Helmut Stamm

NUCLEOPHILIC RING OPENING OF AZIRIDINES

This account of research work on nucleophilic ring opening (NRO) of aziridines (Azs) demonstrates the broad synthetic scope of this reaction, inclusive secondary reactions, and it discusses the special mechanistic fundamentals and details as well as mechanistic variants. Formation of a C–C bond by NRO is the red thread in this report. A central mechanistic aspect is the quality of the leaving group in Az bases, aziridinium ions and activated Azs (acyl, sulfonyl; double activation). Factors controlling the regioselectivity of NRO are dealt with as well as the influence of the nitrogen pyramid. Competing reactions include carbonyl attack (acylated Azs) and electron transfer with cases of pseudo-NRO (multistep radical paths).

Nucleophilic cleavage of 2,2-dimethylaziridines: competition between SN2 and postulated “SET” mechanism.

Abstract Regioselectivity of nucleophilic attack on 2,2-dimethylaziridines depends on the degree of leaving group activation: in highly activated aziridines it occurs at the methylene carbon and in less activated at the tertiary carbon. This latter abnormal ring opening is explained by an SET mechanism.

Homolytic aziridine opening (aza variant of cyclopropylcarbinyl-homoallyl rearrangement) by addition of tributyltin radical to N-acylaziridines. Factors contributing to the regioselectivity

Abstract AIBN initiated reaction of N-acylaziridines 1 with Bu3SnH in refluxing benzene provided products 5 and 8 of reductive ring opening. Yields (practically quantitative in most cases) fell drastically with steric hindrance of the addition of Bu3Sn. to the acyl oxygen of 1. They depended to some extent on the experimental conditions for hydrogen capturing when aziridine homolysis provided a primary radical 3 or 6. The regioselectivity of (probably reversible) ring homolysis can be understood in terms of the stability of the arising radical (3, 6), of stereoelectronic control (e.g. 1i as compared to 1h) and of frontier orbital interactions (1j). A possible difference in bond lengths as explanation for the formation of the primary radical from 1j did not find support from an X-ray structure analysis of N-tosyl-2-methyl-aziridine 11. Isomeric products were obtained only twice (1i, 1j) with a dependence of the ratio 5j:8j on concentration and hydrogen isotope of Bu3SnH. No such dependence was found for the ratio 5:14 (reduction without and with an intervening cyclization of 3 leading to a pyrrolidone) obtained from the N-cinnamoylaziridine 11. This ratio (1:9 for 11 and 1:3 for 1n) must reflect the E-Z isomers in 3. The observed preference for the formation of E-3 from 2 can be explained by stereoelectronic and steric effects. A cinnamoyl double bond in 5 was saturated depending on experimental conditions.

Acylated 2,2-dimethylaziridines: regioselectivity of ring opening by sodium thiophenolate; borderline SN2 due to planarization of nitrogen pyramid☆

Abstract 2,2-Dimethylaziridines 1 carrying a COR group on nitrogen are opened by PhS⊖ with a regioselectivity RS = abnormal:normal ⩾ 20 in MeOH and 5–16 in THF. Practically no influence of COR on RS was found except for the poorest oxidant 1g (R = tBu) that gave the highest RS (95, MeOH). This rules out an SET mechanism for the abnormal opening. Absence of homolytic ring opening is directly shown by the failure to detect products resulting from cyclization of a homolytically formed radical when COR is cinnamoyl (1f). Direct nucleophilic attack is indicated by suppression of any reaction with PhS⊖ when the steric hindrance is increased (N-benzoylaziridine 13). The observed SN2 borderline behaviour with 1 is explained by reaction in a flattened nitrogen conformation of the otherwise poorly reactive 1. Carboxamide resonance in this (nearly) planar conformation generates a substantial positive charge on N which will shift the mechanism closer to SN1 by partial heterolysis of the N-CMe2 bond prior to attack by PhS⊖.

Reactions with aziridines - 39 : Ring opening of activated 2,2-dimethylaziridines by grignard reagents. A mechanistic study

Abstract Reaction of activated 2,2-dimethylaziridines 1 with Grignard reagents RMgHal in boiling THF can yield the products 2 of normal aziridine ring opening, the rearranged opening products 3 , and the methallylamides 4 (isomers of 1 ). The product distribution depends on R, Hal, and experimental conditions, and very strongly on the nature of the activating group A. It is shown that 1 is opened (reversibly for A = sulfonyl) forming 10 through a Lewis acid assisted attack of Halθ on the tert carbon of 1 (abnormal opening by Halθ ). Evidence is presented to show that 4 as well as 3 come from this intermediate.

Reactions with aziridines XXI The (Michaelis-)arbusov reaction with N-acyl aziridines and other amidoethylations at phosphorus.☆

Abstract Heating trialkyl phosphites with N-acyl aziridines produces dialkyl 2-amidoethyl-phosphonates bearing one of the phosphite alkyl groups on nitrogen. Other alkoxy phosphines behave analogously. Dialkyl phosphites furnish the same type of products devoid of the N-alkyl group.

Nitrone—XI Isoxazolidin-verbindungen—VIII : N-substituierte 5-isoxazolidinone durch reformatzky-reaktion mit nitronen

Zusammenfassung Die zweistufige Ausfuhrungsform der Reformatzky-Reaktion bei Nitronen ermoglicht die Synthese von 2-Alkyl-3-aryl-5-isoxazolidinonen aus α-Bromestern und solchen C-Aryl-N-alkyl-nitronen, die fur die einstufige Ausfuhrungsform zu basisch sind. Besonders geeignet fur die Reformatzky-Reaktion bei Nitronen ist α-Brom-methylmalonester, dessen Umsetzung das E-Isomere des betreffenden Isoxazolidinons liefert. Die Umsetzung von α-Brombuttersaureethylester fuhrt uberwiegend zun Z-Isomeren, woraus Ruckschlusse auf den Ubergangszustand des primaren Additionsschrittes gezogen werden.

Intramolecular radical trapping in SET ring opening of N-enoyl aziridines, a new mechanistic probe and a new synthesis of pyrrolidones

Abstract N-Acryloyl aziridines 1a-c form pyrrolidones 4a-c via electron attachment, homolytic ring cleavage of the intermediate ketyl, and intramolecular trapping of the radical by the CC bond of the acryloyl moiety of 1a-c.

Reductive ring opening of N-acylaziridines : Different outcomes of chemical and electrochemical reactions

Abstract Main products from electrochemical reduction of two N-acylaziridines are the corresponding oxazolines which are not formed in chemical reduction, probably due to a coordination of the oxygen with a metal counter-ion.

Vergleich verschiedener auswertemethoden für gleichgewichte schwacher molekülkomplexe

Zusammenfassung Die auf Computer gestellte Auswertung von 1:1-Molekulkomplex-Messdaten (NMR) nach vier Methoden—den iterativ verbesserten Scatchard- und Hanna-Ashbaugh-Methoden (Sc IT und H-A IT ) sowie der Drago-Methode (Dr) und der Methode nach Cresswell-Allred (C-A)—kann bei guten Messdaten im richtigen Sattigungsbereich genau ubereinstimmende Komplex-Parameter liefern. Je fehlerhafter die Messreihe wird, desto starkere Abweichungen in den Resultaten konnen nach verschiedenen Auswertemethoden auftreten. In diesem Falle ergab die C-A-Methode Resultate mit den kleinsten mittleren Abweichungen (bezuglich der gemessenen Shiftwerte), die sich auch in einer weiteren trial-and-error-Suche nicht mehr verbessern liessen.