The neighboring group effect of fluorine in the tritium labeling of organic substrates with [Cp*(PMe3)IrMe(CH2Cl2)]+[BArf]−, a cationic iridium(III) complex

Abstract

SummaryThe cationic Ir(III) complex, [Cp*(PMe 3 )IrMe(CH 2 Cl 2 )][BAr f ] (1, Cpà ¼ Z 5 -C 5 Me 5 , BAr f ¼ MeBðC 6 F 5 Þ 3 ), has been shown to be a useful reagent in the tritium and deuterium labeling of organic substrates. During a recent reaction of 1 with a fluorinated molecule, we observed an unusually high incorporation of tritium ortho to the aromatic fluorines. To probe whether this was an isolated incident or a more general phenomenon, we have investigated the application of 1 towards the tritiation of simple fluorinated organic substrates. Our results indicate that aromatic fluorine indeed does exhibit a neighboring group effect in terms of directing ortho H/T exchange. The directing influence appears to be at least as strong as the hydroxyl moiety reported in previous works.

Preparation of Tritium‐Labeled Compounds by Isotope Exchange Reactions

“…Complex 154 can undergo rapid oxidative addition to sp 2 and sp 3 CÀH bonds of substrate compounds, with concurrent loss of methane, to give new aryl-or alkyliridium (III) complexes. The exception to this trend is that fluoro substituents have been found to be neutral to, or slightly facilitative of, labeling in adjacent positions 226 . The first use of this process with deuterium in place of hydrogen, to achieve deuterium exchange labeling of substrates, was reported 223 Figure 3.58 Structure of active iridium cyclopentadienide complex; regioselectivity of deuterium labeling in model substrates test compounds, and expanded in a subsequent study 224 .…”

Deuterium exchange promoted by iridium complexes formed in situ

“…2 comparable results are obtained using the homologous system, Ir(cod)(Ph 2 AsCH 2 CH 2 CH 2 AsPh 2 )BF 4 (9), which is a useful mediator of exchange into both benzamides and phenylacetamides.…”

“…6 Even after reduction of displaced cyclooctadiene is complete, isotope exchange mediated by 8 is slow, and complete exchange can take up to 5 days. However, the catalyst retains its activity after this time; 2 comparable results are obtained using the homologous system, Ir(cod)(Ph 2 AsCH 2 CH 2 CH 2 AsPh 2 )BF 4 (9), which is a useful mediator of exchange into both benzamides and phenylacetamides. 14 The solution stability of the active catalysts derived from 8 and 9 is very much greater than that of the corresponding dppe and dppp complexes, 2 and is believed to be due to stabilization of a low oxidation state intermediate in the catalytic cycle, as a result of the greater p-acidity of arsenic compared with phosphorus.…”

“…These catalysts are effective stoichiometric mediators of deuteration in methyl esters and at b-positions in naphthalenes, 8 and ortho to fluorine in fluoroarenes. 9 The activation of chloroiridium(III) pincer complexes is carried out in a similar manner (Scheme 1), with the best results obtained for X = SbF 6 ; the reported activity of these complexes is limited, with modest incorporation into aromatic amides and up to 1.7 D incorporated in a nonspecific manner into 2-phenylpyridine. 10 Advantages and disadvantages of in situ complex formation With few exceptions, there is no advantage to be gained by preparing and using an iridium catalyst in situ if that catalyst is conveniently prepared and isolated, and is stable on storage for even a limited period.…”

Organoiridium complexes for hydrogen isotope exchange labeling

“…29 30,31 use of tritium gas was reported on two substrates. 31 The regioselectivity of this labeling is not guided by coordinating functional groups (except perhaps by coordinating substituents such as halo, hydroxyl 32 ), but rather is sensitive to the steric environment, so that the positions labeled tend to be different from those with the other catalyst types.…”