Asymmetric epoxidation secondary amines

The reaction between epoxides and ammonia is a general and useful method for the preparation of P-hydroxyamines. " Ammonia gives largely the primary amine, but also some secondary and tertiary amines. The useful solvents, the ethanolamines, are prepared by this reaction. For another way of accomplishing this conversion, see 10-54. The reaction can be catalyzed with Yb(OTf)3 and in the presence of a-BINOL is l,l -bi-2-naphthol derivative gives amino alcohols with high asymmetric induction. A variation used Yb(OTf)3 at lOkbar or at ambient pressure. Lithium triflate can also be used. Primary and secondary amines give, respectively, secondary and tertiary amines, for example. 

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. 

The [3-hydroxy amines are a class of compounds falling within the generic definition of Eq. 6A.6. When the alcohol is secondary, the possibility for kinetic resolution exists if the Ti-tartrate complex is capable of catalyzing the enantioselective oxidation of the amine to an amine oxide (or other oxidation product). The use of the standard asymmetric epoxidation complex (i.e., T2(tartrate)2) to achieve such an enantioselective oxidation was unsuccessful. However, modification of the complex so that the stoichiometry lies between Ti2 (tartrate) j and Ti2(tartrate)1 5 leads to very successful kinetic resolutions of [3-hydroxyamines. A representative example is shown in Eq. 6A.11 [141b,c]. The oxidation and kinetic resolution of more than 20 secondary [3-hydroxyamines [141,145a] provides an indication of the scope of the reaction and of some... 

Many authors elucidated functionalization of polymers containing reactive oxirane moieties. Epoxidized NR, BR, IR and/or the respective model hydrocarbons, poly (butadiene-co-isoprene, various epoxy resins, poly (2,3-epoxypro-pyl methacrylate) and its copolymers or grafted systems were mostly exploited. Stabilizers based on epoxidized unsaturated rubbers are of the top interest. The mechanism of the functionalization process was studied in details by means of 3,4-epoxy-4-methylheptane and 1,2-epoxy-3-ethyl-2-methylpentane as model compounds [289]. The ring opening of the asymmetric oxirane is regiospecific. Aliphatic primary amines attack the least substituted carbon atom and can be involved in crosslink formation. Aromatic primary and secondary amines are less reactive than aliphatic ones because of their lower basicity the attack on the least substituted carbon atom is however preferred too. 

Two further contributions illustrate how chiral lithium amides can be used as catalysts in asymmetric deprotonation reactions (Schemes 2 and 3). The first example of catalytic chiral lithium amide chemistry was reported [13] by Asami (Scheme 2). In this process an achiral base, in this case LDA, provides a stoichiometric reservoir of amidoli-thium reagent. However, deprotonation of the epoxide is affected primarily by the chiral lithium amide 11 rather than the relative excess of LDA. Turnover is possible since the resulting chiral secondary amine 10 can be deprotonated by the remaining reservoir of LDA thus regenerating the chiral base 11. For example, the deprotonation of cyclohexene oxide 8 in the presence of DBU as an additive gives the allylic alcohol 9 in 74 % ee (82 % yield) using 50 mol% of chiral base 11. 

In 2005 Jorgensen et al. introduced a novel strategy for the asymmetric organocatalytic epoxidation of a,p-unsaturated aldehydes (292) (Scheme 71). Using secondary amine catalysts, a,p-unsaturated aldehydes could be epoxidized stereose-lectively using H2O2 as the oxidant. Mechanistically, the reaction can best be... 

Besides the secondary amine-catalyzed oxygenation reactions (see Sects. 2.3.1. and 3.2.5.) and phase-transfer catalyzed epoxidations (Chap. 6.) already mentioned, asymmetric epoxidation reactions using the method developed by Shi et al. (530) have found to be highly useful in complex total syntheses (531-535). The Shi epoxidation employs the fructose-derived ketone 629 as an easily available namral... 

Two years later, Ftirstner et al. developed a synthesis of azepine 277 based on a selective Sharpless asymmetric epoxidation of divinylcarbinol (Scheme 2.60) [89]. The resulting epoxide 272 was then regioselectively opened with allylamine to give the corresponding diene. Protection of the secondary amine with an N-Boc group provided the precursor 275 for RCM. CycUzation proceeded in 94% yield using [Mo]-I catalyst (CH2CI2, 30 min, reflux, 94%). Subsequent conversion of the... 

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