Multi cascade reactions

A similar picture has been obtained very recently for novel multi-step bio-chemo cascade reactions starting from both galactose-derived polyols and aliphatic mono- and diols [29]. Galactose oxidase and alcohol oxidase show complementary synthetic use for this range of alcohols (Table 13.3) [30], allowing in situ... 

As indicated in Section I.C, we focused on convergent multigeneration strategies employing multicomponent one-pot or multicomponent cascade reactions. Multi-component one-pot reactions offer the possibility to introduce several elements of diversity in one reaction and one reaction vessel.93 Performed in solution or on solid supports, these reactions allow one to synthesize the products in the same format used for screening without having to resort to reaction vessel transfers. 

These cascade reactions are very attractive in view of multi-C-C bond formation in one-pot and are a typically radical specific reaction. 

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>. 

Santra S, Andreana PR (2007) A one-pot, microwave-influenced synthesis of diverse small molecules by multi-component reaction cascades. Org Lett 9 5035-5038... 

The examples depicted so far have made use primarily of single organocatalytic transformations conducted typically quite early in the multi-step sequences applied towards the syntheses of complex natural products. In contrast, more and more reports describing organocatalytic cascade reactions or combined approaches using different organocatalytic key transformations to achieve a complex synthesis have been reported over the last several years (30, 32, 176-178). In this chapter, the application of combined enamine-catalyzed approaches for the syntheses of natural products will be described. Examples using different activation modes (e.g. enamine and iminium activation) will be discussed later. 

Ramachary DB, Jain S (2011) Sequential One-Pot Combination of Multi-component and Multi-catalysis Cascade Reactions An Emerging Technology in Organic Synthesis. Org Biomol Chem 9 1277... 

P. Kotame, B.-C. Hong, J.-H. Liao, Tetrahedron Lett. 2009, 50, 704—707. Enantioselective synthesis of the tetrahydro-6//-benzo[c]chromenes via domino Michael-aldol condensation control of five stereocenters in a quadruple-cascade organocatalytic multi-component reaction. 

Y. Chi, S. T. Scroggins, J. M. J. Erechet, J. Am. Chem. Soc. 2008, 130, 6322-6323. One-pot multi-component asymmetric cascade reactions catalyzed by soluble star polymers with highly branched non-interpenetrating catalytic cores. 

See, for instances (a) S. Santra, R R. Andreana, Org. Lett. 2007, 9, 5035-5038. A one-pot, microwave-influenced synthesis of diverse small molecules by multicomponent reaction cascades, (b) M. Presset, Y. Coquerel, J. Rodriguez, Org. Lett. 2009, 11, 5706-5709. Microwave-assisted domino and multi-component reactions with cyclic acyUcetenes expeditious syntheses of oxazinones and oxazindiones. (c) W.-J. Hao, B. Jiang, S.-J. Tu, X.-D. Cao, S.-S. Wu, S. Yan, X.-H. Zhang, Z.-G. Han, F. Shi, Org. Biomol. Chem. 2009, 7,1410-1414. A new mild base-catalyzed Mannich reaction of hetero-arylamines in water highly efficient stereoselective synthesis of 3-aminoketones under microwave heating, (d) P. Nun, J. Martinez, F. Lamaty, Synthesis 2010, 2063-2068. Microwave-assisted neat procedure for the Petasis reaction. 

D. B. Ramachary, C. Venkaiah, Y. V. Reddy, M. Kishor, Org. Biomol. Chem. 2009, 7, 2053-2062. Multi-catalysis cascade reactions based on the methoxycarbonylketene platform diversity-oriented synthesis of functionalized non-symmet-rical malonates for agrochemicals and pharmaceuticals. 

Ricca, E., Brucher, B., and Schrittwieser, J.H. (2011) Multi-enzymatic cascade reactions overview and perspectives. 

Multi-Enzyme Systems and Cascade Reactions Involving Cytochrome P450 Monooxygenases... 

The use of P450s in artificial cascade reactions is a rather unexplored research field, and corresponding reports are still very rare in the literature. However, their ability to oxyfunctionalize cheap starting molecules to form valuable compounds, combined with their broad natural functions as essential components in xenobiotics degradation and biosynthesis of secondary metabolites, makes P450 enzymes potential candidates for multi-enzyme processes. 

Artificial cascades performed with isolated enzymes in vitro (cell-free extracts or purified enzymes) provide several advantages compared to artificial cascades in recombinant cells. Multi-enzyme reactions based on isolated enzymes can easily be controlled in a desired maimer, including key factors such as enzyme combination in defined ratios and adjustment of specific reaction component ratios (i.e., cofactors). This allows a more detailed control of the biocatalytic multi-enzyme system in contrast to in vivo cascades where the above-mentioned factors are much more difficult to control. 

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