Chemodivergent, Tunable, and Selective Iodine(III)-Mediated Bromo-Functionalizations of Polyprenoids

Abstract

Mild oxidation of bromides by iodine(III) reagents generated active electrophilic bromination species that were reacted with polyprenoids. By simple and minor variations of an I(III)/Br combination, the reactivity could be selectively steered toward dibromination, oxybromination, or bromocyclization, giving access to a wide array of brominated motifs.

Iodine(III)-mediated halogenations of acyclic monoterpenoids

“…In our study on terpenoids [16], the reaction conditions for the dibromination of the distal double bond were easily established from our previous study on the bromination of enamides [11]. Thus, using a slight excess of DIB along with a two-fold amount of lithium bromide at 0 °C in dry acetonitrile rapidly yielded dibromo adduct 2a in 91% yield (Table 1, entry 1).…”

“…Despite the potential sensitivity of the alcohol and the amine functions, both geraniol ( 1c ) and protected geranylamine 1d gave the dibromo adduct 2c [16] and 2d in good yields. Finally, the reaction was performed on myrcene ( 1e ), providing 2e in 78% yield and leaving the diene moiety untouched.…”

“…In this manner, good to excellent yields (57–84%) were obtained for the formation of Z -derivative 3b , alcohol 3c [16], tosylamine 3d and diene 3e (Scheme 3). Once again, the selectivity is excellent as no reactions with the other double bonds or with the aryl ring [19] are observed and only one regioisomer is formed in all cases.…”

“…We have shown that electrophilic halogenations [11–13], or pseudohalogenations [14] can be triggered by combining an iodine(III) derivative with a suitable halide salt. In particular, the chemoselectivity of the reaction can be finely tuned by adjusting several parameters, such as the nature of the halide as well as of the iodine(III) ligands and the halide counterion [15–16]. In the case of polyprenoids, we mostly devoted our efforts to achieve the bromocarbocyclization of aryl-geranyl derivatives using a combination of iodine(III) oxidant and a bromide source.…”

“…Yet in the course of our study we also showed that the reactivity of the key bridged bromonium intermediate could also be steered towards non-cyclizing vicinal difunctionalizations using slightly different combinations of a (diacyloxyiodo)arene and a bromide salt. Indeed, (diacetoxy)iodobenzene (DIB) and lithium bromide yield a dibromo adduct (Scheme 1, reaction 2), whereas a combination of (bis(trifluoroacetoxy)iodo)benzene (PIFA) and tetra- n -butylammonium bromide (TBAB) gives bromo(trifluoro)acetoxylated 3a (Scheme 1, reaction 3) [16]. …”