I. Azidomercurations of alkenes: Mercury-promoted Schmidt reactions. II. Non-stabilized 2-azaallyl anions: An approach to asymmetric 2-azaallyl anion precursors and mechanistic studies.
Hutta, Daniel Adrian
2000
Abstract
The first example of an azidomercuration reaction between an aliphatic azide and an olefin was developed as a new method for promoting the Schmidt reaction of aliphatic azides. For example, treatment of 2-(3-azidopropyl)methylenecyclohexane with either mercury(II) perchlorate trihydrate or mercury(II) trifluoromethane sulfonate resulted in formation of a mercuronium ion that was intramolecularly captured by the aliphatic azide to generate a secondary aminodiazonium ion. Bond migration and displacement of the dinitrogen leaving group resulted in an alpha-mercurio iminium ion that afforded (2<italic>R</italic>*,7<italic> R</italic>*)2-methyl-1-azabicyclo[5.3.0]decane after sodium borohydride reduction. Previous conditions for promoting the Schmidt reaction of aliphatic azides required treating azidoalkenes such as 2-(3-azidopropyl)methylenecyclohexane with trifluoromethane sulfonic acid to generate a carbocation that was captured by the azide. This new mercurio-Schmidt methodology has extended the scope of this reaction by eliminating the need for well stabilized carbocations and by allowing the incorporation of a wide variety of functionality which was not tolerated with the acid-promoted conditions. In addition it was found that treatment of (<italic>E</italic>)-1-azidoundec-4-ene with these mercurio-Schmidt conditions resulted in the formation of a 6-hexylpiperidine <italic>via</italic> an intramolecular 6-<italic>endo-trig</italic> cyclization followed by hydride migration and reduction which compliments aminomercurations which typically undergo 5-<italic>exo-trig</italic> cyclizations in these systems to afford pyrrolidines. Additionally, mechanistic studies of alpha-mercurio iminium ions have established that these species protodemercurate in protic solvents. For example, treatment of 1-(2-mercurioacetate)-cyclohexylidenepyrrolidinium acetate with sodium borodeuteride in D<sub>2</sub>O results in deuteriodemceruation and reduction of the iminium ion to afford N-(1,2-dideuteriocyclohexyl)pyrrolidine. A variety of approaches to a general synthesis of chiral heteroatom-substituted 2-azaallyl anion precursors such as (2<italic>S</italic>)-1-[2-aza-1-methyl-3-(tributylstannyl)-1-butenyl]-2-methoxymethylpyrrolidine, is also described. Although the approaches to this type of compound were ultimately unsuccessful in providing a general route to this class of chiral 2-azaallyl anion precursors, much useful information about the properties of these molecules and the benefits and drawbacks of various bond disconnections was discovered. It would appear, in accordance with previous attempts, that the steric demands of the bulky tributyltin group are problematic in almost all the approaches to chiral heteroatom substituted 2-azaallyl anion precursors that were investigated. A mechanistic study of 2-azaallyl anion cycloaddition reactions was also conducted. For example, in order to determine if the cycloaddition between 1,3-dimethyl-2-azaallyl lithium and styrene could procedure <italic>via</italic> a stepwise rather than concerted pathway, the cyclization precursor (1<italic> R</italic>*,3<italic>R</italic>*)-ethylidene-(1-methyl-3-phenyl-3-tributylstannanylpropyl)amine was synthesized. Treatment of this compound with <italic>n</italic>-butyllithium generated a benzyllithium intermediate that would be expected to form if a 2-azaallyl anion cycloaddition was to proceed through a stepwise mechanism. Formation of this benzyllithium intermediate results in a 5-<italic>endo-trig </italic> cyclization and the formation of pyrrolidine products. As a result, it can be concluded that the reaction of 2-azaallyl anions with anionophiles can potentially form <italic>via</italic> a stepwise mechanism. However, additional studies have demonstrated that while this pathway can be in operation, it does not account for the conservation of the anionophile stereochemistry observed in the cycloaddition of most 2-azaallyl anions. Therefore, while 2-azaallyl anions can cycloadd in a stepwise fashion, they are predominantly concerted processes. Additionally, experiments have demonstrated that these 5-<italic> endo-trig</italic> cyclization reactions have potential synthetic utility for the construction of pyrrolidine compounds.Subjects
Alkenes Anion Precursors Approach Asymmetric Azaallyl Anions Azidomercurations Ii Mechanistic Mercury Non Promoted Schmidt Reactions Stabilized Studies
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