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. 2021 May 25;12(6):969–975. doi: 10.1021/acsmedchemlett.1c00082

Table 4. Reductive Amination Approach to (4R)-9ba.

graphic file with name ml1c00082_0008.jpg

entry (b) step 1 (b) step 2 (b) solvent (4R)-9b:(4S)-9b yield of (4R)-9b (%)
1 2.5 equiv Ti(OPri)4 1.3 equiv NaBH3CN MeOH 1:1  
2 0.6 equiv TiCl4 0.2 equiv Pd/C, H2 MeOH 1:1  
3 0.6 equiv TiCl4 0.2 equiv PtO2, H2 MeOH 2:1 30
4 0.6 equiv TiCl4 0.2 equiv PtO2, H2 CH2Cl2 4:1 50
5 0.7 equiv TiCl4 1.1 equiv BH3 (1 M THF) CH2Cl2 1:1  
6 0.7 equiv TiCl4 1.1 equiv BH3·SMe2 CH2Cl2 6:1 70
7 1.1 equiv Ti(OEt)4 1.1 equiv BH3·SMe2 CH2Cl2 1:1  
8 0.6 equiv TiCl4 and 0.6 equiv Ti(OPri)4 1.1 equiv BH3·SMe2 CH2Cl2 8:1 78
a

Reagents and conditions. (a) step 1: TFA, CH2Cl2, rt, 1 h, 93% yield; step 2: 3,5-di-tert-butylcyclohexa-3,5-diene-1,2-dione, Dowex-50WX8–200 resin, MeOH, 90% yield; (b) step 1 :2 equiv t-BuNH2; step-2: rt 16 h.