Aziridine, preparation from

The V-phtha 1 imidt)aziridine prepared, from benzofuran, was cleaved with hot methanol with good regioselectivity and presumed trans stereochemistry to give 10 and 11, although the trans configuration of the methoxyamine was not shown by HNMR25. 

The yields and diastcrcomcric ratios of the aziridines prepared from alkenes 2 and lead tetraacetate or phenyliodoso diacetate in dichloromethane are reported below. 

Aziridine prepared from acetophenone Cf C S Dewey and R A. BafEord, J Org Chem, 30, 491 (1965). Aziridine prepared from phenylacetaldehyde. 

The resulting 7V (Ses)aziridines are valuable synthetic intermediates. The electron-withdrawing character of the Ses-group allows ring opening of the aziridines by nucleophiles under mild conditions (eq 2), as is the case with activated A-(Ns)aziridines prepared from [7V (/7-nitrobenzenesulfonyl)imino]phenyliodane (PhI=NNs) or 7V-(Ts)aziridines. 

Similarly 2- and 4-disubstituted seienazolidines were prepared from 2-methyl- and 2,2-dimethylaziridines (Table X-17i (74) and 2- and 3-disubstituted seienazolidines were obtained from N-substituted aziridines (Table X-18) (74). 

Side chain modification has been carried out on several aziridines for example, various aziridine methanols have been prepared from 2-methoxycarbonylaziridines (70JOC3424). Aziridine methanols (296) react with thionyl chloride in the presence of base to give both rearranged (299) and unrearranged (298) chlorides (70JOC3428). The rearrangement product is thought to be formed via the azabicyclobutane intermediate (297). 

A solution of hydrazoic acid (prepared from about 30 g sodium azide) in ca. 200 ml chloroform is prepared in a well-ventilated hood. Cholesterol (15 g) is dissolved in the hydrazoic acid solution and 3.5 ml of triethylamine is added. The reaction mixture is then stirred at room temperature while 7 g of A-chlorosuccinimide is added. The reaction mixture is allowed to stand overnight and then the chloroform solution is washed successively with dilute sodium bisulfite, dilute soldium bicarbonate solutions and finally with water. The chloroform extract is then dried (Na2S04) and the solvent removed in vacuo. The residue is crystallized from ethanol to yield ca. 8.5 g of (101) in colorless needles mp 138-139°. The chloro azide is reduced to the aziridine by lithium aluminum hydride according to the foregoing procedure. 

Oxime 26 was prepared from 5,ll-dihydro-dibenzo[a,d]cyclohepten-10-one. The Hoch-Campbell reaction of 26 with 3-dimethylaminopropylmagnesium bromide produced aziridine 27 in 46% yield after acidic workup. Extension of the Hoch-Campbell reaction to steroids has also been reported. Thus, treatment of 3(3-hydroxy-5-pregnen-20-one oxime (28) with methylmagnesium iodide furnished a mixture of diastereomers, 20ot/20P,21-imino-20-methyl-5-pregnen-3P-ol (29) in a 50% combined yield and a 3 1 ratio. On the other hand, homo-adamantan-4-one oxime (30) was transformed to homo-adamantano[4,5-b]-2 -ethylaziridine (31) in 76% yield upon the action of... 

As described in Section 1.7.1, the utility of the Wenker reaction is limited to substrates without labile functionalities because of the involvement of strong acid and then strong base. The Fanta group prepared a variety of aziridines by taking advantage of the Wenker reaction.For example, 6-aza-bicyclo[3.1.0]hexane (14) was produced from the ring-closure of ( )-rra s-2-aminocyclopentanol hydrochloride (13). In a similar fashion, sulfate ester 16 was prepared from A-methyl dl-trans- >-ssmnoA-hydroxytetrahydrofuran (15). Subsequent treatment of sulfate ester 16 with NaOH then delivered aziridine I . " Additional examples of Wenker aziridine synthesis may also be found in references 15-17. 

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. ... 

Tetramethyl-l,2-oxathietane (138) was prepared by diazotization of 139, which was prepared from the aziridine (140) (86JA3811).Tlie reaction presumably involves the decomposition of the sulfonium ion intermediate (141).Tire dichloromethane solution of 138 at -20°C is sufficiently stable to permit exploration of the chemical reactions. Tire oxathietane 138 undergoes a formal [[Pg.248]

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... 

