Aziridines ring opening with nucleophiles

The facility with which oxiranes may be prepared and the ease with which they undergo ring opening with nucleophiles or electrophiles makes them useful synthons. Aziridines and especially thiiranes have been less widely exploited in this respect. 

Nitrogen-based nucleophiles continue to remain popular in ring-opening reactions of aziridines. a-Substituted-a-methoxycarbonyl-V-nosylaziridines were opened with a variety of functionalized amines to provide access to enantiopure a,a -disubstituted (3-lactam scaffolds for ditopic peptidomimetics <07OL101>. A related intramolecular regioselective 3,Y-aziridine ring opening with an a-amino functionality was reported in the synthesis of... 

Table 6 Aziridine ring openings with suifur nucleophiles...

Methylene aziridines have some use as multi-functional synthons. They can be metallated on the ring carbon or ring opened with nucleophiles, giving enaminates that can be further transformed. ... 

A positive charge on the N-atom destabiHzes the ring, as is the case with the aziridines. Ring-opening by nucleophiles proceeds with acid catalysis. Hydrogen chloride yields... 

With Oxygen Nucleophiles Aziridine ring-opening of 111 (Scheme 3.42) with water in the presence of a catalytic amount of TsOH gave the corresponding (3-hydrox-yphenylalanine derivative 121 in 72% yield as the major isomer [74], Treatment of N-(p-tolylsulfmyl) aziridine-2-carboxylates with TFA and subsequent aqueous workup resulted in the formation of j3-substituted serine derivatives [62, 63, 101]. Under these reaction conditions, not only was the aziridine ring opened, but also the N-sulfmyl group was removed treatment of 122 (Scheme 3.43) with TFA at 73 °C, for example, afforded 123 in 75% yield [101],... 

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

The ring-opening reactions of aziridines 16 with amines deserve special attention. Unlike ring-openings with the other nucleophiles examined, they do not require added base, and they do not produce stoichiometric byproducts (as with azide). In certain cases, they do not even require a solvent, as exemplified by the ring-opening of aziridine 18 (Table 12.12, entries 1-3). In addition, the reactions... 

The majority of reactions of aziridines deal with acid-catalyzed ring opening with various nucleophiles. In this review only reactions with aziridine-2-car-boxylic esters are summarized (for other types of aziridines, see ref. [3]). 

Similar to the epoxides, the most frequently encountered synthetic transformation for aziridines is nucleophilic ring-opening, whereby carbon- and heteroatom-based nucleophiles are comparably important. As an example of the former type, aziridine-2-carboxylates 100 can be ring-opened with higher order cuprates to give the protected amino acid derivatives 101, corresponding to attack at the less-substituted aziridine carbon [95TL151],... 

Alkynylation of aziridines can be effected through the copper-catalyzed ring opening with acetylides. For example, lithium phenylacetylide engages in smooth nucleophilic attack of A-tosyl-7-azabicyclo[4.1.0]heptane 160 in the presence of copper(i) triflate to provide the cyclohexyl alkyne 161 in excellent yield (Scheme 42) <2004SL1691>. 

Nitriles can act as nitrogen nucleophiles in aziridine ring-opening reactions. Two examples are shown in Scheme 25 in which a formal [3-1-2] cycloadduct is the final product. Tosylaziridine 147 was reacted with benzoni-trile and BF3 OEt2 catalysis to produce the r-fused imidazoline 148 <2004TL1137>. The utility of the reaction is limited in the case of cyclic aziridines to benzofused aziridines and either aryl or benzyl nitriles. It was also found that the reaction required stoichiometric BF3. Lesser amounts of Lewis acid reduced the chemical yield drastically. 

Aziridine and azetidine are stable, if volatile, members of the saturated nitrogen heterocycle family, and aziridine has some interesting chemistry of its own. Like pyrrolidine and piperidine, aziridine can be acylated by treatment with an acyl chloride, but the product is not stable. The ring opens with attack of chloride, a relatively poor nucleophile, and an open-chain secondary amide results. 

The conversion of epoxides to aziridines by nucleophilic ring-opening with azide ion or amines followed by cyclization was covered in Section 1.01.9.3. The conversion of azirines to aziridines by nucleophilic addition and the conversion of aziridines to azirines by elimination were covered in Sections 1.01.6 and 1.01.7, respectively. 

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