Cascade approach

A one-pot cascade approach to 4-alkylidene-(3-lactams from aryl azides and aryloxyacetyl chlorides has been reported. (4-Methyloxyphenyl)azides reacted with triphenylphosphine in 1,2-dichloroethane to form triphenylphosphazene, which was treated with phenoxyacetyl chloride and Et3N to afford 4-phenoxy-methylene-(3-lactam (Scheme 45), [122]. 

As an alternative method, Qi et al. [14] proposed to use a reactive condenser (see Fig. 4.1) to predict possible top products of a countercurrent reactive distillation column. The feasibility analyses of the reactive condenser and the reactive reboiler are analogous to the flash-cascade approach. The latter authors used transformed... 

For this system, Venimadhavan et al. [7] have studied the bifurcation of the singular points in a reactive reboiler, while Chadda et al. [13] demonstrated the flash-cascade approach. In the present investigation, the same thermodynamic properties and kinetic expression were used (see Tab. 4 in Ref. [7]). 

A cascade approach to isoindole-1-phosphonates 9 starting from from o-alkynyl benzylamides was reported <07OL465>. The cascade sequence presumably involved a 5-exo-dig cyclization, a [1,3]-alkyl shift (or aza-Claisen), and aromatization. 

Figure 38.3 shows the phases within a cascade approach and incremental approach. Each box presents a different phase of the life cycle. The descending arrows mark the passage between one... 

The V-Model commonly used in the pharmaceutical and healthcare industry for computer systems validation is presented in Figure 38.4. The model illustrates the cascade approach and the relationship between specifications and testing. This V-Model can now be developed to fit the incremental approach (see Figure 38.5). 

Several more examples of the application of the dipole-cascade approach to five-membered nitrogen-containing rings from the work of Padwa and co-workers are shown in Scheme 22 (89JA6451 92JA593, 92T7565). 

Zoretic, P. A., Fang, H., and Ribeiro, A.A., Application of a radical methodology toward the synthesis of d,/-5a-pregnanes and related steroids. A stereoselective radical cascade approach, J. Org. Chem., 63, 7213, 1998. 

Scheme 11.17 Cascade approach to a chiral block copolymer combining enantioselective ROP of 4-methyl-e-caprolactone and ATRP of methyl methacrylate.

A stereoselective radical cascade approach to benzo[a]quinolizidines using Et3B was highly effective [18]. When 14 was treated with "Bu3SnH in the presence of... 

Scheme 11. Stereoselective radical cascade approach to benzo[a]quinolizidines...

The second example in Table 5 shows the cyclization-carbonylation-allylation sequence, in which 5-hexenyl radical cyclization precedes CO trapping. Because of the nucleophilic nature of acyl radicals, in a mixed alkene system comprised of an electron deficient alkene and allyltin, they favor the electron deficient alkene first and the resulting product radical, which have an electrophilic character, and then smoothly add to allyltributyltin. This four-component coupling reaction provides a powerful radical cascade approach leading to y -functionalized, -unsaturated ketones, which are not readily accessible by other methods [52]. 

Scheme 1. Chemoenzymaticpolymerization combining ATRP and eROP in two consecutive steps (1) and in a one-pot cascade approach (2).

In a more speculative and intuitive way, 3 and 4 should react in the presence of a base to give intermediates of type 15 (9 compounds), which similarly to entry c should react with 2 to give intermediates 16 (27 compounds) followed by cyclodehydration to yield 17 (27 compounds). Whereas a five component one-pot condensation would maximally yield 243 compounds with one single core structure, the decribed multicomponent cascade approach using reactive building blocks... 

Figure 12.3 shows the phases within a "cascade" approach and an "incremental" approach. Each box shows a different phase of the life cycle. The descending arrows show passage between one phase and the next (enabled only after the approval of "deliverables" related to the prior phase) the ascending arrows show system acceptance step by step (after the execution of the tests related to the specific phase). Note that the same life-cycle phases are still valid inside those different development methodologies. 

In another important application of this methodology, ( )-illudin M (79), a toxic sesquiterpene [91,92] isolated from the jack-o -lantern mushroom, has been synthesized [93] by Kinder and co-workers via the spirocyclic carbonyl ylide 48. Rh2 (OAc)4-mediated decomposition of or-diazo ketone 47 in the presence of cyclopentenone 77 afforded the key cycloadduct 78 as a single diastereomer, bearing the complete skeleton of the natural product. Functional group manipulations of the adduct 78 led to a total synthesis of ( )-illudin M (79) (Scheme 23). Padwa and co-workers also executed the syntheses of illudin, ptaquilosin and the closely related isodehydroilludin [78,94] using carbonyl yUdes. This carbonyl ylide cyclization-cycloaddition cascade approach (Scheme 23) has been further extended towards a short synthesis of the acylfulvenes [95], pterosin [79] and pterosin family of sesquiterpenes [96-99]. 

Grigg, R. and Cook, A. (2006) Catch and release cascades a resin-mediated three-component cascade approach to small molecules. Tetrahedron, 62, 12172-81. 

Scheme 1.33 Dixon s cascade approach to tetracyclic product 137. HA - chiral Br0nsted acid...

When summing up the recent achievements in iminium-activated natural product synthesis, the importance and versatility of this methodology cannot be overemphasized. Besides enamine catalysis, it is due particularly to the considerable achievements made in iminium catalysis that asymmetric organocatalysis has received so much attention over the last few years. As depicted in this chapter, the LUMO-lowering concept originally introduced by MacMillan has found widespread applications in natural product synthesis. In addition, it has been shown, that this activation mode works very well in cascade approaches. This methodology should become more widely utilized in the future (Table 2). 

Professor Larry E. Overman first reported the titled reaction as a young member of the University of California, Irvine faculty. Since his initial report in 1979, the Overman group has used this cascade approach to a variety of natural products, including (+)-strychnine, (-)-pancracine, and ( )-gelsemine. ... 

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