Carboxylic acids acetylenic, rearrangement

Thus, it would be reasonable to expect that the acetylenic group would be metabolized to a carboxylic acid. While the acid metabolite has not been detected, ethinyl estradiol is a suicide substrate inhibitor of CYP2B6 consistent with a reactive ketene being formed as an intermediate (142). In addition, there is a rearrangement product (4) shown in Figure 4.75. 

In the course of investigations on allylic and acetylene-allene rearrangements of 3-substituted quinuclidines, it was found that by oxidation and ozonolysis of compounds with functional groups at positions allylic to the double bond, not only the double bonds but also the adjacent carbon-carbon bonds are broken. For example, in the oxidation of 3-hydroxy-3-vinylquinuclidine (119), with potassium permanganate under mild conditions, and in its ozonolysis, qui-nuclidin-3-one (2) is formed along with 3-hydroxy quinuclidine-3-carboxylic acid.161 The positions of double bonds in such systems can be firmly established by NMR spectroscopy, but not by oxidative methods.101... 

Oxidative cleavage of acetylenes RC=CH (R = Ph, Bu, hexyl, heptyl, cyclopentyl or PhCH2CH2) with bis[trifluoroacetoxy)iodo]pentafluorobenzene in wet benzene gives carboxylic acids RC02H. Alkynes 263 (R, R = H, Me, Et, Pr, Bu or Ph) undergo an oxidative rearrangement by the action of [hydroxy(tosyloxy)iodo] benzene in methanol to yield the esters 264. ... 

Synthesis of amides and peptides. The simplest compound of this type, dimethylaminopropynal (CH3)aNC=CCHO, is known, but it polymerizes within minutes at room temperature. The thermal stability is improved by introduction of bulky constituents. A whole series of these acetylenes have been prepared of these 1 and a few related compounds have been found useful for synthesis of CO—NH bonds by a push-pull mechanism shown in equation (I). The reaction of 1 with a carboxylic acid proceeds by Michael addition to give a, which rearranges by a cyclic intermediate (b) to the enol ester (2). Reaction of 2 with an amine yields an amide (3) and the water adduct (4) of 1. Yields of amides are in the range 85-95y . This sequence cannot be used for esterification of carboxylic acids. 

In 1973, Baldwin and Walker [19] described the Claisen rearrangement of the allylic and acetylenic esters of a-bromo carboxylic acids with zinc at higher temperatures through the Reformatsky procedure. Though the method was better, it was severely restricted as it becomes mandatory to prepare the corresponding bromo-ester from the system of interest before the rearrangement could be effected (Scheme 5.1.7). 

Other applications of NHC-based rhodium catalysts include the cyclization of acetylene carboxylic acids, cyclopropanation of olefins with diazo compounds, or aryl-aryl cross-coupling combined with dynamic kinetic resolution with the help of a lipase or Beckmann rearrangement. Thus, the chemistry of NHC-Rh catalysts is rich and varied, and we expect new catalysts and patterns of reactivity in the years to come. These will provide new tools for synthetic organic chemistry. 

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