Synthetic utility

The MC Strecker reaction is the key step in this synthesis for the preparation of intermediate aminonitrile 81 further acylation of that compound with benzothiadiazine acid 82 under the standard conditions followed by in situ addition of triethylamine provided the desired aminotetramic acid 83. 

More recently, Zhu and coworkers have employed the a-aminonitrile intermediate resulting of this process to generate in two steps polysubstituted 2-amino-5-cyanopyrroles 85 through a [4+1] cycloaddition of a,p-unsaturated imi-doyl cyanide (2-cyano-l-azadienes) with isocyanides, in combination with a previous in situ oxidation of the Strecker adduct (Schone 10.38) [108,109]. 

Strecker, Justus Liebigs Ann. Chem. 1850, 75, 27-45. Ueber die ktlnstliche Bildung der Milchsaure und einen neuen, dem Glycocoll homologen Korper. 

2 (a) H. Bergs, Ger. Pat. 566, 094, 1929. (b) H. T. Bucherer, W. Steiner, J. Prakt. Chem. 1934, 140, 291-316. Syntheses of hydantoins. I. Reactions of a-hydroxy and a-amino nitriles, (c) H. T. Bucherer, V. A. Lieb, J. Prakt. Chem. 1934, 141, 5-43. Syntheses of hydantoins. II. Formation of substituted hydantoins from aldehydes and ketones. 

Rousset, M. Lasperas, J. TaUlades, A. Commeyras, Tetrahedron 1980, 36, 2649-2661. Systemes de strecker et apparentes-XI formation et stabilite de I a-carboxyaminoni-trile. Intemiediaire essentiel dans la synthese des hydantoines selon Bucherer-Bergs. 

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I undertook the present task to give a birds-eye view of the broad field of palladium in organic synthesis. 1 have tried to accomplish this ttisk by citing many references these were selected from a much larger number which I have collected over the years. I tried to be as comprehensive as possible by selecting those references which reported original ideas and new reactions, or evident synthetic utility. Synthetic utility is clearly biased towards catalytic rather than stoichiometric reactions and this emphasis is apparent in the selection of the... 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

The rearrangement of carbonium ions that readily occurs according to the thermodynamic stabiUty of cations sometimes limits synthetic utility of aromatic alkylation. For instance, the alkylation of ben2ene with / -propyl bromide gives mostly isopropylben2ene (cumene) much less... 

Biocatalytic ledox reactions offer great synthetic utility to organic chemists. The majority of oxidase-catalyzed preparative bioconversions are still performed using a whole-ceU technique, despite the fact that the presence of more than one oxidoreductase in cells often leads to product degradation and lower selectivity. Fortunately, several efficient cofactor regeneration systems have been developed (160), making some cell-free enzymatic bioconversions economically feasible (161,162). 

The synthesis of pyrazolines and pyrazoles of the [CCNN + C] type with the creation of two bonds, N(2)-C(3) + C(3)-C(4) (or N(l)-C(5) + C(5)-C(4)), has been studied by several groups. Beam and coworkers have published a series of papers on the synthetic utility of lithiated hydrazones. Thus, the methylhydrazone of acetophenone (598) is converted by butyllithium into the dianion (599), which in turn reacts with methyl benzoate to afford the pyrazole (600) (76SC5). In earlier publications Beam et al. have used aldehydes and acyl chlorides to obtain pyrazolines and pyrazoles by the same method. 

On the whole, the cycloaddition of alkynes to nitrile N-oxides is one of the most important routes to isoxazoles, but in spite of its potentially wide application, its synthetic utility is less than that of the corresponding reaction with alkenes for the following reasons. (1)... 

Another type of (CNO-fC + C) reaction has been reported (77JCS(P1)1196). The reaction of dimethyloxosulphonium 4-nitrobenzylide (382) with benzonitrile iV-oxide gave 4,5-dihydro-4,5-bis(4-nitrophenyl)-3-phenylisoxazole (383) in 31% yield. So far, no synthetic utility for this reaction process has been reported. 

Secondary amines cannot form imines, and dehydration proceeds to give carbon-carbon double bonds bearing amino substituents (enamines). Enamines were mentioned in Chapter 7 as examples of nucleophilic carbon species, and their synthetic utility is discussed in Chapter 1 of Part B. The equilibrium for the reaction between secondary amines and carbonyl compounds ordinarily lies far to the left in aqueous solution, but the reaction can be driven forward by dehydration methods. 

While the oxidation of ketones by peracids (Baeyer-Villiger reaction) has been used in steroids mainly for ring cleavage, it has occasionally been applied to 20-ketopregnanes for conversion to 17-acetoxy- or hydroxyandros-tanes. The synthetic utility of this method is limited since reactive double bonds and other ketones are incompatible with the reagent. 

