Asymmetric aziridination opening

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. 

Terminal epoxides of high enantiopurity are among the most important chiral building blocks in enantioselective synthesis, because they are easily opened through nucleophilic substitution reactions. Furthermore, this procedure can be scaled to industrial levels with low catalyst loading. Chiral metal salen complexes have also been successfully applied to the asymmetric hydroxylation of C H bonds, asymmetric oxidation of sulfides, asymmetric aziridination of alkenes, and the asymmetric alkylation of keto esters to name a few. 

The asymmetric ring opening of oxiranes (and aziridines) with carbon nucleophiles has been reviewed by Pineschi <2006EJO4979>. 

Jacobsen reported in 1990 that Mnm complexes of chiral salen ligands (41) were the most efficient catalysts available for the enantioselective epoxidation of alkyl- and aryl-substituted olefins.118 This stimulated a rapid development in the chemistry and applications of chiral SB complexes, which offer promising catalytic applications to several organic reactions, such as enantioselective cyclopropanation of styrenes, asymmetric aziridination of olefins, asymmetric Diels-Alder cycloaddition, and enantioselective ring opening of epoxides.4,119... 

Given the significant existing knowledge-base in asymmetric catalytic cyclo-propanation (Chap. 16), the discovery that metal ions useful for catalysis of carbene transfer to alkenes were also effective for nitrene transfer to the same substrates opened a clear new direction for research in asymmetric aziridination. Brief mention of the asymmetric catalysis of the aziridination of styrene was made in two early reports on (bisoxazoline)copper-catalyzed asymmetric cyclopropanations [20,21], and subsequently new methods for copper-catalyzed asymmetric aziridination were revealed in two independent studies published simultaneously by Jacobsen and Evans [22,23]. 

Asymmetric ring-opening of aziridines with carbon nucleophiles 06EJO4979. 

In another context, a chiral phase-transfer A-9-anthracenylmethyl O-ada-mantoyl derivatised cinchonine catalyst was shown to promote the asymmetric ring-opening of A7-tosyl protected aziridines with cyclic p-keto esters in the presence of an aqueous base, leading to the formation of chiral aminoethyl... 

Asymmetric Ring Opening of meso-Epoxides and meso-Aziridines... 

A similar catalyst system was also effective for asymmetric ring opening of meso-aziridines with TMSN3. The reaction provided a direct method for the synthesis of optically active 1,2-diamines. In the reaction, bimetallic lanthanide... 

The chiral (salen)Co catalysts have also been applied to cyclization reaction and preparation of intermediates for natural product synthesis [85]. In addition, chiral (salen)Ru catalysts proved to be effective for kinetic resolution of racemic epoxides [86]. Tridentate Schiff base Cr(III) complex (201) derived l-amino-2-indanol acts as a potent catalyst for asymmetric ring-opening reaction of meso-aziridines with trimethylsilyl azide (Scheme 16.60) [87]. The aziridine (200) was readily converted at —30 °C to the corresponding amino-azide in 95% yield with 94% ee. 

Scheme 11.26 Chiral phosphoric acid catalyzed asymmetric ring opening of meso-aziridines.

Fukuta Y, Mita T, Fukuda N, Kanai M, Shihasaki M. De novo synthesis of Tamiflu via a catalytic asymmetric ring-opening of wew-aziridines with TMSN3. J. Am. Chem. Soc. 2006 128(19) 6312-6313. 

Olefins have a rich history in organic chemistry and consequently there is a vast array of transformations available to this fundamental functional group. This chapter discusses the classic methods for stereoselective oxidations of olefins, spanning the range from diastereoselective [16-18] and enantioselec-tive [19-29] formation of epoxides to their asymmetric ring-opening reactions [30-33], stereoselective formation of aziridines [34—37], iodolactoniza-tions and other olefin cyclizations induced by electrophiles [38, 39], dihy-droxylations [40-49], and aminohydroxylations [47, 50] (Figure 9.1). 

In comparison with the asymmetric epoxide-opening reactions described above in Section 9.4, catalytic desymmetrizations of meso-aziridines have relatively limited precedence [151]. Kanai and Shibasaki have disclosed a number of promising results obtained with lanthanide complexes of the chiral phosphinoxide ligand 193 (Scheme 9.24) [152, 153]. These efforts were showcased in the desymmetrization of meso-aziridine 192 with TMSN j to provide azide 194 in 96% yield and 91 % ee. Adduct 194 was subsequently converted into the anti-influenza drug oseltamivir phosphate (Tamiflu, 195) [153]. 

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