Catalyst heterocycle reactions

In the 1990s, the groups of Hiemstra and Larock independently discovered that Pd(OAc)2 in DMSO serves as an effective catalyst for direct dioxygen-coupled catalytic turnover, and this catalyst system was applied widely to oxidative heterocyclization reactions. Examples include the addition of carboxylic acid, phenol, alcohol, formamide, and sulfonamide nucleophiles to pendant olefins (Eq. 26) [146-149]. 

When sugars are treated with aqueous ammonia for a short time at low temperature in the absence of a catalyst, the reaction is arrested before heterocyclic compounds can be formed in appreciable proportion, and the products are mainly epimerization products of the sugars, probably formed by way of their 2,3-enediols. These epimerization products are summarized in Table I which shows the reactions of D-glucose, D-fructose, lactose, maltose, and melibiose with aqueous ammonia for a short time at low temperature. A dark-colored, high polymer is also formed in some instances (the browning reaction). In the ammoniacal solution, the monosaccharides are epimerized the disaccharides are epimerized and, in addition, may be hydrolyzed to monosaccharides that can also be epimerized hence, the variety of products obtained may be considerable. 

Naphthalene and other fused ring compounds generally give poor yields in Friedel-Crafts alkylation, because they are so reactive that they react with the catalyst. Heterocyclic rings are usually also poor substrates for the reaction. Although some furans and thiophenes have been alkylated, a true alkylation of a pyridine or a quinoline has never been described.21,0 However, alkylation of pyridine and other nitrogen heterocycles can be accomplished by a free radical (4-23) and by a nucleophilic method (3-17). 

Aryl, vinyl and heterocyclic bromides and iodides in the presence of H2, CO and a base react to give aldehydes (equation 111). [PdI2(PPh3)2] (114) or its analogues (102) and (110) were used as catalysts. The reaction requires both high temperature and pressure.488 In some cases, aroyl chlorides are also converted to aldehydes under these conditions. 

The use of a strong base in the palladium-catalyzed amination of aryl halides precludes the use of many substrates, such as those with aromatic nitro groups or enolizable hydrogens, esters other than tert-butyl esters, and many substrates with base-sensitive stereochemistry such as some protected amino acids and heterocyclic substrates [191]. Thus, conditions that employ milder bases are required. A solution that involves reaction temperatures as low as those used for reactions conducted with sodium tert-butoxide has not been developed. However, carbonate and phosphate bases can be used with certain catalysts at reaction temperatures comparable to those of reactions involving the first- and second-generation catalysts. 

Certain amines are readily prepared by the reduction of aromatic, aryl aliphatic, and heterocyclic amines. For example, aniline is reduced to cyclohexylamine by high-pressure hydrogenation in the presence of Raney nickel catalyst or a cobalt oxide-calcium oxide catalyst. The reaction occurs at a temperature above 200°, where condensation of the primary amine also takes place, viz., 2CjHiiNHj — (CjHn),NH + NH,. If this side reaction is repressed by the presence of dicyclohexylamine at the start of the reaction, a 94% yield of cyclohexylamine is obtained. Hydrogenation of aryl aliphatic amines proceeds more readily, occurring at moderate temperatures and pressures over platinum catalyst in glacial acetic acid. Other reductions using this catalyst are best performed on the amines in the form of their hydrochlorides. ... 

Rare-earth metal triflates as catalysts in reactions with formation and participation of heterocycles 02CRV2227. 

Heterocyclization reactions using chiral catalysts supported on inorganic materials 02CRV3495. 

The yields of isolated products varied from 45 to 95%. It is not totally proven whether an iminium ion is involved in the formation of 7-morpholinobicyclo[4.1. OJheptane 14. All primarily formed compounds were shown to be ent/o-morpholino isomers. Some derivatives isomerized to the corresponding ejfo-isomers on heating with acidic catalysts. Starting from 13 pure endo-and exo-morpholino compounds could be obtained in the case of the azide 14f and aminal 14k with benzotetrazole as the heterocycle. Reaction of potassium cyanate with 13 gave a trimer of 14e at ambient temperature or the exo-morphohno diastereomer of 14e at higher temperature. ... 

Kantam ML, Chakravaiti R, Sreedhar B et al (2008) Friedel-Crafts alkylation of nitrogen heterocycles using [BMIM][OTf] as a catalyst and reaction medium. Synlett 10 1449-1454... 

Indoles react with epoxides and aziridines in the presence of Lewis acids (see 20.4.1 for reaction of indolyl anions with such reactants) with opening of the three-membered ring and consequent 3-(2-hydroxyethylation) and 3-(2-aminoethylation) of the heterocycle. Both ytterbium triflate and phenylboronic acid are good catalysts for reaction with epoxides under high pressure silica gel is also an effective catalyst, but reactions are slow at normal pressure and temperature. Reaction with aziridines can be catalysed by zinc triflate or boron trifluoride. °... 

Ojima et al. reported the rhodium-catalyzed car-bonylative silylcarbocyclization of the 1,6-enynes 76.105 In the presence of the rhodium catalyst the reaction of the 1,6-enynes 76 with the hydrosilane 77 under CO atmosphere gave the heterocycles 78, which had both silylmethylene and formylmethyl groups, in good yields (Scheme 27). 

