“…To a solution of 1,2-diiodo-4,5-dimethoxy-3-methylbenzene (2.0 g, 4.95 mmol) in 120 mL of a mixture of THF and Et 2 O (1:1) was added dropwise at −78 °C isopropylmagnesium chloride (2 M in THF, 2.72 mL, 5.44 mmol). After the mixture was stirred for 2 h at that temperature, B(O i -Pr) 3 (10.50 mL, 14.84 mmol) was added.…”
Section: Methodsmentioning
confidence: 99%
“…To the concentrated sample, hexane was added, and the resulting precipitate was isolated to give 1.05 g of the pure product as a white solid in 67% yield: mp >163 °C (decomposition); IR (Microscope, cm −1 ) 2959, 1585, 1506, 1373, 1310, 1263, 1199; 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.14 (s, 2H), 7.17 (s, 1H), 6.80 (s, 1H), 3.69 (s, 3H), 3.68 (s, 3H); 13 Preparation of 2-Iodo-3-methyl-4,5-dimethoxyphenylboronic acid 4e. To a solution of 1,2-diiodo-4,5-dimethoxy-3methylbenzene 65 (2.0 g, 4.95 mmol) in 120 mL of a mixture of THF and Et 2 O (1:1) was added dropwise at −78 °C isopropylmagnesium chloride (2 M in THF, 2.72 mL, 5.44 mmol). After the mixture was stirred for 2 h at that temperature, B(Oi-Pr) 3 (10.50 mL, 14.84 mmol) was added.…”
The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.
“…To a solution of 1,2-diiodo-4,5-dimethoxy-3-methylbenzene (2.0 g, 4.95 mmol) in 120 mL of a mixture of THF and Et 2 O (1:1) was added dropwise at −78 °C isopropylmagnesium chloride (2 M in THF, 2.72 mL, 5.44 mmol). After the mixture was stirred for 2 h at that temperature, B(O i -Pr) 3 (10.50 mL, 14.84 mmol) was added.…”
Section: Methodsmentioning
confidence: 99%
“…To the concentrated sample, hexane was added, and the resulting precipitate was isolated to give 1.05 g of the pure product as a white solid in 67% yield: mp >163 °C (decomposition); IR (Microscope, cm −1 ) 2959, 1585, 1506, 1373, 1310, 1263, 1199; 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.14 (s, 2H), 7.17 (s, 1H), 6.80 (s, 1H), 3.69 (s, 3H), 3.68 (s, 3H); 13 Preparation of 2-Iodo-3-methyl-4,5-dimethoxyphenylboronic acid 4e. To a solution of 1,2-diiodo-4,5-dimethoxy-3methylbenzene 65 (2.0 g, 4.95 mmol) in 120 mL of a mixture of THF and Et 2 O (1:1) was added dropwise at −78 °C isopropylmagnesium chloride (2 M in THF, 2.72 mL, 5.44 mmol). After the mixture was stirred for 2 h at that temperature, B(Oi-Pr) 3 (10.50 mL, 14.84 mmol) was added.…”
The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.
“…In addition, the Sonogashira coupling has been employed recently for the connection of an iodinated pyrimidinone to 34-or 36-crown-10 for the selective self-assembly of some hydrogen-bonded heterotrimers, 501 and for the alkynylation of dibenzo-24-crown-8 ethers for complexation studies. 502 Other recent examples of the Sonogashira reaction applied to the preparation of arylene-acetylene macrocycles containing substructures such as copper-cyclobutadiene complexes, 503 cyclopentadienes, 504 allenes, 505 and enediynes 506 can also be found. An example of the latter type is the synthesis of multicyclic cagelike cyclobutene-containing structure 340, which has been prepared after Sonogashira cross-coupling reaction of diethynylpropellane derivative 334 with diethyl-(4-iodophenyl)triazene (335) (Scheme 97).…”
Section: Synthesis Of Molecules For Nanostructuresmentioning
confidence: 99%
“…Other recent illustrative examples of the application of the palladium−copper promoted cross-coupling alkynylation reaction to the synthesis of related phenylene−acetylene macrocycles, the asymmetric synthesis of macrocyclic binaphthol dimers,500a and the synthesis of phenylenebis(ethynyl)-tethered bis-BINOL ligands 500b can be found. In addition, the Sonogashira coupling has been employed recently for the connection of an iodinated pyrimidinone to 34- or 36-crown-10 for the selective self-assembly of some hydrogen-bonded heterotrimers, and for the alkynylation of dibenzo-24-crown-8 ethers for complexation studies 96 97 …”
Section: 9 Synthesis Of Molecules For Nanostructuresmentioning
“…Coupling of 7 with 4-bromocatechol was templated with Cs + and 4-bromo-DB24C8 (8) was obtained in good yield (Scheme 3). 31 Halogen-metal exchange of 8 with i-propyl magnesium chloride or i-propyl magnesium chloride?LiCl at 0 uC 32 did not take place and although improved solubility of 8 (cf. 1) at 278 uC enabled us to carry out bromine-lithium exchange of 8, subsequent transmetalation to zinc was incomplete 33 and emphasises the requirement for magnesium-zinc transmetalation.…”
Preparation of (di)benzocrown-substituted aryl-zinc or -boron reagents and their palladium-catalysed cross-coupling with functionalised aryl halides is described for convenient synthesis of novel crown ether systems.
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