Modular and stereoselective synthesis of hydroxylated angularly fused tricyclic piperidine derivatives via samarium diiodide mediated cyclization

Proline-promoted Mannich reactions of a series of cycloalkanones with formalin and aniline followed by N-acetylation provided precursors 9-12 for samarium diiodide mediated cyclizations. The ketyl-aryl coupling of these compounds furnished angularly fused piperidine derivatives such as 13 in good yields. Highly stereoselective dihydroxylation gave compounds of type 14 with five contiguous stereogenic centers. Our modular approach to this type of compounds involves just four simple steps and is fairly general. For the conversion of 10 into 15 we could demonstrate that the toxic and carcinogenic additive HMPA can be successfully replaced by lithium bromide and 1,3-dimethyl-2-imidazolidinone (DMI).