Aldimines regioselectivity

The reaction is also applicable to a wide structural variety of 1,3-dienes, as demonstrated by the reaction of 2-furfural-p-anisidine imine (Table 9). All dienes react with the aldimine regioselectively at the diene termini bearing the highest electron densities and provide bis-homoallyl amines with excellent 1,3-syn diastereoselectivity. No C4-adducts are formed in these reactions. 

A-Tosyl aldimines, RCH=N-Ts, add regioselectively to the C(2) of pyrroles, to give pyrrole sulfonamides (11), using copper(II) triflate as catalyst.53... 

The synthesis of novel azetidine derivatives remains the subject of intensive study. New procedures for the preparation of this class of compounds include, e.g., rearrangement of /3,7-aziridino-a-amino esters <2007OL4399>, copper-catalyzed multicomponent reactions of terminal alkynes, sulfonyl azides, and carbodiimides <20070L1585>, regioselective addition of 1,3-dicarbonyl dianions to iV-sulfonyl aldimines <2007T4779>, elaboration of a-amino acids <2007TL2471>, palladium-catalyzed iV-arylation of azetidines <2007S243> and... 

Crotyltins react regioselectively with a-alkylimines to give exclusively branched products with an excellent syn/anti selectivity up to 30 1, when the imine activation is conducted at —78 °C prior to the addition of the crotyltin. This selectivity which is consistent with an acyclic transition state is rapidly fading when operating at a higher temperature. This would be the result of an equilibrium between the two imine/Lewis acid complexes (equation 14). There are very few examples with a, /3-unsaturated aldimines, but it has to be noted that under TiCU activation, they are able to undergo a double nucleophilic addition of ketene silyl acetal and allyltributyltin to give the homoallylic amine in a reasonable yield . 

The previous cycloaddition reaction discussed is believed to proceed through an aldimine anion (19). Such delocalized anions can also be generated by treatment of suitable aldimines with a strong base. Subsequent cyclocondensation with a nitrile produces imidazoles [25-28]. The 2-azaallyl lithium compounds (19) are made by treatment of an azomethine with lithium diiso-propylamide in THF-hexane ( 5 1) (Scheme 4.2.9) [29. To stirred solutions of (19) one adds an equimolar amount of a nitrile in THF at —60°C. Products are obtained after hydrolysis with water (see also Section 2.3). If the original Schiff base is disubstituted on carbon, the product can only be a 3-imidazoline, but anions (19) eliminate lithium hydride to give aromatic products (20) in 37-52% yields (Scheme 4.2.9). It is, however, not possible to make delocalized anions (19) with R = alkyl, and aliphatic nitriles react only veiy reluctantly. Examples of (20) (Ar, R, R, yield listed) include Ph, Ph, Ph, 52% Ph, Ph, m-MeCeUi, 50% Ph, Ph, p-MeCeUi, 52% Ph, Ph, 3-pyridyl, 47% Ph, Ph, nPr, 1% [25]. Closely related is the synthesis of tetrasubstituted imidazoles (22) by regioselective deprotonation of (21) and subsequent reaction with an aryl nitrile. Even belter yields and reactivity are observed when one equivalent of potassium t-butoxide is added to the preformed monolithio anion of (21) (Scheme 4.2.9) [30]. 

Aromatic and heteroaromatic aldimines were effectively converted into vinylogous Mannich products 31 with complete y regioselectivity and with typically 80 90% ee. The reaction could easily be run in a three component fashion, starting directly from an aldehyde, para anisidine, and silyl dienolate 30 obviating the need to prepare the imine in a separate reaction. In contrast to most other protocols that required a salicyl imine moiety in the substrate for selectivity issues, here the amine component within the imine could just be a phenyl group or any para substituted phenyl group. 

The pioneering work of Stork and coworkers and Wittig and coworkers on the metallation of ketimines, and their subsequent reaction with a variety of electrophiles, has proven extremely useful for controlled aldol condensation and also for regioselective functionalization of ketones Recently, reactions of chiral lithiated ketimines and aldimines have been established as an important method of asymmetric synthesis, producing chiral ketones in optical yields as high as 95%... 

Table 12 Regioselectivity in the Reaction of Crotyl Organometallic Reagents (46) with Aldimines...

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