Aziridine-2-carboxylates

A variety of carboxylate activating groups convert certain aziridine carboxylates (307) into 3-halogenoazetidin-2-ones (309). The reaction is stereospecific and is believed to proceed via a l-azabicyclo[1.1.0]butan-2-one cation (74JOC902). 

Only one report is concerned with the synthesis, molecular structure, and X-ray analysis of this ring system as 2 (86KGS477). The synthesis of 2 was achieved by the cyclization of 2-aziridine carboxylic acid hydrazide with acetone as shown in Scheme 2. 

In contrast to the epoxides, preparative routes to the aziridines are fairly evenly split between the [C=N + C] and the [C=C + N] routes. Among contributions in the former category, aziridine carboxylate derivatives 110 can be prepared through the lanthanide-catalyzed reaction of imines with diazo compounds, such as ethyl diazoacetate (EDA). In this protocol, iV-benzyl aryl aldimines and imines derived from aromatic amines and hindered aliphatic aldehydes are appropriate substrates <99T12929>. An intramolecular variant of this reaction (e.g.. Ill —> 112) has also been reported <990L667>. 

A chiral enolate derived from a bromoacetyl camphor sultam [(52) in turn prepared from Oppolzer s sultam63a b] undergoes an aza-Darzens reaction with modified amines to produce aziridme derivatives in high de.11 Cleavage yields aziridine carboxylates. 

Ring closing metathesis mediated by Grubbs II catalyst in a type c ring construction process has been used to access stereoisomeric 1,2-disubstituted tetrahydroazepine-3-ol derivatives preparation of the required diene precursor started from an optically pure substituted aziridine carboxylate ester <2007T3321>. 

A method of preparing either cis- or trans-aziridine carboxylates (39) from A-diphenylphosphinylimines (37) and the chiral enolate (36) derived from A-bromo-acetyl 25-2,10-camphorsultam (35) has been reported.54 When the arylimine is substituted in the ortho -position, the product is either a mixture of cis- and trans-aziridine or only the trans-isomer. When the ortho-substituent is H or NO2, only a cz s-aziridine is obtained. The suggested mechanism is partially shown in Scheme 18. Both steric and inductive effects of the ortho- substituent affect the stereochemistry of the addition complex (38) and the stereochemistry of the final aziridine. 

Very recently, an asymmetric synthesis of enantiomerically pure aziridine carboxylic acid derivatives has been published based on a similar reaction type starting from the corresponding a-bromo acrylic acid derivatives135. 

Indole derivatives 157 also serve as carbon-centered nucleophiles in the scandium-mediated opening of aziridine carboxylates 158. The overall process represents a facile synthesis of aryl-substituted tryptophans 159 (Scheme 41) <1998SL754>. 

C5H9FeN04 ferrous glutamate 2896-87-9 377.65 32.265 1,2 5232 C5H9N02 aziridine carboxylic acid ethyl ester 671-51-2 470.75 41.081 2... 

Starting from ethyl 4, 4, 4-trifluorocrotonate, racemic aziridine carboxylic acid 96 was prepared as shown in Scheme 9.22 [46] and was then subjected to lipase-catalyzed esterification. Methyl ester 97 was obtained in 35% yield with excellent enantiomeric purity. Acid-catalyzed ring opening of aziridine 97 proceeded regio- and stereoselectively, affording 2-substituted (2R,3R) or (2/ ,3S)-3-amino-4,4,4-trifluorobutanoates 98 in high yields [47]. 

An optically pure cyclic analogue of aziridine-2-carboxylate ester was prepared from ribose via a Ph3P-promoted conversion of 3-azido-2-tosyl-D-xylofuranoside to its corresponding 2,3-aziridine (95) (Scheme 34) <93T90l>. The procedure is directly applicable to the synthesis of enantiomerically pure 2,3-aziridine carboxylate isomers from D-lyxose. 

Figure 14.4 Tetrahedral intermediates of CALB aziridine-carboxylate complexes. The slow reacting (2R,TR)-diastereomer (b) exhibits an umbrella-like inversion of substituents compared with the fast reacting...

R OCHR CH(NHo)C00H. Aziridine carboxylic acid derivatives have also been... 

The chiral phosphoric acid (165) that catalyzed the aza-Darzens reaction of in situ generated aldimine with diazoacetate (163) proceeded smoothly to furnish cA-aziridine carboxylates (164) in excellent chemical yields and enantioselectivities (Scheme 43). ... 

A final example of a reaction that may involve an azabicyclobutonium ion comes from studies of Deyrup and Clough on the interconversions of aziridine carboxylates and j -lactams. The stereoselectivity of the reaction of certain substrates, e.g., (27), suggests the intermediacy of cations such as (28). The NMR spectrum of the anhydride (29) in liquid SO 2 with added p-nitrobenzenesulfonyl chloride gave evidence of an intermediate. Based on the chemical shift data, the presence of (28) was claimed. The simplicity of the reported spectral data and the fact that (30) apparently did not ionize to (28) upon dissolution into a saturated solution of antimony pentafluoride in liquid sulfur dioxide suggests caution in accepting the conclusion that (28) was observed in the NMR experiments. It was pointed out that concerted reaction pathways are available that could account for the conversion of jS-lactams to aziridine carboxylates. Since a concerted mechanism can also be written to explain the stereospecific conversion of (27) to (30) [Eq. (19)], the intermediacy of (28) remains questionable. 

Only one example was found where this class of amino acids was produced. Oxidation of 7.246 gave a ketone and treatment with boron trifluoride led to the conjugated ketone, 7.247.132 Conjugate addition of azide, reduction to the amine and cyclization gave diastereomeric methyl 9-(3-hexyl-2-aziridino)nonanoic acid (J.248 and 7.249). The final step in that sequence proceeded in only 37% yield. If the alkenyl moiety was converted to an epoxide moiety, aziridine carboxylic acids were prepared in good yield, via the azide.132... 

The use of room temperature ionic liquids offers the advantage of an easy recycling of the catalyst [133] with sometimes a significant rate acceleration and an improvement of the selectivity [134]. Such an approach has been reported with Bi(0Tf)3 %H20 for the FC acylation of aromatics [50a,b], the synthesis of ds-aziridine carboxylates [135], aldol additions [32d,e], and various ring opening of epoxides [86b, 136]. 

At almost the same time, Akiyama et al. developed a similar aza-Darzens reaction using aldimines derived from aryl glyoxals and ethyl diazoacetate promoted by chiral BlNOL-derived phosphoric acid catalysts, such as 90 (Scheme 37.17) [159]. In this case, the reaction rendered exclusively the corresponding cis-aziridine carboxylates in both excellent yields (95-100%) and enantioselectivities (92-97% ee). However, the scope of the method seemed to be quite narrow since only aromatic glyoxals were employed. 

Akiyama found that a three-component condensation of phenyl glyoxal 72, p-anisidine 7a, and ethyl diazoacetate 73 could also be realized in the presence of chiral phosphoric acid 5g, leading to ais-aziridine carboxylates 74 with excellent enantioselectivities (Scheme 2.20) [31],... 

SCHEME 40.34. Multicomponent organocatal3ftic synthesis of aziridine carboxylic ester. 

SCHEME 40.39. Synthesis of azetidine from aziridine carboxylic ester. 

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