Aziridines quaternary

Recently, Uneyama reported that treatment of (R)-l-tosyl-2-trifTuoromethylazir-idine 76 (Scheme 3.24) with w-BuLi at -100 °C and subsequent trapping of the anion with electrophiles such as chloroformates produced aziridine-2-carboxylates 77 in good to excellent yields [71]. The retention of the configuration of the tri-fluoromethylated quaternary carbon center in the course of the reaction was confirmed by derivatization of the product and by X-ray studies. 

Typically, the stereospecific formation of quaternary centers is as problematic as selective nucleophilic attack at the more substituted carbon of aziridines. Interestingly, a copper mediated methodology has been reported that does both <060L5105>. Although N-tosyl aziridines show favorable results, A-nosyl aziridines gave the best results. The reaction of 89 with a variety of phenols yielded 90 in moderate yields. 

An application of copper-catalyzed propargylic etherification has been reported in the synthesis of ustiloxin D (Equation (63)).248 Here, a quaternary center was generated from the unprecedented reaction of a phenol with an ethynyl aziridine. 

C=0)-halogen, 0-(C=0)-halogen, S02-halogen, N=C=0, N=C=S, N-C(=S)-N Acyclic C(=0)-S, acyclic C(=S)-0, acyclic N=C=N Anhydride, aziridine, epoxide, ortho ester, nitroso Quaternary amines, methylene, isonitrile Acetals, thioacetal, N-C-O acetals Nitro group, >1 chlorine atom... 

Cleavage of aromatic amines or quaternary ammonium salts 0-82 Reduction of quaternary ammonium salts or aziridines... 

Many aziridines form picrates and other salts which are stable in the crystalline state. - 4 Attempts to rocrystallize such compounds frequently result in decomposition. The quaternary azjridinium salts (XLII) are somewhat more stable, and have been much studied in connexion with the reaction of the jU-chloroalkyl tertiary amines ( nitrogen mustards ). 

A very efficient catalytic system has been developed by He and coworkers using, under solvent-free conditions, quaternary ammonium bromide-functionalized polyethylene glycol (0.25 mol% 373 K, 8MPa, 5-20min) [68d]. The catalyst worked well for a variety of l-alkyl-2-aryl-substituted aziridines, and could be easily recovered by centrifugation and reused, without any significant loss of catalytic activity and selectivity. 

Du Y, Wu Y, Liu A-H et al (2008) Quaternary ammonium bromide functionalized polyethylene glycol a highly efficient and recyclable catalyst for selective synthesis of 5-aryl-2-oxazolidinones from carbon dioxide and aziridines under solvent-free conditions. J Org Chem 73(12) 4709-4712... 

Substrates susceptible to Sn 1 attack and those bearing leaving groups other than halides have also been employed in the Michaelis-Arbuzov reaction, for example, dialkyl sulfates, alkyl mesylates, alkyl tosylates, quaternary ammonium species, activated acetates as have other electrophiles, for example, alkyl fluoroborates, lactones, lactams, aziridines, sulfones, iminium cations, and orf/io-quinonoids.6,13-15,18... 

The formation of covalent branching points is avoided in the cationic polymerization of -substituted aziridines. Chain transfer to polymer occurs, however, leading to formation of branched (or cyclic) quaternary ammonium ions, unreactive in further propagation [165). 

Consequently, for polymerization of N-substituted aziridines with small substituents like N-methylaziridine, limited conversions to relatively low molecular weight polymers were observed [165,166]. On the other hand, in the polymerization of N-f-butylaziridine chain transfer to polymer is practically eliminated [167]. No other transfer or termination reaction involving quaternary ammonium active species with, e.g., BF4-counterion has been detected ... 

Substitution of proton on the nitrogen with alkyl group, as in the case of aziridines, simplifies the mechanism of polymerization. In the polymerization of 1-methylazetidine, termination due to the chain transfer to polymers is still detectable [176], Further substitution at carbon atoms reduces the extent of chain transfer to polymer and in the cationic polymerization of 1,3,3-trimethylazetidine the concentration of active species, quaternary azetidinium ions ... 

Diels-Alder reactions of enantiomerically enriched 2H-azirine 3-phosphon-ates (281), a new class of chiral iminodienophiles, and dienes stereoselectively furnish optically pure, bicyclic aziridine adducts (282). Hydrogenation of (282) results in a ring opening that affords the first examples of optically pure quaternary piperidine phosphonates. Two step synthesis of an enantiomeric pure cyclic phosphite (283) and its application as a chiral phosphorus nucleophile in the asymmetric Michael addition to nitroalkenes (284) provides an efficient... 

Table 14 Preparation of Aziridines from Oximes (Quaternary Hydrazones) and Grignard Reagents...

The quaternary salts of the aziridine (67) react with hydrochloric acid in water to give the indanobenzazepine and in... 

Michael additions are rather sensitive to steric hindrance hence, an addition of a nucleophile to yS-disubstituted a, S-unsaturated esters is nearly impossible. On the other hand, the application of high pressure alleviates this limitation and even allows the formation of two adjacent quaternary centers. The reaction of methyl tert-butylcyclohexylidenebromoacetate (107) with benzylamine in refluxing methanol as described by Duhamel et al. gave a mixture of the ester 108a and the amide 108b (Scheme 8.26) [57]. At room temperature another reaction channel is opened which leads to the aziridines 109 and 110. In this reaction, a Michael addition first takes place and this is followed by an intramolecular nucleophilic substitution. At atmospheric pressure, however, a reaction time of 60 days was necessary to obtain an 82 % yield. In contrast, at 1.1 GPa the addition took less than 4 days and the diastereomeric ratio rose from 1 1.7 at ambient pressure to 1 10 at 1.1 GPa in favor of 110. 

Azetidines are thermally stable and less reactive than aziridines. They behave in their reactions almost like secondary alkylamines. The value of azetidine is 11.29 and so it is more basic than aziridine (pAT = 7.98) and even dimethylamine ( Ka = 10.73). Azetidines unsubstituted on the N-atom react with alkyl halides to give 1-alkylazetidines which can react further to give quaternary azetidinium salts. With acyl halides, they produce acylazetidines and with nitrous acid, they give 1-nitrosoazetidines. 

If the cyclic sulfate is initially opened with a sec-amine, the intramolecular displacement leads to a quaternary aziridine ion 229, which can be opened by a second nucleophile in a sequential triple displacement (95TL9241) leading to substituted amines 230, as shown in Scheme 58. 

Forbeck, E.M., Evans, C.D., Gilleran, J. A. et al. (2007) A regio- and stereoselective approach to quaternary centers from chiral trisubstituted aziridines. Journal of the American Chemical Society, 129, 14463-14469. 

In comparison to the previously discussed monomers, the polymerization of N-substituted aziridines is easier to control since the side reactions by proton transfer are eliminated because of the absence of primary and secondary amines. Nonetheless, termination by nucleophilic attack of the cationic propagating chain end into polymeric tertiary amines results in the formation of unreactive quaternary ammonium groups, that is, termination. As a result, the polymerization of N-substituted aziridines usually stops at limited conversion as was first demonstrated for A-methylaziridine by Jones [129]. Detailed evaluation of the polymerization kinetics as well as the evolution of molar mass during the polymerization revealed that termination mainly occurs via intramolecular backbiting... 

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