Ketone arylation catalytic system

Addition of small quantities of EtsN transformed the inactive RhCl(PPh3)3 into an active catalyst for ketone reduction. Catalytic systems of similar activity were prepared in situ from rhodium diene derivatives and also other aryl phosphines in presence of bases like EtsN. 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

For the synthesis of u-aryl-ZV-methylnitrones a silica gel-NaOH catalytic system has been used. The reaction proceeds without solvents and in good yields, irrespective of the electron-donor or electron-acceptor nature of the substituents in benzaldehyde. Under similar reaction conditions ketones do not undergo the reaction therefore, it makes it possible to carry out selective syntheses in cases where the system contains both aldehyde and ketone groups (154). 

In a recent review it was argued that such additives of copper, benzoquinone, and HPMOV are not really needed all that is needed is the presence of oxidation-resistant ligands that prevent palladium metal formation [15]. Indeed, activation of the C-H bond is not as slow as, for example, the Wacker reaction of ethene in which reoxidation of palladium must be performed by copper oxidation, although in this catalytic system the additives may still play a role in stabilizing the intermediate low-valent palladium species and thus prevent catalyst decomposition. This thesis was corroborated by the work of de Vos and Jacobs, who showed that addition of benzoic acid to the oxidative arylation reaction in the presence of oxygen led to superior results in the coupling of a variety of substituted arenes with acrylates, cinnamates, and ,/f-unsaturated ketones. Very good yields and TON up to 762 were obtained at 90 °C. A mixture of the o, m, and p isomers is obtained if substituted arenes are used [16]. 

Optically active alcohols, amines, and alkanes can be prepared by the metal catalyzed asymmetric hydrosilylation of ketones, imines, and olefins [77,94,95]. Several catalytic systems have been successfully demonstrated, such as the asymmetric silylation of aryl ketones with rhodium and Pybox ligands however, there are no industrial processes that use asymmetric hydrosilylation. The asymmetric hydrosilyation of olefins to alkylsilanes (and the corresponding alcohol) can be accomplished with palladium catalysts that contain chiral monophosphines with high enantioselectivities (up to 96% ee) and reasonably good turnovers (S/C = 1000) [96]. Unfortunately, high enantioselectivities are only limited to the asymmetric hydrosilylation of styrene derivatives [97]. Hydrosilylation of simple terminal olefins with palladium catalysts that contain the monophosphine, MeO-MOP (67), can be obtained with enantioselectivities in the range of 94-97% ee and regioselectivities of the branched to normal of the products of 66/43 to 94/ 6 (Scheme 26) [98.99]. 

Beside the preparation of aryl alkyl carbinol, many other secondary alcohols have been prepared in good to excellent optical purity through the use of this method, although improvements of the catalytic system have to be found to obtain good results with all types of ketones, especially dialkyl ketones. Numerous complex target molecules have been prepared where the asymmetric reduction is a key step. The Corey reduction is now a standard reaction for laboratory-scale preparation. 

Substituted benzaldehydes, with a formyl substituent as directing group, were selectively arylated at their ortho-position with aryl bromides as electrophiles in the presence of palladium(O) catalysts [50]. The use of a ruthenium complexes within a cooperative multi-catalytic system [51] altered the chemoselectivity dramatically [52]. Thus, reactions of 8-formylquinoline (39) with iodoarenes proceeded regioselectivity at the formyl group itself to give the corresponding ketones in moderate to very good yields (Scheme 9.15) [52],... 

Imines derived from aryl/alkyl ketones can be reduced enantioselectively using the CuH-based catalytic system developed by Lipshutz. In general, high ees can be obtained (94—99% ee) using this procedure, but it is limited to the hydrosilylation of N-dixylylphosphinylimines such as (3.189). 

The rhodacarborane complex (Scheme 15) in [Q yr closo-G iiV i2) IL is an efficient catalytic system for the asymmetric hydrogenation of unsymmetrical aryl ketones. The extraordinary performance of this catalyst system is probably related to the stabilization of ionic organometallic species induced by the IL. ... 

The Inamoto group [44] has reported that the NHC-based pincer complex 30 is an effective catalyst for the cross-coupHng of aryl haUdes and butyl acrylate (Eq. (5.33)). This catalytic system is appHcable to aryl iodides, aryl bromides, and activated aryl chlorides, and compatible with functional groups including nitrile, ketone, and aldehyde. Notably, the reaction of 4-bromobenzonitrile can be retarded by a drop of mercury, suggesting that the catalytic system may be heterogeneous. 

