Evaluation of sparteine-like chiral diamines in the enantioselective lithiation-electrophilic trapping of an O-alkyl carbamate

Seven (+)-sparteine-like diamines and (-)-sparteine were evaluated in the diamine-mediated asymmetric lithiation - trapping of an O-alkyl carbamate. The (+)-sparteine-like diamines (>= 98 : 2 er by chiral shift NMR spectroscopy) were prepared from (-)- cytisine (> 99 : 1 er by chiral HPLC of N-benzyl cytisine) and two new (+)-sparteine-like diamines containing N-CD3 substituents were included as part of this study. The following results from the ligand evaluation study were obtained: (-)- sparteine is unrivalled in its ability to induce near-perfect enantioselectivity ( 99 : 1 er); N-methyl diamine and the two N-CD3-substituted diamines are the optimal (+)-sparteine surrogates ( up to 96 : 4 er); sterically more hindered N-alkyl substituents gave reduced enantioselectivity (N-iso-propyl: 86 : 14 er; N-CH2 tBu: 54 : 46 er). From a synthetic point of view, these results show that either enantiomer of alpha-substituted O-alkyl carbamates can be obtained by enantioselective lithiation - trapping using (-)-sparteine and the N-methyl (+)-sparteine surrogate.