Discodermolide, asymmetric aldol reaction

Altogether, our total synthesis of (+)-discodermolide uses four asymmetric boron aldol reactions and proceeds in 27 steps and 7.7% overall yield (for the longest linear sequence starting from commercial methyl (S)-3-hydroxy-2-methylpropionate). 

Even with more atom-economical, catalytic, asymmetric aldol options available, the use of chiral auxiliaries on large scale should not always be avoided based on the perception of poor AE. The following example toward discodermolide (82) from Novartis Process Chemistry, where AE, process greenness, and waste minimization are of great concern, demonstrates that aldol transformations with auxiliaries are possible on multi-kg scale [66] (Scheme 13.12). After aldol reaction and cleavage of the chiral controller to produce 80, they were able to recover 81 in 67% yield via crystallization. 

Paterson, I. and Florence, G.J. (2000) Synthesis of (+)-discodermolide and analogues by control of asymmetric induction in aldol reactions of y-chiral (Z)-enals. Tetrahedron Lett., 41, 6935-6939. 

Paterson, L, Delgado, O., Florence, G.J., Lyothier, L, Scott, J.P., and Sereinig, N. (2003) 1,6-Asymmetric induction in boron-mediated aldol reactions Application to a practical total synthesis of (+)-discodermolide. Org. Lett., 5, 35-38. 

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