In addition to THIQs that could act as the typical substrates for the asymmetric CDC reactions, glycine derivatives were also well tolerated in this kind of transformation. Xie and Huang reported a facile approach to iV-aryl amino acid derivatives via the CDC reactions between Af-substituted glycine esters with unmodified ketones under the cooperative catalytic system consisting of Cu(0Ac)2 H20 and pyrrolidine. TBHP and DDQ were proved to... 

DTBNpP and palladium(II) acetate provided an efficient catalytic system for the a-arylation of ketones. Aryl bromides were coupled with ketones using 0.25-0.5 mol% Pd(OAc)2/DTBNpP in toluene at 50 °C. Coupling of 2-bromophenol with ketones using the Pd/DTBNpP system provided an efficient route for the synthesis ofbenzo[f>]furans (14EJ07395). 

In 2006, the group of Artok showed that 5-aryl-2(5H)-furanones could be prepared in moderate to good yields by a rhodium-catalyzed carbonylative arylation of internal alkynes with aryl boronic acids (Scheme 1.9a) [22]. a,P-Unsaturated ketones (chal-cone derivatives) were formed as the major product when some TFA (trifluoroacetic acid) was added under the same reaction conditions [23a]. By varying the catalytic system, indanones could be produced as the main product [23b]. The chemical behavior of terminal alkynes is different, and either a,P-unsaturated ketones or furans starting from propargylic alcohols can be achieved (Scheme 1.9b) [24, 25]. In the case of vinyl ketones, 1,4-diketones were obtained by rhodium-catalyzed coupling of arylboronic acids in the presence of 20-40 bar of CO [26]. In 2007, Chatani demonstrated that indenones could be accessed by a carbonylative rhodium-catalyzed cyclization of alkynes with 2-bromophenylboronic adds (Scheme 1.9c) [27]. Here, the key intermediate is a vinylrhodium(I) spedes that is formed by transmetaUation of RhCl with 2-bromophenylboronic acid followed by insertion of... 

Recently, Phan et al. (2013) prepared an open metal site MOF Cu(BDC) and successfully applied it to the modified Friedlander reaction. In the presence of 3-5 mol% Cu(BDC), several 2-aryl quinolines were efficiently synthesized from 2-aminobenzyl alcohol and methyl ketones (Scheme 4.42). Different from the previous reports, the reaction of p-methoxyacetophenone or p-nitroacetophenone did not occur in this catalytic system. 

Asymmetric Transfer Hydrogenation of Ketones. The first reports on asymmetric transfer hydrogenation (ATH) reactions catalyzed by chiral metallic compounds were published at the end of the seventies. Prochiral ketones were reduced using alcohols as the hydrogen source, and Ru (274,275) or Ir (276) complexes were used as catalysts. Since then, many chiral catalytic systems for homogeneous ATH of ketones, imines, and olefins have been developed (37,38,256,257,277-289). The catalytic systems are usually based on ruthenium, rhodium, or iridium, and the ATH of aryl ketones is by far the most studied. Because of the reversibility of this reaction, at high conversions, a gradual erosion of the ee of the product has been frequently reported. An azeotropic 5 2 mixture of formic acid/triethylamine can be used to overcome this limitation. 

There are a limited number of group VHI-X metal-based catalytic systems active and selective in asymmetric hydrosilylation of 0=0 bond. These few systems include Fe(OAc)2/DUPHOS active in hydrosilylation of aryl methyl ketones with (EtO)2MeSiH or PMHS (301,302), ruthenium complexes bearing oxazolinylferrocenephosphine ligand (303), or chiral bis(paracyclophane)-substituted (NHC) ligands in hydrosilylation of aryl alkyl ketones with H2SiPh2 (304) and iridium(I)/DIPOF system active in hydrosilylation of acetophenone with diphenylsilane. 

The first example of the use of aryl benzenesulfonates as arylating species in a-arylation reactions of acyclic and cyclic ketones was reported by Buchwald and coworkers [49] in 2003. A catalytic system composed of a mixture of Pd(OAc)2 and 2-dicyclohexylphosphino-2, 4, 6 -triisopropylbiphenyl (XPhos), allowed the synthesis of the required a-arylated ketones in very good yields (Scheme 8.21) [49]. 

---