De Novo Synthesis of the DEF-Ring Stereotriad Core of the Veratrum Alkaloids

The synthesis of the stereotriad core in the eastern portion of the Veratrum alkaloids jervine ( 1 ), cyclopamine ( 2 ), and veratramine ( 3 ) is reported. Starting from a known β-methyltyrosine derivative ( 8 ), the route utilizes a diastereoselective substrate-controlled 1,2-reduction to establish the stereochemistry of the vicinal amino alcohol motif embedded within the targets. Oxidative dearomatization is demonstrated to be a viable approach for the synthesis of the spirocyclic DE ring junction found in jervine and cyclopamine.