Carbonyl compounds stoichiometric

Although stoichiometric ethynylation of carbonyl compounds with metal acetyUdes was known as early as 1899 (9), Reppe s contribution was the development of catalytic ethynylation. Heavy metal acetyUdes, particularly cuprous acetyUde, were found to cataly2e the addition of acetylene to aldehydes. Although ethynylation of many aldehydes has been described (10), only formaldehyde has been catalyticaHy ethynylated on a commercial scale. Copper acetjlide is not effective as catalyst for ethynylation of ketones. For these, and for higher aldehydes, alkaline promoters have been used. 

The main strategy for catalytic enantioselective cycloaddition reactions of carbonyl compounds is the use of a chiral Lewis acid catalyst. This approach is probably the most efficient and economic way to effect an enantioselective reaction, because it allows the direct formation of chiral compounds from achiral substrates under mild conditions and requires a sub-stoichiometric amount of chiral material. 

The intermolecular McMurry reaction is first of all a suitable method for the synthesis of symmetrical alkenes. With a mixture of carbonyl compounds as starting material, the yield is often poor. An exception to this being the coupling of diaryl ketones with other carbonyl compounds, where the mixed coupling product can be obtained in good yield. For example benzophenone and acetone (stoichiometric ratio 1 4) are coupled in 94% yield. ... 

Of course, the most practical and synthetically elegant approach to the asymmetric Darzens reaction would be to use a sub-stoichiometric amount of a chiral catalyst. The most notable approach has been the use of chiral phase-transfer catalysts. By rendering the intermediate etiolate 86 (Scheme 1.24) soluble in the reaction solvent, the phase-transfer catalyst can effectively provide the enolate with a chiral environment in which to react with carbonyl compounds. 

High enantioselectivities may be reached using the kinetic controlled Michael addition of achiral tin enolates, prepared in situ, to a,/i-unsaturated carbonyl compounds catalyzed by a chiral amine. The presence of trimethylsilyl trifluoromethanesulfonate as an activator is required in these reactions236. Some typical results, using stoichiometric amounts of chiral amine and various enolates are given below. In the case of the l-(melhylthio)-l-[(trimethylsilyl)thio]ethene it is proposed that metal exchange between the tin(II) trifluoromethanesulfonate and the ketene acetal occurs prior to the 1,4-addition237,395. 

Kuwajima (75) has provided full details of the regiospecific monoalkylation of carbonyl compounds via their silyl enol ethers, using stoichiometric amounts of fluoride ion. Noyori (76) has given more information on the use of the complex fluoride source (2) (Chapter 18)... 

Metal-induced reductive dimerization of carbonyl compounds is a useful synthetic method for the formation of vicinally functionalized carbon-carbon bonds. For stoichiometric reductive dimerizations, low-valent metals such as aluminum amalgam, titanium, vanadium, zinc, and samarium have been employed. Alternatively, ternary systems consisting of catalytic amounts of a metal salt or metal complex, a chlorosilane, and a stoichiometric co-reductant provide a catalytic method for the formation of pinacols based on reversible redox couples.2 The homocoupling of aldehydes is effected by vanadium or titanium catalysts in the presence of Me3SiCl and Zn or A1 to give the 1,2-diol derivatives high selectivity for the /-isomer is observed in the case of secondary aliphatic or aromatic aldehydes. 

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... 

Wittig reactions are versatile and useful for preparing alkenes, under mild conditions, where the position of the double bond is known unambiguously. The reaction involves the facile formation of a phosphonium salt from an alkyl halide and a phosphine. In the presence of base this loses HX to form an ylide (Scheme 1.15). This highly polar ylide reacts with a carbonyl compound to give an alkene and a stoichiometric amount of a phosphine oxide, usually triphenylphosphine oxide. 

Stoichiometric, nucleophilic addition of alkylcobalt compounds to carbonyl compounds were reviewed in 1996.374 This chapter focuses on recent progress in the reactions of cobalt enolates with carbonyls and cobalt-catalyzed coupling reactions. 

Since nucleophilic addition to a metal-coordinated alkene generates a cr-metal species bonded to an -hybridized carbon, facile 3-H elimination may then ensue. An important example of pertinence to this mechanism is the Wacker reaction, in which alkenes are converted into carbonyl compounds by the oxidative addition of water (Equation (108)), typically in the presence of a Pd(n) catalyst and a stoichiometric reoxidant.399 When an alcohol is employed as the nucleophile instead, the reaction produces a vinyl or allylic ether as the product, thus accomplishing an etherification process. 

Organylzirconocene derivatives do not show any useful reactivity toward a,[5-unsaturated carbonyl compounds, but the reaction can be promoted by the addition of CuOTf [14], The initial version was stoichiometric in Cu [14], but a Cu-catalyzed version was subsequently developed [112,113]. Adaptation of the Ni salt + DIBAH catalysts for cross-coupling [10] to conjugate addition led to the Ni-catalyzed conjugate addition of alkenylzirconocene chlorides [16,17] (Scheme 1.25). 

With an operating catalytic cycle for the reductive opening of epoxides at hand, we decided to investigate the preparatively more important formation of carbon—carbon bonds. Inter-molecular addition reactions to a,(3-unsaturated carbonyl compounds have been described for the stoichiometric process of Nugent and RajanBabu [5], The general concept behind the catalytic conditions is outlined in Scheme 12.16. 

The Ras proteins were then allowed to react with the MIC-modified peptides in stoichiometric amounts. The maleimido group1261 reacts specifically with mercapto groups of proteins by conjugate addition of the thiol to the a, 3-unsaturated carbonyl compound. The Ras mutants reacted smoothly with the MIC modified peptides and in... 

