Skip to main content
. Author manuscript; available in PMC: 2021 May 26.
Published in final edited form as: ACS Catal. 2020 Feb 10;10(5):3241–3248. doi: 10.1021/acscatal.0c00211

Table 1.

Optimization of the Enantioselective Hydrogenation of Isoquinolines to afford THIQsa

graphic file with name nihms-1561287-t0010.jpg
entry ligand Solvent % conversionb cis:transb % ee of cisc
1 L1 PhMe:AcOH >95 >20:1 −49d
2 L2 PhMe:AcOH >95 3.2:1 84
3 L3 PhMe:AcOH 66 4.5:1 63
4 L4 PhMe:AcOH 92 4.9:1 3
5 L5 PhMe:AcOH >95 2.0:1 89
6 – PhMe:AcOH >95 >20:1 0
7 L5 CH2Cl2:AcOH >95 1.5:1 84
8 L5 dioxane:AcOH 66 5.5:1 87
9 L5 THF:AcOH >95 9.7:1 90
10 L5 CPME:AcOH 38 >20:1 88
11 L5 2-MeTHF:AcOH >95 9.5:1 90
12e L5 THF:AcOH >95 15.7:1 92
graphic file with name nihms-1561287-t0011.jpg
a

Conditions: 0.04 mmol 7a, 1.25 mol % [Ir(cod)Cl]2, 3 mol % ligand, 7.5 mol % TBAI, 60 bar H2 in 2.0 mL 9:1 solvent:AcOH.

b

Determined from crude 1H NMR using 1,3,5-trimethoxybenzene as standard.

c

Determined by chiral SFC analysis of Cbz-protected product.

d

Opposite enantiomer of ligand used.

e

Reaction performed on a 0.2 mmol scale at 23 °C, 20 bar H2, and 0.1 M concentration of 7a.