External Flash Generation of Carbenoids Enables Monodeuteration of Dihalomethanes.

In this study, incorporation of one deuterium atom was achieved by H-D exchange of one of the two identical methylene protons in various dihalomethanes (halogen=Cl, Br, and I) through a rapid-mixing microflow reaction of lithium diisopropylamide as a strong base and deuterated methanol as a deuteration reagent. Generation of highly unstable carbenoid intermediate and suppression of its decomposition were successfully controlled under high flow-rate conditions. Monofunctionalization of diiodomethane afforded various building blocks composed of boryl, stannyl, and silyl groups. The monodeuterated diiodomethane, which served as a deuterated C1 source, was subsequently subjected to diverted functionalization methods to afford various products including biologically important molecules bearing isotope labelling at specific positions and homologation products with monodeuteration.

Generation and Reaction of Functional Alkyllithiums by Using Microreactors and Their Application to Heterotelechelic Polymer Synthesis.

Flow microreactors enabled the successful generation of various functional alkyllithiums containing electrophilic functional groups, as well as the use of these alkyllithiums in subsequent reactions. The high reactivity of these series of reactions could be achieved by the extremely accurate and selective control of residence time. Moreover, integrated flow microreactor systems could be used to successfully synthesize heterotelechelic polymers with two functionalities, one at each end, via a process involving controlled anionic polymerization initiated by functional alkyllithium compounds, followed by trapping reactions with difunctional electrophiles.

Alkyllithium Compounds Bearing Electrophilic Functional Groups: A Flash Chemistry Approach.

Flash chemistry based on flow microreactor systems allowed alkyllithiums bearing electrophilic functional groups to be successfully generated and used for subsequent reactions. The series of reactions with high reactivity was achieved by extremely accurate control over residence time in a controlled and selective manner.

Benzyllithiums bearing aldehyde carbonyl groups. A flash chemistry approach.

Reductive lithiation of benzyl halides bearing aldehyde carbonyl groups followed by reaction with subsequently added electrophiles was successfully accomplished without affecting the carbonyl groups by taking advantage of short residence times in flow microreactors.