Bimolecular cyclization

In an attempt to prepare polymers of type Ic or Id from acid amides and 1,3-dichlorodisiloxanes or 1,5-dichlorotrisiloxanes, it was found that bimolecular cyclization prevailed over polycondensation and cyclic bis(silylamides) in the amido (la) or imidato (lb) isomeric forms were exclusively formed in high yields... 

Bimolecular cyclizations, as might be expected, are more sensitive to the nature of the polymeric medium. Several studies have been reported of examples of the cycloaddition reaction... 

Table 1 Bifunctional initiator, coupling agent, and reaction conditions used for the preparation of cyclic polystyrene by end-to-end bimolecular cyclization...

Cyanamides [33,36,46] and ethyl thiocyanate 90 could be used as well in such bimolecular cyclizations (Scheme 1.25). 

Solid-supported [2 - - 2 - - 2] cycloadditions were also tested by Young and Deiters in the case of bimolecular cyclizations leading to fused pyridines (Scheme 1.28)... 

Other radicals undergo rearrangement in competition with bimolecular processes. An example is the 5-hexenyl radical (5). The 6-heptenoyloxy radical (4) undergoes sequential fragmentation and cyclization (Scheme 3.8).1S... 

The attachment of an electron to an organic acceptor generates an umpolung anion radical that undergoes a variety of rapid unimolecular decompositions such as fragmentation, cyclization, rearrangement, etc., as well as bimolecular reactions with acids, electrophiles, electron acceptors, radicals, etc., as demonstrated by the following examples.135"137... 

Intramolecular arylation of alkenes. The intramolecular palladium-catalyzed condensation of aryl halides with an alkene group (Heck arylation5) can actually proceed more readily than the original bimolecular version. These intramolecular cyclizations typically proceed in acetonitrile at room temperature, particularly when catalyzed by Ag2C03, which also inhibits isomerization of the double bond of the product. They can be used to obtain spiro, bridged, and fused systems. Even tetrasubstituted alkenes can participate, with formation of quaternary centers.6... 

For the cyclization of the less nucleophilic sulfonamides, this conversion can only be achieved via this two-step protocol. The addition of I2 was highly regioselective, addressing the terminal C=C bond, whereas the second step could deliver several products including the SN2-substitution, SN2 -substitution and bimolecular double substitution products 297-299, depending on the length of the tether connecting the amine and the allene moiety [144, 145],... 

The extension of the cyclization from tetrahydrofurans and pyrrolidines to car-bocycles leads to a sharp decrease in the yield of cyclized product. This is due to the slower cyclization rate of 5-hexenyl radicals compared to 5-(3-oxahexenyl) radicals, which favors the competing bimolecular coupling to the acyclic product. Three measures help to increase the yield in these cyclizations. 

Homolytic substitution reactions including homolytic allylation, radical [2,3]-migrations and stereochemical reactions been reviewed. The review also highlights the possible applications of homolytic substitution reactions. ni reactions at silicon (by carbon-centred radicals in the a-position of stannylated silyl ethers) are efficient UMCT reactions producing cyclized alkoxysilanes. Bimolecular reactions can also be facilitated in good yield (Schemes 32 and 33). ... 

In another approach, several ct-hydroxydimethylacetals 258, available according to Scheme la, undergo bimolecular loss of MeOH under acid catalyst, to yield the corresponding 1,4-dioxanes 259 (84JOC4581) (Eq. 42). In the case of 3,3-dimethoxy-2-pentanol (260), which is prepared from 3-pentanone, the cyclization gives dioxane 261 rather than the expected 262 (Scheme 65). The rearrangement of 260 to a mechanistically reasonable precursor of 261 is well known from the work of Creary and Rollin (77JOC4231). 

This intennediate is then involved in the cyclization step [132]. However, it has been shown in another series of experiments that enecarboxylate radical-anions dimerize rapidly before protonation when only traces of water are present [43]. On the basis of these findings, it seems more likely that, as originally proposed, intramolecular cyclization occurs at the level of the radical-anion, and that this process is faster than the alternative bimolecular dimerization. 

High concentrations of monomers favor linear polymerization since cyclization is a unimo-lecular (intramolecular) reaction, while linear polymerization is a bimolecular (intermolec-ular) reaction. The ratio of cychzation to linear polymerization varies inversely with the first power of monomer concentration according to... 

All these protocols allow us to form a new carbocycle in a bimolecular process. The cyclization involving two different molecules besides CO has been realized, involving carbapalladation of norbornene, migratory insertion of CO, and subsequent intramolecular Heck-like attack at thiophene residue. Thallium acetate is required as electrophilic co-catalyst (Scheme 18). ... 

For this discussion, bioactive peptides will be defined as peptides which interact specifically with a target macromolecular acceptor or are derived from domains involved in a critical protein-protein interaction and, therefore, can compete effectively to mimic or disrupt this bimolecular interaction. Once the structure-activity relationship of a bioactive peptide is revealed, one can identify the termini and/or positions in which introduction of a caging group will be disruptive for target recognition. Alternatively, caging the peptide in an inactive conformation can be accomplished by end-to-end or end-to-side-chain cyclization. 

Redox and homolytic substitution reactions almost never directly form C—C, C—N and C—O bonds. Such bonds are generated in radical addition reactions (Scheme 14). Intermolecular addition reactions are presented in this chapter. Cyclization reactions have important similarities with, and differences from, bimolecular additions, and they are presented in Chapter 4.2 of this volume. Falling under the umbrella of addition reactions are radical eliminations (the reverse of addition) and radical migrations (which are usually, but not always, comprised of an addition and an elimination). 

Addition reactions of carbon radicals to C—O and C—N multiple bonds are much less-favored than additions to C—C bonds because of the higher ir-bond strengths of the carbon-heteroatom multiple bonds. This reduction in exothermicity (additions to carbonyls can even be endothermic) often reduces the rate below the useful level for bimolecular additions. Thus, acetonitrile and acetone are useful solvents because they are not subject to rapid radical additions. However, entropically favored cyclizations to C—N and C—O bonds are very useful, as are fragmentations (see Chapter 4.2, this volume). 

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