P‐Stereogenic Phosphonates via Dynamic Kinetic Resolution: A Route towards Enantiopure Tertiary Phosphine Oxides

Abstract

Asymmetric synthesis of P-stereogenic phosphonates presents a great challenge. Following this target we disclose herein a DKR strategy towards the O-P coupling reaction between an easily accessible enantiopure phenol bearing a chiral sulfinyl auxiliary and a commercially available or easily accessible racemic H-phosphinate. Although moderate to high chiral P-stereogenic organophosphorus compounds are an important class of valuable products with widespread applications particularly in asymmetric catalysis. [1] Over the last twenty years the synthesis of molecules with a P-stereogenic center has received significant attention. [2] Accordingly, several modern approaches such as enantioselective metal-couplings and C-H activation based reactions have been reported. [3] Besides, the development of chiral separation techniques provided an alternative approach. [4] However, these transformations are generally strongly limited by the generation of only specific P-stereogenic scaffolds and/or are inadequate for a large-scale synthesis. Accordingly, diastereoselective synthesis of P-stereogenic compounds, calling for a use of an enantiopure auxiliary, is still the most general and widely applied methodology to build up an array of P-stereogenic molecules. Indeed, already in 1967 Mislow had illustrated a great potential of cheap and abundant menthol for the resolution of tertiary phosphines. [5] Due to the versatility of this diastereoselective approach, this method greatly contributed to the design of P-stereogenic ligands such as DiPAMP or Mini-Phos, and their applications in asymmetric catalysis (Scheme 1a). [6] Later Jugé showed that chiral amines such as ephedrine were also very powerful chiral auxiliaries delivering the corresponding P-stereogenic oxazaphospholidine in high yield and diastereoselectivity (Scheme 1b). [7] Similar strategies developed by Han in 2013 and Framery in 2015 involved [a]

Recent Advances of the Atherton-Todd Reaction

“…手性亚砜是一类重要的结构片段, 作为手性辅剂诱 导合成了许多重要手性分子, 其在天然产物不对称全合 成中的应用也非常广泛 [65] . 2019 年, Colobert 课题组 [66] 通过重结晶方法获得手性纯的 2-苯酚亚砜类化合物 65, 借助这类手性辅剂成功实现了一系列氧膦氢化合物 64 的不对称转化(Scheme 30). 遗憾的是, 该反应手性诱导 效率较中等, 最高以 90∶10 的非对映选择性得到目标 产物.…”