Benziodoxole-based hypervalent iodine reagents for atom-transfer reactions

Abstract

In the last decades, hypervalent iodine reagents have raised from chemical curiosities to mainstream reagents in organic synthesis. The use of benziodoxole-derived reagents has been especially successful in oxidation methods, whereas non-cyclic iodinanes have been used both for oxidation and atom-transfer reactions. On the other hand, the exceptional properties of 10 benziodoxole reagents for atom-transfer reactions have only started to attract the attention of the synthetic community more recently. In this review, progress in the use of these compounds for C-X and C-C bond formations will be presented. In particular, recent breakthroughs in trifluoromethylation and alkynylation reactions have been realized since 2006 bas ed on benziodoxole-derived reagents and these results are the main focus of this article.

General and Practical Formation of Thiocyanates from Thiols

“…Under the optimized conditions CBX (10) or CDBX (11) (1.1 eq) was added in one portion to a solution of the thiol 13a (1.0 eq) and DBU (1.05 eq) in THF at room temperature and stirred for five minutes in an open-air flask to give the thiocyanate 14a in 96% isolated yield (Scheme 3A). The cyanation of thiophenol (13b) and 2-thionaphthalene (13c) gave the corresponding products 14b and 14c in 90% and 95% respectively.…”

“…The higher electronegativity of the nitrogen atom could further stabilize the formed charge and lower the energy of the transition state. (10) and computed geometries (M06-2X/def2-SVP level) for Van der Waals complex V and transition state IV with thiophenolate (13b'), thiophenol radical (13b'') and thiophenol (13b). [21] In addition to thiophenolate (13b'), thiophenol radical (13b'') and thiophenol (13b) itself could also lead to thiocyanate formation.…”

“…Table 1. Optimization of thiocyanate formation [a] entry 10-12 base solvent yield 14a [b] yield 15a [b] [a] 4-Tertbutylthiophenol (13a, 0.50 mmol), cyanide transfer reagent (10)(11)(12)0.550 mmol), base (0.525 mmol), solvent (5.0 mL), 23 °C, 5 min, open flask. [b] Isolated yield of spectroscopically pure product.…”

“…Recently, the use of cyclic hypervalent iodine reagents, especially benziodoxol(on)es, has led to important breakthroughs in atom-transfer reactions. [10] In the field of thiol functionalization in particular, Togni and co-workers reported the first example of trifluoromethylation, [11] whereas our group developed a practical alkynylation of thiols using EthynylBenziodoXolone (EBX) reagents. [12] However, to the best of our knowledge, hypervalent iodine reagents have never been used for the synthesis of thiocyanates starting from thiols.…”

Alkynylation with Hypervalent Iodine Reagents

“…One classical approach to enhance the stability of hypervalent iodine reagents is to incorporate the iodine atom into a cyclic structure fused to an aromatic ring (usually benzene [17,18]). Through the more rigid structure, the overlap of orbitals between the iodine atom and the benzene ring is further improved, which leads to increased stabilization.…”