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% d 1 and 40% ee) from ( R )-(−)-mandelic acid is described. Cyclometalation of racemic 1 - d using K 2 PdCl 4 in aqueous methanol affords the dimer {Pd(μ-Cl)[κ C α,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 K 2 PdCl 4, PdCl 2, or Pd(OAc) 2 affords 2 which is converted to PdCl[κ C α,N -8-(CRMe)quinoline](NH 2 R) (R = H, D; NH 2 R = (+)-α-phenethylamine ( 6a ) or (+)- endo -bornylamine ( 6b )) and to Pd[κ C α,N -8-(CRMe)quinoline](κ O,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.