Configurational Assignment of 'Cryptochiral' 10-Hydroxystearic Acid Through an Asymmetric Catalytic Synthesis

An asymmetric catalytic total synthesis of (S)-10-hydroxystearic acid (1) for comparison of its absolute configuration to that of samples obtained by fermentative hydration of oleic acid is reported. The synthesis involves two catalytic key-steps, namely Ru-catalyzed anti-Markovnikov hydration of 9-decynoic acid (7) to 10-oxodecanoic acid (5), followed by titanium-mediated asymmetric catalytic addition of dioctylzinc (25) to 5 in presence of the chiral ligand N,N'-((1R, 2R)-cyclohexane-1,2-diyl)bis(1,1,1-trifluoromethanesulfonamide) (6). The synthesis is short and efficient and avoids use of protecting groups. Ozonolysis of 10-undecynoic acid (9) to 5 provides an alternative entry point into the synthetic route. The double dehydrobromination of (omega,omega-1)-dibromoalkanoic acids to omega-alkynoic acids under a variety of conditions was investigated with 10,11-dibromoundecanoic acid (11) as model substrate and using qNMR to quantify all reaction products. The synthetic approaches presented here have the potential to be generalized to the asymmetric catalytic synthesis of a variety of n-hydroxy-fatty acids.