Aziridines 2-aminoalcohols

In general, the method of enzymatic cyanohydrin synthesis promises to be of considerable value in asymmetric synthesis because of the synthetic potential offered by the rich chemistry of enantiomerically pure cyanohydrins, including their stereoselective conversion into other classes of compounds such as a-hydroxy carboxylic acids or respective esters, w c-diols, / -aminoalcohols, aziridins, a-azido(amino/fluoro)nitriles, and acyloins [501, 516]. 

It has been proposed that aziridines may be more widespread in biological systems than is generally realized [190]. Many drugs such as ephedrine (124 Scheme 11.18) and pronethalol (125) and endogenous metabolites such as adrenaline (126) contain a P-aminoalcohol moiety, which may act as a precursor to an aziridine metabolite that may explain the known carcinogenicity of some of these compounds such as pronethalol. 

Diethoxytriphenylphosphorane (the product of insertion of triphenylphosphine into diethyl peroxide) finds use as a mild, neutral reagent which initiates cyclodehydration of N- and C-substituted g-aminoalcohols to form aziridines in excellent yield,... 

There are a few reports on the use of oximes as electrophilic amination reagents. Since 1984, ketone O-sulfonyloxknes have found applicability as amino transfer reagents to car-banions. In the reaction of organometaUic compounds with oximes, carbanions attack the carbonyl carbon of the oxime, giving Af-substituted hydroxylamines as addition products (Scheme 53, path a). However, a number of scattered reports have been also published on the formation of aziridines by a-deprotonation, followed by addition (path b) or formation of azirines by a-deprotonation before addition (path c). Addition of carbanions to azirines also yields aziridines, which are hydrolyzed to a-aminoalcohols. 

Hydroxymethylaziridine 67 undergoes ring opening in the presence of either carbon- or heteroatom-based nucleophiles upon treatment with 2 equiv of potassium hydride to provide the t)7aminoalcohol derivative 69. The key step of the reaction is considered to be an aza-Payne rearrangement of the deprotonated aziridine methanol to the... 

Reports on the preparation and use of type I fused-ring aziridinium ions is significantly less than that of the corresponding aziridine. A couple of examples have been reported. A typical method for the synthesis of an aziridinium ion and subsequent reaction with (i )-l,l -binaphthol has been reported <2004TA3847>. The plan here was to carry out an enantioselective reaction between aziridinium 232 and binaphthol. The aziridinium 232 was prepared by treating racemic aminoalcohol 231 with methanesulfonyl chloride and triethylamine. As is usually done, the aziridinium is not isolated but the binaphthol is simply added to the reaction. A 60% yield of (—)-(R,R,R)-233 was isolated along with 30% of a 1 1 mixture of the (R,R,R)- and (R,A,A)-diastereomers (Scheme 40). 

Table 1 Cyclization of j -aminoalcohols and their JV-derivatives to aziridines.

The activated aziridine derivative that suffers nucleophilic attack can also be formed in situ by ring closure. Chiral aminoalcohol 171 was converted via aziridinium chloride 172 to chloramine 173 with inversion of conhguration in 91% yield. 

A method has been reported this past year for the direct synthesis of N-diphenylphosphinyl (DPP) protected aziridines 135 from 2-aminoalcohols 134. The DPP group combines the advantanges of (1) activation of the aziridine ring towards nucleophilic attack and (2) subsequent ease of removal [94SL14S]. 

Similar ring-opening reactions are known for aziridines. Hydrolysis constitutes an important process for the synthesis of aminoalcohols (Scheme 10.2). This is usually performed with aqueous acid an aziri-dinium cation is first formed and then is opened by reaction with water. 

Aziridines and 2-aminoalcohols from 2-chloracylamines Stereospecific ring closure... 

Triphenylphosphine dibromide Aziridines from 2-aminoalcohols Ring closure with Walden inversion... 

Utilizing steroid substrates, MEH was able to hydrolyze not only epoxides, but also the corresponding heteroatom derivatives such as aziridines to form trans-, 2-aminoalcohols albeit at slower rates (Scheme 2.90) [583]. The thiirane, however, was inert towards enzymatic hydrolysis. The enzyme responsible for this activity was assumed to be the same microsomal epoxide hydrolase, but this assumption was not proven. 

A related case (Scheme 40) is the intramolecnlar reaction of bntene-l,4-aminoalcohol derivative bearing an electron-withdrawing gronp at nitrogen, to afford vinylaziridines. Note that a i-2,3-disubstituted aziridines are more stable than the tram isomers and that vinylaziridine formation is reversible under Pd(0) catalysis. 

Ethylenimines from 2-aminoalcohols via 2-aminosulfuric acid monoesters Wenker aziridine ring synthesis... 

As mentioned above, the stereochemistry of the thiazolidinone structure is quite important for acaricidal activity. In order to regulate the stereochemistry, a number of synthetic pathways were considered as shown in Scheme 1. In this scheme, we focused our attention on aziridines, chloroamines and aminoalcohols as key-intermediates. We investigated the synthetic process to obtain both cis and trans or erythro and threo isomers of these intermediates (5-6). Here we intend to describe the stereoselective synthesis of the trans isomers which are important for the acaricidal activity ( Schemes 2-4 ). 

Synthesis of 1,2-aminoalcohols via cross-coupling of imines with ketones or aldehydes can be achieved using TifOPr-r /c-CsHgMgCl in Et20, although some ketones form cm-2,3-dialkyl aziridines predominantly. ... 

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