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Electrochemically-induced intermolecular cross-dehydrogenative #-O coupling of #-diketones and #-ketoesters with carboxylic acids Oleg V. Bityukov, Olesya K. Matveeva, Vera A. Vil', Vladimir A. Kokorekin, Gennady Ivanovich Nikishin, and Alexander Olegovich Terent'ev J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02791 • Publication Date (Web): 08 Jan 2019 Downloaded from http://pubs.acs.org on January 8, 2019
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The Journal of Organic Chemistry
Electrochemically-induced intermolecular cross-dehydrogenative С-O coupling of β-diketones and β-ketoesters with carboxylic acids Oleg V. Bityukov, a Olesya K. Matveeva,a,b Vera A. Vil’, a Vladimir A. Kokorekin, a,c Gennady I. Nikishin,a Alexander O. Terent’ev a,b* a
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky
prosp., 119991, Moscow, Russian Federation [phone +7 (499) 1356428; fax, +7 (499) 1355328, e-mail,
[email protected]] b D.
I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, Moscow 125047, Russian Federation
c
Sechenov First Moscow State Medical University, Trubetskaya st. 8-2, 119991, Moscow, Russian Federation
TABLE OF CONTENTS GRAPHIC
O R1
O
O R2
R3COOH
KBr DMSO/H2O CCE, undivided cell air tolerable
O
R1 O
R2 O
R3 yields up to 92%
Abstract The electrochemically-induced cross-dehydrogenative С-O coupling of β-diketones and βketoesters (C-H reagents) with carboxylic acids (O-H reagents) was developed. An important feature of this reaction lies in the selective formation of intermolecular С-O coupling products in high yields, up to 92 %, using DMSO as a solvent with a broad substrate scope in undivided cell equipped with carbon and platinum electrodes at high current density. Electric current acts as a stoichiometric oxidant.
Introduction The oxidative cross-coupling (cross-dehydrogenative coupling) is promising and thriving field of modern organic synthesis. The construction of the new bond occurs with high atom efficiency and no functional groups are required.1-5 Among all types of oxidative coupling 1 ACS Paragon Plus Environment
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reactions, the coupling to form the С–О bond between the partners is more difficult6, 7 for the reason that it is generally accompanied by the oxidation of a C-partner into carbonyl products.8-10 The present study comprises two aspects of modern synthetic chemistry: the selective oxyfunctionalization of carbonyl substrates and electrochemistry as an efficient tool in crossdehydrogenative coupling reactions.11-16 The α-oxy-β-dicarbonyl fragment is an important structural part of natural products and pharmaceuticals.17-20 Series of naturally occurring α-acyloxy ketones exhibit antifungal,21-23 antimicrobial,24-27 antiviral28, 29 and others30 types of activity. Thus, the search of methods for the efficient acyloxy-functionalization of the β-dicarbonyl group is a desirable and timely task. Previously C-O functionalization of β-dicarbonyl compounds and their hetero analogs were limited to hydroxylation,31-50 peroxidation,51-54 and the coupling of N–O fragments55,
56
and
phenols.57 In this paper, the attention is focused on electrochemically-induced intermolecular acyloxylation of β-dicarbonyl compounds. Similar transformations with stoichiometric amounts of chemical oxidants were performed using hypervalent iodine compounds,58-60 Bu4NI/tBuOOH,61,
62
manganese(III) acetate,63,
64
lead(IV) acetate,65 and iron(III) salts.66
Benzoyloxylation of the β-dicarbonyl compounds by benzoyl peroxide is based on their preliminary transformation into enamines,67-70 copper complexes71 or enolates.72-74 Methods for the intermolecular oxidative acyloxy-functionalization of β-dicarbonyl compounds by diacyl peroxides have been discovered.75-77 Concerning electrochemical intermolecular acetoxylation, it was found that anodic oxidation of enol acetates led to α-acetoxycarbonyl compounds.78, 79 One of the main ideas of our work lies in the replacement of chemical oxidants applied for intermolecular oxidative C-O coupling of carbonyl compounds with carboxylic acids by electric current mostly with involvement of anodic processes. Electrolysis was implemented in many industries and synthetic applications.80-83 