Thiol-free synthesis of oseltamivir and its analogues via organocatalytic michael additions of oxyacetaldehydes to 2-acylaminonitroalkenes

Article abstract of DOI:10.1055/s-0031-1290396

The organocatalytic addition of substituted oxyacetaldehydes to 2-acylaminonitroethenes proceeded with good to high diastereoselectivities and enantioselectivities. The resulting adducts reacted with ethyl 2-(diethoxyphosphoryl) acrylate to afford highly functionalized cyclohexenes. A thiol-free protocol for cyclization has been developed that leads to a separable mixture of two diastereoisomers. The unwanted diastereoisomer can be efficiently epimerized. The resulting cyclohexenes are precursors to oseltamivir and its analogues. The synthesis of the key reagent, 3-pentyloxyaldehyde, was also improved. Georg Thieme Verlag Stuttgart · New York.