The synthesis of heterocycles by means of Lewis bases has been carried out using the reactions described above. For instance, the dipole resulting from the reaction of pyridine with DMAD was intercepted with phenylisocyanate giving a 1,4 dipole that ultimately led to pyrimidindione derivatives. Wang and coworkers have described the synthesis of benzoxazoles by reaction of ynals with N-protected-2-aminophenols using pyrrolidine as catalyst. Salicylaldehyde has been the starting material for the synthesis of many benzoheterocycles. When using DBU as catalyst, it was transformed into benzopyran derivatives by reaction with 2,2-disubstituted allene esters. When DABCO is used as catalyst, the reaction of AT-tosylimines with ethyl... 

Recently, the Ye group found the [3 -I- 4] annulation of enals with aurones in the presence of a bifunctional N-heterocyclic carbene catalyst. The reaction gave the corresponding benzofuran-fused s-lactones 130 in good yields with good diastereoselectivities and excellent enantioselectivities (Scheme 20.55). 

Due to the unique bivalent carbene and diversity of the N-heterocyclic motif, NHCs have been demonstrated to be efficient organocatalysts for various enantioselective reactions. In addition to the traditional thioazolium and imidazolium NHCs, triazolium NHCs have become the most successful organocatalysts. Recently, NHC/Lewis acid cocatalysis and bifunctional NHCs have shown a very promising future. Beyond the classic NHC-catalysed umpolung of aldehydes, the extended umpolung of functionalised aldehydes are extremely successful. A series of NHC-catalysed reactions of ketenes have been developed for the synthesis of various enantioriched heterocycles. Esters, anhydrides, carboxylic acids and even Michael acceptors are useful alternative substrates for NHC-catalysed reactions. With increasing interest and rapid development of NHC catalysis, new structures of the catalysts, new reaction modes, and synthetic applications can be expected in the near future. 

In many cases, complexes of hindered monodentate alkylphosphines and N-heterocy-clic carbenes are less stable as catalysts for reactions of primary amines than for reactions of secondary amines and are less stable for coupling of halogenated heterocycles, such as pyridines, than they are for coupling of haloarenes. " One factor that could lead to this reduced activity is the displacement of the ligand by the primary amine and the basic heterocycle. This point has been debated, but turnover numbers for coupling of these two classes of substrate have tended to be higher for reactions catalyzed by complexes of bisphosphines. ... 

Later, Heck also reported the synthesis of amide from various aryl, heterocyclic, and vinylic halides and primary or secondary amines in the presence of a palladium catalyst.The reaction was carried out under an atmosphere of carbon monoxide, and a tertiary amine was generally added to neutralize the hydrogen halide formed in the reaction. The reaction is also highly stereospecific with cis- and trans-winyl halides (Table 3). 

In 2011, a palladium-catalyzed ring opening of furans as a source of a,p-unsaturated aldehydes was developed.In the presence of a palladium catalyst, heterocyclic compounds can be produced. In this procedure, furans may be ring-opened via pallado-catalyzed reactions leading to a,p-unsaturated aldehydes and ketones tethered to indole and isoquinoline moieties. Fu and co-workers developed a simple and efficient copper-catalyzed one-pot tandem method for the synthesis of benzimidazo[l,2-Z>]isoquinolin-ll-one derivatives... 

Taylor and co-workers prepared cyclic diaiylborinic acids and applied them in the synthesis of benzannulated heterocycles in 2014. In the presence of a palladium catalyst, the reaction underwent two-fold Suzuki-Miyaura coupling with dihaloarenes or ge n-dibromoolefins and the corresponding macroheterocycles were produced in good yields (Scheme 4.2). ... 

A new simplified synthesis which combines, in a one-pot reaction, silylation of the heterocyclic base, formation of the silylated condensation catalyst, and reaction of the base with peracylated sugar derivatives, giving nucleosides in high yield, is summarized in Scheme 1. Using this method, 5-methoxyuridine cytidine, and iV -benzoyladenosine were synthesized in 60—70% yield, and 2, 3, 5, -tri-O-benzoyluridine in 84% yield. When 1,2-dichloroethane was... 

Along the same lines, He reported the direct addition of heterocycles to activated olefins, using 5 mol% of gold(iii) chloride as catalyst. The reactions proceeded at room temperature and the authors highlighted that most of the reactions could also be carried out under neat conditions, affording the products in similar or better yields to those obtained in acetonitrile (Scheme 16.51)/ °... 

Nevado and de Haro later reported a gold-catalyzed arene ethynylation reaction in which both the sp C—H and sp C—H were activated by the gold catalyst. Heterocycles such as Ai-benzyl pyrrole and Ai-benzyl indole were suitable substrates for this reaction but in the former case, ethynylated regioisomers were obtained. 

To more fully elucidate the role of the cerium(III) ion in these additions, Pratt suggested that the influence of the Lewis add catalyst in reactions of 6-chloro-5,8-quinolinequinone was exerted primarily through the heterocyclic nitrogen atom the resulting N-Ce interaction also allows the cerium ion to assume a position in close proximity to the 8-carbonyl oxygen, with concomitant 6-position activation. 

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