FR900490 (264 Scheme 3.96), a new immunomodulator, has been prepared from aziridine-2-carboxylic ester 261 [146, 147]. This aziridine reacts with (S)-histi-dine (262) in the presence of 1 n sodium hydroxide, giving 263 in 31-44% yield... 

Reduction of iV-(3-bromopropyl) imines gives a bromo-amine in situ, which cyclizes to the aziridine. Five-membered ring amines (pyrrolidines) can be prepared from alkenyl amines via treatment with N-chlorosuccinimide (NCS) and then BusSnH. " Internal addition of amine to allylic acetates, catalyzed by Pd(PPh3)4, leads to cyclic products via a Sn2 reaction. Acyclic amines can be prepared by a closely related reaction using palladium catalysts. Three-membered cyclic amines (aziridines)... 

Enantiopure a-amino aldehydes are valuable synthons in natural product synthesis [57]. However, problems are often encountered with their configurational instability [58]. Aziridine-2-carboxaldehydes are also a-amino aldehydes and accordingly have a potential synthetic value. We found that M-tritylaziridine-2-carboxaldehyde 56 is a perfectly stable compound and therefore comparable to Garner s aldehyde (ferf-butyl 2,2-dimethyl-4-(S)-formyl-oxazolidine-3-car-boxylate). Aldehyde 56 can readily be prepared from aziridine-2-carboxylic ester 12 by the sequence shown in Scheme 42 [59]. 

N,N-Dibenzyl (z -amino a-chloroketimines 202 can be prepared from the corresponding ketones, which in turn are available by the addition of chloromethyllithium to esters of natural cz-amino acids. Reduction of 202 with sodium cyanoborohydride directly afforded a-aminoalkyl-substituted aziridines 203 with high syn diastereoselectivity, which was only moderately affected by the size of the substituent [96] (Scheme 30). A complemen-... 

A new type of mechanism-based enzyme-inactivators, which are related to conduritol epoxides with respect to activation at the active site, was introduced by Tong and Ganem, " who prepared the aziridine 37 from the o-galacto analog of 1-deoxynojirimycin. Compound 37 proved to be a pp-... 

I".a designed to make more extended heterobridged [n]polynorbomanes, the bis-aZ n n. was prepare from the dioxasesquinorbomadiene anhydride 116 <97T3975>. The re ate is-epoxi e was secured, in the N-methoxyethyl succinimide series, from the bis-cyc o utene t at was derived from 119 (Scheme 20) using the standard protocols described earlier. It is noteworthy that only the aziridine protocol tolerates the anhydride group. 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

Trifluoromethyl derivatives of aziridine are intensively studied as biologically active substances. (Trifluoromethyl)aziridines 4 were prepared from (trifluoromethyl)ketoximes 3 and Grignard reagents (equation 2). However, this reaction is not general. For example, reaction does not occur with phenyl and allyl Grignard reagents, but when it works the Z stereoisomer is formed . 

Steiically congested cw-aziridines such as 137 were prepared from the deiivatized amino allyl alcohol precursor 136 through a palladium-catalyzed cyclization reaction <99TL1331>. This methodology has also been extended to the cyclization of amino allenes <99JOC2992>. 

Chemla and Ferreira effected lithiozincation of TMS propargyl chloride to prepare chloroal-lenylzinc bromide reagents (Table 21)33. Subsequent reaction of these reagents with N-t-butyl-substituted sulfoximines yielded the related traws-sulfoxinyl aziridines, arising from internal displacement of the chloride substituent of the anti sulfinamide adduct. A transition state in which the f-BuSO group is eclipsed with the alkynyl (vs R) substituent accounts for the preferred formation of the major A-sulfinyl diastereomer (equation 41). 

The prochiral aziridine 1 is easily prepared from cyclooctene. Paul Muller of the University of Geneva has shown (Helv. Chim. Acta 2004,87,227) that metalation of 1 in the presence of the chiral amine sparteine leads to the bicyclic amine 3 in 15% , by way of intramolecular C-H insertion by the intermediate chiral carbene 2. The sparteine can be recovered and recycled. 

Scheiner has shown that triazolines undergo both direct and sensitized photoelimination of molecular nitrogen to yield aziridines.463 With the triazolines prepared from phenyl azide and cis- or trans-fi-methylstyrene, direct photolysis produces a mixture of aziridines in which the starting geometry has been largely retained. Sensitized photolysis, however, is totally nonstereospecific. 

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