A Cascade Reaction

Nonetheless, it was a fairly short step from octopus compounds to dendrimers, and the step was taken by Vogtle in the late 1970s when he attempted to use a cascade reaction to prepare a molecule of the dendrimer type that would now be considered a dendron rather than a fully developed dendrimer. It began with the addition of acrylonitrile to an anfine, followed by reduction of the nitrile to amine. This was followed by a further reaction with acrylonitrile, and the process was repeated several times to yield highly branched macromolecules. There were initially problems with the reduction step but these were overcome, and the preparation of these poly(propylene imine) dendrimers was later commercialized. 

In 2006, Poe et al. reported a cascade reaction employing two incompatible catalysts, one of which was microencapsulated [19]. In this case, an organic amine was encapsulated and used in conjunction with a nickel-based Lewis acid catalyst (Scheme 5.4). 

A cascade reaction involving multiple C-H functionalizations has been employed for the formation of bicyclic heterocycles with palladium catalysis (Equation (160)).134... 

Using sodium tetraphenylborate under anhydrous conditions and [RhCl(COD)]2 as a catalyst, a cascade reaction of dienyne 292 has been carried out, which ends by acylation of the alkylrhodium intermediate and the subsequent Rh -OMe formation, to afford bicyclo[2.2.1]-heptan-2-one 293 in good yield (Scheme 75).282... 

Keyword Carbocycles a Cascade Reactions a Cycloadditions a Combinatorial Chemistry a Domino Reactions a Enantioselective Transformations a Ene Reactions a Eieterocydes a Natural products a Preservation of Resources and Environment a Sigmatropic Rearrangements a Tandem Reactions a Transition Metal-Catalyzed Transformations... 

When the cyclic acetylene 260 is generated from a suitable precursor, it undergoes an isomerization reaction spontaneously generating naphthalene (263) and benzo-fulvene (264) as the finally isolable products. Very likely the process begins with a retro-Diels-Alder reaction to the [3]cumulene 261, which in a cascade reaction via the semicydic allene 262 rearranges to 263 and 264 [111]. 

Strictly speaking a catalytic cascade process is one in which all of the catalysts (enzymes or chemocatalysts) are present in the reaction mixture from the outset. A one-pot process, on the other hand, is one in which several reactions are conducted sequentially in the same reaction vessel, without the isolation of intermediates. However, not all of the reactants or catalysts are necessarily present from the outset. Hence, a cascade process is by definition a one-pot process, but the converse is not necessarily true. Clearly a cascade process is a more elegant solution, but a one-pot process that is not, according to the strict definihon, a cascade reaction may have equal practical uhlity. In this chapter we shall be primarily concerned with enzymatic cascade processes, but the occasional chemocatalytic step may be included where relevant and sometimes a sequential one-pot procedure may slip through the net. 

Chain growth polymerizations (also called addition polymerizations) are characterized by the occurrence of activated species (initiators)/active centers. They add one monomer molecule after the other in a way that at the terminus of each new species formed by a monomer addition step an activated center is created which again is able to add the next monomer molecule. Such species are formed from compounds which create radicals via homolytic bond scission, from metal complexes, or from ionic (or at least highly polarized) molecules in the initiating steps (2.1) and (2.2). From there the chain growth can start as a cascade reaction (propagation 2.3) upon manifold repetition of the monomer addition and reestablishment of the active center at the end of the respective new product ... 

In step growth reactions, on the other hand, neither are specific activated centers present to force the connection of the monomers, nor does the process occur as a cascade reaction. Instead, the monomers are tied together in discreet, independent steps via conventional organic reactions such as ester-, ether-, amide-, or urethane formation. Depending on whether small molecules are set free in the connection step, one distinguishes between polycondensations (2.9) and polyadditions (2.10) ... 

Recently, List has described a cascade reaction promoted by phosphoric acid 1 in combination with stoichiometric amounts of achiral amine, which transforms various 2,6-diketones to the corresponding ds-cyclohexylamines (Scheme 5.28) [50]. This three-step process involves initial aldolization via enamine catalysis to give conjugate iminium ion intermediate A. Next, asymmetric conjugate reduction followed by a diastereoselective 1,2 hydride addition completes the catalytic cycle. 

