Supplementary information files for Organocatalytic enantioselective synthesis of bicyclo[2.2.2]octenones via oxaziridinium catalysed ortho‐hydroxylative phenol dearomatization

Supplementary information files for article Organocatalytic enantioselective synthesis of bicyclo[2.2.2]octenones via oxaziridinium catalysed ortho‐hydroxylative phenol dearomatization

Hydroxylative dearomatization reactions of phenols (HPD) offer an efficient way to assemble complex, biologically relevant scaffolds. Despite this, enantioselective hydroxylative phenol dearomatizations for the construction of bicyclo[2.2.2]octenones are classically limited to stoichiometric chiral reagents, and a practical, enantioselective catalytic method has remained elusive. Herein, we describe a highly enantioselective, organocatalytic tandem o-HPD-[4+2] reaction. Our methodology utilizes a chiral oxaziridinium organocatalyst, that is available in both enantiomeric forms, to afford dearomatized products in high enantioselectivity over a range of phenol substitution patterns. This approach was applied to the highly enantioselective synthesis of (+)-biscarvacrol (99 : 1 e.r.) and (−)-bis(2,6-xylenol) (94 : 6 e.r.). The practicality of our conditions was demonstrated at gram-scale, using an amine precatalyst, accessible in a single synthetic step.

本篇论文的补充信息文件，详述了通过氧化亚胺催化邻羟基化酚的亲电脱芳构化反应，实现了双环[2.2.2]辛酮的有机催化立体选择性合成。酚的羟基化脱芳构化反应（HPD）为构建复杂、生物相关的骨架结构提供了一种高效的方法。尽管如此，对于构建双环[2.2.2]辛酮的立体选择性羟基化脱芳构化反应，传统上仅限于化学计量学的手性试剂，而一种实用且具有立体选择性的催化方法一直难以寻觅。本研究中，我们描述了一种高度立体选择性的有机催化串联邻羟基化酚- [4+2] 反应。我们的方法利用了一种手性氧化亚胺有机催化剂，该催化剂以两种对映体形式存在，能够在多种酚取代模式中提供高度立体选择性的脱芳构化产物。该策略已被应用于合成 (+)-双卡瓦酮（外消旋比 99:1 e.r.）和 (−)-双(2,6-二甲苯酚)（外消旋比 94:6 e.r.）。通过使用胺前催化剂，并在单一合成步骤中易于获取，我们证明了该方法在克级规模上的实用性。