A flow-microreactor approach to protecting-group-free synthesis using organolithium compounds

Kim, Heejin; Nagaki, Aiichiro; Yoshida, Jun

doi:10.1038/ncomms1264

Cited by 239 publications

(113 citation statements)

References 66 publications

(40 reference statements)

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“…The intrinsic advantages of the microfluidic system, such as enhanced heat transfer due to the high surface to volume ratio and efficient mixing due to the short diffusion paths, facilitate control of the C6 carbohydrates with low thermal stability. [15][16][17][18][19][20] In particular, the facile control of the retention time by varying the flow rate may prevent over-reactions from producing the unwanted black char residue. In addition, it is expected that the heterogeneous catalysts are readily immobilized in the microchannel and recycled without the loss of high stability, which eliminates the catalyst separation step.…”

Section: Introductionmentioning

confidence: 99%

One-flow syntheses of diverse heterocyclic furan chemicals directly from fructose via tandem transformation platform

et al. 2015

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The sustainable green chemistry associated with lignocellulosic biomass is of current interest for producing various chemical feedstocks via multi-step transformation processes. Here we introduce a chemical platform system for the multicomponent cascade transformation of natural lignocellulosic biomass resources. We demonstrate the concept by developing an integrated continuous two-step microfluidic system as a tandem transformation platform for direct conversion of fructose to diverse furan chemicals with excellent yields up to 99% via decarbonylation, etherification, oxidation and hydrogenolysis of a 5-hydroxymethylfurfural (HMF) intermediate. A sequential two-step process is utilized to complete the dehydration of fructose in the surface acid catalyst at 150°C for 6 min, which is followed by the four types of HMF conversion in a binary or ternary phase to produce furfuryl alcohol (94% yield), 5-ethoxymethylfurfural (99%), 2,5-diformylfuran (82%) and 2,5-dimethylfuran (90%) with magnetic-based heterogeneous catalysts at 70-150°C for 6-60 min. This innovative tandem microfluidic platform enables precise control of the reaction temperature and time for each individual biomass conversion step in a one-flow manner with no separation and purification steps for intermediates and catalysts.

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Section: Introductionmentioning

confidence: 99%

One-flow syntheses of diverse heterocyclic furan chemicals directly from fructose via tandem transformation platform

et al. 2015

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“…This example is a clear demonstration of the advantages associated with the use of microscale devices 44. A further relevant example was reported recently, which showed the principle of controlling highly unstable chiral organometallic intermediates to provide a method for the asymmetric carbolithiation of enynes 45…”

Section: Extreme Temperaturesmentioning

confidence: 79%

Machine‐Assisted Organic Synthesis

et al. 2015

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In this Review we describe how the advent of machines is impacting on organic synthesis programs, with particular emphasis on the practical issues associated with the design of chemical reactors. In the rapidly changing, multivariant environment of the research laboratory, equipment needs to be modular to accommodate high and low temperatures and pressures, enzymes, multiphase systems, slurries, gases, and organometallic compounds. Additional technologies have been developed to facilitate more specialized reaction techniques such as electrochemical and photochemical methods. All of these areas create both opportunities and challenges during adoption as enabling technologies.

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“…A flow microreactor also enables protecting-group-free organolithium reactions without protecting ketone carbonyl groups [73]. By greatly reducing the residence time (0.003 s or less) in an integrated microreactor, in which two micromixers and one microreactor (M2, R2, and M3 are integrated in a single device) are combined, aryllithiums bearing ketone carbonyl groups are generated by I-Li exchange of the corresponding aryl iodides with mesityllithium, and the resulting aryllithium species are reacted with various electrophiles without affecting ketone carbonyl groups.…”

Section: Protecting-group-free Synthesis Using Flow Microreactorsmentioning

confidence: 99%