A considerable extension of the synthetic utility of the hypoiodite reaction is achieved if the steroid hypoiodite (2) is generated from the alcohol and acetyl hypoiodite and then decomposed in a nonpolar solvent. In this case ionic hydrogen iodide elimination in the 1,5-iodohydrin intermediate (3) is slow, thereby allowing (3) to be converted into an iodo hypoiodite (5). 

A 17a-methyl in the product of ring D homo-annulation of 17-hydroxy-20-keto steroids may limit the general synthetic utility of the reaction. On the other hand, the 17a-hydroxyl group gives additional flexibility in planning further transformations. Moreover, by adjusting reaction conditions, the stereochemistry of the products can be changed. 

Fluoroxy reagents became of general synthetic utility after the discovery of a relatively simple preparation of acetyl hypofluorite [i5] (equation 2)... 

The fluonnation of both mono and dinitro enolates proceeds well with perchloryl fluoride. The mononitro fluorinated intermediates have been used to develop fluorinated materials of general synthetic utility [III, 113] (equation 63)... 

Table 14. Synthetic Utility of Fluorinated Phosphonium Salts Prepared From Dibromodifluoromethane [40 ...

Fluorinated esters have synthetic utility m Claisen condensations [24, 25] (equation 21) and Dieckmann cyclizfitions [26]. 

A representative list of aziridinium salts prepared by reaction of iminium salts with diazomethane is given in Table 9. The reactions of aziridinium salts are many and varied, but will not be given here since their synthetic utility has been explored and reported elsewhere 109,112-114). The products from the reaction of iminium chlorides and diazomethane are reported in Table 10. Many more examples are available in the literature 16). 

The synthetic utility of enamines presupposes their general accessibility. In most cases, ketones are readily converted to enamines by condensation of the carbonyl compound with a secondary amine such as pyrrolidine, morpholine, or piperidine and azeotropic removal of water with a solvent such as benzene (3-19). 

These and similar reactions have considerable synthetic utility. Other reactions which result m bond cleavage by the addition of one electron are ... 

Some structural aspects of the organometallic compounds of the alkali metals have already been briefly mentioned in Section 4.3.6. The diagonal relation of Li with Mg (p. 76), coupled with the known synthetic utility of Grignard reagents (pp. 132-5), suggests that Li, and perhaps the other alkali metals, might afford synthetically... 

This reaction, now termed hydroboration, has opened up the quantitative preparation of organoboranes and these, in turn, have proved to be of outstanding synthetic utility. It was for his development of this field that H. C. Brown (Purdue) was awarded the 1979 Nobel Prize in Chemistry . Hydroboration is regiospecific, the boron showing preferential attachment to the least substituted C atom (anti-Markovnikov). This finds ready interpretation in terms of electronic factors and relative bond polarities (p. 144) steric factors also work in the same direction. The addition is stereospecific cis (syn). Recent extensions of the methodology have encompassed the significant development of generalized chiral syntheses. 

When hexamethylphosphoramide, (NMe2)3PO, is used as solvent only the second reaction occurs. The synthetic utility of KSiHa can be gauged from Table 9.7 which summarizes some of its reactions. In addition, PCI3 gives polymeric (PH) t, CO2 gives CO plus HCO2K (formate), and N2O gives N2 + H2 (plus) some Sifli in each... 

In 1962, Corey and Chaykovsky described the generation and synthetic utility of... 

The Jacobsen-Katsuki epoxidation reaction has found wide synthetic utility in both academia and industrial settings. As described previously, the majority of olefin classes, when conjugated, undergo Mn(salen)-catalyzed epoxidation in good enantioselectivity. In this section, more specific synthetic utilities are presented. 

The AE reaction has been applied to a large number of diverse allylic alcohols. Illustration of the synthetic utility of substrates with a primary alcohol is presented by substitution pattern on the olefin and will follow the format used in previous reviews by Sharpless but with more current examples. Epoxidation of substrates bearing a chiral secondary alcohol is presented in the context of a kinetic resolution or a match versus mismatch with the chiral ligand. Epoxidation of substrates bearing a tertiary alcohol is not presented, as this class of substrate reacts extremely slowly. 

Not surprising, the most prevalent synthetic utility is the assembly of the pyrrolidine ring. N-Chloroamine 27 was obtained by treatment of N-methyl-2-cyclopentylethylamine (26) with N-chlorosuccinimide. Under classic Hofmann-Loffler-Freytag reaction conditions, 27 was rearranged either thermally or by UV irradiation in sulfuric acid to bicyclic amine... 

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