Recently, we have shown that titanium enolates of N-glycolyloxazolidinethiones are useful substrates for generating anti aldol adducts in good yields and high diastereoselectivity. This powerful carbon-carbon bond forming technique, which complements the well-documented methods to form the syn isomers, allows for the construction of differentially protected 1,2-diols with high asymmetric control.   

"

This methodology is used to form the C3-C4 bond in our approach towards the total synthesis of brevetoxin A. Key steps for the synthesis of the B ring also include an asymmetric glycolate alkylation at C9 and a β-chelation controlled vinyl Grignard addition at C8. Ring closing metathesis generates a tri-substituted olefin at C6-C7, which is selectively hydrogenated to set the C6 stereochemistry. Selective methyl Grignard addition provides the tertiary alcohol at C8, completing the B ring with all necessary stereocenters and appendages for subsequent ring formations.