Atom-efficient methods

The asymmetric hydroformylation of alkenes is an exceptionally atom-efficient method for the synthesis of enantiomerically-pure carbonyl-containing compounds.[1] The hydroformylation of vinylacetate, in particular, represents an excellent method for the preparation of ot-alkoxy aldehydes and, through their reduction, homochiral 1,2-diols. The use of the novel chiral ligand, ESPHOS (1),[2] in a rhodium(I) complex, results in hydroformylation of vinyl acetate in high branched linear selectivity and exceptional ee (Figure 12.1).[3]... 

An example of direct one-step synthesis is the direct fluorination employing elemental fluorine (see above) [42,43]. Another example involves the direct synthesis of hydrogen peroxide starting from H2 and O2 over a palladium catalyst. Although this is an environmentally benign and atom-efficient method, it involves the handling of an explosive gas mixture. Such reaction conditions can be safely performed with microreactor technology [45]. 

The addition of N-H bonds to alkenes is an atom-efficient method for the preparation of amines. When activated alkenes such as acrylates were used as substrates, this process is referred to as an aza-Michael addition. Using this approach, a great variety of amines and related compounds have been generated through systematic variation of the nitrogen-bearing substrate and alkene. In many cases, a catalyst was not needed for the addition reaction [19]. 

Transition metal-catalyzed cycloisomerizations have been the subject of particular attention as atom-efficient methods for the construction of carbo- and heterocyclic molecules, which are fundamental constituents of natural products, pharmaceutical compounds, and functional materials. In view of their importance, several studies concerning their metal-catalyzed cyclization mechanisms have been undertaken in a,oo-bifunctional substrates such as dienes, enynes, and diynes. 

When possible, quantitative analyses are best conducted using external standards. Emission intensity, however, is affected significantly by many parameters, including the temperature of the excitation source and the efficiency of atomization. An increase in temperature of 10 K, for example, results in a 4% change in the fraction of Na atoms present in the 3p excited state. The method of internal standards can be used when variations in source parameters are difficult to control. In this case an internal standard is selected that has an emission line close to that of the analyte to compensate for changes in the temperature of the excitation source. In addition, the internal standard should be subject to the same chemical interferences to compensate for changes in atomization efficiency. To accurately compensate for these errors, the analyte and internal standard emission lines must be monitored simultaneously. The method of standard additions also can be used. 

The acidic character of the hydrogen atoms of C-methyl groups linked to the pyrazolium ring (Figure 22 Section 4.04.2.1.1(11)) facilitates a number of reactions difficult to carry out with neutral pyrazoles. Since efficient methods of dealkylation have been described (Section 4.04.2.3.lO(ii)), the synthesis via the pyrazolium salt is a useful alternative. The same behaviour is observed for indazolium salts, for example, nucleophilic addition to aromatic aldehydes (78JOC1233). 

Thus, efficient methods for the addition of one or two carbon atoms to 17-keto steroids were of some importance, especially because of the high cost of the starting materials. A balancing factor, however, was the relatively low level of use of the natural and synthetic steroids which was in part a reflection of the cost of treatment. 

The plausible mechanism is based on the proposal by Jana and coworkers (Scheme 14). In this case, the sp-hybridized vinyl cation can be attacked by halide, instead of water, to give the ElZ isomer of the alkenyl halide. Compared with the systems using stoichiometric Lewis acid and strong base to prepare substituted alkenyl halides, the present method would provide an excellent alternative due to the environmentally benign system and atom efficiency. 

For example, a microwave discharge on H2 in an inert diluent, such as argon gas, is an efficient method for producing H atoms as reactants. Subsequent reaction of these H atoms with NO2 will yield OH and NO, and can serve as a useful source of hydroxyl radicals. These methods of reactant formation are well suited for experiments involving either static or flow reactor systems. 

A fairly efficient method of selective detection of active forms of oxygen by means of sensors is the preliminary separation of their mixture with the aid of filters designed for the purpose, filters that vigorously de-excite this or that form of oxygen. It has been mentioned in Section 5.4 that freshly atomized films of Ag efficiently absorb O-atoms from the gaseous phase, mildly de-excite 02 molecules. To de-excite the singlet oxygen molecules proper, use should be made of filters with... 

Redox reactions are considered as being able to provide versatile and efficient methods for bringing about ring transformations. Transition metal complexes in particular are able to induce or catalyze oxidative or reductive transformations of small ring compounds. Organometallics, such as metal-lacycles derived by the insertion of metal atoms into rings, are involved as key intermediates in many cases, allowing subsequent functionalization or carbon-carbon bond formation. 

Some aspects of synthetic chemistry have changed in response to environmental needs. For example, in the pharmaceutical industry the classical methods produce, on the average, about nine times as much disposable waste as desired product. This has led to the demand for procedures that have atom efficiency, in which all the atoms of the reacting compounds appear in the product. Thus (as discussed earlier) the demand for atom economy offers additional opportunities for creative invention of transformations. 

---