Asymmetric Hydroformylation-Initiated Tandem Sequences for Syntheses of (+)-Patulolide C, (−)-Pyrenophorol, (+)-Decarestrictine L, and (+)-Prelog Djerassi Lactone

Four
different Rh-catalyzed asymmetric hydroformylation (AHF) tandem
reactions have been developed in the context of the total syntheses
of (+)-patulolide C, (−)-pyrenophorol, (+)-decarestrictine
L, and (+)-Prelog–Djerassi lactone. A total synthesis of (+)-patulolide
C has been accomplished in three steps utilizing a Rh­(I)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of a known
alkyne to give a Z-enol acetate with excellent selectivity.
An AHF/intramolecular Wittig olefination cascade was utilized to set
the C4-hydroxyl stereochemistry, E-olefin geometry,
and form the macrolactone. In addition, both (−)-pyrenophorol
and (+)-decarestrictine L have been synthesized from the enantiomeric
(4R)- and (4S)-4-(tert-butyldimethylsiloxy)-1-pentyne in five and four steps, respectively.
These syntheses feature Ru­(II)-catalyzed Z-selective
anti-Markovnikov hydroacetoxylation of terminal alkynes followed by
AHF/Wittig olefination sequences to rapidly establish functionality
and stereogenicity. A synthesis of (+)-Prelog–Djerassi lactone
was accomplished in three isolations from the known 1-vinyl-4-methyl-2,6,7-trioxabicyclo[2.2.2]­octane
ortho ester. An AHF/crotylation tandem sequence has been developed
to set the C2–C4 stereochemistry. An asymmetric hydrogenation
was employed to set the C6 stereochemistry, resulting in an especially
efficient enantioselective synthesis from achiral starting material.
In summary, these syntheses have greatly improved efficiency in terms
of atom-economy, catalytic stereoselective transformations, inexpensive
reagents, step-counts, and overall yield when compared with previous
synthetic attempts.