Stoichiometric reactions substrate scope

Suzuki [201] reported in 2007 that pyridines, which are electron-deficient heteroarenes, could undergo a homocoupling by dinuclear ruthenium complexes. For example, Cp Ru( a-H)4RuCp and (Cp Ru)2(]i.-PMe2)(]i.-H)( a- ) 7 -C5H 5) [202] promote the dimerization of 4-methoxypyridine to give 4,4 -dimethoxy-2,2 -bipyridine. Although the reaction suffers some limitations such as stoichiometric Ru complexes, high temperature, and narrow substrate scope, this is so far the only report in which simple pyridines can be homocoupled at their C-H bonds. 

Oxidation of organic substrates by nickel oxide has been known for more than a century. The substrate scope of the nickd oxide hydroxide oxidation method is quite broad, and includes alcohols, aldehydes, phenols, amines, and oximes. However, an extensive review covering the major part of these reactions demonstrates the requirement of stoichiometric amounts of nickel oxide hydroxide [28]. Recent findings have led to a new oxidation method utilizing catalytic amounts of nickel(II) salts and excess of bleach (5% aqueous sodium hypochlorite) under ambient... 

This first plan for a decarboxylative cross-coupling carried with it certain weaknesses for potential industrial applications. It was to be expected that the salt metathesis between alkali metal carboxylates and late transition metal halides would be thermodynamically disfavored. We expected the formation of a palladium benzoate complex i from palladium bromide complexes c and potassium benzoate (g) to proceed well only in the presence of a stoichiometric quantity of silver to capture bromide ions [27]. However, we did not like the idea of using stoichiometric quantities of silver salts or of expensive aiyl triflates in the place of aryl halides. Finally, the published substrate scope of the oxidative Heck reactimi led to concerns that palladium catalysts mediate the decarboxylation rally of a narrow range of carboxylates, precluding use of this reaction as a general synthetic strategy. 

Aiming to develop an efficient route to 1,2-dihydropyridines, Ogoshi et al. performed extensive mechanistic studies with a stoichiometric amount of nickel complex [16]. These studies revealed a plausible mechanistic pathway for this particular cycloaddition reaction. Further experimentation revealed that the use of electron-donating, sterically hindered phosphines actually renders the reaction catalytic. Three catalytic examples were reported. These include the cycloaddition of alkyl-aryl alkynes (72 and 73) and trimethylsilyl acetylene (74) (Scheme 2.19). The moderate yields of cycloadducts and small substrate scope still need to be addressed. 

In 2009, Fagnou et al. discovered a Rh(III)-catalyzed synthesis of substituted isoquinolines 45 by oxidative annulation between N-tBu aromatic aldimines and internal alkynes [28a]. The -Bu leaving group was eliminated as isobutene in the reaction process and avoided the generation of a mixture of isoquinolines. However, the substrate scope was limited to aldimines, and a stoichiometric amount of Cu(0Ac)2-H20 was used as an external oxidant. Mechanistic studies omitted the ort/zo-alkenylation/64 -electrocyclization/oxidation pathway, and intermediate H2 was crucial for the C-N reductive elimination to proceed (Eq. (5.44)). At the same time, Satoh and Miura groups also exploited a Rh(III)-catalyzed oxidative cyclization of N-H benzophenone imine and internal alkynes to give isoquinolines [28b]. Both aromatic and aliphatic alkynes were agreeable for this protocol, but a stoichiometric amount of the Cu(II) salt was required. 

Jones and coworkers described the formation of 7-methyl indoles from ruthenium-catalyzed C(sp )-H bond activation of 2,6-xylylisocyanide in 1986 (Eq. (7.1)) [6]. The catalytic reaction proceeded by using ruthenium(II) complex Ru(dmpe)2H2 or Ru(dmpe)2(2-naphthyl)H as catalyst (20mol%) in CgDg at high temperature (140°C). Further studies indicated that the substrate scope is restricted to 2,6-disubstituted (2,6-dimethyl, 2-ethyl-6-methyl, 2,6-diethyl) isocyanides, since less substituted isocyanides only produced stoichiometric indole N-H oxidative addition adducts with [Ru(dmpe)2]. 

In 1987, Semmelhack et al. [21] published a paper concerning metal carbonyl promoted rearrangement of phenylcyclopropenes to naphthols (Scheme 17.26), which can also be classified as a [5+1] cycloaddition. The reaction can be promoted by a stoichiometric amount of Cr(CO)s or Mo (CO)5, or a catalytic amount of Mo(CO)5 but with lower yields and rates. With respect to the substrate scope, the authors found that the substituent was crucial only when was methoxy or hydrogen, the desired naphthol products can be obtained in good yields (35-78%). Otherwise, low... 

The most widely employed methods for the synthesis of nitrones are the condensation of carbonyl compounds with A-hydroxylamines5 and the oxidation of A+V-di substituted hydroxylamines.5 9 Practical and reliable methods for the oxidation of more easily available secondary amines have become available only recently.10 11 12 13. These include reactions with stoichiometric oxidants not readily available, such as dimethyldioxirane10 or A-phenylsulfonyl-C-phenyloxaziridine,11 and oxidations with hydrogen peroxide catalyzed by Na2W044 12 or Se02.13 All these methods suffer from limitations in scope and substrate tolerance. For example, oxidations with dimethyldioxirane seem to be limited to arylmethanamines and the above mentioned catalytic oxidations have been reported (and we have experienced as well) to give... 

Substrates possessing an allene that participate in the Alder-ene reaction are less common, but a few examples are known. Malacria [11] and Livinghouse [12] have independently used cobalt to effect intramolecular allenic Alder-ene reactions but the scope of these reactions was not investigated. Sato has performed an allenic Alder-ene reaction to form five-membered rings, using stoichiometric amounts of titanium [13], and Trost has shown that 1,3-dienes can be prepared via an intermolecular Alder-ene reaction between allenes and enones using a ruthenium(II) catalyst [14]. 

The main drawback of the DHAP-dependent aldolases is their strict specificity for the donor substrate. Apart from the scope limitation that this fact represents, DHAP is expensive to be used stoichiometrically in high-scale synthesis, and labile at neutral and basic pH, and therefore its effective concentration decreases over time in enzymatic reaction media, hindering the overall yield of the aldol reaction. In addition, due to the presence of a phosphate group in both DHAP and the... 

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