Abstract
The McKenna reaction is a well-known and popular method for the efficient and mild synthesis of organophosphorus acids. Bromotrimethylsilane (BTMS) is the main reagent in this reaction, which transforms dialkyl phosphonate esters into bis(trimethylsilyl)esters, which are then easily converted into the target acids. However, the versatile character of the McKenna reaction is not always used to its full extent, due to formation of side products. Herein, demonstrated by using model examples we have not only analyzed the typical side processes accompanying the McKenna reaction, but also uncovered new ones. Further, we discovered that some commonly recommended precautions did not always circumvent the side reactions. The proposed results and recommendations may facilitate the synthesis of phosphonic acids.
Highlights
The McKenna reaction is a tool for the synthesis of organophosphorus acids from their esters and known for over 40 years [1,2]
The McKenna reaction involves two steps: In the first step an alkyl ester is transformed into the corresponding trimethylsilyl ester [9], which is cleaved in the second step, upon solvolysis, forming the final product (Scheme 1)
We evaluated experiments that did not work, the so called “dark data” [21], and we demonstrated that contrary to common belief: 1) BTMS itself led to the cleavage of tert-butyl carboxyesters, and 2) amines, a commonly used standard additives in the McKenna reaction were not generally safe and may promoted side reactions in the presence of certain functional groups
Summary
The McKenna reaction is a tool for the synthesis of organophosphorus acids from their esters and known for over 40 years [1,2] The importance of this class of compounds is widely recognized as phosphorus acids and esters are prevailing in nature [3,4], and the compounds found wide applications as therapeutics [5,6], probes [7] or in materials science [8]. BTMS acted as a brominating agent and reagent for the formation of silyl enol ethers [10]. These reactions often required higher temperatures (up to 100 °C) or were applicable to only certain types of functional groups, such as methoxymethyl ethers [10].
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