During the last decade, the Roush group has developed double allylboration methods involving a bis-boron intermediate able to react with two different aldehydes in a single operation. This approach permits the stereoselective construction of all possible isomers of 1,5-pentene-diol, and has been successfully applied to the total synthesis of complex polyketides. We describe here the extension of this double allylboration chemistry to the use of N-silyl imines as one of the electrophilic reaction partners, and then also the use of the resulting unprotected 1,5-syn-(Z)-aminoalcohols as precursors to trans-1,2,3,6-tetrahydropyridines via direct Mitsunobu cyclization. We demonstrate the utility of this chemistry to total synthesis of andrachcine. In fact, we have accomplished highly stereoselective total syntheses of both stereostructures assigned in the literature for andrachcine, thus establishing with certainty the absolute and relative configuration of the natural product. This work opens the door to the application of the double allylboration strategy to more complex alkaloids. The story behind this work, problem-solving, mechanism and results will be discussed.

Enantio- and diastereoselective synthesis of 1,5-syn-(Z)-aminoalcohols via imine double allylboration: Synthesis of trans-1,2,3,6-tetrahydropyridines and total synthesis of andrachcine

254th National Meeting (2017)

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