A Domino Approach for the Synthesis of α‐Iodo‐β‐dicarbonyl Compounds from α‐Epoxycarbonyls

Abstract

A series of a-iodo-b-dicarbonyl compounds have been synthesized from a-epoxycarbonyl compounds through a consecutive reaction by ring opening of epoxide followed by the oxidation in presence of NH 2 OH·HCl and NaIO 4 . To the best of our knowledge, this is the first time report for the use of aepoxycarbonyls as a key starting material for the synthesis of aiodo-b-dicarbonyl compounds. Various functional groups are well tolerated under the present reaction conditions. The epoxy carbonyl compound containing alkyl part is also effective for this conversion. The reactions were carried out in open atmosphere and are not sensitive to air and moisture. All of the synthesized compounds have been characterized by spectral and analytical data. The potential synthetic applicability of this method was investigated on a gram scale using the model reaction. The advantages of the present method are operational simplicity, short reaction time, general applicability, good tolerance to scale-up synthesis, as well as readily available reagents. A plausible mechanism has been proposed on the basis of an intermediate isolated from the reaction mixture.The synthetic pursuit of iodo-containing compounds is very useful conversion due to their extensive applications in organic synthesis, in the pharmaceutical industry, and in materials science. [1] In organic synthesis a-halogenation of 1,3-dicarbonyl compounds is an important task as these are used as versatile intermediates in various synthetic organic transformations. [2] Since the monosubstituted product is always accompanied by a small amount of disubstituted product; a-monohalogenation of 1,3-dicarbonyl compounds attracted more attention and is considered as a challenging problem. Several methods are available in literature for a-monohalogenation (Br, Cl, I) of 1,3-dicarbonyl compounds [3] but due to the poor electrophilic strength of iodine, simple iodination of 1,3-dicarbonyl compounds is difficult and requires the presence of an activating agent in order to produce a strongly electrophilic I + species. Methods involve mainly the modification of N-iodosuccinimide, [3a-c] use of HIO 4 /Al 2 O 3 , [3d] using elemental iodine and oxone. [3e] In addition, other reagents have been less investigated. [3f] So, all the reported syntheses of a-monohalogenated-1,3-dicarbonyl compounds involve the simple conversion of 1,3-dicarbonyl compounds to its a-halo-derivatives (Scheme 1a).There is no other approach in literature for its synthesis using different precursor involving other organic functionalities. We are actively engaged to develop new reagents and reaction conditions in organic synthesis [4] and as outcome recently we have developed a new reagent combination (NH 2 OH·HCl and NaIO 4 ) for selective oxidation of alcohols to corresponding carbonyl compounds, [5] synthesis of b-iodo-b'-hydroxy ethers, b-iodo ethers, b-iodohydrin, and b-iodo acetoxy compounds [6] and 1,2-diiodo carbonyl compounds. [7] Our developed methodologies [4][5][6] are very mild and efficient. Inspired by the...

A Domino Approach for the Synthesis of α,β‐Epoxy Ketones from Carbonyl Compounds under Neat Conditions at Ambient Temperature

“…The reactions with aliphatic aldehydes and acetophenone gave interesting results. We have tested two different aliphatic aldehydes such as butyraldehyde (8) and isobutyraldehyde (9) Table 6. Substrates scope on both aryl aldehydes and acetophenones.…”

“…α,β‐Epoxy carbonyl compound is one of the very important moiety as it can be easily converted to various functionalities like α,β‐hydroxy carbonyl compounds, α,β‐epoxy alcohol, allylic alcohol, 1,3‐diols and α‐iodo‐β‐dicarbonyl compounds . As reported in literature it could be synthesized by two ways.…”

“…[3] a,b-Epoxy carbonyl compound is one of the very important moiety as it can be easily converted to various functionalities like a,b-hydroxy carbonyl compounds, [4] a,b-epoxy alcohol, [5] allylic alcohol, [6] 1,3-diols [7] and a-iodo-b-dicarbonyl compounds. [8] As reported in literature it could be synthesized by two ways. Firstly, by the reactions of a,b-unsaturated ketones with hydroperoxides under basic conditions [9] and different catalytic systems were also developed such as rare-earth metal amides [(Me 3 Si) 2 N] 3 RE(m-Cl)Li(THF) 3 (RE = Yb, La, Sm, Y, Lu), [10] hetero bimetallic complexes [REL 2 ]-{[(THF) 3 Li]2(m-Cl)} (RE = Yb (1), Y (2), Sm (3), Nd (4), H 2 L = (S)-2,4-di-tert-butyl-6-[[2-(hydroxydiphenylmethyl)pyrrolidin-1-yl]methyl]phenol), [11] organocatalysts, [12] La(O-i-Pr) 3 , [13] a-D-glucose, a-D-mannose-based crown ethers [14] and KF-Al 2 O 3 [15] using TBHP as oxidant following the classical concept with common organic solvent.…”