According to some authors, the success in the establishment of infection by the oral route is associated with the expression of gp82, a surface glycoprotein, which binds to mucin and gastric epithelial cells. This molecule promotes the entrance of trypomastigotes through a cascade reaction that culminates with the mobilization of intracellular calcium (Ruiz et al., 1998). 

The treatment of tricycle 238 with TFA in THF triggered a cascade reaction, which led to the formation of tetracycle 239, an intermediate of (—Hemonomycin alkaloid (08SL2443). 

A related one-pot, three-component synthesis of fi-amino carbonyl compounds has been achieved using a cascade reaction of anilines with aromatic aldehydes and car- (g) bonyl compounds, catalysed by zinc triflate.19... 

A radical cyclization controlled by sulfur yields the tetrahydroisoquinoline (Equation 49) <1997J(P1)2291>. In the absence of the sulfur groups, only the reduced product is isolated. Further reactions that utilize radical cyclizations with vinylsulfides show a cascade reaction eventually forming the benzo[ ]quinolizine system <1999TL1149> (Equation 50). 

These examples demonstrate that a selective Heck-Diels-Alder sequence with two different alkenes is only possible either in a stepwise manner, if an alkene reacts much faster in the Heck reaction than in the subsequent cycloaddition so that the 1,3-diene can be isolated, or as a real cascade reaction if one alkene is more reactive and thus selectively reacts as a coupling partner, whereas the other one is a better dienophile. Both concepts have been used by Kollar et al. for the annelation of cyclohexene rings onto the steroidal skeleton 26 (Scheme 4) [28-30]. At 60 °C the cycloaddition was sufficiently suppressed so that the Heck coupling product 29 could be isolated and subsequently subjected to Diels-Alder reactions with different dienophiles. For a domino reaction with both methyl acrylate and dimethyl fumarate (28) present in the reaction mixture, the conditions had to be precisely adjusted so that the mixed products 31 and 32 were formed predominantly along with only small amounts of the products of a twofold reaction of either 27 (R = CC Me) or 28 with 26. These conditions also proved suitable for a cascade reaction of 26 involving allyl alcohol 27 (R = CH2OH) or allyl acetate 27 (R = CH2OAc) and dimethyl fumarate (28). 

Scheme 6 A cascade reaction consisting of a Heck coupling and a transmissive Diels-Alder reaction [37,38]...

In the presence of a Rh catalyst and a chiral BINAP, 3-(2-hydroxyphenyl)cyclobutanones 46 undergo a cascade reaction in which addition to the carbonyl group is followed by opening of the cyclobutane ring with asymmetric elimination of the p-carbon. The final product is a 3,4-dihydrocoumarin obtained in high yield and excellent ee <07JA12086>. 

In an exploration of multi-component reactions for the synthesis of a diverse array of heterocyclic scaffolds Martin et al. demonstrated a cascade reaction involving the imine, formed from the condensation of 2-azidobenzaldehyde 97 with propargylamine, acetyl chloride and ketene acetal 98 to furnish the triazolo-fused benzodiazepine 99 via an intramolecular [3+2] cycloaddition <07OL4223>. 

On the basis of preceding experience in the synthesis of methylenecyclopentanes, Curran discovered a cascade reaction proceeding via a 4 + 1 radical annulation mechanism that led to a new synthesis of cyclopenta-fused quinolines [60] (Scheme 16.15). 

This may favor the subsequent complexation with more macromolecules of 23b due to the suppressed thermal fluctuation and the solvation of the cations, and initiates a cascade reaction until most of the 23b is consiuned. In the case of added polyanions, however, the IPC is overall anionic, but with the negative charges on the surface of the complex. Therefore, the solvation is favored and an association of excess 23b is unfavorable. The equilibriiun at step 1 corresponds to chain initiation, and steps 2 and 3 to chain propagation. The observed phenomenon is useful for the selective separation of charged polymer systems. 

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