Aziridines amino

Aziridines amino alcohols.1 The 1,2-cyclic sulfates (1) of chiral diols react with RNH2 to form 3-amino sulfates (2), which are convertible into aziridines or amino alcohols. 

Hydroxide ions oxiranes glycols aziridines amino alcohols. 

The synthetic utility of this method is clear it provides easy manipulation of the products to give various important chiral building blocks such as chlorohydrins, epoxides, aziridines, amino acids, and amino alcohols [257-259], and is readily applicable to natural product synthesis [260]. 

Reaction with Oxygen Nucleophiles. In the presence of strong acids, eg, H2SO4, HBF, or BF, aziridines react with alcohols to form P-amino ethers (93) ... 

Oxidative cleavage of P-aminoacyl complexes can yield P-amino acid derivatives (320,321). The rhodium(I)-catalyzed carbonylation of substituted aziridines leads to P-lactams, presumably also via a P-aminoacyl—metal acycHc compound as intermediate. The substituent in the aziridine must have 7T or electrons for coordination with the rhodium (322,323). 

Aziridines also undergo ring enlargement when treatment with thiocyanic acid, cis- and tran5-2,3-Dimethylaziridine (470) with thiocyanic acid gave exclusively trans- and cis-1-amino-4,5-dimethyl-2-thiazoline (471) (72JOC4401). 

C in D2O. Extensive tables are found in Lehn s review <70MI50100). Calculations of inversion barriers have met with mixed success. The MNDO SCF method gives results which compare well with experimental values, including the high barriers of Af-halo- and N-amino-aziridines, and the low ones for Af-trimethysilyl- and Af-phosphino-aziridines <80JCS(P2)1512). 

Certain bifunctional nucleophiles allow cyclization after ring opening. The formation of 2-thiazolium salts (71JHC40S) and the analogous production of 2-amino-2-thiazolines (191) from aziridines and thiocyanic acid fall into this category (72JOC4401). 

N- Aminoaziridines have been converted to alkenes by reaction with a variety of oxidizing agents (70JA1784). Usually, the deamination reaction is stereospecific. The oxidation of l-amino-2,3-diphenylaziridines with manganese dioxide, however, was not stereospecific. The trans compound gives entirely frans-stilbene, whereas the cfs-aziridine forms a mixture of 85% trans- and 15% c -aikene. cw-Stilbene is not isomerized to trans under the reaction conditions, and the results are explained in terms of an azamine intermediate which can isomerize through a tautomeric equilibrium. 

A number of 2-acylazetidines have been prepared by reaction of 1,3-dihaloacyl compounds with amino derivatives (Section 5.09.2.3.l(m)). This is illustrated for azetidine 2-carboxylic acid (56), the only known naturally occurring azetidine. Ring expansion of activated aziridines (43) and contraction of 4-oxazolines (55) has also found limited use (Section 5.09.2.3.2(f) and Hi)). 

Aziridine, alkylidene-N-ethoxycarbonyl thermolysis, 7, 78 Aziridine, /V-amino-... 

The Wenker aziridine synthesis entails the treatment of a P-amino alcohol 1 with sulfuric acid to give P-aminoethyl sulfate ester 2 which is subsequently treated with base to afford aziridine 3. Before the discovery of the Mitsunobu reaction, wbicb transforms an amino alcohol into an aziridine in one step under very mild conditions, the Wenker reaction was one of the most convenient methods for aziridine synthesis. However, due to the involvement of strong acid and then strong base, its utility has been limited to substrates without labile functionalities. 

A related aziridine synthesis is the Gabriel reaction (a.k.a. Gabriel-Cromwell reaction), which involves an intramolecular Sn2 reaction of a P-amino halide. However, the reaction has become so common that the name Gabriel is not tightly related to the transformation. 

Mesylates and tosylates may be used as variants of the 0-sulfate ester. For instance, 55% of aziridine 7 was obtained from base-mediated cyclization of amino mesylate 6. In comparison, the classic Wenker protocol only gave 3% of 7. In another instance, A-tosyl amino alcohol 8 was tosylated to give 9, which was transformed to aziridine 10 in 64% yield, along with 29% of the P-elimination product due to the presence of the ester moiety. Likewise, aziridine 12 was assembled from tosylate 11 in two steps and 60% yield. ... 

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. ... 

A cold mixture of sulfuric acid (98%, 4 g), and water (4 mL) was added to an amino-alcohol 25 (40 mmol) in water (2.4 mL) at 0-5°C. The mixture was heated to 120°C and then water was carefully distilled off in vacuo. The solid sulfate residue was treated with 6.2 M potassium hydroxide, and steam-distilled. The distillate was saturated with potassium hydroxide pellets and the upper organic layer, which separated, was fractionally distilled from potassium hydroxide through a short column to give a colorless oil aziridine 26 in 96% yield. 

