Samarium diiodide-mediated reductive couplings of chiral nitrones with aldehydes/ketones and acyl chlorides

The SmI2-mediated and H2O-promoted reductive cross-coupling reactions of the l-tartaric acid derived nitrone (3S,4S)-8 with aldehydes/ketones, and the l-malic acid derived nitrone (S)-6 with aliphatic acyl chlorides have been investigated, respectively. (2R,3S,4S)-1,3,4-Trihydroxyprolinol derivatives 9a–f were obtained with high C-2/C-3 trans-selectivities, and 72:28–85:15 diastereoselectivities at the carbinol center from aromatic ketones/aldehydes, while low diastereoselectivities for aliphatic aldehydes. Conditions have been established for the syntheses of (2R,3S,4S)-3,4-dihydroxyprolinol derivatives such as 18, by N–O bond cleavage of the corresponding N-hydroxyprolinol derivatives 9b–f, or more conveniently by a one-pot reductive coupling of nitrone 8 and in situ N–O bond cleavage of the resultant coupling product. The 2-acyl-3-benzyloxy-1-hydroxypyrrolidines 10a–f were formed in 48–82% yields, and in 74:26–78:22 diastereoselectivities. It was revealed that the amount of water required for the reaction is substrate-depending.