Isotopic labeling, alkynes

VI. THE PREPARATION AND USES OF ISOTOPICALLY LABELLED ALKYNES A. Synthesis of Labelled Alkynes... 

A wide variety of labelled compounds can be synthesized by a two-step process involving the formation of a trialkyl- or triarylstannyl derivative. In the first step, a trialkyl- or triaryltin group is added to (i) a jt bond of an alkene or an alkyne, or (ii) an aryl group in the substrate. Then, in the second step, the trialkyl- or triarylstannyl group is replaced by either (i) an isotope of hydrogen or (ii) an isotopically labelled group78,125,126. 

The intermediacy of a platinum vinylidene in Yamamoto s reaction was supported by the results of isotopic labeling studies. D FT calculations were used to further probe the proposed reaction mechanism. In contrast to the prevailing model of alkyne/ vinylidene interconversion for Rh(I)-catalysts, direct Ca Cp 1,2-H-migration is implicated in the formation of vinylidene 130. Direct C—H insertion via a single... 

Supporting evidence for the above mechanistic patterns in the majority of metal systems was first established in elegant isotopic labeling studies, which showed clearly that no intermediate with the symmetry of a cyclobutadiene was involved.In one system, the reaction of a cobaltacyclopentadiene with MeC>2CC CC02Me, benzene formation does not involve direct complexation of the third alkyne to the metal. It has therefore been suggested that the conventional insertion process has been here replaced by a direct Diels-Alder reaction with the metallacycle, perhaps as a result of electronic factors (Scheme 25). o ... 

The reaction between sodium acetylide and alkyl halides in liquid ammonia is the most general method of preparing substituted acetylenes. It has very often been used to prepare labelled alkynes . Appropriately labelled alkyl halides have to be prepared first (a review of the preparation of the most common ones has already been given ), but more and more are now commercially available. The yield of the condensation in liquid ammonia is about 75% and, under experimental conditions, no isotopic exchange has been found the isotopic purity of the final alkynes is the same as that of the starting alkyl halides. 

For acyclic alkenes, the facile rearrangement process obviates most possibilities of stereoselective transformation. The one exception is that of stereospecific isotopic labelling, for which hydrozirconation is a potentially powerful technique compounds of type Bu CHDCHDX (36), useful for NMR-based mechanistic studies, are conveniently obtained as in Scheme 9. This requires that four separate processes — hydrozirconation of alkyne, cleavage of alkeiiylzirconium, hydrozirconation of alkene and cleavage of alkylzirconium — all be completely stereospecific. 

The preparation and immediate reaction of alkyllithium for deprotonation of various acidic compoimds precisely illustrate this aspect (Fig. 34).i 8 representative reaction is the quantitative formation in a few minutes of 2-lithio-1,3-dithiane by sonication of f-butyl chloride, lithium, and 1,3-dithiane in THF. In situ generated butyllithium was used for the deprotonation of alkynes and phosphonium salts. With secondary amines, the strongly basic lithium amides are produced (p. 368). This procedure avoids the use of organolithium auxiliaries with solvent and temperature adjustments. o The isotopically labeled Li hexamethyl disilazide was obtained by this method.i i... 

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