Page 184 - Read Online

He et al. Chem Synth 2023;3:35 https://dx.doi.org/10.20517/cs.2023.14 Page 5 of 9

Scheme 2. Substrates scope. Reaction conditions: pre-cat. A (20 mol%), NaHCO (1.5 equiv), 1 (0.1 mmol), and 2 (0.12 mmol) in THF
3
(1.5 mL).

ketoester indoles with different N-protecting groups also worked well in this process under the current
reaction condition, and the desired products were generated in good to excellent yields and optical purities (
3k-3m, 97%-98% ee). However, the N-electron withdrawing protecting group (such as Boc) showed lower
reaction activity and enantioselectivities. Furthermore, the enantioselectivity of the reaction has a slight
decrease without an N-protecting group (3n, 87% ee). This may be due to the steric resistance effect of the
N-protecting group. Encouraged by these results, the generality of α-bromocinnamaldehyde 2 was further
investigated with β-ketoester indole 1a [Scheme 2]. Substituents with different electronic properties at the
orthoposition (3o, 65% yield, 95% ee) and the paraposition (3p-3r, 93-97% ee) of the phenyl group were well
tolerated. Para-F on the phenyl ring led to some decrease in reaction yield (3p, 50% yield). Replacement of
the phenyl substituent with 2-furanyl had little effect on the reaction outcomes (3s, 68% yield, 83% ee). In
addition, trace desired products were obtained by employing alkyl-substituted aliphatic aldehydes.