Ethyl Lithiodiazoacetate: Extremely Unstable Intermediate Handled Efficiently in Flow. Issue 34 (13th July 2016)

• Record Type: Journal Article
• Authors: Müller, Simon T. R.; Hokamp, Tobias; Ehrmann, Svenja; Hellier, Paul; Wirth, Thomas
• Is Part Of: Chemistry. Volume 22:Issue 34(2016)
• Page Start: 11940
• Page End: 11942
• Publication Date: 2016-07-13
• Subjects: diazo compounds -- flow chemistry -- hazardous intermediates -- lithiation; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201602133
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Only flow synthesis allows the rapid generation and safe handling of ethyl lithiodiazoacetate as an extremely unstable, but highly versatile building block for flexible synthesis (see scheme; LDA=lithium diisopropylamide).