October 2023

Catalytic photooxygenation of amyloid-β is a leading therapeutic strategy for the treatment of Alzheimer disease; however, the limited tissue permeability of light hampers its clinical application. We here report an alternative catalytic sonooxygenation strategy to circumvent this problem. Amyloid-β aggregates were oxygenated by using rose bengal as a sonosensitizer under ultrasound irradiation. Structure–activity relationships revealed that xanthene-derived catalysts containing halogen atoms furnished a superior amyloid oxygenation activity.

Highly volatile organic compounds (VOCs) with boiling points (bp) around or below room temperature are generally difficult to manipulate precisely in liquid-phase organic reactions although they offer significant atom-economic advantages. We have developed a novel approach using a jacketed syringe pump to enable the formylation of organolithium species in a continuous-flow system under ambient pressure. Methyl formate (bp 32 °C) worked as a formylating agent and was successfully delivered to the continuous operation for over 30 minutes in our microflow system. This methodology was successfully expanded to the application of acetaldehyde (bp 21 °C) and heptafluoropropyl bromide (bp 12 °C).

Stereodivergent synthesis of N-heterocycle frameworks bearing 1,3-nonadjacent stereogenic centers through a single transformation remains a high-priority challenge in organic synthesis. Herein, we highlight our recent discovery of stereodivergent access to such useful structural motifs using Pd-catalyzed [4+2] annulation reactions of vinyl benzoxazinaones and seven-membered cyclic N-sulfonyl aldimines. A wide range of N-heterocycles with 1,3-nonadjacent stereogenic centers were obtained in high efficiency and stereodivergency. Importantly, the polarity of solvents was found to play a key role in switching the diastereoselectivity. Furthermore, good enantioselectivities of these reactions were achieved by the employment of commercially available Wingphos as the chiral ligand.

A ruthenium-catalyzed selective C–H functionalization/annulation cascade reaction of biindoles and sulfoxonium ylides has been developed. The reaction selectively provides pyrido[1,2-a:4,3-b′]diindole (5H-benzo[2,3]indolizino[7,8-b]indole) derivatives in good yields. A possible mechanism for the reaction pathway is proposed. More importantly, the present study provides a useful method for the construction of pyrido[1,2-a:4,3-b′]diindole frameworks.