Carbonyl compounds, kinetic activation

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. 

As demonstrated in this review, photoinduced electron transfer reactions are accelerated by appropriate third components acting as catalysts when the products of electron transfer form complexes with the catalysts. Such catalysis on electron transfer processes is particularly important to control the redox reactions in which the photoinduced electron transfer processes are involved as the rate-determining steps followed by facile follow-up steps involving cleavage and formation of chemical bonds. Once the thermodynamic properties of the complexation of adds and metal ions are obtained, we can predict the kinetic formulation on the catalytic activity. We have recently found that various metal ions, in particular rare-earth metal ions, act as very effident catalysts in electron transfer reactions of carbonyl compounds [216]. When one thinks about only two-electron reduction of a substrate (A), the reduction and protonation give 9 spedes at different oxidation and protonation states, as shown in Scheme 29. Each species can... 

The mechanism of the enantioselective 1,4-addition of Grignard reagents to a,j3-unsaturated carbonyl compounds promoted by copper complexes of chiral ferrocenyl diphosphines has been explored through kinetic, spectroscopic, and electrochemical analysis.86 On the basis of these studies, a structure of the active catalyst is proposed. The roles of the solvent, copper halide, and the Grignard reagent have been examined. 

For simple carbonyl compounds, the equilibrium between an aldehyde or a ketone and its corresponding enol is usually so shifted towards the keto form that the amount of enol at equilibrium can neither be measured nor detected by spectroscopy. Nevertheless, as recently emphasised by Hart (1979), this does not mean that the enol cannot exist free, not in equilibrium with ketones and aldehydes. Several examples of kinetically stable enols in the gas phase or in aprotic solvents have been reported. Broadly speaking, it appears that enols have relatively large life-times when they are prepared in proton-free media [e.g. the half-life of acetone enol was reported to be 14 s in acetonitrile (Laroff and Fischer, 1973 Blank et al., 1975) and 200 s in the gas phase (MacMillan et al., 1964)]. These life-times are related to an enhanced intramolecular rearrangement, indicated by the very high energies of activation (85 kcal mol-1 for acetaldehyde-vinyl alcohol tautomerization) which have been calculated (Bouma et al., 1977 Klopman and Andreozzi, 1979) It has therefore been possible to determine most of the spectroscopic properties of simple enols [ H nmr,l3C nmr (CIDNP technique), IR and microwave spectra of vinyl alcohol... 

The kinetically controlled nucleophilic addition of preformed lithium enolates onto carbonyl compounds is reversible with a low activation barrier, and the thermal conditions are likely to have a major impact on the stereoisomeric ratio of the final aldols through the retroaldolization and the thermodynamic equilibration of lithium enolates76. The tendency of aldolates to undergo retroaldolization increases with the stability of enolates, and when going from lithium to potassium. On the other hand, boron enolates usually undergo completely irreversible aldol reaction511,512. 

The reaction sequence is called the Regitz diazo transfer and requires active methylene compounds as substrates/ Hence it is common to use formic esters to create P-carbonyl compounds from ketones or aldehydes in an aldol reaction. These are used as substrates for deformy-lative diazo transfer reactions in which the diazo group is transferred and the formyl group is removed in one concerted step. The mechanism of the deformylative diazo transfer is shown below. In this case the bulky base NaHMDS ensures deprotonation at the less-hindered a-position of 3, forming the so-called kinetic enolate 13. This enolate is formylated by ethyl formate yielding the P-formyl ketone 14, which is used as substrate in the deformylative diazo transfer. 

Systematics are also available for the 8 0-values of the compounds in queshon [56[ carboxyl and carbonyl functions in isotopic equilibrium with the surrounding water are, due to equilibrium isotope effects, enriched in 0 relative to this water by 19 and by 25 to 28%o, respectively. From here, the 8 0-values of natural alcohols, mostly descendants of carbonyl compounds, will have (maximally) similar 8 0-values, provided the precursors have attained isotopic equilibrium with water and their reduction has not been faster than their equilibration. Alcohols from addihon of water to C=C double bonds or from exchange of halogen functions by OH groups, typical for synthetic alcohols, will have 8 0-values close to or even below that of the water, due to kinetic isotope effects. The few available results [246, 289, 290] seem to confirm this expectation. The 8 0-values of natural (and also synthetic) esters and lactones can be, especially in the carbonyl group, extremely high (up to 50%o), probably as a consequence of an intramolecular kinetic isotope effect on the activation of the carboxyl function. 

The reaction has a wide applicability but is subject to certain interferences. In general, any material that will react with iodine in the reagent mixture will cause an interference. Common organic interferences are active carbonyl compounds, ascorbic acid, quinone, mercaptans, and diacyl peroxides (Mitchell, 1961). Several of these interferences can be eliminated or minimized by appropriate modifications to the method such as prereaction to remove interfering materials and extrapolation of the observed endpoint to the true endpoint based on kinetically slow interfering reactions. Care must also be taken to avoid introducing extraneous moisture from the atmosphere and to be sure that the reaction has reached completion. 

The potassio intermediates give excellent results in a number of derivatizations. For other functionalizations, particularly those with carbonyl compounds, potassium has to be replaced by lithium, this can be done most simply by addition of an equivalent amount of anhydrous lithium bromide, dissolved in THF. Although both vinyl ethers and the corresponding sulfides can be metallated in a short time, it is quite clear from the preparative experiments that the sulfides react faster [9]. A similar difference between oxygen and sulfur compounds has been observed in retaliations of other types of substrates. Some authors have invoked d-orbital effects to explain the easier retaliations of sulfur compounds [83], but an explanation on the basis of polarizability seems more satisfactory [84]. Using the kinetically very active bases mentioned, clean a-metallations of simple vinylic ethers and -thioethers can be realized at low temperatures. Under modified conditions two other processes have been observed [9,85] ... 

Ort/io-metallated palladium complexes of azo and hydrazobenzene catalyze the reduction by H2 of nitroaromatics, alkenes, alkynes, and aromatic carbonyl compounds. A palladium-aryl or bond in the precursor complex is a requirement for catalytic activity. The ligands are themselves susceptible to reduction. The kinetics of the reaction under 1 atm H2 have been measured. Palladium(O) complexes catalyze the hydrostannolysis of allyl and allyloxy carbonyl groups. The reaction can be applied to the selective protection-deprotection of aminoacid derivatives see equation (9). Alkenyl cyclopropanes carrying electron-withdrawing substituents are selectively hydrogenolyzed by Pd(0)/PBu3 catalysts... 

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