Mirabella S, Fibbi G, Matassini C, Faggi C, Goti A, Cardona F
Department of Chemistry "Ugo Schiff", University of Firenze, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy.
Org Biomol Chem. 2017 Nov 7;15(43):9121-9126. doi: 10.1039/c7ob01848g.
A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is disclosed. The procedure involved Grignard addition either to a carbohydrate-derived aldehyde or to a nitrone derived thereof, and took advantage of an efficient ring-closure reductive amination strategy in the final cyclization step. An opposite diastereofacial preference was demonstrated in the nucleophilic attack to the two electrophiles, which would finally produce the same piperidine diastereoisomer as the major product. However, use of a suitable Lewis acid in the Grignard addition to the nitrone allowed reversing the selectivity, giving access to 2-substituted piperidines with the opposite configuration at C-2.
公开了一种用于合成2-取代三羟基哌啶的双重合成策略。该方法包括将格氏试剂加成到碳水化合物衍生的醛或其衍生的硝酮上，并在最后的环化步骤中利用有效的闭环还原胺化策略。在对两种亲电试剂的亲核进攻中表现出相反的非对映面选择性，最终会产生相同的哌啶非对映异构体作为主要产物。然而，在将格氏试剂加成到硝酮的反应中使用合适的路易斯酸可以逆转选择性，从而得到在C-2位具有相反构型的2-取代哌啶。
