Stereochemistry at Carbon of the Cyclometalation of 8-(α-Deuterioethyl)quinoline by Palladium(II) Salts

The stereochemistry at carbon of the known cyclometalation of 8-ethylquinoline by Pd(II) salts has been examined. The preparation of (R)-(−)-8-(α-deuterioethyl)quinoline ((R)-1-d, 91% d1 and 40% ee) from (R)-(−)-mandelic acid is described. Cyclometalation of racemic 1-d using K2PdCl4 in aqueous methanol affords the dimer {Pd(μ-Cl)[κCα,N-8-(CRMe)quinoline]}2 (2, R = H, D) with a kinetic isotope effect of >11 and no detectable isotopic scrambling. Cyclometalation of (R)-1-d using K2PdCl4, PdCl2, or Pd(OAc)2 affords 2 which is converted to PdCl[κCα,N-8-(CRMe)quinoline](NH2R) (R = H, D; NH2R = (+)-α-phenethylamine (6a) or (+)-endo-bornylamine (6b)) and to Pd[κCα,N-8-(CRMe)quinoline](κO,N-(+)-leucine) (7a, R = H, D). Analysis of 7a shows 17−36% de (44−94% net stereospecificity), and comparison with the known absolute configuration of 7a establishes that the C−H activation proceeds with retention of configuration at carbon.