StereoPHIP: Stereoselective Parahydrogen-Induced Polarization

Parahydrogen-induced polarization (PHIP) followed by polarization transfer to ¹³ C is a rapidly developing technique for the generation of ¹³ C-hyperpolarized substrates. Chirality plays an essential role in living systems and differential metabolism of enantiomeric pairs of metabolic substrates is well documented. Inspired by asymmetric hydrogenation, here we report stereoPHIP, which involves the addition of parahydrogen to a prochiral substrate with a chiral catalyst followed by polarization transfer to ¹³ C spins. We demonstrate that parahydrogen could be rapidly added to the prochiral precursor to both enantiomers of lactic acid (D and L), with both the (R,R) and (S,S) enantiomers of a chiral rhodium(I) catalyst to afford highly ¹³ C-hyperpolarized (over 20 %) L- and D-lactate ester derivatives, respectively, with excellent stereoselectivity. We also show that the hyperpolarized ¹ H signal decays obtained with the (R,R) and (S,S) catalysts were markedly different. StereoPHIP expands the scope of conventional PHIP to the production of ¹³ C hyperpolarized chiral substrates with high stereoselectivity.