Achiral iminium cations

The resulting achiral iminium cations, with chiral phosphate counteranion, were then enantioselectively reduced using an achiral Hantzsch ester (dihydropyridine) providing enantioenriched amines. During this imine reduction study, one example was shown in which acetophenone and p anisidine [16] were prestirred in the presence of toluene and 4 A molecular sieves [17] for 9h (imine formation), after which the temperature was raised to 35 °C, and the Hantzsch ester (1.4 equiv) and phosphoric acid (TRIP, 5 mol%) were added to give the amine product in 88% ee over an additional 45 h. This is an exciting observation and while not a reductive amination, it is an operational improvement over simple imine reduction which requires imine isolation. 

Rueping and Antonchick [51] have examined the phosphoric acid diester-catalyzed 2-aza-Cope rearrangement [52], a transformation that provides an efficient entry to chiral homoallylic amines. They assumed that a phosphoric acid diester would both promote the in situ formation of an allyl iminium cation from an aldehyde and an achiral homoallylic amine, and the subsequent 2-azonia-Cope rearrangement. In a separate hydrolysis step, the rearranged homoallylic amine would furnish the target chiral amine (Scheme 40.42). 

The enantiotopic protons of the prochiral methyl groups in the iminium salt 36 exhibited distinct resonances in the presence of Eu(hfc)3 . As already discussed for achiral lanthanide S-drketonates, the system likely forms an ion pair between the organic cation and the species [Ln( S-dik)3X]. The spectrum of racemic 37, which as its bromide salt has been studied as an ionic liquid, exhibits nonequivalence in the presence of Eu(tfc)3 and Eu(hfc)3. No splitting of the resonance occurs in the presence of Eu(fod)3. In addition to the likely ion-pairing interaction of 37 with [Ln(/ -dik)3X] , rather substantial shifts of some of the OCH2 protons implied that the ether oxygen atoms also likely coordinated with the europium ion. A similar ion-paired system explains the enantiomeric discrimination observed in the spectrum of the tris(phenanthroline) complexes of Ru(II) ([Ru(phen)3]Cl2) in the presence of Eu(tfc)3 . 

In the last few years, several groups have developed enantioselective domino reactions catalysed by combinations of organocatalysts with palladium complexes. As an example, Murkheqee and List have reported a domino synthesis of p-all earbon quaternary amines on the basis of a highly enantioseleetive a-allqrlation of a-branched aldehydes, involving an achiral palladium catalyst and a chiral phosphoric acid. Under the catalysis of phosphoric acid, a secondary allylamine reacted with an a-branehed aldehyde to form an enammonium phosphate salt, which upon reaction with palladium catalyst afforded a cationic 7t-allyl palladium complex (Scheme 7.2). This intermediate resulted in the formation of an a-allylated iminium ion, whieh eould be reduced to the corresponding final chiral amine in high yield and exeellent enantioselectivity of 97% ee. The synthetic utility of this transformation was also demonstrated hy a formal synthesis of (+)-cuparene. 

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