Asymmetric epoxidation chiral amines

Some representative data showing the use of chiral Ru-porphyrins for asymmetric epoxidation using amine oxides or PtilO as 0-donors are given in Table 1. The Ru(porp-D4)CO/Cl2pyNO system effects epoxidation with 5-88% yields and 28-77% ee values. Either Ru(porp-D4)CO or Ru(porp-D4)-... 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

In 1998, Page and coworkers reported a series of dihydroisoquinoline-related iminium salts which can be readily synthesized in three steps from a chiral amine (Scheme 14) [140-143], Among the catalysts tested for asymmetric epoxidation, iminium salts 74 were found to be efficient catalysts (Fig. 24, Table 7, entries 2, 4-6, 17-19). Iminium salts 74a can epoxidize 4-phenyl-1,2-dihydronaphthalene in up to 63% ee (Table 7, entry 17). 

In conjunction with the chiral anion TRIP (156) (10 mol%), diamine 157 (10 mol%) can be used in the catalytic asymmetric epoxidation of a,p-unsaturated ketones (>90% ee) [196], while the secondary amine 158 (10 mol%) can be used for the epoxidation of both di- and trisubstituted a,P-unsaturated aldehydes (92-98% ee) (Fig. 15) [211], The facile nature of these reactions, using commercially available peroxides as the stoichiometric oxidant, together with the synthetic utility of the epoxide products suggests application in target oriented synthesis. 

Aggarwal et al. have proposed a catalytic cycle for asymmetric epoxidation of olefins by chiral amines (Scheme 7.13), which involves the initial formation of ammonium... 

Kawahata and Goodman utilized a chiral aziridine 166 as a simple precursor for the synthesis of / -aminoacids <1999TL2271>. The chiral aziridine is prepared in five steps from the corresponding allylic alcohol via a Sharpless asymmetric epoxidation. A one-electron reduction of aziridine 166 with SmG provided the ring-opened aziridine. Protection of the resulting amine as the BOC-derivative provided a 1.6 1 mixture of the BOC-amino ester diaster-eomers 167a and 167b in 66% yield (Equation 50). 

Some epoxides carry functional groups. The compound (lR,2S)-(-)-(l,2)-cpox-ypropyl phosphonic acid (fosfomycin) is a clinically important drug with wide-spectrum antibiotic activity. It was isolated originally from a fermentation broth of Streptomyces fradiae and prepared mainly by epoxidation of cfs-l-propenylpho-sphonic acid (CPPA) [42] followed by optical resolution of the racemic epoxide with chiral amines. Recently, chiral W (salen) and Mo (salen) complexes have been used in the asymmetric epoxidation of CPPA [43]. 

Recently, two other groups have shown that exocyclic iminium salts can be useful mediators in asymmetric epoxidation. Komatsu has developed a system based on ketiminium salts [14], prepared through the condensation of aliphatic cyclic amines with ketones. A chiral variant was also produced, derived from prolinol and cyclohexanone, which gave 70% yield and 39% ee for cinnamyl alcohol (Scheme 5.7). 

With a modification of this procedure, using an oxaziridine, Armstrong was able to demonstrate the synthetic utility of this method by introducing a chiral amine to afford enantiomerically enriched products, and greater than 98% ee was obtained for (7), which is a terminal epoxide, typically very testing substrates for asymmetric epoxidation (Scheme 5.10) [17], A loss of selectivity was, however, observed when the chain length between the aldehyde and the alkene exceeded three atoms. 

A range of structurally different chiral primary amines was converted into the corresponding iminium tetraphenylborate salts (Fig. 5.3) and tested in the asymmetric epoxidation of a standard test substrate, 1-phenylcyclohexene, using Oxone (4 equiv) as the stoichiometric oxidant, sodium carbonate (8 equiv) as base, in acetonitrile/water (2 1) at 0 °C (Table 5.1) [19,21]. 

M-K. Wong, L-M. Ho, Y-S. Zheng, C-Y. Ho, D. Yang, Asymmetric epoxidation of olefins catalyzed by chiral iminium salts generated in situ from amines and aldehydes, Org. Lett. 3 (2001) 2587. 

T. Hashihayata, Y. Ito, T. Katsuki, The first asymmetric epoxidation using a combination of achiral (salen)manganese(III) complex and chiral amine. Tetrahedron 53 (1997) 9541. 

Observation of the stereoselective manner of chiral substrates binding to these asymmetric metal-salen complexes was not confined to [VO(l,3)] or chiral epoxides. Recently we showed how asymmetric copper salen complexes, [Cu(l)] and [Cu(4)] (Fig. 1), could also discriminate between chiral amines (R-IS-methylbenzylamine, MBA) as evidenced by multi-frequency CW and pulsed EPR, ENDOR, HYSCORE and DPT [45]. The discrimination of the MBA enantiomers was directly observed by W-band EPR. By simulating the W-band EPR spectra of the individual diastereomeric adduct pairs (i.e. R,R -[Cu(4)]+R-MBA and R,/ -[Cu(4)]-l-5-MBA), accurate spin-Hamiltonian parameters could be extracted for each adduct. The EPR spectmm of the racemic combinations (i.e. ra -[Cu(4)]+rac-MBA) was then simulated using a linear combination of the g/A parameters for the homochiral (R,R -[Cu(4)]+R-MBA) and heterochiral (R,R -[Cu... 

In 2005, J0rgensen and co-workers [170] developed the first asymmetric organo-catalytic epoxidation of a-p-unsamrated aldehydes using a chiral amine and H2O2 as the oxidant (Scheme 12.30). Prolinol derivative 32a turned out to be an excellent catalyst for the reaction. Although CH2CI2 was the solvent of choice to study the... 

In 2008, List s group developed an epoxidation using asymmetric counteranion-directed catalysis (ACDC) [177]. In this work, the epoxidation of 1,2-disubstituted enals (33) and (3,(3-disubstituted, a, 3-unsaturated aldehydes (115) was explored. Instead of using a chiral amine (e.g. Jprgensen-Hayashi s catalyst), an achiral amine and a chiral counteranion (a phosphoric acid derived from BINOL), were employed. 

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