomeric purity by a mild oxidation of the propanol 688 under Swem-type conditions using bis(trichloromethyl)car-bonate (triphosgene)-DMSO [203]. Triphosgene is a white crystalline solid that is easily handled, and it is a safe alternative for such other DMSO activators as phosgene or diphosgene dimer. 

Alternatively, 689 is available from lactate esters 401 or 402 by partial reduction with diisobutylaluminum hydride at —78 °C [117,129,148]. Yields for this process typically range from 76-100%. 

The avermectins (696) represent an important class of macrolides used in the control of parasitic disease. Two skeletal fi-agments have been synthesized using TBS-lactaldehyde 689 as the source of chirality. 

The first, synthon 697, establishes the stereochemistry at C-12 and C-13 of the macrolide nucleus (afl er introduction of the methyl group at C-12). As an added bonus, the pyridine ring behaves as a masked form of the desired diene. Its synthesis is readily accomplished by a Darzens-type condensation of selenomethyl pyridine 698 with 689. The resulting adduct 699 is formed as an 84 16 mixture of diastereomers. Oxidation of the selenium followed by intramolecular displacement of the phenylselenone by the hydroxyl group affords 697 in 45% overall yield [205]. 

Epoxidation of the olefin leads to a mixture of unstable epoxides which, when ring opened with 2% triethylamine in pyridine, gives allylic alcohols 703 and 704 in 49 and 26% yields respectively. Compound 704, called osmundalactone, is the aglycone of a naturally occurring glycoside isolated from the Vermont royal fern. 

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