Department of Chemistry, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA.
J Am Chem Soc. 2011 Jun 22;133(24):9216-9. doi: 10.1021/ja202900h. Epub 2011 May 23.
A convergent and stereodivergent pathway to highly substituted 1-aza-7-oxabicyclo[2.2.1]heptanes is described. It begins with a coupling reaction involving allylic alcohol, aldehyde, and LiHMDS to produce stereodefined primary homoallylic amines. Subsequent N-oxidation and condensation with formaldehyde or glyoxylate defines a convenient entry to densely functionalized homoallylic nitrones whose intramolecular annulation can be controlled to deliver one of two distinct heterocyclic skeletons, each with ≥20:1 stereoselection. Control of the stereochemistry in these reactions results from both control of the nitrone geometry and selective partitioning of the reaction pathway between direct [3 + 2] cycloaddition and tandem [3,3] rearrangement/[3 + 2] cycloaddition.
本文描述了一种高度取代的 1-氮杂-7-氧杂双环[2.2.1]庚烷的汇聚和立体发散途径。它始于涉及烯丙醇、醛和 LiHMDS 的偶联反应，以产生立体定义的仲烯丙基伯胺。随后的 N-氧化和与甲醛或乙醛酸的缩合定义了一种方便的方法，可以获得稠合官能化的偕亚硝胺，其分子内环化可以控制得到两种不同的杂环骨架中的一种，每种骨架都具有≥20:1 的立体选择性。这些反应中立体化学的控制源自对硝酮几何形状的控制以及反应途径在直接[3+2]环加成和串联[3,3]重排/[3+2]环加成之间的选择性分配。
