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 <br> 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. <br> <br>论文《经由氧吖啶鎓（oxaziridinium）催化的邻位羟基化苯酚脱芳构化反应实现双环[2.2.2]辛烯酮的有机催化对映选择性合成》的补充信息文件 苯酚羟基化脱芳构化反应（Hydroxylative Dearomatization of Phenols, HPD）为构建复杂且具有生物相关性的骨架提供了高效途径。尽管如此，用于构建双环[2.2.2]辛烯酮的对映选择性苯酚羟基化脱芳构化反应，传统上仅能使用化学计量的手性试剂，而实用的对映选择性催化方法始终未能实现。 本文报道了一种高对映选择性的有机催化邻位HPD-[4+2]串联反应。该方法采用可获取两种对映体形式的手性氧吖啶鎓（oxaziridinium）有机催化剂，能够在多种苯酚取代模式下，以高对映选择性得到脱芳构化产物。 该策略被应用于(+)-香芹醇二聚体（biscarvacrol，对映体比例er=99:1）与(-)-双(2,6-二甲苯酚）（bis(2,6-xylenol)，对映体比例er=94:6）的高对映选择性合成。通过单步合成即可获取的胺类预催化剂，在克级规模下验证了该反应条件的实用性。