Imines heteroatom-stabilized

ADDITION REACTIONS OF HETEROATOM-STABILIZED IMINE ANIONS... 

The heteroatom version of the vinylcyclopropane rearrangement serves to facilitate alkaloid construction. Scheme 13 outlines a strategy for the pyrrolizidine alkaloid isoretronecanol 211 90). Use of a carboxaldehyde (i.e. 213) as a synthon for the primary alcohol provides an ability to adjust stereochemistry. It also sets up formation of the pyrrolidine ring bearing the aldehyde by an aldol-type condensation of an enol of the aldehyde onto an imine derived from 214. Because of the lability of such systems, introduction of X=PhS imparts stability. The resultant azacyclopentene translates to an imine 215 using the iminocyclopropane rearrangement methodology. Simple condensation of the primary amine 216 with aldehyde 37a then initiates this... 

A stereocontrolled Staudinger cycloaddition reaction has been reported to be performed on vinylketenes, possessing a y-heteroatom, and imines to produce frans-vinyl-(3-lactams [112]. The vinyl side chain adopted stereoselectively the (Z) configuration in the transition state, stabilizing the vinyl ketene and leading, exclusively, to the frans-3-vinyl-(3-lactam (Scheme 37). 

N-Metallated azomethine ylides 140 of ester-stabilized types are tautomeric to the metal ester enolates (141) of chelate-stabilized types. The only structural difference is which heteroatom between the imine nitrogen and the ester carbonyl oxygen is connected with the metal (M) by a covalent bond. The difference in chemical properties expected for the ylidic forms 140 and enolate forms 141 is not yet clear. 

Enamines. The condensation of a secondary amine and a ketone to make an enamine is a well known reaction which has seen wide use in organic synthesis [176-178]. Imines of a primary amine and a ketone exist in a tautomeric equilibrium between the imine and secondary enamine forms, although in the absence of additional stabilization factors cf. Scheme 5.33), the imine is usually the only detectable tautomer. Nevertheless, the enamine tautomer is very reactive toward electrophiles and Michael additions occur readily [179]. The mechanism of the Michael additions of tertiary and secondary enamines are shown in Scheme 5.34. For tertiary enamines, the Michael addition is accompanied by proton transfer from the a -position to either the a-carbon or a heteroatom in the acceptor, affording the regioisomeric enamine as the initial adduct [180]. The proton transfer and the carbon-carbon bond forming operations may not be strictly concerted, but they are nearly so, since conducting the addition in deuterated methanol led to no deuterium incorporation [180]. 

The C=X bond in these substrates is polar and the preferred transition state must be that depicted in Scheme 6.54 (32) with the negative X atom binding the metal, and leading to the formation of M-X and C-R bonds. Usually, the heteroatom X in the substrate has lone pairs and can also bind the metal as a monodentate ligand (31, Scheme 6.54). The attainment of the transition state for insertion requires the /c -coordination of the substrate or at least a slippage that places the C atom close enough to interact with the M-R bond [171]. Then a high stability of complex 31, can be a serious drawback for the observation of the insertion reaction in some substrates (e.g. imines) [169]. 

Nucleophilic additions to alkenes and alkynes are also possible, but these reactions generally require that the substrate have substituents that can stabilize a carbanionic intermediate. Therefore, nucleophilic additions are most likely for compoimds with carbon-heteroatom multiple bonds, such as carbonyl compounds, imines, and cyano compounds. We may distinguish two main types of substituents that activate alkenes and alkynes for nucleophilic attack. The first type consists of those activating groups (labeled AG in equation 9.79) that can stabilize an adjacent carbanion by induction. ... 

Other groups capable of stabilizing the anion generated by decarboxylation may be present in place of the ketone group. These include esters (so that the substrate is a malonate), nitriles, nitro groups, imines and sulfones. Even alkynes may be used, although the stereochemical outcome of the reaction indicates that, in this case at least, the nucleophile remains bound to palladium (Scheme 9.61). Decarboxylation of heteroatom derivatives, such as allyl carbamates, is included in Section 9.2.8. 

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