Novel Oxygenations with IBX

Abstract

Over the past years, the value of 2-iodoxybenzoic acid [1] (IBX, 1) as a mild, practical, and synthetically useful oxidizing agent has been continually increased.[2] Even though the simple oxidation of alcohols to the corresponding carbonyl compounds still remains the primary application of IBX, [3,4] a huge variety of unique oxidative transformations has been developed.[5] Thus, IBX has emerged as an oxidant being of rather ubiquitous use in organic synthesis. Of particular significance, IBX induces the dehydrogenation of simple carbonyl compounds as described by Nicolaou and co-workers.[6] Typically, such reactions of ketones and aldehydes with IBX require elevated temperatures (65-85 8C) to produce the corresponding a,b-unsaturated products.[6b] On the other hand, the direct dehydrogenation of 2-oxonitriles proceeds smoothly at ambient temperature in a highly selective manner and in excellent yields, as we found recently in the case of nitrile 2 [Eq. (1)]. [7] We also found in the course of our previous investigations in the field that the behavior of enolizable carbonyl compounds, when subjected to IBX, strongly depends on the type of additional functional groups in the a-position. This becomes apparent in the reactivity of a-alkynyl carbonyl compounds, which in the presence of IBX predominantly yield tertiary alcohols resulting from aoxygenation rather than undergoing dehydrogenation [Eq.(2)]. [8] In fact, oxidative processes involving the transfer of an oxygen atom from IBX are not uncommon.[9] Hence, it seems all the more remarkable that only the selective oxidation of benzylic positions [10] and most notably the hydroxylative dearomatization of phenols [11] have attained major synthetic importance. The related direct a-hydroxylation of carbonyl compounds upon exposure to IBX has received much less attention [e.g., Eq. (2)]. [4b,c, 8] In part, this neglect is due to the fact that there are rigorous structural constraints on those carbonyl compounds that are currently known to react this way. The true value of IBX-mediated a-hydroxylation of carbonyls can only be garnered when the basic factors are determined that favor the oxygenation pathway rather than other oxidative processes such as dehydrogenation. In this context, we expected that ketones A lacking an a-alkynyl substituent might still be able to participate in oxygen-transfer reactions with IBX provided that they are sufficiently activated by a suitable functional group Z (Scheme 1).[12]Herein, we present novel IBX-induced oxygenations of various easily accessible substrate classes by use of an operationally simple and broadly applicable protocol.To probe the feasibility of the projected transformation for Z = CO 2 R, we first examined the conversion of keto ester 6 a into tertiary alcohol 7 a in the presence of IBX (Table 1). Due to the low solubility of IBX in most common solvents, conversion of 6 a was only detectable when using the polar solvent DMSO.[13] The reaction in pure DMSO was invariably accompanied by the formation of significant amoun...

Selectfluor-Mediated Simultaneous Cleavage of C–O and C–C Bonds in α,β-Epoxy Ketones Under Transition-Metal-Free Conditions: A Route to 1,2-Diketones

“…13 Note that there is also an equilibrium between 6 and its hydrate form 6′. When the mixture of 6 and 6′ was subjected to the standard reaction conditions, 2a was indeed produced in 62% yield (eq 1, Scheme 3), thus confirming that 1,2,3-trione was an intermediate for the formation of 2.…”

“…13 Although these reactions failed to give 1,2-dicarbonyl compounds 4, the formation of diketo ester 5 led us to speculate that 1,2,3-trione might be an intermediate for the generation of diketone 2 from α,β-epoxy ketones 1.…”

“…16 Subsequent oxidation of I by Selectfluor gave 1,2,3-trione intermediate 6. 13,17 Then, 6 may undergo a 1,2-Wagner−Meerwein-type rearrangement of a benzoyl group through F + -or H + -assisted activation of the carbonyl group in 6 to yield intermediate II. 18 Finally, a carbon monoxide was released from intermediate II followed by a proton abstraction with a base from resulting…”

2‐Iodoxybenzoesäure – ein einfaches Oxidationsmittel mit einer Vielfalt an Anwendungsmöglichkeiten

“…Oxidation von 2-Benzopyriliumsalzen. [185] Schema 49. a-Hydroxylierung von Carbonylverbindungen nach Kirsch et al [188,189] Schema 50. Effekt von Yb(OTf) 3 als Additiv.…”

Practical Azidation of 1,3‐Dicarbonyls

“…Inspired by our recent study on the oxygenation of 3-oxoesters, [17] and given their inherent reactivity with various electrophiles, [18,19] our goal was to develop a reliable and operationally simple azidation reaction that provides straightforward access to a variety of organic azides. We anticipated Abstract: An operationally simple, direct azidation of 1,3-dicarbonyl compounds has been developed.…”