Page 183 - Read Online

Page 4 of 9 He et al. Chem Synth 2023;3:35 https://dx.doi.org/10.20517/cs.2023.14

a a
Figure 2. Optimization of the reaction conditions . Reaction conditions: pre-catalyst (20 mol%), base (1.5 equiv), 1a (0.1 mmol), and 2a
b
c
d
(0.12 mmol) in solvent (1.5 mL). Isolated yield. Determined by chiral HPLC analysis. 5Å molecular sieves (10 mg) were used as an
f
e
g
i
h
additive at room temperature. pre-catalyst (10 mol%). The temperature was 0 °C. The temperature was 35 °C. THF = 3 mL. THF = 1
mL. Mes = 2,4,6-trimethylphenyl.
optimization studies revealed that high enantioselectivity with low reaction yield (entry 9, 68% yield, 97% ee)
was delivered when the reaction was performed with 10 mol% pre-catalyst A. Then, the reaction
temperature was investigated. When the reaction proceeded at 0 ℃, the yield was dramatically decreased to
8%, and the enantioselectivity was slightly decreased to 92% [Figure 2] (entry 10). Higher reaction
temperature did not result in better yield or enantioselectivity [Figure 2] (entry 11). While the changing of
reactant concentration led to lower yields (entries 12-13). The best reaction condition was established with a
20 mol% pre-catalyst, 1.5 equiv NaHCO , and 1.0:1.2 reactant ratio at room temperature.
3
After establishing the optimized reaction conditions, the scope of the reaction was examined. First, we
studied variations of the β-ketoester indoles [Scheme 2]. Substrates with electron-releasing and electron-
3
withdrawing groups on the benzene ring of the indole group of 1,3-dicarbonyl compound (R ) underwent a
cycloaddition reaction, affording the compounds in moderate to good yields (61%-80% yield) and excellent
enantioselectivities (3a–3j, 92%-98% ee). It is worth mentioning that the enantioselectivity of the reaction
can reach 98% when the C5 position of the indol-phenyls is NO . Subsequently, we investigated different N-
2
protecting groups on the indole skeleton, such as Me, PMB, or tert-butyl benzyl. To our great delight, β-