Ring systems asymmetric reactions

Nemeto, H., Yoshida, M., Fukumoto, K. and lhara, M. (1999) A novel strategy for the enantioselective synthesis of the steroidal framework using cascade ring expansion reactions of small ring systems - asymmetric total synthesis of (-l-)-equilenin. Tetrahedron Lett., 40, 907-10. 

RajanBabu has developed an asymmetric protocol for the heterodimerization of vinyl-arenes and ethenej The use of Hayashi s novel, weakly chelating phosphine 91 is critical to the success of this asymmetric reaction (Scheme 68). 1,6-Dienes (e.g., 92) also undergo direct cycloisomerization in the presence of bis[allyl(bromo)nickel] to afford meth-ylenecyclopentane products (e.g., 93 Scheme 69). The scope of the intramolecular process allows preparation of a variety of carbocyclic and heterocyclic ring systems. A reaction mechanism involving in situ generation of a nickel hydride catalyst, alkene hydro-metalation, cyclization, and p-hydride elimination has been proposed. ... 

This section describes Michael-analogous processes in which, mostly under electrophilic conditions, ally - or alkynylsilanes undergo addition to enones or dienones (Sakurai reactions). The intramolecular addition of allylsilanes is an extremely useful reaction especially for the construction of carbocyclic ring systems, which occurs in a diastereoselective manner, in many cases with complete asymmetric induction. 

The asymmetric synthesis of a galanthamine alkaloid relies also on the intramolecular Heck reaction for the preparation of the benzo[h]furan-based key intermediate with a crucial chiral quaternary center, which eventually leads to the synthesis of (-)-galanthamine <00JA11262>. A similar approach towards the construction of galanthamine ring system via an intramolecular Heck reaction has also been investigated <00SL1163>. 

Rhodium catalysts have also been used with increasing frequency for the allylic etherification of aliphatic alcohols. The chiral 7r-allylrhodium complexes generated from asymmetric ring-opening (ARO) reactions have been shown to react with both aromatic and aliphatic alcohols (Equation (46)).185-188 Mechanistic studies have shown that the reaction proceeds by an oxidative addition of Rh(i) into the oxabicyclic alkene system with retention of configuration, as directed by coordination of the oxygen atom, and subsequent SN2 addition of the oxygen nucleophile. 

There are also many examples of alkylation reactions involving the norbornyl ring system in which the enolate can be either endo- or c.vo-cyclic. Both the endo-cyclic (6, 7) and evo-cyclic (8) enolates exhibit high levels of asymmetric induction due to the rigid ring system. Scheme 2-8 presents some examples for alkylation involving the norbornyl ring system.15... 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

Miscellaneous Iminium Catalyzed Transformations The enantioselective construction of three-membered hetero- or carbocyclic ring systems is an important objective for practitioners of chemical synthesis in academic and industrial settings. To date, important advances have been made in the iminium activation realm, which enable asymmetric entry to a-formyl cyclopropanes and epoxides. In terms of cyclopropane synthesis, a new class of iminium catalyst has been introduced, providing the enantioselective stepwise [2 + 1] union of sulfonium ylides and ot,p-unsaturated aldehydes.As shown in Scheme 11.6a, the zwitterionic hydro-indoline-derived catalyst (19) enables both iminium geometry control and directed electrostatic activation of sulfonium ylides in proximity to the incipient iminium reaction partner. This combination of geometric and stereoelectronic effects has been proposed as being essential for enantio- and diastereocontrol in forming two of the three cyclopropyl bonds. 

Gilbertson and co-workers were also able to facilitate the rhodium-catalyzed [4-i-2-1-2] carbocyclization reaction with a substrate having an all-carbon tether (Eq. 13). This methodology has been extended to the asymmetric rhodium-catalyzed [4-t 2-1-2] reaction (Eq. 14). Although the exact origin of asymmetric induction was not discussed, the ability to accomplish the asymmetric rhodium-catalyzed [4-i-2-1-2] reaction provides a novel approach to eight-membered ring systems. 

The carbo- and hetero-Diels-Alder reactions are excellent for the constmction of six-membered ring systems and are probably the most commonly applied cycloaddition. The 1,3-dipolar cycloaddition complements the Diels-Alder reaction in a number of ways. 1,3-Dipolar cycloadditions are more efficient for the introduction of heteroatoms and are the preferred method for the stereocontrolled constmction of five-membered heterocycles (1 ). The asymmetric reactions of 1,3-dipoles has been reviewed extensively by us in 1998 (5), and recently, Karlsson and Hogberg reviewed the progress in the area from 1997 and until now (6). Asymmetric metal-catalyzed 1,3-dipolar cycloadditions have also been separately reviewed by us (7-9). Other recent reviews on special topics in asymmetric 1,3-dipolar cycloadditions have appeared. These include reactions of nitrones (10), reactions of cyclic nitrones (11), the progress in 1996-1997 (12), 1,3-dipolar cycloadditions with chiral allyl alcohol derivatives (13) and others (14,15). 

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