Visible-Light-Promoted Oxidative Amidation of Bromoalkynes with

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

pubs.acs.org/OrgLett

Visible-Light-Promoted Oxidative Amidation of Bromoalkynes with Anilines: An Approach to α‑Ketoamides Ke Ni,† Ling-Guo Meng,*,† Kuai Wang,† and Lei Wang*,†,‡ †

Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P. R. China State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032, P. R. China

‡

S Supporting Information *

ABSTRACT: A convenient and practical synthetic route to α-ketoamides from bromoalkynes and anilines through phototriggered organic transformations via a C−N cross-coupling and an oxidation of CC was developed. The reaction could be furnished without an external photocatalyst at ambient conditions, and a wide range of α-ketoamides were obtained in good yields. Scheme 1. Different Routes to α-Ketoamides

T

he pursuit of a facile and practical platform for the synthesis of α-ketoamides has attracted the attention of synthetic chemists,1 because these structural units exist in bioactive molecules, such as BMS190914 and SNJ-1945, which are used as a calpain inhibitor and retinoic acid receptor selective ligand, respectively (Figure 1).2 Furthermore, the α-

Recently, visible-light-initiated organic reactions as the most important and novel platform for chemical transformations have received much attention due to exhibition of synthetic efficiency and practicability.10 In general, occurrence of a photoreaction relies on metal complexes or organic dyes used as intermediates to transfer the luminous energy into a chemical reaction.11 Although some photoreactions proceeded without photosensitizers, those reactions occurred with an oxidant,12 additive,13 or ultraviolet light14 irradiation.15 Therefore, the development of more feasible and practical visible-light-induced organic transformations has great value. Very recently, we have discovered that simple alkenes and alkynes could be used as good photoreaction substrates for the construction of complicated molecules using organic dye as a photocatalyst under visible light irradiation.16 After further investigation, we are delighted to find that bromoacetylenes exhibit more reactivity in the presence O2 under visible light irradiation and reacted with anilines smoothly to afford α-ketoamides (Scheme 1, eq 2). Obviously, this synthetic method supplies a direct and practical platform to α-ketoamides, compared with the previous reports, as shown in Scheme 1. Herein, we report a visible-light-promoted directly oxidative amidation of bromoal-

Figure 1. Biological molecules containing α-ketoamide moiety.

ketoamide structure was also found in an analytical reagent that acts as a fluorescent probe candidate for H2O2.3 The general preparation route to α-ketoamides is the condensation of amines with α-keto acids (α-keto acyl halides).4 In addition, other synthetic reactions, such as transition-metal catalyzed double carbonylation,5 peroxide oxidation reaction,6 and so on,7 have been developed for the formation of α-ketoamides. Interestingly, Jiao employed terminal alkynes as the precursor for the preparation of α-ketoamides in the presence of a Cucatalyst and O2,8 and a similar transformation also could be achieved under metal-free conditions (Scheme 1, eq 1).9 However, prominent deficiencies of the above methods require a transition-metal catalyst, or harsh and complicated reaction conditions. Accordingly, the development of a more convenient and practical approach for these classic molecules remains a challenge for chemists. © XXXX American Chemical Society

Received: February 18, 2018

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DOI: 10.1021/acs.orglett.8b00586 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Scheme 2. Scope of Bromoalkynesa,b

kynes with anilines in the presence of O2 under ambient conditions without any photosensitizers and additives. We commenced our study by using 2,4-dibromo-6-fluoroaniline (1a) and phenylethynyl bromide (2a) as the model substrates for optimizing the reaction conditions, and the results are shown in Table 1. The reaction of 1a with 2a in the Table 1. Optimization of the Reaction Conditionsa

entry

light source

solvent

yieldb (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

blue LED blue LED  blue LED blue LED blue LED blue LED blue LED blue LED blue LED blue LED blue LED blue LED blue LED purple LED green LED red LED

DCE DCE DCE DCE toluene EtOAc CH3CN CH2Cl2 CHCl3 THF acetone EtOH DMF DMSO toluene toluene toluene

37c 64