Kumada-type Cross-coupling Reaction Research Articles

Synthesis of Tofisopam by Way of Photoinduced CO2 Fixation.

Herein reported is a unique synthetic route of Tofisopam, an anxiolytic drug containing a 2,3-benzodiazepine core structure. 3,4-Dimethoxypropylbenzene and 3,4-dimethoxybenzoic acid, which are both of plant origin, and CO2 constitute its carbon skeleton. These three renewable substances are united by two C-C bond forming reactions, i.e., a Friedel-Crafts acylation reaction and a photoinduced carboxylation reaction to construct the major carbon framework. Finally, a methyl group is introduced by a Kumada-type cross-coupling reaction to furnish Tofisopam. Various analogs of Tofisopam are readily synthesized by introducing other substituents than a methyl group at the last C-C bond forming step.

Iron-Catalyzed Cyclization of Alkynols with Diorganyl Diselenides: Synthesis of 2,5-Dihydrofuran, 3,6-Dihydro-2H-pyran, and 2,5-Dihydro-1H-pyrrole Organoselanyl Derivatives.

An iron-catalyzed system, using diorganyl diselenides as an organoselenium source, was used for the cyclization of 1,4-butyne-diols in the preparation of 3,4-bis(organoselanyl)-2,5-dihydrofurans. The optimized reaction conditions are compatible with many functional groups in 1,4-butyne-diols and diorganyl diselenides. In addition, this catalyst system was also efficient with diorganyl disulfides, but it did not work for diorganyl ditellurides. The same reaction conditions were also extended to pentyne-1,5-diol for the preparation of 4,5-bis(organoselanyl)-3,6-dihydro-2H-pyrans and to 4-amino-butynol for the preparation of 2,5-dihydro-1H-pyrrole derivatives. The synthetic utility of these heterocycles was studied using 5-bis(organoselanyl)-3,6-dihydro-2H-pyrans as substrate in a Kumada-type cross-coupling reaction.

Difunctionalized {closo‐1‐CB11} Clusters: 1‐ and 2‐Amino‐12‐ethynylcarba‐closo‐dodecaborates

Carba-closo-dodecaborate anions with two functional groups have been synthesized via a simple two-step procedure starting from monoamino-functionalized {closo-1-CB11 } clusters. Iodination at the antipodal boron atom provided access to [1-H2 N-12-I-closo-1-CB11 H10 ](-) (1 a) and [2-H2 N-12-I-closo-1-CB11 H10 ](-) (2 a), which have been transformed into the anions [1-H2 N-12-RCC-closo-1-CB11 H10 ](-) (R=H (1 b), Ph (1 c), Et3 Si (1 d)) and [2-H2 N-12-RCC-closo-1-CB11 H10 ](-) (R=H (2 b), Ph (2 c), Et3 Si (2 d)) by microwave-assisted Kumada-type cross-coupling reactions. The syntheses of the inner salts 1-Me3 N-12-RCC-closo-1-CB11 H10 (R=H (1 e), Et3 Si (1 f)) and 2-Me3 N-12-RCC-closo-1-CB11 H10 (R=H (2 e), Et3 Si (2 f)) are the first examples for a further derivatization of the new anions. All {closo-1-CB11 } clusters have been characterized by multinuclear NMR and vibrational spectroscopy as well as by mass spectrometry. The crystal structures of Cs1 a, [Et4 N]2 a, K1 b, [Et4 N]1 c, [Et4 N]2 c, 1 e, and [Et4 N][1-H2 N-2-F-12-I-closo-1-CB11 H9 ]⋅0.5 H2 O ([Et4 N]4 a⋅0.5 H2 O) have been determined. Experimental spectroscopic data and especially spectroscopic data and bond properties derived from DFT calculations provide some information on the importance of inductive and resonance-type effects for the transfer of electronic effects through the {closo-1-CB11 } cage.

Arylcalcium halides as substrates in Kumada-type cross-coupling reactions

A precondition of a Kumada-type cross-coupling reaction with arylcalcium halides is the easy availability of these organometallics. Arylcalcium halides are accessible with high yields via reduction of arylhalides with activated calcium in ethers such as tetrahydrofuran. In order to demonstrate the generality of this Grignard-type reduction of haloarenes, [(4-BrC6H4)CaI(thf)4] (1) and [(β-naphthyl)CaBr(thf)4] (2) are prepared. First investigations regarding arylcalcium halides as substrates in cross-coupling reactions are undertaken choosing [(C6H5)CaI(thf)4] (3) and [(4-CH3C6H4)CaI(thf)4] (4) as the organometallic substrate in a cross-coupling with chlorobenzene and 4-chlorotoluene. The nickel-mediated conversion of arylcalcium iodides and chloroarenes to (substituted) biphenyls proceeds with moderate yields and significant amounts of homo-coupling products are observed.

