Amino-epoxides

Aziridines from Amino Epoxides by a Modified Payne... 

A modified Payne rearrangement of amino epoxides catalyzed by Lewis acid or induced by base, represents an interesting but a limited method for the synthesis of fonctionalized aziridines of high enantiopurity. The limitations are primarily due to the accessibility of the starting materials (Scheme 6) [15]. 

Methyl 2,3-epoxypropanoate can be prepared by reaction of potassium glycidate with dimethyl sulfate and one equivalent of benzyltriethylammonium chloride in methylene chloride at room temperature (65% yield).14 The reactions of this ester with organolithium or organomagnesium reagents at low temperature afford optically pure epoxy ketones14 that may be transformed via reductive amination to anti amino epoxides.15... 

Some limitations have been discussed320 in the dimethyldioxirane oxidation of glucals321. Dimethyldioxirane induces epoxidation of enanimes (e.g. 206), which subsequently dimerize to 1,4-dioxanes (208)322. The stability of the a-amino epoxides 207 depends on the type of substitution at the nitrogen323. 

In a totally selective ring opening of amino epoxides with ketones, enantiopure (2R,3S)- and (2S,3S)-3-aminoalkane-l,2-diols have been prepared in high yield, total diastereoselectivity, and without epimerization, using BF3.Et20 catalysis.335... 

A concise and practical synthesis of HIV-1 protease inhibitor 2 was developed by Askin and coworkers, using the rigid tricyclic aminoindanol acetonide as a chiral platform.11 The diastereo-selective alkylation of (Z)-lithium enolate of amide 48 with amino epoxide 49 gave intermediate 50 in >90% yield and >98% de (Scheme 24.9). Lithium carbamate salt of 49 presumably activated the epoxide toward electrophilic epoxide opening, and alkylation of the (Z)-enolate occurred from the less hindered (3-face. The amino alcohol was deprotected by treatment with camphorsulfonic acid and gave 2 in good yield. 

Treatment of certain 2-(hydroxymethyl)aziridines with base can lead to an intramolecular ring-opening reaction to yield an cc-amino epoxide, a reaction analogous to the Payne rearrangement of (hydroxymethyl)epoxides. For example, treatment of the aziridine 109 with potassium tert-butoxide provides the epoxide 110 in good yield. 

The use of the optically active (camphorylsulphonyl)oxaziridine did not afford enantioselectivity. A possible explanation for this lack of stereocontrol lies in the mechanism proposed (Scheme 56). It involves formation of an a-amino epoxide, its nucleophilic ring opening and either loss of a proton (route a) or hydrolysis (route b) (Scheme 56). 

The reaction of terminal epoxides with hindered lithium amide bases followed by organometallic reagents generates alkenes <2004JA12250>. Related reactions are the formation of enamines <2004JA6870> from terminal epoxides, 2-ene-l,4-diols from terminal epoxides <20050L2305>, and allylamines from amino epoxides <20060L349>. 

Oxidation of Enamines. Enamines are rapidly oxidized by (+)-(camphorylsulfonyl)oxaziridine (1). Disubstituted enamines give rise to racemic ot-amino ketones, while trisubstituted enamines afford, after hydrolysis, ot-hydroxy ketones (eq 2). A mechanism involving initial oxidation of the enamine to an a-amino epoxide is suggested to account for these products. 

Stevens and Pillai prepared and isolated the azirane (60 equation 26), a rare example of an a-amino epoxide. This remaricably stable material required vigorous heating in o-dichlorobenzene to effect the ring expansion to (61) the remainder was converted to polymeric material. 

Disubstituted enamines (94 R2 = H) give a-amino ketones (95) on treatment with (63a) while trisubstituted enamines give a-hydroxy ketones (96) following hydrolysis <88TL4365>. Reduction of the a-amino ketones afford (1-amino alcohols <90TL544l>. A mechanism involving initial oxidation of (94) to an a-amino epoxide was proposed (Scheme 19). Imines (RCH=N—R) are oxidized to nitrones (RCH=N(0)—R) <85TL379i>. 

The starting amino epoxides are usually prepared by methods similar to those used for dianhydro derivatives678 (see, for example, 170— 171— 172) or by the reduction of azido epoxides740 (see, for example, 174- 175- 152). 

The aziridine ring is more stable than the oxirane ring in alkaline solution, as demonstrated by the low reactivity in attempts to accomplish isomerization of the hydroxyepimines to amino epoxides in alkaline media at room temperature, which contrasts with the rapid epoxide migration (see Sect. V,2). Isomerization of hydroxyepimines occurs only at high temperatures, and leads finally to the formation of amino derivatives of 1,6-anhydrohexoses.379,740 For example, when 166 is heated in 5% potassium hydroxide, 2-amino-l,6-anhydro-2-deoxy-/3-D-mannopyranose (168) is formed as the main product this can be explained by transient formation of 2-amino-l,6 3,4-dianhydro-2-deoxy-/3-D-altropyranose (167), and its subsequent, diaxial hydrolysis.379 Compound 167 is probably in equilibrium with epimine 166. Acid hydrolysis of the aziridine ring in 153 also follows a diaxial mechanism, without scission of the 1,6-anhydride bond, to give 4-amino-l,6-anhydro-4-deoxy-)8-D-mannopyranose756 (177). 

Electrooxidations can also make use of mediators In this case they proceed at lower potentials and need milder conditions . Enamines derived from aldehydes and bearing a )5-hydrogen atom were oxidized, using KI as a mediator, into the corresponding -keto amines. In the mechanism proposed, an unknown active species, T is assumed to be formed by oxidation of 1 and to add to the double bond. The resulting iodohydrin cyclized into an a-amino epoxide and subsequently is ring opened into a jS-ketoamine, by a 1,2-hydrogen shift (Scheme 81). 

The azabicyclic ketone 114 was prepared from 4-vinylcyclohexene by the route summarized in Scheme 25, via azide 111 and the amino epoxide intermediate 112, which underwent a smooth in situ cyclization to amino-alcohol 113. 

In the reaction of enantiopme amino epoxides 82 with carbon dioxide in the presence of BFs, the corresponding carbonates 83 are obtained . 

The most common classes of thermosetting materials are alkyds, aminos, epoxides, phenolics, polyesters and silicones. The approximate consumption of these materials in the United Kingdom during 1970 was as follows ... 

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