Reduction and reductive coupling reactions using samarium (II) iodide

Abstract

A series of functionalized cyclopropyl ketones were reacted with 2 equivalents of $SmI_2$ in THF at $-78^\circleC$ to give the ring-opened products in good yields. It is noteworthy that the reactions are both regio-and chemo-selective. On the application of the $SmI_2$-promoted 1,4-reduction of $\alpha$, $\beta$-unsaturated esters, it was also found that conjugated vinylcyclopropanes 3a-c were reductively cleaved on treatment with $SmI_2$ to give the ring-opened products 4a-c in excellent yields under the mild conditions. As described in the ring opening of cyclopropyl ketones, it was also important that the ester group substituted at $C_2$ carbon atom of a cyclopropane ring took an important role in the ring opening of conjugated vinylcyclopropanes. A $SmI_2$-promoted ketyl-isothiocyanate cyclization process provided a new strategy for the construction of heterocyclic compounds. A series of acyclic and cyclic substrates were reacted with 2 equivalents of $SmI_2$ in THF to give the corresponding $\alpha$-hydroxy thiolactams in good yields. The low stereoselectivity was observed in the case of acyclic systems, however, cyclic substrates were cyclized to the bicyclic $\alpha$-hydroxy thiolactams in a stereoselective fashion. Trans (3R,6S) isomer 5h was cyclized to the cis-ring fused isomer 6h in 78% yield as a single diastereomer. On the other hand, Cis (3R, 6R) isomer 5i was cyclized to the trans-ring fused isomer 6i in a stereospecific fashion. When isothiocyanatic ketone 5h was treated with 4 equivalents of $SmI_2$ in the presence of t-BuOH at room temperature for 8 h, only the bicyclic thiolactam 7f was obtained in 89\% yield as a single diastereomer. The formation of 7f could be explained by a sequential radical cyclization/deoxygenation process. On the application of the concepts of the $\beta$-coupling of an activated alkenes, we have attempted the cyclization of $\alpha$, $\beta$-unsaturated esters tetherd to isothiocyanates. A simple new general method f...