Microwave-Assisted Kumada-Type Cross-Coupling Reactions of Iodinated Carba-closo-dodecaborate Anions

The microwave-assisted Pd-catalyzed Kumada-type cross-coupling reaction of iodinated carba-closo-dodecaborate anions requires smaller amounts of Grignard reagent and catalyst and results in higher yields in much shorter reaction times in comparison to a reaction with conventional heat transfer. 12-Ph(3)P-closo-1-CB(11)H(11) was identified as the side product of the cross-coupling reactions that use [PdCl(2)(PPh(3))(2)]. The inner salt, which is the first example for a {closo-1-CB(11)} cluster with a B-P bond, was selectively synthesized via a related microwave-assisted cross-coupling protocol and characterized by NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. In addition, the crystal structures of the tetraethyl ammonium salts of [12-Ph-closo-1-CB(11)H(11)](-), [12-(4-MeOC(6)H(4))-closo-1-CB(11)H(11)](-), and [12-(H(2)C═(Me)CC≡C)-closo-1-CB(11)H(11)](-) are described.

A Structure–Activity Study of Ni-Catalyzed Alkyl–Alkyl Kumada Coupling. Improved Catalysts for Coupling of Secondary Alkyl Halides

A structure-activity study was carried out for Ni catalyzed alkyl-alkyl Kumada-type cross coupling reactions. A series of new nickel(II) complexes including those with tridentate pincer bis(amino)amide ligands ((R)N(2)N) and those with bidentate mixed amino-amide ligands ((R)NN) were synthesized and structurally characterized. The coordination geometries of these complexes range from square planar, tetrahedral, to square pyramidal. The complexes had been examined as precatalysts for cross coupling of nonactivated alkyl halides, particularly secondary alkyl iodides, with alkyl Grignard reagents. Comparison was made to the results obtained with the previously reported Ni pincer complex [((Me)N(2)N)NiCl]. A transmetalation site in the precatalysts is necessary for the catalysis. The coordination geometries and spin-states of the precatalysts have a small or no influence. The work led to the discovery of several well-defined Ni catalysts that are significantly more active and efficient than the pincer complex [((Me)N(2)N)NiCl] for the coupling of secondary alkyl halides. The best two catalysts are [((H)NN)Ni(PPh(3))Cl] and [((H)NN)Ni(2,4-lutidine)Cl]. The improved activity and efficiency was attributed to the fact that phosphine and lutidine ligands in these complexes can dissociate from the Ni center during catalysis. The activation of alkyl halides was shown to proceed via a radical mechanism.

Carba-closo-dodecaborates with One or Two Alkynyl Substituents Bonded to Boron

Salts of the carba-closo-dodecaborate anion with one or two phenyl- or trimethylsilylalkynyl substituents were synthesized by Pd-catalyzed Kumada-type cross-coupling reactions of the corresponding iodinated clusters with alkynyl Grignard reagents. Selective monofunctionalization in the 7- and 12-position of the {closo-CB(11)} cluster was achieved, resulting in salts of the anions: [1-R-12-R'C[triple bond]C-closo-CB(11)H(10)](-) (R = H, Ph; R' = Ph, Me(3)Si (1-4)), [12-Hal-7-PhC[triple bond]C-closo-CB(11)H(10)](-) (Hal = F (5), Cl (6), Br (7)), and [12-F-7-Me(3)SiC[triple bond]C-closo-CB(11)H(10)](-) (8). Furthermore, the disubstituted derivatives [7,12-(RC[triple bond]C)(2)-closo-CB(11)H(10)](-) (R = Ph (9), Me(3)Si (10)) are described. All salts were characterized by multi-NMR, IR, and Raman spectroscopy as well as by mass spectrometry (MALDI). The crystal structures of Cs(+)1 and [Et(4)N](+)6 were determined by single-crystal X-ray diffraction. The spectroscopic and structural properties are compared to values derived from DFT calculations and to data of related boron species with alkynyl groups.

Facile Synthesis of Multisubstituted Buta‐1,3‐dienes via Suzuki—Miyaura and Kumada Cross‐Coupling Strategy of 2,4‐Diiodo‐buta‐1‐enes with Arylboronic Acids and Grignard Reagents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Facile synthesis of multisubstituted buta-1,3-dienes via Suzuki–Miyaura and Kumada cross-coupling strategy of 2,4-diiodo-buta-1-enes with arylboronic acids and Grignard reagents

One-pot Suzuki-Miyaura-type and Kumada-type cross-coupling reactions of 2,4-diiodo-buta-1-enes with arylboronic acids and alkyl/aryl magnesium bromides were carried out in the presence of accessibly simple catalysts under mild conditions. As a result, some 1,1,2-trisubstituted buta-1,3-dienes were obtained including the Tamoxifen-type, which have potential adjuvant therapy in women who have suffered from breast cancer and cyclooxygenase-2-type (COX-2-type) inhibitors, some of which have been proved to elicit efficient anti-inflammatory analgesic activities and less adverse gastrointestinal side effects and to be very useful in the prophylactic treatment of a wide variety of cancers and neurodegenerative disorders.