Chemoselective Oxidation of Equatorial Alcohols with N-Ligated λ³-Iodanes

Abstract

The site-selective and chemoselective functionalization of alcohols in complex polyols remains a formidable synthetic challenge. Whereas significant advancements have been made in selective derivatization at the oxygen center, chemoselective oxidation to the corresponding carbonyls is less developed. In cyclic systems, whereas the selective oxidation of axial alcohols is well known, a complementary equatorial selective process has not yet been reported. Herein we report the utility of nitrogen-ligated (bis)cationic λ 3 -iodanes (N-HVIs) for alcohol oxidation and their unprecedented levels of selectivity for the oxidation of equatorial over axial alcohols. The conditions are mild, and the simple pyridine-ligated reagent (Py-HVI) is readily synthesized from commercial PhI(OAc) 2 and can be either isolated or generated in situ. Conformational selectivity is demonstrated in both flexible 1,2-substituted cyclohexanols and rigid polyol scaffolds, providing chemists with a novel tool for chemoselective oxidation.

Morita-Baylis-Hillman Reaction Inspired [3,3]-Rearrangement of Aryl Iodanes with α,β-Unsaturated Oxazolines

“…After TMSOTf activates PhI(OAc) 2 to give PhI(OTf) 2 , [42][43][44][45] stage I generates an intermediate IM2 for the subsequent rearrangement process. The stage takes place by assembling PhI(OTf) 2 with E-3c to give EIM1, [46][47][48][49] followed by a MBH-like nucleophilic addition of 4-methylpyridine (denoted as Py) to an alkene carbon of EIM1. As depicted in Figure 2, Py can attack EIM1 from either side of the alkene plane via (R)ETS1 or (S)ETS1, leading to (R)IM2 or (S)IM2.…”

Reactions of PhIX2 I(iii) oxidants with heavy triphenyl pnictines

“…11 Wengryniuk has recently shown the efficacy of these oxidants in oxidative ring formation reactions. [12][13][14] In the main group we have explored the chemistry of these dicationic I(III) oxidants with aromatic group 16 rings, which largely resulted in electrophilic aromatic substitution type reactions on the ring or ring substitutents. 15,16 We also reported one reaction in group 15, the reaction of Ph3P with [PhI(4-DMAP)2] 2+ , which resulted in oxidation of phosphorus to P(V) and ligation of a 4-DMAP giving dicationic complex 6 (Scheme 4), 17 previously reported by Burford using the oxidation/halide abstraction method from the phosphine.…”

Umpolung Strategy for Arene C−H Etherification Leading to Functionalized Chromanes Enabled by I(III) N‐Ligated Hypervalent Iodine Reagents

“…[5] Unfortunately, yields were only moderate and the scope was limited to electron-rich arenes. In 2007, Ochiai reported a cascade sequence to give chromanyl(phenyl)λ 3 -iodanes (8) via cyclization on to a putative cationic intermediate (9) and subsequent electrophilic aromatic substitution from a 3-aryl-propanol (7), however scope studies were not included. [6] Finally, a recent report from Zakarian combined I(III) arene activation with Cu(I) catalysis for the synthesis of dihydrobenzofurans via an in situ generated aryl iodonium salt, however the formation of larger ring sizes was prohibited, presumably as a result of the intermediacy of a Cu(III) metallocycle (11), and initial iodonium formation necessitated an activating group para to the site of functionalization.…”

“…[7] Common to all the HVI-based approaches shown in Scheme 1 is the basic mechanism of initial arene activation and subsequent attack by the pendant alcohol. As part of our laboratory's ongoing interest in umpolung heteroatom activation with I(III) reagents, [8] we envisioned a different approach wherein initial alcohol activation would lead to an electrophilic oxygen center (14), which could then undergo CÀ O bond formation via an umpoled cyclization event (Scheme 1c). It was postulated that this new reaction manifold could engage a broader substrate scope, allowing the formation of different ring sizes and overcoming the need for electron-rich aromatic rings.…”