Radical synthons

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 process can be interrupted at the stage of ketyl 171, thereby providing access to an acyl radical synthon. The radical character of the intermediate is... 

Table 8. Cyclization of carboxylic acids onto alkenes acyl radical synthon...

Miyazoe et al. introduced silyltellurides as partners for group-transfer three-component couplings with isocyanides (Scheme 60) [ 170]. The reaction probably started through initial addition of silyl radicals to a carbonyl derivative, yielding ketyl radical 185, which underwent addition to phenylisocyanide (a Cl radical synthon). Final phenyltelluride group transfer to intermediate... 

This is then followed by homolytie )8-scission to form acetate and the ethyl formate radical synthon. 

Interestingly, the reaction of an alkyl radical with carbon monoxide as a Cl radical synthon has been extensively studied in recent years [47]. The efficient trapping of CO by a variety of alkyl radicals in a radical chain has been demonstrated since 1990 but is discussed separately in this book (Volume 2, Chapter 1.2). 

R ) relative configuration stereosymbol, 360 r synthons. See Radical synthons Racemates, resolution of. See Optical resoiution Racemization prevention in peptide synthesis, 145, 231-232, 234... 

Syntheses of alkenes with three or four bulky substituents cannot be achieved with an ylide or by a direct coupling reaction. Sterical hindrance of substituents presumably does not allow the direct contact of polar or radical carbon synthons in the transition state. A generally applicable principle formulated by A. Eschenmoser indicates a possible solution to this problem //an intermolecular reaction is complex or slow, it is advisable to change the educt in such a way. that the critical bond formation can occur intramolecularly (A. Eschenmoser, 1970). 

Treatment of O-silyl enols with silver oxide leads to radical coupling via silver enolates. If the carbon atom bears no substituents, two such r -synthons recombine to symmetrical 1,4-dicarbonyl compounds in good vield (Y. Ito, 1975). 

The quiaones have excellent redox properties and are thus important oxidants ia laboratory and biological synthons. The presence of an extensive array of conjugated systems, especially the a,P-unsaturated ketone arrangement, allows the quiaones to participate ia a variety of reactioas. Characteristics of quiaoae reactioas iaclude nucleophilic substitutioa electrophilic, radical, and cycloaddition reactions photochemistry and normal and unusual carbonyl chemistry. 

It should be noted that addition of the tributyltin radical to 1-fluoro-1-(phenylsulfonyl)ethene provides phenyl vinyl sulfone as the only isolated product. However, 2-trimethylsilyl-1-fluoro-1-(phenylsulfonyl)ethene reacts with tributyltin hydride in the presence of AIBN to provide (E)-2-trimethylsilyl-1-fluoro-1-tributylvinylstannane. The vinylstannane is an equivalent for the synthon "H2C=CF " providing a convenient route to 2-fluoro-1-alkenes.8 The trimethylsilyl group can be removed with potassium fluoride in dimethyl sulfoxide-water or oxalic acid-methanol at the end of the reaction sequence. 

For the route A, acyl radicals donors like iS are readily generated from acyl selenides (ISa) or acyl cobalt derivatives (iSb) and radicals acceptors 2S are usually multiple bonds as in methyl vinyl ketone (2Sa) -although some homolytic substitutions are possible. On the other hand, nitriles GSal are useful acceptors (3S) in radical cyclisations and 4Sa is an obvious synthon equivalent of radical donor 4S (See Table 7.2). 

TABLE 7.2. Equivalent synthons of radical donors and radical acceptors... 

Library of Congress Cataloging in Publication Data. Main entry under title Organic chemistry, syntheses and reactivity. (Topics in current chemistry 88) Contents Riichardt, C. Steric effects in free radical chemistry. -Birkhofer, L. and Stuhi, O. Silylated synthons. [etc.] 1. Chemistry Organic-Addresses, essays, lectures. 

The reduction of trifluoromethylimines with Mg(0) affords A-silyl difluoroena-mines." These synthons are very interesting for the preparation of difluoro- S-amino alcohols and of difluoro amino acids (cf. Chapter 4). They can also add onto radicals, react with sulfur ylides to afford difluoromethylaziridines, or even undergo intramolecular ene reactions (Figure 2.26)." ... 

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