Application in Natural Product Synthesis

Aziridine-2-carboxylates are playing important roles in the synthesis of natural products and pharmaceutically useful molecules. In this section, applications of chiral nonracemic aziridine-2-carboxylates in the synthesis of natural products are discussed. 

1 (a) J. A. Deyrup in Small Ring Heterocycles Hassner, A. Ed , Wiley New York, 1983 Vol. 1, p. 1. (b) W. H. Pearson, B. W. Lian, S. C. Bergmeier, Aziridines and Azir-ines Monocyclic, in Comprehensive Heterocyclic Chemistry II Padwa, A., Ed. Perga-mon Oxford, 1996, p. 1. 

14 (a) P. Wipf, C. P. Miller, Tetrahedron Lett. 1992, 33, 6267. (b) K. Nakajima, H. Sasaki, M. Neya, M. Morishita, S. Sakai, K. Okawa, Pept. Chem. 1982, 19 Chem. Ahstr. 1983, 99, 122863y. 

Legters, L. Thijs, B. Zwanenburg, Reel. Trav. Chim. Pays-Bas 1992, 111, 1. 

Polyak, T. Dorofeeva, R. Sturkovich, Y. Goldberg, Synth. Commun. 1991, 21, 239. 

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Applications in Natural Product Syntheses and Syntheses of Compounds with Potentially Useful Properties... 

The intramolecular alkoxypalladation has been developed into a remarkable (catalytic) methodology which exhibits a great synthetic potential, especially in combination with carbonyla-tion. This is reflected by convincing applications in natural product syntheses. This chemistry opens reliable and highly diastereoselective approaches to several hydropyran and hydrofuran systems. The development of efficient enantioselective protocols for the various chirogenic transformations is still a challenging goal for the future. 

Sonawane, H. R., Bellur, N. S., Kulkarni, D. G., Ahuja, J. R. Photoinduced vinylcyclopropane-cyclopentene rearrangement (photo-VCP-CP) a methodology for chiral bicyclo[3.2.0]heptenes and their application in natural product syntheses. Syn/eff 1993, 875-884. 

A comprehensive treatment of the benzannulation of Fischer carbene complexes with alkynes is not possible in this review, and thus instead the material presented here will hopefully serve to give the reader an overview of its scope and limitations. The first report of this reaction was in 1975 by Dotz in which he describes the formation of the naphthol chromium tricarbonyl complex (236) from the reaction of the phenyl chromium complex (la) with diphenylacetylene. In the intervening years over 100 papers have been published describing various aspects of this reaction.The reaction of the generic cartene complex (233 Scheme 34) with alkynes will serve to focus the organization of the scope and limitations of the benzaimulation reaction. The issues to be considered are (i) the regioselectivity with unsymmetri-cal alkynes (ii) possible mechanisms (iii) applications in natural product syntheses (iv) the effect of substitution on the aryl or alkenyl substituent of the carbene carbon (v) functionality on the alkyne (vi) effects of the solvent and the concentration of the alkyne (vii) tandem applications with other reactions of carbene complexes (viii) reactions where aromatization is blocked (cyclohexadienone annulation) (ix) annulation of aryl versus alkenyl carbene complexes (x) the effect of the ligands L on the metal (xi) the effect of the ancilliary substituent RX and (xii) reactions with —C X functionality. 

Facile formation of five- and six-membered rings has wide application in natural product syntheses. The tricyclic synthetic intermediate of the galantamine alkaloid 216 was prepared by intramolecular HR of 215. A single double bond isomer was obtained in the presence of Ag2C03 as a weak base [98,99]. 

Meanwhile, the Ireland-Claisen rearrangement of protected a-hydroxy aUylic esters found various applications in natural product syntheses, what clearly underlines the potential of this synthetic protocol. Several examples are described by Kallmerten et al. For example, rearrangement of (Z)-configured ester 35 gave rise to the required anti rearrangement product 36, which was converted in five steps into the dilactone 37, a precursor of the antifungal metabolite avenaciolide (Scheme 5.2.11) [23]. 

Hypervalent Iodine-Induced Oxidative Couplings (New Metal-Free Coupling Advances and Their Applications in Natural Product Syntheses)... 

Scheme 25. Stereoselective exocyclic Claisen rearrangements of a C3-alkylidene furanose and applications in natural product syntheses [52-56]...

Mukaiyama s procedure became a classic with manifold applications in natural product syntheses [93] and was followed by the development of various chiral Lewis acids that led to improved versions of the asymmetric catalytic Mukaiyama aldol addition. Thus, the research groups of Yamamoto [94], Masamune [95],... 

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