Faculté de Pharmacie, UMR 7200, CNRS-Université de Strasbourg, Laboratoire d'Innovation Thérapeutique 74, route du Rhin, F-67401, Illkirch, France.
J Org Chem. 2012 Mar 2;77(5):2246-53. doi: 10.1021/jo202455c. Epub 2012 Feb 13.
A multicomponent reaction (MCR) based on a cyclohydrocarbonylation (CHC) driven by hydroformylation was set up toward the efficient diastereoselective preparation of oxazolopiperidines (4a-e) and -azepines (7a-d). The bicyclic oxazolidines were obtained from chiral N-alkenylamino alcohols via transient cyclic iminium intermediates that underwent an intramolecular cyclization from the appendant oxygen. On the basis of a series of different experimental conditions, the diastereocontrol observed during the formation of the oxazolidines is best explained by the stereoelectronic effect induced by an A(1,3)-strain in a common cyclic iminium intermediate (A). This new sequence is suitable for diversity oriented syntheses, allowing the preparation of enantiopure (S)- and (R)-coniceine in five steps from commercially available material.
建立了一种基于环烃化（CHC）的多组分反应（MCR），该反应由氢甲酰化驱动，用于高效对映选择性制备恶唑并哌啶（4a-e）和-氮杂环庚烷（7a-d）。双环恶唑烷是通过手性 N-烯基氨基醇经过瞬态环状亚胺中间体获得的，该中间体从附加的氧发生分子内环化。根据一系列不同的实验条件，在形成恶唑烷时观察到的立体控制最好通过常见的环状亚胺中间体（A）中 A(1,3)-应变诱导的立体电子效应来解释。这个新序列适合多样性导向合成，允许从商业可得的材料出发，通过五步制备对映纯的（S）-和（R）-coniine。
