Application to Natural Product Synthesis

This section is devoted to illustrating the manifold applications of the Ireland-Claisen rearrangement in natural products synthesis. The examples were generally chosen because they illustrate the first example of a particular variant of the Ireland-Claisen rearrangement to natural products synthesis. 

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The Boekelheide reaction has found utility in a number of synthetic applications. A notable example of its application to natural product synthesis was described by... 

The final chapter in this volume by R. Kumar and R. Chandra (University of Delhi, India) deals with stereocontrolled additions to di- and tetrahydropyridines and particularly their application to natural product synthesis. 

Novel indole synthesis and its application to natural product synthesis 98JHC1043. 

Chemoselective reduction of a,(3-epoxy carbonyl compounds to aldols and their analogs by organoseleniums and its application to natural product synthesis 98YGK736. 

Bellemin-Laponnaz S, Twedel J, Ruble JC, Breitling FM, Fu GC (2000) The kinetic resolution of allylic alcohols by a non-enzymatic acylation catalyst application to natural product synthesis. Chem Conunun 1009-1010... 

Currently, these reactions are typically conducted with Rh(l) or Ir catalysts. The Pauson-Khand-type reaction of allenynes has also witnessed important developments, especially in its applications to natural products synthesis.388 Brummond s group has been very productive in both areas. Duality in the reaction of allenynes is shown below. In the context of diversity-oriented synthesis, simply changing the reaction conditions gives versatile heterocycles in high yields (Scheme 116).389... 

In conclusion, the ene reaction has undergone a synthetic renaissance with the advent of Lewis acid and transition metal-catalyzed protocols. The carbonyl-ene, imino-ene, and Alder-ene reactions have all experienced tremendous growth due to the mild conditions in which these reactions can be performed, the high functional group compatibility and high stereoselectivity. As a confirmation of the synthetic utility of the ene reaction, there are many applications to natural product synthesis, and some of these are highlighted in Section 10.12.6. Finally, it should be mentioned that these catalyzed ene reactions are still in their infancy, so much remains to be learned. 

A relatively recent application to natural product synthesis stems from efforts to synthesize a sesquiterpene called 1-sterpurene 7 [17]. This substance is thought to be the causative agent of the so-called silver leaf disease that affects certain species of shrubs and trees. The strategy focuses on three key steps (a) electrochemical cyclization of the bis unsaturated ester 11 to produce the five-membered ring of 10, (b) a Ruhlman-modified acyloin condensation to... 

In another early application to natural product synthesis, Fleming and coworkers utilized this approach in the efficient formation of the gelsemine model (47) from 45 according to Scheme 8. The cyclization step to form the spiro-oxindole (46) proceeded in 85% yield and provided a means of generating the spiro-fused quaternary carbon without the need for carbenium ion or carbanion chemistry. 

Applications to natural product synthesis probe the limits of any synthetic method, as situations arise that would never have been considered in the course of first developing the method. Recent syntheses of valienamine 6, agelastatin 9 and tonantzitlolone 15 pressed the limits of ring-closing metathesis. 

K. Toshima and K. Tatsuta, Recent progress in O-glycosylalion methods and its application to natural products synthesis, Chem. Rev. 93 1503 (1993). 

S. M. Sieburth in Advances in Gycloaddition. The Inter- and Intra-Molecular [4+4]-Photocycloaddition of 2-Pyridones and Its Applications to Natural Product Synthesis , M. Harmata, Ed. Jai Press, Greenwich, CT, 1999, vol. 5, p. 85. 

CONTENTS The Synthesis of Seven-Membered-Rings General Strategies and the Design and Development of a New Class of Cycloaddition Reactions, Paul A. Wender and Jennifer A. Love. Recent Advances in Diels -Alder Cycloadditions of 2-Pyrones, Benjamin T. Woodard and Gary H. Posner. The Inter- and Intramolecular [4 + 4] Photocycloaddition of 2-Pyridones and Its Application to Natural Product Synthesis, Scott McN. Sieburth. 3 + 4 Annulations Between Rhodi- J s... 

T. Money, Remote Functionalization of Camphor Application to Natural Product Synthesis, in Organic Synthesis Theory and Applications (T. Hudlicky, Ed.), 1996, 3, JAI, Greenwich, CT. 

M. Toyota, M. Ihara, Development of Palladium-Catalyzed Cycloalkenylation and its Application to Natural Product Synthesis, Synlett 2002, 1211-1222. 

Sieburth S McN. The inter- and intramolecular [4+4] photocycloaddition of 2-pyridones and its application to natural product synthesis. In Advances of Cycloaddition. Harmata M, ed. Greenwich, CT JAI, 1999 85-118. 

We summarize here the applications to natural product synthesis of this method for ring construction. 

Although most of the work with Rh-mediated intramolecular C-H insertion has focussed on five-membered ring construction, the first application to natural product synthesis, by Cane, involved establishment of a six-membered ring. Thus, on exposure to Rh2(OAc>4, diazoketone 2 was cyclized to the tricyclic lactone 3 [2. This product had previously been transformed by Paquette into pentalenolactone E (4) [3]. 

Application to Natural Product Synthesis. Selected Examples. 218... 

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