Stereoselective Rearrangements with Chiral Hypervalent Iodine Reagents

Abstract

Organic molecules bearing hypervalent iodine moieties have fascinated chemists over the years. Mild reaction conditions and environmentally friendly behavior through replacement of toxic heavy metals have led to their recent renaissance in organic synthesis. [1] Their use not only as selective oxidants [2] but also as enantiomerically pure reagents [3] make them versatile reagents for many organic transformations, such as the oxidation of sulfides to sulfoxides, [4] the a-oxygenation [5] and a-arylation of carbonyl compounds, [6] the dearomatization of phenols, [7] and the dioxygenation, [8] diamination, [9] aminohydroxylation, [10] and aminofluorination [11] of alkenes. The nature of hypervalent iodine(III) compounds to react as electrophiles and then act as excellent leaving groups make them highly suitable reagents for generating cationic intermediates, which can either directly react with nucleophiles or lead to rearranged products [12] under ring expansion, [13] ring contraction, [14] or aryl migration. [8d, 15] Similar rearrangements have been performed with much more toxic thallium reagents. [16] We recently reported a novel oxidative rearrangement of aryl substituted unsaturated carboxylic acids for the facile access of furanones. [17] Calculations were conducted to investigate the interplay of various cationic intermediates. Other studies have also confirmed the involvement of aryl moieties in cationic intermediates of rearrangement reactions. [18] The use of chiral hypervalent iodine reagents in asymmetric rearrangement reactions seems to be a very promising area of research and, to our knowledge, no reactions of this type have been reported to date. Herein, we describe the first stereoselective rearrangements of aryl substituted alkenes with high enantioselectivites mediated by chiral hypervalent iodine reagents. We have investigated chalcones of type 1, which are easily accessible through an aldol condensation between methyl ketones RCOMe and aryl aldehydes ArCHO. Oxidative rearrangements of such compounds to a-arylated carbonyl compounds have been known for some time. [19] The reaction of aryl-substituted alkenes 1 with electrophilic chiral iodine reagents results in the formation of phenyliodinated intermediates 2, which can be stabilized by the formation of phenonium ions [20] followed by the reaction with a second alcohol nucleophile to give the 1,2-migration products 3 (Scheme 1).Initially the reaction of (E)-1,3-diphenyl prop-2-en-1-one 1 a with only (diacetoxyiodo)benzene [PhI(OAc) 2 ] was investigated, but its reactivity with 1 a is too low and no conversion was observed (Table 1, entry 1). As already described, [19] an activation of the hypervalent iodine(III) reagent is necessary, and addition of 50 % aqueous H 2 SO 4 as a Brønsted acid to the reaction mixture [21] resulted in the rearranged product in 64 % yield. When using [bis(trifluoroacetoxy)iodo]benzene as an iodine(III) source, the yield increased to 82 % (Table 1, entries 2 and 3). Scheme 1. Rearrangement of 1 to 3 via ph...

Rearrangements Induced by Hypervalent Iodine

“…Reaction of enones such as 59 with the modified Fujita reagent 60 developed by Ishihara and coworkers [14] transforms them into α-substituted ketones 61 as shown in Scheme 18 [15]. Although yields are higher when chalcones are employed, the reaction also proceeds with aliphatic ketones (R ¼ Me, 10%) and esters (R ¼ OMe, 12%, 96% ee).…”

Adventures in Ring-Contraction Reactions

“…91 From 1,2-dihydronaphthalene, the corresponding ring-contraction product was obtained in 72% yield and 59% enantiomeric excess (ee). By changing the conditions (solvent, additive, and temperature), the ee increased to 70%, but the yield dropped to 30% only (Scheme 27).…”

Asymmetric Ring Contraction Reactions Mediated by Chiral I(III)

“…1 The development of reaction processes controlled by chiral hypervalent iodine reagents with high enantioselectivity has drawn extensive and enduring attention because of their environmentally friendly profile and avoids the issue of toxicity. 2,3 Rearrangement reaction is one of the important reactions promoted by I(III). 1,3,4 Herein, we describe asymmetric ring contraction reactions mediated by chiral hypervalent iodine reagents.…”

“…2,3 Rearrangement reaction is one of the important reactions promoted by I(III). 1,3,4 Herein, we describe asymmetric ring contraction reactions mediated by chiral hypervalent iodine reagents.…”