In addition, an Organic Synthesis procedure of preparing aziridine from P-amino alcohol exists. ... 

Thus, in contrast to benzothiepins, dibenzo compounds can be synthesized by direct acid-catalyzed elimination of water from hydroxy derivatives, or of amines from amino derivatives, at elevated temperatures due to their thermal stability. As in the case of benzothiepins, dibenzo derivatives can also be prepared by base-catalyzed elimination from the corresponding halo derivatives however, the yields are somewhat lower compared to the acid-catalyzed reactions. As a special case, an aziridine derivative was deaminated by palladium-catalyzed hydrogenation to afford the corresponding dibenzothiepin.69... 

The action of nitrous acid on the benzodiazepine A -oxide 38 gives the nitrosoamino derivative 39,234 which reacts with alcohols, ethanethiol and various amino compounds, such as hydrazines and guanidine, by replacement of the methyl(nitroso)amino group.235 Reaction with aziridine affords the aziridinyl compound 40f or the 2-(aziridin-l-yl)ethylainino derivative 40g, depending on the conditions. 

The substrate scope is limited, as electron-withdrawing groups (X = p-N02 or p-CF3) on the aromatic substituent are not tolerated. However, this route does provide valuable intermediates to unnatural a-amino phosphonic acid analogues and the sulfimine can readily be oxidized to the corresponding sulfonamide, thereby providing an activated aziridine for further manipulation, or it can easily be removed by treatment with a Grignard reagent. 

Amino alcohols are also good substrates for aziridination under Mitsunobu conditions. The rfs-1,4-amino alcohols 48, obtained by reductive cleavage of the nitrogen-oxygen bonds of the hetero Diels-Alder adducts 47, underwent syn-SN2 -type displacement on treatment with PPh3 and DEAD to give cyclic vinylaziridines 49 (Scheme 2.15) [27]. 

Scheme 2.20 Palladium(0)-catalyzed aziridination of a-amino allene 66.

Ring-opening of diastereomerically pure vinylaziridine 131, prepared by azir-idination of butadiene with 3-acetoxyaminoquinazolinone 130 [52], yielded acetate 132 with inversion of configuration, together with amino alcohol 133 with retention (Scheme 2.34) [53]. The formation of 133 can be explained by assuming participation by the quinazolinone carbonyl oxygen, which produces an intramolecular reaction with the aziridine carbon with retention of configuration. 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

A variety of methods for the asymmetric syntheses of aziridine-2-carboxylates have been developed. They can be generally classified into eight categories based on the key ring-forming transformation and starting materials employed (i) cyclization of hydroxy amino esters, (ii) cyclization of hydroxy azido esters, (iii) cyclization of a-halo- and ot-sulfonyloxy-(3-amino esters, (iv) aziridination of ot, 3-unsaturated esters, (v) aziridination of imines, (vi) aziridination of aldehydes, (vii) 2-carboxylation of aziridines, and (viii) resolution of racemic aziridine-2-carboxylates. 

The earliest method developed for the preparation of nonracemic aziridine-2-car-boxylates was the cyclization of naturally occurring (3-hydroxy-a-amino acid derivatives (serine or threonine) [4]. The (3-hydroxy group is normally activated as a tosyl or mesyl group, which is ideal for an intramolecular SN2 displacement. The cyclization has been developed in both one-pot and stepwise fashion [4—9]. As an example, serine ester 3 (Scheme 3.2) was treated with tosyl chloride in the presence of triethylamine to afford aziridine-2-carboxylate 4 in 71% yield [9]. Cyclization of a-hydroxy- 3-amino esters to aziridine-2-carboxylates under similar conditions has also been described [10]. 

Aziridine-2-carboxylates 12 (Scheme 3.4) have also been prepared from 3-hy-droxy-a-amino esters 9 by treatment with sulfuryl chloride in place of tosyl or mesyl chloride. Treatment of 9 with thionyl chloride in the presence of triethylamine, followed by oxidation of 10 with sodium periodate and a catalytic amount of... 

Cydization of P-hydroxy-a-amino esters under Mitsunobu reaction conditions is an alternative approach to aziridine-2-carboxylic esters [6b, 13-16], In this case the P-hydroxy group is activated by a phosphorus reagent. Treatment of Boc-a-Me-D-Ser-OMe 13 (Scheme 3.5) with triphenylphosphine and diethyl azodicarboxylate (DEAD), for example, gave a-methyl aziridinecarboxylic acid methyl ester 14 in 85% yield [15]. In addition to PPh3/DEAD [13b, 15], several other reagent combi-... 

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