Multistep cascade reactions

Multistep Cascade Reactions Synthesis of Bis-1,3,4-thiadiazolo-1,3,5-triazinium Halides... 

There are also cases where addition of thiyi radicals to unsaturated carbon-carbon bonds is the crucial step for thiophene ring formation. Flash vacuum pyrolysis (FVP) of the phosphorus ylide 90 affords initially the alkyne 91, which produces thiyi radical with loss of methyl radical. Cyclization of the resulting radical affords thienothiophene 92 as the final product with loss of one more methyl radical (Scheme 20) <1995SL53>. FVP of ylide 93 results in a multistep cascade reaction leading to 7-(2-benzothienyl)benzofuran 94 (Scheme 21) <2001SL228>. 

Sharp regular edges are not always obtained. The diazotization of 4-amino-benzoic acid (7) on (101) with nitrogen dioxide (Scheme 2.1.3) is a typical example for a very large increase in the surface features upon the sudden phase transition that follows gradual phase rebuilding (Fig. 2.1.9). Preparatively, this is a waste-free quantitative synthesis of the solid diazonium nitrate 8 in a complicated multistep cascade reaction [9, 28]. 

Moreover, Friedel-Crafts reactions have been applied as a crucial step in multicomponenti as well as multistep cascade reactions. These approaches have considerable importance from the economic and environmental point of view since they allow the building of fargef compounds with great structural complexity through a one-pot process. 

Dioxines (157) reacted with the 5oc-protected phosphonoglycine (158) via a multistep cascade reaction to give p-cyclopropyl amino acid... 

SCHEME 8.21 Multistep cascade reaction catalyzed by the combination of three different solid catalysts in a single vessel. 

The use of multiple otherwise incompatible catalysts allows multistep reactions to proceed in one reaction vessel, providing many potential benefits. In this chapter, literature examples of nanoencapsulation for the purpose of process intensification have been discussed comprehensively. Current efforts in the literature are mostly concentrated in the areas of LbL template-based nanoencapsulation and sol-gel immobilization. Other cascade reactions (without the use of nanoencapsulation) that allow the use of incompatible catalysts were also examined and showcased as potential targets for nanoencapsulation approaches. Finally, different methods for nanoencapsulation were investigated, thereby suggesting potential ways forward for cascade reactions that use incompatible catalysts, solvent systems, or simply incompatible reaction conditions. 

Nonetheless, a wide variety of potential methods are available to achieve the goal of nanoencapsulation for the purpose of facilitating the use of two or more incompatible catalysts in cascade reactions. The many multistep reactions that are of importance in the fine chemicals industry are prime targets for the application of the principles of nanoencapsulation and, therefore, of green chemistry. 

Chemoenzymatic polymerizations have the potential to further increase macro-molecular complexity by overcoming these limitations. Their combination with other polymerization techniques can give access to such structures. Depending on the mutual compatibility, multistep reactions as well as cascade reactions have been reported for the synthesis of polymer architectures and will be reviewed in the first part of this article. A unique feature of enzymes is their selectivity, such as regio-, chemo-, and in particular enantioselectivity. This offers oppormnities to synthesize novel chiral polymers and polymer architectures when combined with chemical catalysis. This will be discussed in the second part of this article. Generally, we will focus on the developments of the last 5-8 years. Unless otherwise noted, the term enzyme or lipase in this chapter refers to Candida antarctica Lipase B (CALB) or Novozym 435 (CALB immobilized on macroporous resin). 

This chapter has reported various examples to evidence how the new advances in catalyst design allow us to perform selectively in one-pot multistep reactions. These, which apply in particular for fine chemicals production, are often called cascade reactions, because they effectively involve the desorption from one site to react on another site physically distant from the first. It is thus a different concept from that shown in Figure 2.66 w-butane to maleic anhydride on (V0)2P207 catalysts, where all the reaction pathway proceeds only on the catalyst surface without desorption of reaction intermediates. However, in cascade reactions there is no separation of the products and thus they all occur in the same reactor. This is the reason for the indication one-pot reactions. 

This chapter will focus on the use of zeolites in cascade reactions, i.e. combined catalytic reactions without intermediate recovery steps [17]. Here nature serves as the shining example numerous multistep cascade syntheses are executed in the cells of living organisms without separation of intermediates. By contrast, in fine chemicals syntheses generally a step-by-step approach is applied in which intermediate products are isolated and purified for each next conversion step. 

Cascade reactions of substituted 1,2,4-triazines are of great interest as simple ways to a dramatic increase in molecular complexity, from planar 1,2,4-triazine unit into a polycyclic system. Indeed, in this multistep process, the diallylamine and cyclopentanone react first in situ to give the corresponding enamine, which undergoes an inverse electron demand cycloaddition reaction with 1,2,4-triazine to give an intermediate dihydropyridine compound. A spontaneous intramolecular Diels-Alder reaction between the allyl moiety and the dihydropyridine gives the tetracyclic compound (Scheme 99) <2004JA12260>. 

Application of solid-state chemistry for quantitative multistep cascades in a ball mill is also demonstrated by reaction of enamine ketone 291 with 1,2-dibenzoylethene 292 (Scheme 3.78). Pyrrole derivative 293 was obtained by Kaupp et al. in quantitative yield through four reaction steps (vinylogous Michael addition, imine/enamine rearrangement, cyclization, and elimination), without the use of add catalysts [18]. 

Recently, multistep enzyme-catalyzed reactions have attracted the attention of chemists and biotechnologists, as they can be combined in a modular manner and often lead to high-value compounds. All naturally occurring metabolic pathways are basically cascade reactions. Based on natural principles, synthetic chemists search for universal multistep processes applicable to a vast number of chemical compounds. Multistep enzyme-catalyzed reactions involving nonphysiological substrates and selective enzymes are of particular interest because they may lead to tailor-made complex molecules with desired properties. Moreover, one of the most important advantages of multistep enzyme-catalyzed reaction sequences... 

A particular field of interest for the application of aldolases is in multistep and cascade reactions for the preparation of carbohydrate-hke compounds and analogs... 

Microreactors are ideal for directing complex enzymatic synthesis, such as multienzyme catalysis and cascade reactions. There have been a grovdng number of studies [173-178] that represent the implementation of microreactions for multistep enzymatic catalysis and a list is presented in Table 10.5. Microfluidic biocatalytic... 

A typical synthesis of complex organic molecules involves multiple reaction steps with intermediate purification of the intermediates. Such synthetic routes require a lot of labor-intensive manipulations and generate a lot of waste (e.g., solvents). With the atom-efficient biosynthetic pathways in cells as a model, several approaches have been developed in order to facilitate synthetic chemistry, such as protecting group-free syntheses [46], one-pot syntheses [47], cascade reactions [48], and multicomponent reactions [49]. More recently, synthetic chemists have been attracted by flow chemistry since it allows to combine all these processes in a single streamlined continuous process (i.e., multistep one-flow synthesis) [50]. Several strategies have been developed. 

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