Last years, more and more attention has been paid to the use of electrochemistry in redox processes of organic synthesis by the following reasons: availability and low cost of electric current, variety of electrochemical reaction mechanisms and decreasing of waste amounts.84-89 Electrolysis can be carried out in a divided or undivided cell under controlled potential (CPE) or constant current conditions (CCE).90 Using of undivided cell is more practical but at the same time more difficult to implement because the active species electrogenerated at one electrode can undergo undesirable reactions with species electrogenerated simultaneously at another electrode.91 Advances of constant current (CCE) conditions are high current density, electrodes with small surface, and compact reaction vessels permitting to save a solvent.92 2 ACS Paragon Plus Environment
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The Journal of Organic Chemistry
Recently, more unambiguous due to monomolecular kinetic electrochemical processes of intramolecular lactonization have been reported (Scheme 1, b).93 In the present work we decided more challenging task on electrochemically-induced intermolecular cross-dehydrogenative С-O coupling of β-dicarbonyl compounds with carboxylic acids with high yields at CCE in undivided cell (Scheme 1, c). Despite the fact that many processes of anodic nature,83,
94-96
such as
hydroxylation,97-99 halogenation,100 dimerization101 and cathodic nature, for example carbonyl group reduction,102-107 can take place in similar systems (Scheme 1, a), acyloxy-product is selectively formed in our conditions. a) Possible transformation of carbonyl compounds in undivided cell O O O O R2 1 2 2 2 electrolysis R R R R or 1 or R1 R1 R1 R anodic R2 Hal OH processes O ref. 97-99 ref. 100 ref. 101 O R
R1
OH
electrolysis
2
cathodic processes
R2
R1
ref. 102-107
b) Intramolecular C-O cross-coupling O O electrolysis R1 R1 HO
ref. 93
O
O
O
c) This work: Intermolecular C-O cross-coupling O R1
O R
2
+ R3COOH
electrolysis
R2
R1 O
O R3
Scheme 1. Electrochemical oxidative transformation of carbonyl compounds.
Results and Discussion To carry out the oxidative coupling, β-ketoesters 1a-e and β-diketones 1f-i were used as the C-H reagents and carboxylic acids 2a-l were chosen as O-H reagents. As a result, coupling products 3aa-ia, 3ab-al were obtained (Scheme 2).
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O O R
O
1
R
2
R3COOH
1a-i
CCE, undivided cell supporting electrolyte solvent
R1 O
R2 O
R3 3aa-ia, 3ab-al 3x,y (x = a-i, y = a-l)
2a-l
1a: R1 = Ph, R2 = OEt 1b: R1 = Me, R2 = OEt 1c: R1 = iBu, R2 = OEt 1d: R1 = Ad, R2 = OEt 1e: R1 = Me, R2 = OBut
O
1f: R1 = Me, R2 = Me 1g: R1 = iBu, R2 = Me 1h: R1 = Ph, R2 = Me 1i: R1 = 2-Cl-Ph, R2 = Me
2a: R3 = Me 2b: R3 = Et 2c: R3 = Ph 2d: R3 = Pentyl 2e: R3 = CH2Ph 2f: R3 = 2-I-Ph
2g: R3 = (CH2)2-cyclohexyl 2h: R3 = (CH2)2Ph 2i: R3 = CH=CHPh 2j: R3 = CH=CHCH=CHCH3 2k: R3 = CH2NHC(O)Ph 2l: R3 = 2-Thienyl
Scheme 2. Intermolecular cross-dehydrogenative С-O coupling of β-dicarbonyl compounds 1a-i with carboxylic acids 2a-l (in the codification of 3 the first letter index refers to the β-dicarbonyl compound 1 moiety, the second letter index to the carboxylic acid 2 moiety). Influence of supporting electrolyte and its amount, molar ratio of starting reagents, solvent type, the amount of passed electric current and its density and also electrode materials were investigated in the model of C-O coupling reaction of ethyl benzoylacetate 1a with acetic acid 2a (Table 1). Table 1. Optimization of the reaction conditions. a O
O
Ph
OEt 1a
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13
Electrolyte (molar ratio: mol per mol 1a) KI (1) NH4I (1) NaBr (1) KBr (1) NH4Br (1) n-Bu4NBr (1) HBr (1) KCl (1) KBrO3 (1) LiClO4 (1) NaBF4 (1) KBr (1) KBr (1)
CH3COOH 2a
CCE, undivided cell supporting electrolyte solvent
Molar ratio 2a / 1a 10 10 10 10 10 10 10 10 10 10 10 180 10
Solvent DMSO/H2O DMSO/H2O DMSO/H2O DMSO/H2O DMSO/H2O DMSO/H2O DMSO/H2O DMSO/H2O DMSO/H2O DMSO/H2O DMSO/H2O AcOH/H2O THF/H2O c 4
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O
O
Ph
OEt OAc 3aa
Electricity passed, F/mol 1a
Yield 3aa, %
4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5 4.5
50 76 80 81 67 58 n.d. n.d. 27 n.d. n.d. n.d.
