Step economy

Sheridan and co-workers reported a novel photo-assisted [5 + 2 + 2]-reaction based on the reactions of 77S-cyclodienyl Mn complexes160,161 or Cr complexes162 and two alkynes. Decomplexation of the metal gives cycloadducts in moderate to good overall yields (Scheme 66, Equation (42), and Scheme 67). It should be noted that the authors refer to this reaction as a [5 + 2]-, [3 + 2]- or a [5 + 2]-, homo-[5 + 2]-reaction. This reaction leads to the formation of impressively complex tricyclic products that would be otherwise difficult to prepare with step economy. 

Synthesis as a sequence of unequivocal steps. Economy conversion, selectivity and yield. Starting materials... 

Scheme 13.1 New reactions and step economy a three-step total synthesis of silphinene.

Scheme 13.2 The Diels-Alder reaction convergency and complexity increase to favor step economy.

Our initial studies focused on the transition metal-catalyzed [4+4] cycloaddition reactions of bis-dienes. These reactions are thermally forbidden, but occur photochemically in some specific, constrained systems. While the transition metal-catalyzed intermole-cular [4+4] cycloaddition of simple dienes is industrially important [7], this process generally does not work well with more complex substituted dienes and had not been explored intramolecularly. In the first studies on the intramolecular metal-catalyzed [4+4] cycloaddition, the reaction was found to proceed with high regio-, stereo-, and facial selectivity. The synthesis of (+)-asteriscanoHde (12) (Scheme 13.4a) [8] is illustrative of the utihty and step economy of this reaction. Recognition of the broader utiHty of adding dienes across rc-systems (not just across other dienes) led to further studies on the use of transition metal catalysts to facilitate otherwise difficult Diels-Alder reactions [9]. For example, the attempted thermal cycloaddition of diene-yne 15 leads only... 

It is dear from the variety of natural products described in this chapter that multi-component reaction strategies encompass a very broad scope of synthetic transformations. The development of new MCRs constantly generates new opportunities, and it is likely that the application of these powerful processes in natural product synthesis is still in its infancy. Appealing characteristics of MCR strategies such as convergence and step-economy are expected to draw more and more synthetic chemists to design and implement MCRs in the total synthesis of complex natural products. 

The range of synthetic problems in this volume is also impressive including alkaloids, heterocycles, macrolides, terpenoids, polyketides, designed targets, sensors and many other systems that defy easy description. Infused in these analyses is the preeminent importance of step economy as it is becoming increasingly clear that the length of a synthesis influences if not determines most other economies and measures. This is clearly addressed by several contributors and perhaps... 

New synthetic methods should be designed in concert with new concepts of modem chemistry. These key concepts involve atom and step economies and the use of highly efficient catalytic reactions. The hydroformylation reaction follows these guidelines. It requires a low catalyst loading, allows the creation of three new chemical bonds, and introduces a highly reactive aldehyde. We have already demonstrated that its combination with other chemical reactions in well-developed domino sequences shows its potential in the synthesis of complex molecules. The few previously synthesized natural molecules demonstrated that the robustness of the catalyst system and other domino reactions are possible to create even more complexity and diversity. 

The total and partial synthesis of artemisinin, a potent antimalarial agent, investigated in the last three decades (14SC1987), and the evolution of synthetic strategies, mainly modern approaches focused on step economy and overall cost, and new reaction developments (14SL751) were reviewed. 

The RBR sequence is most often initiated by substitution of an organohalide 33 with a thiol 32, affording a tMoether 34 that contains the full carbon skeleton (see Scheme 8.161. Typically, this intermediate is isolated, as with the Julia reaction but unlike the Wittig-type protocols. The next step is oxidation to a sulfone 35, followed by the key RBR. This makes the overall process a three-step sequence, which has disadvantages with regard to step economy. Nonetheless, the multistep sequence has greater synthetic flexibility, which is beneficial in... 

Step economy and the overall yield compared with the previous procedures [51], using a biocatalytic desymmetri-zation and two MCRs (Passerini SCR and Ugi-3CR) as the crucial synthetic steps. 

INTRODUCTION AND BACKGROUND 1.1 Step Economy in Organic Synthesis... 

FIG. 1 Strategies to improve step economy in organic synthesis. 

Transition metal-catalyzed cyclopropane-based cycloadditions provide efficient strategies for the construction of (poly)cyclic structures. More importantly, the cycloadditions feature atom- and step-economy, good regio- and stereoselectivity, and excellent functional group tolerance. More and more total syntheses of natural products benefit fi om the rich cycloaddition chemistry of VCPs and MCPs. To date, numerous total syntheses of natural products have been accomplished utilizing these methodologies as key steps. Listed in Fig. 4 are some selected examples. 

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