Müller Simon T R, Hokamp Tobias, Ehrmann Svenja, Hellier Paul, Wirth Thomas
School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff, CF10 3AT, UK.
Pierre Fabre Médicament, Parc Industriel de la Chartreuse, 81106, Castres CEDEX, France.
Chemistry. 2016 Aug 16;22(34):11940-2. doi: 10.1002/chem.201602133. Epub 2016 Jul 13.
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.
重氮乙酸乙酯（EDA）是最著名的重氮试剂之一。它常用于金属卡宾型反应。然而，EDA在碱催化下也可作为亲核试剂。虽然使用有机碱就可以将EDA加成到醛上，但将EDA加成到其他羰基亲电试剂上则需要使用有机金属试剂，如二异丙基氨基锂（LDA）。生成的重氮乙酸锂乙酯具有很高的反应活性，即使在低温下也会迅速分解。在此，我们报道了一种连续流动方法，该方法克服了与重氮乙酸锂乙酯瞬间分解相关的问题。将重氮乙酸锂乙酯加成到酮上能够以良好的产率直接得到叔重氮醇。