Kinetic studies established that tetra-n-butylammonium borohydride in dichloromethane was a very effective reducing agent and that, by using stoichiometric amounts of the ammonium salt under homogeneous conditions, the relative case of reduction of various classes of carbonyl compounds was the same as that recorded for the sodium salt in a hydroxylic solvent, i.e. acid chlorides aldehydes > ketones esters. However, the reactivities, ranging from rapid reduction of acid chlorides at -780 C to incomplete reduction of esters at four days at 250 C, indicated the greater selectivity of the ammonium salts, compared with sodium borohydride [9], particularly as, under these conditions, conjugated C=C double bonds are not reduced. 

Stoichiometric reduction of carbonyl compounds with tetraalkylammonium borohydrides... 

Reduction of conjugated carbonyl compounds using stoichiometric amounts of the ammonium salt shows little advantage over the sodium salt in acidic methanol [11] with both reagents producing allylic alcohols (58-88% for acyclic compounds and 15-64% for cyclic compounds) by selective 1,2-reduction of the conjugated systems. Aldehydes, ketones and conjugated enones are also reduced by tetra-n-butylammonium cyanoborohydride in HMPA [11, 12], whereas haloalkanes and alkanesulphonic esters are cleaved reductively under similar conditions [13]. 

A stereoselective tandem iodination and aldol-type condensation has been described for the reaction of methyl propiolate and carbonyl compounds in the presence of a stoichiometric amount of tetra-n-butylammonium iodide and zirconium chloride to yield Z-3-iodo-2-(l-hydroxyalkyl)propenoates, as the major products [48]. No reaction occurs in the absence of the Lewis acid. There does not appear to be any control on the chirality of the hydroxyl centre. 

Superoxide anion formed in situ in a solution exposed to air (i.e. with only a small concentration of O2) has been used as an EGB to generate nitroalkane anions that may add to activated alkenes or to carbonyl compounds [130, 131]. An example is shown in Scheme 33. The reaction is catalytic since the product anion can act as a base toward the nitroalkane. Using the nitroalkane as the solvent favors the proton transfer pathway over the competing addition of the product anion to a second molecule of activated alkene, a pathway that may lead to polymerization [130]. In some cases, better yields of the Michael addition product were obtained if a stoichiometric amount of the anion was formed ex situ (with O2 as the PB), and the activated alkene added subsequently ]130, 132]. 

The Barhier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Sml2, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barhier-type allylation of carbonyl compounds in an SmH-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amount of SmCfi [570]. 

Thus it has been shown that some metal-carbonyl compounds can be activated by electrochemical reduction generating reactive anionic species. Without going into details, it is worth pointing out that the synthesis of aldehydes can be obtained by electrolyzing a stoichiometric mixture of alkyl halides and ironpentacarbonyls (Eq. 17) [124, 125] ... 

Oxidation of alcohols to carbonyl compounds is an important reaction. Stoichiometric oxidants such as chromates, permanganates and MO4 (M = Ru, Os) are the commonly used reagents [19a,59,60]. However, they are going out of favour increasingly because they create heavy metal wastes . In view of this, development of environmentally friendly heterogeneous catalysts for alcohol oxidation is very important. In the use of catalytic amounts of transition metal salts or complexes as homogeneous catalysts for the oxidation of alcohols [61-64], separation of the catalyst from the reaction mixture and its subsequent recovery in active form is cumbersome. Heterogeneous catalysts for this kind of reaction are therefore necessary [65]. Clearly, encapsulation and/or immobilization of known... 

From the equation showing the mechanism it is evident that 1 mol of lithium aluminum hydride can reduce as many as four molecules of a carbonyl compound, aldehyde or ketone. The stoichiometric equivalent of lithium aluminum hydride is therefore one fourth of its molecule, i.e. 9.5 g/mol, as much as 2 g or 22.4 liters of hydrogen. Decomposition of 1 mol of lithium aluminum hydride with water generates four molecules of hydrogen, four hydrogens from the hydride and four from water. 

Aqueous chromic acid acting on a solution of the alcohol in an inert water insoluble solvent [14] is a well known oxidation procedure giving the carbonyl compound. A stoichiometric amount of reagent is required. The aqueous solution of chromiura(lii) residues can be electrochemically oxidised to the chromium(vr) state [15], however few studies have been made on coupling this process with the excell the oxidation of alcohols. 

Tetrahydrofuran itself can be opened using either the stoichiometric or the catalytic version of arene-promoted lithiation, but both cases need the activation by boron trifluoride. The catalytic reaction was performed by treating the solvent THF 324 with the complex boron trifluoride-etherate and a catalytic amount (4%) of naphthalene. The intermediate 325 was formed. Further reaction with carbonyl compounds and flnal hydrolysis yielded the expected 1,5-diols 326 (Scheme 95), which could be easily cyclized to the corresponding substituted tetrahydropyrans under acidic conditions (concentrated FlCl). 

Allylic acetates are usually prepared by esterification from allylic alcohols. However, the corresponding alcohols are often only accessible by the fairly expensive hydride reduction of carbonyl compounds. Consequently, direct allylic functionalization of easily available olefins has been intensively investigated. Most of these reactions involve peroxides or a variety of metal salts.However, serious drawbacks of these reactions, (e.g. toxicity of some metals, stoichiometric reaction conditions, or nongenerality) may be responsible for their infrequent use for the construction of allylic alcohols or acetates. 

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