New Umpolung Catalysts: Reactivity and Selectivity of Terpenol-Based Lithium Phosphonates in Enantioselective Benzoin-Type Couplings

Two new classes of terpenol-based lithium phosphonates, i.e. phenylfenchyl phosphonates and 2,2'-biphenyldiylbis(terpenyl) phosphonates, are employed as umpolung catalysts for the enantioselective cross benzoin coupling. The structural characteristics of the phosphonates were investigated by means of X-ray, P-31-NMR analyses as well as DFT computations. The chiral lithium phosphonates were found to catalyze the cross benzoin coupling with enantioselectivities up to 54 % ee. For the phenylfenchyl phosphonates, the catalyst reactivities highly depend on the substituents in benzylic position. Modification of benzylic >CH2 to >C(CF3)(2) significantly increases the yield from 19 to 92%. For phenylfenchyl phosphonate pre-catalysts, substitution of the benzylic >CH2 group by >C(CF3)(2) changes the sense of enantioselectivity from S- to the R-configured benzoin product.