Yutaka Tomida

Asymmetric Carbolithiation of Conjugated Enynes: A Flow Microreactor Enables the Use of Configurationally Unstable Intermediates before They Epimerize

We found that a flow microreactor system enables the generation of a configurationally unstable chiral organolithium intermediate and allows for its use in a reaction with an electrophile before it epimerizes. Based on this method, the enantioselective carbolithiation of conjugated enynes followed by the reaction with electrophiles was accomplished to obtain enantioenriched chiral allenes.

Flow microreactor synthesis of disubstituted pyridines from dibromopyridinesviaBr/Li exchange without using cryogenic conditions

A flow microreactor method for the synthesis of disubstituted pyridines by generation of pyridyllithiums followed by reactions with electrophiles has been developed. By using a short residence time and efficient temperature control, the cryogenic conditions required for conventional batch macro processes can be avoided. Sequential introduction of two different electrophiles into dibromopyridines has been achieved using an integrated flow microreactor system composed of four micromixers and four microtube reactors, to obtain disubstituted pyridine compounds.

Synthesis of unsymmetrically substituted biaryls via sequential lithiation of dibromobiaryls using integrated microflow systems

Summary A microflow system consisting of micromixers and microtube reactors provides an effective method for the introduction of two electrophiles onto dibromobiaryls. Selective monolithiation of dibromobiaryls, such as 2,2′-dibromobiphenyl, 4,4′-dibromobiphenyl, 2,7-dibromo-9,9-dioctylfluorene, 2,2′-dibromo-1,1′-binaphthyl, and 2,2′-dibromobibenzyl with 1 equiv of n-butyllithium followed by the reaction with electrophiles was achieved using a microflow system by virtue of fast micromixing and precise temperature control. Sequential introduction of two different electrophiles was achieved using an integrated microflow system composed of four micromixers and four microtube reactors to obtain unsymmetrically substituted biaryl compounds.

Carbolithiation of Conjugated Enynes with Aryllithiums in Microflow System and Applications to Synthesis of Allenylsilanes

Carbolithiation of conjugated enynes with aryllithiums generated by Br-Li exchange reaction followed by reaction of the allenyllithium compounds with chlorosilanes was carried out in a microflow system to obtain various allenylsilanes in good yields.

Perfluoroalkylation in flow microreactors: generation of perfluoroalkyllithiums in the presence and absence of electrophiles†

Perfluoroalkyllithiums were effectively generated from perfluoroalkyl halides in the presence and absence of electrophiles using flow microreactor systems. The in situ trapping with electrophile is conducted at much higher temperatures than those required for batch macro reactors. The subsequent trapping method is quite effective for highly reactive electrophiles that are not compatible with the lithiation process.

Homocoupling of aryl halides in flow: Space integration of lithiation and FeCl3 promoted homocoupling

Summary The use of FeCl3 resulted in a fast homocoupling of aryllithiums, and this enabled its integration with the halogen–lithium exchange reaction of aryl halides in a flow microreactor. This system allows the homocoupling of two aryl halides bearing electrophilic functional groups, such as CN and NO2, in under a minute.

Generation and Reactions of Pyridyllithiums via Br/Li Exchange Reactions Using Continuous Flow Microreactor Systems

A continuous flow microreactor method for generating and carrying out reactions on pyridyllithiums has been developed based on Br/Li exchange reactions of bromopyridines and dibromopyridines. The reactions can be carried out without using cryogenic conditions by virtue of short residence times and efficient heat transfer, while very low temperatures such as –78 or –110°C are required for conventional batch macro methods. Moreover, sequential introduction of two different electrophiles has been successfully achieved using dibromopyridines in an integrated flow microreactor system composed of four micromixers and four microtube reactors.