Cascade reactions derivatives

The same system was used by Frechet s group of to achieve a multicomponent one-pot cascade reaction with mutually interfering acid and proline-derived pyrrolidine catalysts [31]. The concept is illustrated in Figure 5.1. The protonation of imidazo-lidone (3) by the immobilized PSTA (5) gives the desired iminium catalyst (6), while... 

Cascade Blue cadaverine and Cascade Blue ethylenediamine both contain a carboxamide-linked diamine spacer off the 8-methoxy group of the pyrene trisulfonic acid backbone. The cadaverine version contains a 5-carbon spacer, while the ethylenediamine compound has only a 2-carbon arm. Both can be coupled to carboxylic acid-containing molecules using a carbodiimide reaction (Chapter 3, Section 1). Since Cascade Blue derivatives are water-soluble, the carbodiimide EDC can be used to couple these fluorophores to proteins and other carboxylate-containing molecules in aqueous solutions at a pH range of 4.5-7.5. The reaction forms amide bond linkages (Figure 9.39). 

Figure 9.39 The side-chain primary amine group of this Cascade Blue derivative can be coupled to carboxylate-containing molecules using a carbodiimide reaction.

As mentioned in Section 11.20.5.1 discussing the reactivity of these ring systems, the ring closure reactions to 53-55 have been coupled in several cases with subsequent condensation reactions with arylaldehydes to yield benzylidene derivatives of these ring systems (e.g., 13) which transformations can be considered as cascade reactions. 

Grigg and co-workers described a novel three-component indium-palladium-mediated allylation reaction [67]. As exemplified by Eq. 14.16, 3,3-disubstituted oxi-ndole derivative 133 was obtained smoothly from phenyl iodide, the easily available isatin imine 132 and 1,2-propadiene (131). Excellent levels of diastereoselectivity were obtained in this cascade reaction employing imines derived from enantiopure sulfmamides. 

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... 

The third group of target molecules comprises chiral carboxylic acid and their derivatives esters, amides and nitriles. Enantiomerically pure esters are prepared in an analogous manner to the enantiomerically pure alcohols discussed earlier [i.e. by esterase- or lipase-catalyzed hydrolysis or (trans)esterification]. However, these reactions are not very interesting in the present context of cascade reactions. Amides can be produced by enantioselective ammoniolysis of esters or even the... 

The various, complex, cascade reactions described above converted simple saturated and aromatic heterocycles into polycyclic pentathiepins and their chlorinated and rearranged derivatives this strikingly illustrates the extensive reactivity of S2CI2 and its complexes with bases, particularly DABCO. This reactivity encompassed dehydrogenation of tetrahydroaromatics, chlorination and sulfuration of aromatics and their conversion into SSCl derivatives. 

Bowman et al. reported the total synthesis of ellipticine (228) involving an imidoyl radical cascade reaction (730). For this key step, the required imidoyl radical was generated from the imidoyl selanide 1290, which was obtained from ethyl 2-(4-pyridyl)acetate (1286). Reaction of 1286 with LDA, followed by addition of methyl iodide, led to the corresponding methyl derivative 1287. Treatment of 1287 with 2-iodoaniline (743) in the presence of trimethylaluminum (AlMes) afforded the amide 1288. Using Sonogashira conditions, propyne is coupled with the amide 1288 to afford the aryl acetylene 1289. The aryl acetylene 1289 was transformed to the... 

Chiral l,3-dioxin-4-ones photochemically react intermolecular with (cyclic) ethers, acetals, and secondary alcohols to give the addition products in reasonable yields. The radical addition was completely stereoselective at C-6 of the heterocycle <1999EJO1057>. The exocyclic diastereoselectivity, where relevant, was about 2 1 (Equation 30). In analogy, an intramolecular cascade reaction of a 1,3-dioxin -one derived from menthone was used to get a terpenoid or a steroid framework in optically active form <1997JA1129, 1999JA4894>. 

The successful utilization of nitrogen-based nucleophiles in the previously described cascade reactions has allowed for the synthesis of complex polycyclic structures from simple and readily available starting materials. The fact that carbamates can participate as nucleophiles has provided the opportunity for development of diastereoselective ring closures onto the halocyclopropane-derived allyl cation. 

Rewcastle and co-workers have also reported a concise synthesis of an indole-fused analogue 320, together with some of the dimeric derivative 321 [01T7185], while Rees et al. have described a novel oxime 322 to pentathiepine 324 cascade reaction induced by S2CI2 the 1,2,3-dithiazole 323 is also formed [01CC403],... 

In the dipole cascade reaction, a proton must be removed from the a-carbon atom in order to generate the azomethine ylide. When the a-position of the pyrrolidine ring was blocked by a benzyl group, formation of the azomethine ylide dipole could not occur. In fact, treatment of diazoketone 186 with rhodium(II) acetate in the presence of dimethyl acetylenedicarboxylate afforded only the carbonyl ylide-derived cycloadduct 187 in 95% yield [117]. 

A three-component palladium-catalyzed cascade process has been employed by Grigg and co-workers for the one step preparation of 3-substituted isoindohn-l-ones 103 [91]. This cascade reaction involves Pd-catalyzed car-bonylation of aryl iodide 102 and subsequent trapping of the acyl palladium species by an amino derivative. The resulting amide undergoes an intramolecular Michael addition leading to the bicyclic systems 103 isolated in moderate to good yields (Scheme 39). 

A spectacular application allowed the synthesis of fenestranes by a three-step sequential action of cobalt nanoparticles and a palladium catalyst [131]. The cascade reaction started with a PKR of enyne 105, accomplished by the cobalt catalyst giving 106, followed by the formation of allyl-7r3 palladium complex 107 which reacted with a nucleophile derived from diethyl malonate, to give enyne 108. The final step was a second PKR that gave 109 in good yield. They used cobalt nanoparticles as with Co/charcoal the third step did not take place, apparently due to damage in this catalyst after the allylation step (Scheme 31). 

This rather large field of applications of cascade reactions has recently undergone tremendous developments and we will focus on this aspect. We will divide this part into two sections. The first section will deal with precursors already incorporating a carbenoid species (mostly diazo derivatives) the second section will cover cascades in which an incipient carbenoid species originating from one or two catalytic steps intervenes. 

The simultaneous construction of the B and C rings leading to compound 33 was accomplished by a radical cascade reaction. The mechanistic details of this cascade are summarized in Scheme 6, where the reaction of 34 with phenyl isonitrile (8) is shown [12]. First, a trimethylstan-nyl radical, derived from hexamethyldistannane, attacks the C-Br bond of 34. The resulting pyri-done radical 35 reacts intermolecularly with the isonitrile 8 to yield the radical intermediate 36. 

Intermediate samarium enolates derived from ketones 1522 or 1525 could stereoselectively be trapped with allyl halides, leading to tricycles 1524 and 1526. The intramolecular alkylation by the chloroalkyl terminus of compound 1527 led to tetracyclic compound 1528 with satisfactory efficiency. These cascade reactions selectively generate three continuous stereogenic centers, including a quaternary carbon atom at the 3-position of the dihydroindole moiety, a structural motif of many indole alkaloids. 

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