Asymmetric Aziridination of Olefin

82% ee using CuHY/ligand 54% ee using Cu/OTfjg/iigand 

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Benzylidene derivatives of the enantiomers of 1,2-diaminocyclohexane are also excellent ligands for the Cu(I)-catalyzcd asymmetric aziridination of olefins with 64, but the enantioselectivities using acyclic alkenes were about the same as those using ligand (S, S )-6658. When (5, 5 )-bis-(2,4-dichlorobenzylidenediamino)cyclohexane [(S,S)-67] was employed with C.u(I) triflate, 6-cyano-2,2-dimethylchromene (68) was converted to (R,R) 69 in a 75% yield with an ee greater than 98%58. 

Asymmetric Aziridination of Olefins with Chiral Nitridomanganese Complexes... 

In order to increase the yield and/or the enantioselectivity of the reaction, the reaction temperature and additives were examined. Although aziridination was found to proceed smoothly at 0 °C, the product was not obtained at lower temperatures. Katsuki and co-workers have reported that pyridine /V-oxide is an effective additive for the asymmetric epoxidation catalyzed by salen-manganese(IH) complexes [24], and applied these findings to the asymmetric aziridination of olefins with Phi = NTs [9f]. Thus, the addition of pyridine /V-oxide at 0°C improved the enantioselectivity and allowed the reaction to proceed even at -20 °C (Table 6.1). Other additives, such as 4-phenylpyridine IV-oxide, 4-methylmorphorine N-oxide and 1-methylimidazole were used in the place of pyridine JV-oxide, but positive effects were not observed. 

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... 

Significant recent interest in the transition metal catalyzed reactions of imidoiodanes was initiated in the 1990s by the pioneering works of Evans [586, 763, 764] and Jacobsen [765,766] on the asymmetric aziridination of olefins using copper catalysts (2-10 mol%) with chiral dinitrogen ligands and PhD JTs as the nitrene precursor. Since these initial publications, research activity in this area has surged and the copper-catalyzed aziridination of alkenes has been utilized in numerous syntheses. For example, Dodd and coworkers applied the Evans aziridination procedure to 2-substituted acrylates and cinnamates 649 [767] and to steroids 650 (Scheme 3.257) [768]. 

Asymmetric reactions that can exhibit this type of behavior include atom and group transfer reactions, such as the asymmetric oxidation of sulfides, some asymmetric epoxidations of olefins, " asymmetric aziridination of olefins, - and as)rmmetric cyclo-propanation of olefins. In the asymmetric oxidation of sulfides, a non-racemic, cliiral, low-valent metal complex is oxidized, in this case by iodosobenzene, to generate a highly reactive 0x0 intermediate. The 0x0 is then transferred directly to the sulfur to form the sulfoxide in the enantioselectivity-determining step. A representative example is illustrated in Equation 14.12 that involves a chiral salen-based catalyst. ... 

In more recent years, a number of discoveries involving the use of nitre-noid or carbenoid intermediates have been made [35-37]. In 1993, Evans [139] and Jacobsen [140] independently described the asymmetric aziridination of olefins with Phi = NTs mediated by Cu(I) catalysts [141]. The chiral ligands included bisoxazoline 173 (Equation 29) [139] and diimine 176 (Equation 30) [140]. The methods displayed complementary substrate... 

Table 6.5 Asymmetric aziridination of rran -substituted styrene derivatives with complex 15 Olefin Conditions Aziridine Yield (%) ee (%)...

With this ligand, aziridination of chromene 7.40 (X = O, R = Me, R = 4-CN) takes place at -78°C with an ee superior to 98% and aziridination of 7.40 (X = CH2, R=R =H) takes place with 87% ee. From other olefins, disappointing results are observed. Evans and coworkers recommended bis-oxazolines 3.28 (R = Ph, R = H, R" = Me) as copper ligands for asymmetric aziridination of cinnamic esters [965] (Figure 7.35). These reactions take place in benzene at room temperature in the presence of molecular sieves. However, other olefinic substrates again do not give high selectivities. 

Scheme 16.40 Asymmetric aziridination of A7-aiyl hydroxamic acids with electron-deficient olefins.

Catalytic Nitrene Transfer to Heteroatoms. The experimental procedure described above for the copper-catalyzed aziridination of olefins can be applied to the imidation of sulfides, where CuOTf in conjunction with PhI=NTs mediates the formation of siilfimides in good yields (eq 95). Spontaneous [2,3] sigma-tropic rearrangements occur in the case of allylic sulfides. Chiral bis(oxazoline)-CuOTf complexes catalyze both reactions with acceptable enantioselectivities (eq 96). Chloratnine-T is also a suitable but less efficient nitrene precursor. Selenides undergo the same catalytic asymmetric imidation to afford selenimides albeit with lower yields and enantioselectivities. ... 

Instead of using chloramine-T (pKa 13.5), the employment of more nucleophilic chloramine salt, A-chloro-A-sodiobenzyloxycarbamate (pKa 15.3), allows for an efficient aziridination of electron-deficient olefins (Michael acceptors) in the presence of a solid-liquid phase-transfer catalyst (Scheme 2.38) [57]. The reaction would involve an ionic pathway where the Michael-addition of chloramine salt to alkenes and the following back-attack of the resulting enolate at the electrophilic N-center to cyclize. This reaction was successfully extended to the asymmetric aziridination of the enones that have an auxiliary, to produce chiral aziridines with good enantioselectivities up to 87% ee. Another option to aziridinate electron-deficient alkenes is the utilization of... 

Jacobsen et al. reported that a different type of dintrogen ligand (48), fe[(2,6-dichlorophenyl)-methylideneaminojcyclohexane, was an efficient chiral ligand for copper-mediated asymmetric aziridination (Scheme 35).154 The reactions of conjugated c/.v-olefins show high enantioselectivity with this catalyst, but enantioselectivity of the reactions of simple olefins such as styrene and indene is moderate. 

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. 

In this chapter, the recent development of catalytic asymmetric epoxidation and aziridination of simple olefins bearing no pre-coordinating substituent is discussed. 

The most impressive methodology utilizing CT, which has been developed by the group of Sharpless, is the vicinal aminohydroxylation of olefins catalyzed by osmium tetroxide [15]. The method has been elegantly extended to a practical asymmetric synthesis [16]. The reaction system was employed to the achiral aminohydroxylation of a,P-unsaturated amides to afford two hydroxysulfonamide regio-isomers. The crude mixtures were cyclized to the aziridines in a one-pot procedure, without the need for purification of the intermediates [17] (Scheme 10). 

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