Design, Synthesis and Application of C2-Symmetric Cycloglycerodiphosphate Catalysts

Chiral phosphoric acids (CPAs) and their salts are the privileged catalysts in a plethora of asymmetric transformations. All of the scaffolds of efficient CPAs rely on C2-symmetry and axial chirality, while the only examples of punctually chiral CPAs are TADDOL derivatives. Herein, we present the design and the synthesis of C2-symmet- ric cycloglycerophosphates (cGPAs) and their appli- cation throughout the addition of trimethylsilyl cyanide (TMSCN) to aldehydes and ketones, to obtain the corresponding cyanohydrins in yields between 77 and 99% and ee between 84.2 and 99.5% (27 examples). A DFT computational model is moreover performed to rationalize the reaction mechanism and its stereochemical outcome.