New Cascade Reaction

The addition of phenylenediammonium to a mixture of 19 and 21 thus caused two distinct rearrangements to occur initial (covalent) imine exchange followed immediately by (coordinative) ligand exchange, resulting in the exclusive formation of mixed-ligand complex 22. 

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A new cascade reaction of aromatic aldehydes with terminal conjugated alkynes produces a range of polycyclic aromatic hydrocarbons.195 The effect of temperature on regioselectivity is discussed. 

To further expand the scope of this new silver(I)-mediated reaction sequence, interrupted Nazarov cyclizations were explored using the halocyclopropane chemistry, an investigation that was prompted by the discovery of an intriguing result. It was found that treatment of the phenethyl-substituted compound 76 with 1.5 equiv of silver tetrafluoroborate in dichloromethane provided benzohydrindenone 77 as the sole product, with no apparent formation of the simple a-chlorocyclopentenone (Scheme 4.24). This prompted an examination of appropriately substituted gem-dichlorocyclopropane substrates in analogous interrupted Nazarov processes to ascertain the scope of this new cascade reaction sequence. 

Generation of non-stabilized alkyl radicals. Malacria has developed several new cascade reactions taking advantage of selective hydrogen atom abstractions by alkenyl radicals [145]. Recently, he achieved the preparation of a linear triquinane from an acyclic precursor. The last steps of the reaction sequence are a hydrogen abstraction by a vinyl radical at the /i-position of the sulfone followed by the elimination of a sulfonyl radical, affording the final product in 50% yield (Scheme 44)... 

Af-Benzyl and phenyl hydroxylamines 45 and 46, the mononucleophiles triggered a new cascade reaction sequence (Scheme 27.4) with both 27 leading to... 

More recently, Qin has developed a new cascade reaction to afford 3-substituted hexahydropyrroloindole III-38 [67]. The key steps are the formation of a cyclopropane intermediate III-36 and the consecutive nucleophilic attack of a pendant amine on the C=N bond of the resulting indolenium ni-37 (Scheme 4.18). This methodology has been applied for the total synthesis of (-)-ardeemin. [69]... 

Siva Kumar, K., Mahesh Kumar, R, Sreenivasa Rao, V., Jafar, A. A., Meda, C. L. T, Kapavarapu, R., Parsa, K. V. L., Pal, M. (2012). A new cascade reaction concurrent construction of six and five membered rings leading to novel fused quinazolinones. Organic Biomolecular Chemistry, 10, 3098-3103. 

In an effort to develop new cascade reactions, Zhang et al. envisioned that a linear aldehyde can also be genaated in situ via an extra iminium catalysis from an ot,p-unsaturated aldehyde prior to the triple cascade reaction. Therefore, there would be a possibility of extending the triple cascade reactions to four-component cascade reactions. Based on this design, a four-component quadruple cascade reaction through iminium-enamine-iminium-enamine sequential activation initiated by oxa-Michael addition of alcohol to acrolein in moderate yield (about 50%), excellent diastereoselectivities (>20 1), and excellent enantioselectivities (>99% ee) was accomplished (Scheme 1.33) [47]. 

Beyond the organic chemists initial imagination, two unique interconvertible enamine and iminium activation modes have produced a number of unprecedented powerful cascade processes in the formation of diverse complex stractures with high efficiency and excellent stereoselectivities. This not only expands the scope of amino catalysis significantly, but more important, affords new and efficient synthetic methods in organic synthesis. It is expected that new cascade reactions with activation modes will continue to be developed to meet the synthetic danand. 

Both new cascade reactions were carried out in basic medium (tertiary amines). However, the key difference of this two cascade processes is as follows. The initial reaction step in the C-glycoside formation process is a Knoevenagel condensation, whereas the chain elongation cascade starts with a Knoevenagel-addition reaction of the acyclic form of the carbohydrates. This difference is dictated by the application of either 2-hydroxypyridine (Knoevenagel-addition reaction) or proline (Knoevenagel condensation). The intermediately formed Knoevenagel addition or condensation products determinate the subsequent reaction steps. Based on that, a different outcome of these cascade reactions is observed (Scheme 2.17). 

A new cascade reaction of isocyanides, chromone 3-carboxylic acid (311), and nucleophiles (ROH, RNH2, and NaN3), catalysed by Sc(OTf)3 under microwave irradiation, has been developed as a multicomponent method for the preparation of chromone-2-carboxamides and chromone-2-carboxamido-3-esters (313). The sequence apparently commences by the Michael addition of RN=C to generate intermediate (312). ° ... 

The vesicles made from lipid bilayers are analogous to polymersomes, which are vesicles formed from high molecular weight amphiphilic block copolymers [94—96], Unlike the micelles discussed earlier from the similar copolymer components, the presence of bilayer walls formed from the aggregation of hydrophobic domains provides new properties. They can be designed to respond, for example, by opening or by disassembly, to external stimuli such as pH, heat, light, and redox processes [97]. This makes them usable as scaffolds for cascade reactions, even those with combinations of enzymes [98, 99]. 

