Addition-fragmentation intramolecular

Scheme 13. Intramolecular radical addition/fragmentation in Boger s synthesis of (+)-CC-1065.

In the case of allyl peroxides (12 X= CH2, A=CH2, BO),1 1 1 intramolecular homolytic substitution on the 0-0 bond gives an epoxy end group as shown in Scheme 6.18 (1,3-Sn/ mechanism). The peroxides 52-59 are thermally stable under the conditions used to determine their chain transfer activity (Table 6.10). The transfer constants are more than two orders of magnitude higher than those for dialkyi peroxides such as di-f-butyl peroxide (Q=0.00023-0.0013) or di-isopropyl peroxide (C =0.0003) which are believed to give chain transfer by direct attack on the 0-0 bond.49 This is circumstantial evidence in favor of the addition-fragmentation mechanism. 

An intramolecular mechanism of the rearrangement has been shown in the special ESR study (refs. 21, 22), conducted on the model radicals, generated by abstraction of a bromine atom from T2 " the rate constant K2, equal to (5.0 + 0.3) X 104 sec- at 22°C, has been also determined. In addition, fragmentation of radical... 

If the insertion step following oxidative addition occurs on one of the two fragments resulting from oxidative addition, an intramolecular catalytic reaction (C—O — C—C rearrangement) takes place (example 40, Table III). It is interesting to note that two different products—2,6- and 3,6-heptadienoic acids—can be obtained from allyl 3-butenoate. Their ratio can be controlled by adding 1 mole of the appropriate phosphine or phosphite to bis(cyclooctadiene)nickel or similar complex. Bulky ligands favor the 2,6 isomer. It is thus possible to drive the reaction toward two different types of H elimination, namely, from the a or y carbon atoms. 

Intramolecular group-transfer reactions can involve either direct displacements or addition-fragmentation reactions that are discussed in Section 4.2.4. A direct displacement is shown in the reaction of aryl radical 1, produced from the corresponding bromide. Cyclization of 1 is fast enough to compete efficiently... 

When the alkoxyl radical and the hydrogen to be abstracted are not properly disposed for the Barton reaction, the reactions of the alkoxyl radical, for example -fragmentation, intramolecular addition to the double bond, disproportionation or a-hydrogen fission, and intermolecular hydrogen abstraction, compete with the Barton reaction or result in an exclusive reaction. Among these reactions, /l-frag-... 

Scheme 2.113 One-pot synthesis of cesium pental

Multiblock copolymers comprising NIPAAm and N,N-dimethylacrylamide (DMAAm) with variable length of blocks of both components prepared by reversible addition-fragmentation chain transfer polymerization were also investigated and their phase behavior was found to exhibit protein-like behavior exhibiting intramolecular collapse upon heating, forming unimolecular flower-like micelles above the thermal phase transition temperature." ... 

Jones and EHidly developed an effective two-step strategy for the synthesis of benzo-fused indanes 65 the tandem addition/fragmentation of vinylogous acyl tri-flates 64 and the copper-catalyzed intramolecular benzannulation of o-alkynylphenyl ketones 59 (Scheme 15.26) [38]. 

Clayden and coworkers reported intramolecular Michael-addition— fragmentation leading to 3-vinyl- and 3-aryl-substituted 3-pyrrolin-2-ones (20040L609). For example, treatment of the carboxamide 178 (DEB = 1,1-diethylbutylcarbonyl) with LDA gives 3-pyrrolin-2-one 180 through a fragmentation of the initial Michael adduct 179 (Scheme 39). 

The use of a vinylphosphonium salt as the source of the QQ fragment instead of the more commonly employed 1,2-dicarbonyl substrate is illustrated by the pyrrole synthesis in Scheme 79b (8UOC2570). A particularly interesting feature is the intramolecular Wittig reaction with an amide carbonyl group. A very useful synthesis of pyrroles depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,/3-unsatur-... 

Most diaziridines are not sensitive towards alkali. As an exception, diaziridines derived from 2-hydroxyketones are quickly decomposed by heating with aqueous alkali. Acetaldehyde, acetic acid and ammonia are formed from (162). This reaction is not a simple N—N cleavage effected intramolecularly by a deprotonated hydroxy group, since highly purified hydroxydiaziridine (162) is quite stable towards alkali. Addition of small amounts of hydroxybutanone results in fast decomposition. An assumed reaction path — Grob fragmentation of a hydroxyketone-diaziridine adduct (163) — is in accord with these observations (B-67MI50800). 

Peroxyacetals 58106 and peresters such as 61107 are also effective transfer agents, however, at typical polymerization temperatures ( 60 CC) they are thermally unstable and also act as initiators. Compounds such as 62 which may give addition and 1,5-intramolecular substitution with fragmentation have also been examined for their potential as chain transfer agents (l,5-SHi mechanism).108... 

Another example of a [4S+1C] cycloaddition process is found in the reaction of alkenylcarbene complexes and lithium enolates derived from alkynyl methyl ketones. In Sect. 2.6.4.9 it was described how, in general, lithium enolates react with alkenylcarbene complexes to produce [3C+2S] cycloadducts. However, when the reaction is performed using lithium enolates derived from alkynyl methyl ketones and the temperature is raised to 65 °C, a new formal [4s+lcj cy-clopentenone derivative is formed [79] (Scheme 38). The mechanism proposed for this transformation supposes the formation of the [3C+2S] cycloadducts as depicted in Scheme 32 (see Sect. 2.6.4.9). This intermediate evolves through a retro-aldol-type reaction followed by an intramolecular Michael addition of the allyllithium to the ynone moiety to give the final cyclopentenone derivatives after hydrolysis. The role of the pentacarbonyltungsten fragment seems to be crucial for the outcome of this reaction, as experiments carried out with isolated intermediates in the absence of tungsten complexes do not afford the [4S+1C] cycloadducts (Scheme 38). 

XLOGP [67, 68] is a further atom-additive method, as expressed by its almost exclusive use of atomic contributions. However, in contrast to pure atom-based methods correction rules are defined, to account for intramolecular interactions, which is typical for fragmental methods. 

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