Abstract
Horner-Wadsworth-Emmons reaction (HWE reaction) is known as a reliable and powerful method for carbon-carbon bond formation by coupling between β-ketophosphonate and aldehyde to give α,β-unsaturated compound with high stereoselectivity. In general, the β-ketophosphonate used as the HWE reaction precursor is needed to be synthesized from a readily accessible material. However, these procedures sometimes encounter troubles in purification due to its high polarity or side products. To avoid these problems, we planned one-pot synthesis of the α,β-unsaturated ketone with aldehyde, acyl fluoride and trimethylsilylmethylphosphonate through HWE reaction according to the sequential reaction illustrated in Scheme 1. The reaction conditions were optimized by examining bases, reaction time, and equivalent of reagents as shown in Table 1. With the optimized conditions (Table 1. Entry 7), wide variety of substrates (aldehyde, acyl fluoride, and phosphonate) bearing various functional groups were coupled to give α,β-unsaturated ketone in high yields with E geometry. (Table 2) Z-α,β-Unsaturated ketones were also prepared with high stereoselectivity by using one-pot procedure. (Table 3)