Diels-Alder reaction of the 1,3,4-oxadiazole with the pendant olefin and loss of N2, the C2-C3 7t bond participates in a subsequent 1,3-dipolar cycloaddition with the carbonyl ylide to generate complex polycycles such as 45 as single diastereomers with up to six new stereocenters. That the cascade reaction is initiated by a Diels-Alder reaction with the alkene rather than with the indole is supported by the lack of reaction even under forcing conditions with substrate 46, in which a Diels-Alder reaction with the indole C2-C3 n bond would be required [26a]. 

A new triethylamine-catalyzed cascade reaction of aromatic aldehydes and propiolates was developed to prepare various benzo[ >]furan-based polycyclic aromatics. Interestingly, the chemical outcome of this process depended on the reaction temperature and was selectively tailored by an appropriate choice of experimental conditions <06OL1241>. 

New cascade oxidation-dehydrogenation-double-Heck reaction. 

The radical carboazidation of alkenes has been achieved in water using triethylborane as initiator [118]. This efficient process is complete in one hour at room temperature in an open to air reaction vessel (Scheme 54, Eq. 54a). These new tin-free carboazidation conditions are environmentally friendly and allow to run reactions with an excess of either the alkene or the radical precursor. They are also suitable for simple radical azidation of alkyl iodides as well as for more complex cascade reactions involving annulation processes (Eq. 54b). In both reactions (Eq. 54a and 54b), an excess of triethylborane (3 equivalents) is required to obtain a good yield. This may be an indication that the chain process, more precisely the reaction between the phenylsul-fonyl radical and Et3B, is not efficient. 

Carbonylation of unsaturated substrates has been known for decades but the reaction selectivity has been progressively improved by tuning the coordination sphere of late transition metal-based catalysts. Palladium assumes a privileged place in this chemistry and its versatility allows the use of mild conditions for the selective incorporation of CO into acyclic and cyclic compounds. Further improvements open a path to more sophisticated reactions, particularly cascade reactions. Similarly, asymmetric versions of most of these carbonylations can be envisioned. Atom economy and the green character of the process will probably be the key criteria for evaluating any new catalytic system. 

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 ... 

Further progress will most likely include other types of reactions and new types of polymers as well as new solvent-stable nanofiltration membranes. Another promising field is the combination of chemo- and biocatalysis in cascade reactions... 

In contrast with 17, complex 21 (Scheme 1.18) did not undergo ligand substitution with the copper(I) bis(biquinoline) complex, possibly as a result of the different steric properties of the two complexes. The imine exchange reaction with phenylenediammonium worked well, creating the possibility of a new kind of domino or cascade reaction (Scheme 1.18). The intermediate product 18 (from... 

Six fused isoxazolidines of general structure 110 were synthesised through a new palladium-catalysed allene insertion-intramolecular 1,3-DC cascade reaction. The m-ring junction stereochemistry of 110 was established by X-ray analysis <02CC1754>. 

This new multicomponent cascade reaction can also be performed with a large variety of aryl halides, most favorably iodides (Scheme 7). The yields in this coupling-cycloaddition sequence are particularly high with the parent... 

However, the latter type of metal-catalyzed cascade reactions turns out to be even more challenging since issues of selectivity and efficiency are crucially dependent on the particular catalyst structure. This type can either be performed in a parallel or sequential fashion [16,21], Whereas parallel catalysis is significantly more difficult to develop, sequential catalysis offers the possibility of altering reaction conditions and additives from step to step in the sense of bi- or multicatalytic one-pot processes, assisted tandem catalysis, or auto tandem catalysis [1]. Therefore, a demanding goal is the development of one-catalyst multireaction sequences that set the stage for new reactions in diversity-oriented syntheses of complex molecular structures (for reviews on diversity-oriented syntheses see [27-33]). 

Abstract The Pauson-Khand [2 + 2 + 1 ] cycloaddition is one of the best ways to construct a cyclopentenone. It implies the formation of three new bonds and one or two cycles in the intermolecular or intramolecular versions, respectively. Furthermore some groups have enhanced the synthetic power of this transformation by combining the PKR with other processes. In addition, some unexpected results imply that successive events have occurred, usually after the cycloaddition process. This review aims to point out the most recent advances in cascade reactions in which the Pauson-Khand and PK-type... 

Nature accomplishes many syntheses-even those of complex molecules-by sequences of elementary steps. In the last few decades, the blueprint of catalyzed cascade reactions has found fertile soil through the advent of transition metal catalysis in laboratories. Scrutinizing catalytic cycles and mechanistic insight has paved the way for designing new sequential transformations catalyzed by transition metal complexes in a consecutive or domino fashion. In particular, transition metal-catalyzed sequences considerably enhance structural complexity by multiple iterations of organometalhc elementary steps. All this has fundamentally revolutionized synthetic strategies and conceptual thinking. 

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