Highly Diastereoselective Chelation-Controlled 1,3-<i>anti</i>-Allylation of (<i>S</i>)-3-(Methoxymethyl)hexanal Enabled by Hydrate of Scandium Triflate

Abstract

En route to the total synthesis of (+)-Neopeltolide, we explored Lewis acid-assisted diastereoselective allylation of MOM-protected 3-hydroxylhexanal with β-(2,2-diethoxyethyl)-substituted (allyl)tributylstannane. The hydrated form of scandium triflate was found to be essential for attaining high 1,3-anti-diastereoselectivity (d.r. 94:6), while the use of anhydrous catalyst resulted in a modest diastereocontrol (d.r. 76:24). The preferred 1,3-anti-selectivity in this transformation can be rationalized in the framework of the Reetz chelate model of asymmetric induction. The 1,3-anti-configuration of the product was confirmed by its conversion into the known C7-C16 building block of (+)-Neopeltolide. We also report an improved protocol for the synthesis of β-(2,2-diethoxyethyl)-substituted (allyl)tributylstannane, which can be utilized as a cost-efficient bipolar isoprenoid-type C5-building block in the synthesis of natural compounds.

Keywords

• Reetz–Keck-type allylation
• stannylation
• Lewis acids
• organotin compounds
• β-oxyaldehydes
• scandium triflate