Tritide reagents

Aromatic dehalogenation suffers from the disadvantage that only 50% of the tritium is incorporated, the rest appearing as waste. This situation is even more marked for borotritide reductions but the problem can be overcome by using some of the new tritide reagents that have recently become available as a result of the synthesis of carrier-free lithium tritide (Scheme 13.1) [22], Their reactivity can be fine-tuned through the elements (e. g. B, Al, Sn) to which the tritium is attached and by the electronic and steric nature of the substituents at the central atom. 

The development of H NMR spectroscopy has made possible many new applications and in the process has stimulated research into the development of new labelling reagents and hence new/improved labelling procedures. One such area is that of tritide reagents. Essentially carrier-free LiB H4 can now be obtained via the two-step sequence ... 

There is a much wider variety of indirect replacement approaches. In most cases these approaches introduce the labels at structurally predefined positions generated by (formally) oxidative processes, which are then followed in a second step by reductive operations. Examples of such approaches preferentially designed for the introduction of tritium include halogenation followed by tritiodehalogenation, the introduction of carbon-carbon multiple bonds followed by catalytic tritiation, the oxidation of carbon-heteroatom bonds followed by reduction using tritide reagents, etc. These approaches, which do not alter the skeleton of the target in the process, are discussed in Chapter 4, Sections 1-3 and Chapter 10, Sections 10.1.1.2. ... 

Carbon-carbon multiple bonds are most commonly reduced by means of catalytic tritiation methods. Polarized multiple bonds such as those of carbonyl, carboxyl and nitrile groups are less often reduced by catalytic tritiation, since the use of tritide reagents is often more convenient and can provide greater selectivity (see Section 4.3). 

While catalytic tritiodehalogenation of aromatic halides plays a dominant role in the preparation of substrates of high specific activity, aliphatic halides are more often treated with strong tritide reagents (see Section 4.3). However, sp halides activated by a neighboring functional group such as aryl-, heteroaryl, or carbonyl are often viable substrates for catalytic... 

Tor the sake of convenience, tritide reagents designated by their formulas will always be written, as here, as if they contained only tritium. In reality, all reagents contain a mixture of tritium and hydrogen that varies with the specific activity of the reagent. For example, lithium borotritide of specific activity 80 Ci/mmol has the average formula approximately LiB H2.7Hi.3, and probably consists of a mixture of all possible isotopomers LiBH4, LiB HHj, LiB HoHz, LiB HoH and LiB H.. 

It is only when an excess of tritide reagent is used that a KIE may be expected. The availability in the reaction of more tritide/hydride equivalents than are needed to reduce aU substrate molecules provides the opportunity for hydrides to outcompete tritides, and tritium incorporation into substrate will be less than statistical. 

Preparation of Tritium-Labeled Compounds by Chemical Synthesis 161 nucleophilic tritide reagents... 

Scheme 4.1 The range of tritide reagents available from highly reactive lithium tritide...

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