Department of Chemistry, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK.
Angew Chem Int Ed Engl. 2022 Jul 25;61(30):e202205278. doi: 10.1002/anie.202205278. Epub 2022 Jun 10.
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.
酚的羟基化去芳构化反应（HPD）为组装复杂的、具有生物学相关性的支架提供了一种有效的方法。尽管如此，用于构建双环[2.2.2]辛烯酮的对映选择性羟基化苯酚去芳构化反应在经典上仅限于计量手性试剂，而实用的对映选择性催化方法仍然难以捉摸。在此，我们描述了一种高对映选择性的有机催化串联 o-HPD-[4+2]反应。我们的方法利用手性恶唑烷𬭩有机催化剂，其两种对映异构体均可用，在广泛的苯酚取代模式下以高对映选择性提供去芳构化产物。该方法应用于（+）-双（香芹酚）（99：1 e.r.）和（-）-双（2,6-二甲苯酚）（94：6 e.r.）的高度对映选择性合成。使用在单个合成步骤中可获得的胺前催化剂，在克级规模上证明了我们条件的实用性。
