Synthons, synthesis

Supramolecular structuring, 12 5-6 Supramolecular synthons, synthesis and structures of, 24 39-40 Supramolecules, formation of, 24 34 Supraventricular arrhythmias, 5 88, 104 Supraventricular tachycardia, 5 88, 101, 105, 108 Suprilent... 

Cazes, B. Julia, S. Preparation and utilization of two C5 conjugated ketene dithioacetals as isoprene synthons. Synthesis of (-)-(E)-lanceol. Tetrahedron Lett. 1978, 4065—4068. 

B. B. Lohray, Cyclic Sulfites and Cyclic Sulfates Epoxide Like Synthons, Synthesis 1992, 1035-1052. J. B. Sweeney, Aziridines Epoxides Ugly Cousins Chem. Soc. Rev. 2002, 31, 247-258. 

B. B. Lohray, Cyclic sulfites and cyclic sulfates Epoxide like synthons, Synthesis 1992,1035-1052. 

Ballini, R. and Rosini, G. 1988. Functionalized nitroalkanes as useful reagents for alkyl anion synthons. Synthesis, 11 833 7. 

Alkaloid synthons, synthesis, 191 Alkylation, zeolitic solid acid catalyzed, kinetics, 105-114 Alternative feedstocks and starting materials... 

Takeuchi, N., K. Ochi, M. Murase, and S. Tobinaga An Easy Two Synthon Synthesis of a Sweet Dihydroisocoumarin (+ )-Phyllodulcin. Chem. Commun. 1980, 593. 

An Easy Two-Synthon Synthesis of a Sweet Dihydroisocoumarin ( )-Phyllo-... 

Vasil tsov, A.M., A.V. Ivanov, LA. Ushakov et al. 2007. Selective thiylation of 1-vinyl-pyrrole-2-carbaldehydes Synthesis of 2-[bis(ethylsulfanyl)methyl]-l-vinylpyrroles and l-(2-ethylthioethyl)pyrrole-2-carbaldehydes - novel pyrrole synthons. Synthesis 3 452-456. 

Ichikawa J, Fukui H, Ishibashi Y. 1-Trifluoromethylvinylsilane as a Cp2=C -CH2 synthon synthesis of functionalized... 

Reagent A compound which reacts to give an intermediate in the planned synthesis or to give the target molecule itself. The synthetic equivalent of a synthon. 

Synthesis Again the enamine can be used to proyide the enolate synthon ... 

Synthesis The vinyl anion synthon can either be the vinyl Grignard reagent or the acetylide arrion, in which case the synthesis becomes ... 

The vinyl anion synthon is best represented by an acetylide ion (frame 33). Synthesis ... 

The carbene synthon might be difficult, but since the olefin is conjugated with a carbonyl group we could try a sulphur ylid as a nucleopliilic carbene equivalent (as in frame 283). Synthesis The diene could be made by this route ... 

The formal carbanions and carbocations used as units in synthesis are called donor synthons and acceptor synthons. They are derived from reagents with functional groups. 

There exist a number of d -synthons, which are stabilized by the delocalization of the electron pair into orbitals of hetero atoms, although the nucleophilic centre remains at the carbon atom. From nitroalkanes anions may be formed in aqueous solutions (e.g. CHjNOj pK, = 10.2). Nitromethane and -ethane anions are particularly useful in synthesis. The cyanide anion is also a classical d -synthon (HCN pK = 9.1). 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

In the synthesis of complex organic molecules d -synthons have not become as important as their d and d counterparts. 

In the synthesis of molecules without functional groups the application of the usual polar synthetic reactions may be cumbersome, since the final elimination of hetero atoms can be difficult. Two solutions for this problem have been given in the previous sections, namely alkylation with nucleophilic carbanions and alkenylation with ylides. Another direct approach is to combine radical synthons in a non-polar reaction. Carbon radicals are. however, inherently short-lived and tend to undergo complex secondary reactions. Escheirmoser s principle (p. 34f) again provides a way out. If one connects both carbon atoms via a metal atom which (i) forms and stabilizes the carbon radicals and (ii) can be easily eliminated, the intermolecular reaction is made intramolecular, and good yields may be obtained. 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

The last group of reactions uses ring opening of carbonyl or 1-hydroxyalkyl substituted cyclopropanes, which operate as a -synthons. d -Synthons, e.g. hydroxide or halides, yield 1,4-disubstituted products (E. Wenkert, 1970 A). (1-Hydroxyalkyl)- and (1-haloalkyl)-cyclopropanes are rearranged to homoallylic halides, e.g. in Julia s method of terpene synthesis (M. Julia, 1961, 1974 S.F. Brady, I968 J.P. McCormick, 1975). 

The 1,6-difunctional hydroxyketone given below contains an octyl chain at the keto group and two chiral centers at C-2 and C-3 (G. Magnusson, 1977). In the first step of the antithesis of this molecule it is best to disconnect the octyl chain and to transform the chiral residue into a cyclic synthon simultaneously. Since we know that ketones can be produced from add derivatives by alkylation (see p. 45ff,), an obvious precursor would be a seven-membered lactone ring, which is opened in synthesis by octyl anion at low temperature. The lactone in turn can be transformed into cis-2,3-dimethyicyclohexanone, which is available by FGI from (2,3-cis)-2,3-dimethylcyclohexanol. The latter can be separated from the commercial ds-trans mixture, e.g. by distillation or chromatography. 

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