106017-74-7Relevant academic research and scientific papers
A Spectacular Example of the Importance of Rotational Barriers: The Ionization of Meldrum's Acid
Arnett, Edward M.,Harrelson, John A.
, p. 809 - 812 (1987)
The free energy of ionization of Meldrum's acid (I) is 11.68 kcal/mol more spontaneous than that of its acyclic analogue, dimethyl malonate.This energy difference must represent one of the largest stereoelectronic effects in the literature of organic chemistry and demands careful elucidation.This paper probes the problem by comparing the effects of various structural contributions to the carbon acidity of Meldrum's acid.The most dramatic effect results from increasing the size of the bislactone ring system.There is a rapid decrease in acidity between the 6-membered and 10-membered ring until the 13-membered ring has the same pKa as dimethyl malonate.The obvious conclusion from the assembled results is that the difference between the acidities Meldrum's acid and the larger ring bislactones or diesters lies in the barrier to rotation around the ester bonds.Over half of the 11.68-kcal/mol effect may be explained empirically through the 3-4-kcal/mol stabilization of the Z conformation of esters relative to the E conformation.Another 3 kcal/mol may be assigned to the cyclization effect seen also in the β-diketone series.
Macrolactonization Reactions Driven by a Pentafluorobenzoyl Group**
Ciofini, Ilaria,Force, Guillaume,Leb?uf, David,Mayer, Robert J.,Perfetto, Anna
supporting information, p. 19843 - 19851 (2021/08/13)
Macrolactones constitute a privileged class of natural and synthetic products with a broad range of applications in the fine chemicals and pharmaceutical industry. Despite all the progress made towards their synthesis, notably from seco-acids, a macrolactonization promoter system that is effective, selective, flexible, readily available, and, insofar as possible, compatible with manifold functional groups is still lacking. Herein, we describe a strategy that relies on the formation of a mixed anhydride incorporating a pentafluorophenyl group which, due to its high electronic activation enables a convenient access to macrolactones, macrodiolides and esters with a broad versatility. Kinetic studies and DFT computations were performed to rationalize the reactivity of the pentafluorophenyl group in macrolactonization reactions.
