Synthesis of propionate motifs: Diastereoselective tandem reactions involving anionic and free radical based processes

Reported herein is a strategy employing a Mukaiyama reaction in tandem with a hydrogen transfer reaction for the elaboration of propionate motifs. The nature of the protecting groups on the chiral fl-alkoxy aldehyde and the t ype of Lewis acid used are varied to modulate the stereochemical outcome of the tandem reactions. The mode of complexation is thus controlled (monoden tate or chelate) for the Mukaiyama reaction to give access to either syn or anti aldol products, precursors of the free radical reduction reaction. Th e endocyclic effect is subsequently capitalized upon to control the hydroge n transfer step so that the syn-reduced product may be achieved. Proceeding with excellent yield and diastereoselectivity, the synthetic sequence prop osed gives access to syn-syn and syn-anti propionate motifs. Also considere d is a complementary approach using a chelation-controlled Mukaiyama reacti on in tandem with a free radical allylation reaction under the control of t he endocyclic effect that leads to the anti-anti product.