Kinetic and Spectroscopic Studies of Aerobic Copper(II)-Catalyzed Methoxylation of Arylboronic Esters and Insights into Aryl Transmetalation to Copper(II)

Abstract

We previously reported a preliminary mechanistic study of aerobic Cu(OAc)2-catalyzed methoxylation of 4-tolylboronic ester (King, et al. J. Am. Chem. Soc., 2009, 131, 5044–5045), which revealed that aryl transmetalation from the boronic ester to CuII is the turnover-limiting step. In the present study, more-thorough kinetic and spectroscopic studies provide additional insights into transmetalation pathway and the identity of the CuII catalyst resting state(s). EPR spectroscopic studies show that at least two copper(II) species are present under catalytic conditions and their relative populations vary as a function of reaction time and acidity of the arylboronic ester, and are influenced by addition of acetic acid or acetate to the reaction mixture. Analysis of kinetic data and 11B NMR and EPR spectra under diverse reaction conditions suggests that aryl transmetalation occurs from a tetracoordinate, anionic boronate to a cationic CuII species, mediated by a methoxide-bridge.

Aerobic Copper-Catalyzed Organic Reactions

“…These reports include: reviews (Section I), 1149,1150,1151,1152 oxygenation of unactivated benzylic substrates (Section IIA.2), 1153,1154,1155 alkane oxidation (Section II.B), 1156,1157,1158 epoxidation of alkenes (Section II.C.2), 1159 oxidation difunctionalization of alkenes (Section II.C.3), 1160,1161,1162,1163,1164 cross coupling with alkynes (Section II.D.3), 1165 oxidation difunctionalization of alkynes (Section II.D.4), 1166,1167,1168 arene hydroxylation (Section II.E.1), 1169 reactions involving nucleophilic arenes (Section II.E.2), 1170 direction insertion of arenes (Section II.E.3), 1171,1172,1173,1174,1175 functionalization of acidic arene positionos (Section II.E.4), 1176,1177,1178 coupling of carbanion equivalents with boronic acids (Section III.C), 1179,1180,1181,1182,1183,1184,1185 alcohol oxidation (Section IV.A.1),1186,1187,1188,1189,1190,1191,1192,1193,1194,1195,1196,1197,1198,1199 tandem reaction with alcohol oxidation (Section IV.D), 1200,1201,1202,1203,1204,1205,1206,1207,1208 oxidation of aldehydes to amides (Section V.A), 1209 enolate oxiation without cleavage (Section V.C), 1210,1211 oxidative coupling of enolates (Section V.C.1), 1212 α-oxygenation of carboxylic acids (Section V.E), 1213 reaction of hydrazones (Section V.G), 1214 oxidation of hydrazones with cyclization (Section V.G), 12151216 reactions of enamines (Section VI.A), 1217,…”

Oxidative Coupling of Aryl Boron Reagents with sp3‐Carbon Nucleophiles: The Enolate Chan–Evans–Lam Reaction

“…However our current hypothesis is that the steps mirror that of the Chan-EvansLam reaction as outlined by Stahl and co-workers. [7] Future work will aim to cast light on this issue.…”

“…[2] First reported by Chan, Lam and co-workers, [3] and Evans et al, [4] functionalized aniline and phenol derivatives can be prepared from stable,r eadily available aryl boron species at room temperature by employing simple copper salts and mild organic bases.I na ddition to N-and O-based nucleophiles,s ulfur,s elenium, tellurium, and halogen nucleophiles are also suitable partners in these reactions. [2,5,6] Despite the success of Chan-Evans-Lam-type reactions in carbon-heteroatom bond construction processes,aswell as an increasing appreciation for the mechanism of these transformations, [7] ageneral method for the copper-mediated arylation of stabilized sp 3 -carbon-based nucleophiles with organoboron reagents has not been established. This is particularly noteworthy in light of the importance of a-aryl carbonyl compounds in synthetic organic and medicinal chemistry,and the considerable body of literature concerning transition-metal-based methods for their synthesis by the coupling of sp 2 electrophiles.…”

Enantioselective α-Alkenylation of Aldehydes with Boronic Acids via the Synergistic Combination of Copper(II) and Amine Catalysis

“…As outlined in Scheme 1, we proposed that an oxidase-style mechanism (as first delineated by Stahl 11 for the Chan–Evans–Lam reaction) 12 could be employed to generate a transient electrophilic organocopper(III) species 4 from a simple boronic acid substrate (Scheme 1). More precisely, the transmetalation of copper(II) catalyst 1 with a boronic acid would furnish organocopper(II) 3 which, after oxidation by copper(II), would deliver the desired alkenylcopper(III) 4 .…”