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Copper-catalyzed Direct Synthesis of Diaryl 1,2Diketones from Aryl Iodides and Propiolic Acids Hongkeun Min, Thiruvengadam Palani, Kyungho Park, Jinil Hwang, and Sunwoo Lee J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 17 Jun 2014 Downloaded from http://pubs.acs.org on June 19, 2014

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The Journal of Organic Chemistry

Copper-catalyzed Direct Synthesis of Diaryl 1,2-Diketones from Aryl Iodides and Propiolic Acids Hongkeun Min, Thiruvengadam Palani, Kyungho Park, Jinil Hwang, Sunwoo Lee* Department of Chemistry, Chonnam National University, Gwangju, 500-757, Republic of Korea, Corresponding Author : email : [email protected]

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GRAPHIC ABSTRACT

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The Journal of Organic Chemistry

ABSTRACT Benzil derivatives such as diaryl 1,2-diketones are synthesized via the direct decarboxylative coupling reaction of aryl propiolic acids and their oxidation. The optimized condition is that the reaction of aryl propiolic acids and aryl iodides is conducted at 140 oC for 6 h in the presence of 10 mol% CuI/Cu(OTf)2 and Cs2CO3, and then HI (aq) is added and further reacted. It showed good functional group tolerance toward ester, aldehyde, cyano and nitro groups. In addition, symmetrical diaryl 1,2-diketones are obtained from aryl iodide and propiolic acid in the presence of palladium and copper catalysts.

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INTRODUCTION

1,2-Diketones are one of the most important skeletons in the biological active molecules1 and very useful building blocks that are able to be easily transformed to a variety of another chemicals, especially to the heterocyclic compounds.2 Among 1,2-diketones, benzil derivatives also exhibited bioactivities in antitumor application.3 A number of methods for the preparation of 1,2-diketone have been developed and they mostly contained the oxidation process of various substrates such as olefins, methylene ketones and alkynes. The oxidations of olefins with selenium dioxide, potassium permanganates and ruthenium catalyst were reported [Scheme 1 (a)].4 In addition, it has been reported that the intermolecular coupling with terminal alkene and nitroalkane provided the diketone [Scheme 1 (b)].5 The methylene ketone derivatives including alpha halo and alpha hydroxyl ketones have been oxidized to the 1,2-diketone with iodine, oxygen, Al2O3/CuBr2, oxothiazoline vinyl bromide,

pyridine

N-oxide,

sodium

hypobromite,

bismuth

nitrate-copper acetate,

trichlorooxovanadium [Scheme 1 (c)].6 However, these methods have some drawbacks such as vigorous reaction conditions, the discharge of large amount of metal or organic wastes and the preparation of starting materials. Since some of them were synthesized from the alkynes, the direct oxidation of internal alkynes may be one of the most widely used and most straightforward method to synthesize 1,2-diketone.7 Furthermore, the internal alkynes were easily prepared via Sonogashira coupling reaction [Scheme 1 (d)].8 Recently a number of transition metal catalyzedoxidations of the internal alkynes have been reported, they employed iron, palladium, copper, gold, silver and ruthenium as catalysts and/or co-catalyst with oxidants [Scheme 1 (e)].9

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Scheme 1. Synthesis of 1,2-diketones

Although these methods have been attractive in the synthetic aspect, they have several drawbacks: 1) the preparation process of the internal alkynes is still needed, 2) metal catalysts used are expensive in most cases, 3) most of the oxidation reactions require toxic or expensive reagents, and 4) there is no report of the direct synthesis of 1,2-diketone from aryl halides. Alkynyl carboxylic acids have been intensively used as terminal alkyne surrogates in the Sonogashira type decarboxylative coupling reactions10 because their preparation process were much simpler and easier than those of terminal alkynes.11 As part of our ongoing research to expand the decarboxylative coupling of alkynyl carboxylic acid,12 we found that benzil was formed when iodobenzene and phenyl propiolic acid were allowed to react with copper catalyst in the absence of base. Inspired by this result, we investigated the development of one-pot synthesis of 1,2-diketone from the aryl iodides and aryl alkynyl carboxylic acid by using copper catalyst without the need of isolation of diarylalkynes. To the best of our knowledge, there is no report of the direct synthesis of 1,2-diketone from the aryl halides and alkynes.

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RESULTS AND DISCUSSIONS

To study the direct one-pot synthesis of 1,2-dikeonte, iodobenzene and phenyl propiolic acid were reacted in the variety of reaction conditions. The results are summarized in Table 1.

Table 1. Optimized condition for the synthesis of 1,2-diketone.a

Entry

Ratio (1a/2)

Catalyst

Additive (equiv)

Solvent

3a Product(%)

1

1/1

CuI

-

DMSO

Copper-catalyzed direct synthesis of diaryl 1,2-diketones from aryl iodides and propiolic acids.

Benzil derivatives such as diaryl 1,2-diketones are synthesized via the direct decarboxylative coupling reaction of aryl propiolic acids and their oxi...
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