title: Ethyl Lithiodiazoacetate: Extremely Unstable Intermediate Handled Efficiently in Flow.
abstract: Ethyl diazoacetate (EDA) is one of the most prominent diazo reagents. It is frequently used in metal-carbene-type reactions. However, EDA can also be used as a nucleophile under base catalysis. Whilst the addition of EDA to aldehydes can be performed using organic bases, the addition of EDA to other carbonyl electrophiles requires the use of organometallics such as lithium diisopropylamide (LDA). The generated ethyl lithiodiazoacetate is highly reactive and decomposes rapidly, even at low temperatures. Herein, we report a continuous flow protocol that overcomes the problems associated with the instantaneous decomposition of ethyl lithiodiazoacetate. The addition of ethyl lithiodiazoacetate to ketones provides direct access to tertiary diazoalcohols in good yields.
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff, CF10 3AT, UK.
authors.forename: Simon T R
authors.initials: ST
authors.lastname: Müller
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff, CF10 3AT, UK.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hokamp
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff, CF10 3AT, UK.
authors.forename: Svenja
authors.initials: S
authors.lastname: Ehrmann
authors.affiliation: Pierre Fabre Médicament, Parc Industriel de la Chartreuse, 81106, Castres CEDEX, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Hellier
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff, CF10 3AT, UK. wirth@cf.ac.uk.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-8990-0667
authors.initials: T
authors.lastname: Wirth
keywords: diazo compounds; flow chemistry; hazardous intermediates; lithiation