Table 1 Optimisation of reaction conditions

From: Highly enantioselective catalytic synthesis of chiral pyridines

Entry Solvent L, mol%a Lewis acid, equiv.b Conv. (%)c ee (%)d
1 DCM L1, 6 BF3Et2O, 1.1 0
2 DCM L1, 6 B[PhF5]3, 1.1 0
3 DCM L1, 6 TMSOTf, 1.5 89 89
4 DCM L1, 6 TMSOTf, 2.0 85 85
5 DCM L1, 6 TMSOTf, 3.0 91 89
6 DCM L1, 12 TMSOTf, 1.5 91 92
7 DCM L1, 12 TMSOTf, 2.0 95 93
8 DCM L1, 12 TMSOTf, 3.0 100 93
9 Et2O L1, 12 TMSOTf, 3.0 62 95
10 MTBE L1, 12 TMSOTf, 3.0 67 96
11 Toluene L1, 12 TMSOTf, 3.0 79 87
12 DCM L2, 12 TMSOTf, 3.0 76 45
13 DCM L3, 12 TMSOTf, 3.0 93 81
14 DCM L4, 12 TMSOTf, 3.0 95 90
  1. a6 or 12 mol% of L was used in combination with 5 or 10 mol% of CuBr·SMe2 respectively
  2. bEquivalents of EtMgBr used correspond to that of the Lewis acid
  3. cDetermined by 1H NMR spectroscopy
  4. dDetermined by chiral HPLC