Amino alcohols epoxidation

The enantioseiective hydrogenation of a-amino ketones has been applied extensively to the synthesis of chiral drugs such as the / -agonist SR 58611 (Sanofi Cie). m-Chlorstyreneoxide was obtained via carbene-induced ring closure of the amino alcohol. Epoxide-opening by a chiral amine obtained via a ruthenium-catalyzed hydrogenation of an enamide has led to the desired compound where... 

Amino alcohols. Epoxide opening by amines catalyzed by SmClj is regioselective and stereoselective. The nucleophiles attack from the less substituted carbon atoms. 

Type of reaction C-N bond formation Reaction condition solvent-free Keywords silica gel, 2-amino alcohol, epoxide... 

P-Amino alcohols. Epoxides are opened by amines in water at 60°, Er(OTf)3 shows catalytic activity for this transformation. ... 

Amino alcohols. Epoxides are op trimethylsilyl azide in the presence of P-cm Terephthalic acid. Benzene is selecttv... 

Synthesis of azindines Irom epoxides via amino alcohols or azido alcohols and reaction with phosphines or phosphites... 

Nucleophilic ring opening of epoxides by ammonia (Section 16.12) The strained ring of an epoxide is opened on nucleophilic attack by ammonia and amines to give p-amino alcohols. Azide ion also reacts with epoxides the products are p-azido alcohols. 

Due to the abundance of epoxides, they are ideal precursors for the preparation of P-amino alcohols. In one case, ring-opening of 2-methyl-oxirane (18) with methylamine resulted in l-methylamino-propan-2-ol (19), which was transformed to 1,2-dimethyl-aziridine (20) in 30-35% yield using the Wenker protocol. Interestingly, l-amino-3-buten-2-ol sulfate ester (23) was prepared from l-amino-3-buten-2-ol (22, a product of ammonia ring-opening of vinyl epoxide 21) and chlorosulfonic acid. Treatment of sulfate ester 23 with NaOH then led to aziridine 24. ... 

Substitution of an additional nitrogen atom onto the three-carbon side chain also serves to suppress tranquilizing activity at the expense of antispasmodic activity. Reaction of phenothia zine with epichlorohydrin by means of sodium hydride gives the epoxide 121. It should be noted that, even if initial attack in this reaction is on the epoxide, the alkoxide ion that would result from this nucleophilic addition can readily displace the adjacent chlorine to give the observed product. Opening of the oxirane with dimethylamine proceeds at the terminal position to afford the amino alcohol, 122. The amino alcohol is then converted to the halide (123). A displacement reaction with dimethylamine gives aminopromazine (124). ... 

Epoxidations of chiral allenamides lead to chiral nitrogen-stabilized oxyallyl catioins that undergo highly stereoselective (4 + 3) cycloaddition reactions with electron-rich dienes.6 These are the first examples of epoxidations of allenes, and the first examples of chiral nitrogen-stabilized oxyallyl cations. Further elaboration of the cycloadducts leads to interesting chiral amino alcohols that can be useful as ligands in asymmetric catalysis (Scheme 2). 

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. 

By combining several click reactions, click chemistry allows for the rapid synthesis of useful new compounds of high complexity and combinatorial libraries. The 2-type reaction of the azide ion with a variety of epoxides to give azido alcohols has been exploited extensively in click chemistry. First of all, azido alcohols can be converted into amino alcohols upon reduction.70 On the other hand, aliphatic azides are quite stable toward a number of other standard organic synthesis conditions (orthogonality), but readily undergo 1,3-dipolar cycloaddition with alkynes. An example of the sequential reactions of... 

An amino alcohol can be formed in situ by the reaction of an iV-formylpiperizine 79 with epoxide 78 which then can be induced to cyclize to give the spiroaziridinium salt 80 (Equation 17) <2004TL4175>. The spiroaziridinium was not isolated but instead trapped by reaction with an amine nucleophile (cf. Section 12.20.6.1). 

One of the most well used methods for the synthesis of aziridines involves a two (or sometimes more) step process in which an epoxide is opened by a nitrogen nucleophile. The resulting P-amino alcohol (e.g. 79) is then converted to an aziridine via a number of different processes. This method is generally not broadly applicable when a variety of different groups on the nitrogen of the aziridine are desired. A useful method to convert an epoxide to a number of different /V-sulfonyl aziridines (e.g. 80) has been reported <06S425>. Simple addition of a sulfonamide to an epoxide provides high yields of 79 which is readily closed to form the aziridine. 

An efficient synthesis of A-alkylated-4-substituted isothiazolidine-dioxides (sultams) 251 has been developed utilizing epoxides 248 <06TL4245>. Addition of a secondary sulphonamide 247 to epoxide 248 in hot 1,4-dioxane affords the amino alcohol 249, which is... 

Various catalytic or stoichiometric asymmetric syntheses and resolutions offer excellent approaches to the chiral co-side chain. Among these methods, kinetic resolution by Sharpless epoxidation,14 amino alcohol-catalyzed organozinc alkylation of a vinylic aldehyde,15 lithium acetylide addition to an alkanal,16 reduction of the corresponding prochiral ketones,17 and BINAL-H reduction18 are all worth mentioning. 

The regioselective ring-opening of epoxides 34 (R1 = Me, vinyl, Ph etc.) with aminolead compounds R23 PbNEt2, prepared from lithium diethylamide and R23 PbBr, gives good yields of the amino alcohols 3567. 

The regioselective ring-opening of the chiral epoxides 36 (R1 = Me, Pr or Ph) with aliphatic amines 37 (R2 = t-Bu, PI1CH2 or C6H13) in the presence of titanium tetraiso-propoxide leads to mixtures of the amino alcohols 38 and 39, in which the former predominate70. 

A variety of ie.so-epoxidcs could be selectively ring-opened this way with e.e. s as high as 97% [28], The azides can be converted to 1,2-amino alcohols, which are very desirable synthetic intermediates. Surprisingly, the mechanism of the ARO (asymmetric ring-opening) was more complicated than expected [29], First, it turned out that the chloride ion in Cr-salen was replaced by azide. Secondly, water was needed and HN3 rather than Me3SiN3 was the reactant nucleophile. Thirdly, the reaction rate was found to be second order in catalyst concentration, minus one in epoxide (cyclopentene oxide), and zero order in HN3 [30],... 

Enantiomerically pure 3-amino alcohols which are important intermediates for many bioactive compounds can be directly synthesized by the ARO reaction of readily accessible racemic and meso epoxides with appropriate amines. Indeed, some simple and multifunctional p-amino alcohols have been obtained using this strategy by the promotion of chiral BINOL [30-32,88,89], salen [35,52], bipyridine [33,40,90-94] and proline-A,JV-dioxide based metal complexes [95]. However, none of these systems demonstrated the recyclability of the precious chiral catalyst. 

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