Imines from unsaturated heterocycles

Reactions of Endocyclic Imine Anions Derived from Unsaturated Heterocycles... 

Another recent exciting addition to the catalyst armamentarium has resulted from studies of chiral N-heterocyclic carbenes. Bode utilized the steri-cally encumbered N-heterocyclic carbene 270 as a chiral catalyst to effect inverse-electron-demand hetero-Diels-Alder reactions of a,j8-unsaturated imines and unsaturated aldehyde 268 (Equation 28) [136, 137]. The addition of carbene 270 to aldehyde 268 in a 1,2-manner, followed by a critical proton-transfer step, leads to the formation of an enolate. This enolate possesses well differentiated diastereofaces as depicted in the proposed endo transition state assembly 272. A range of unsaturated imines participated in the reaction to give the product dihydropyridinones in excellent optical purity, as exemplified by the formation of 271 in 99% ee and 90% yield [136]. 

Eight-membered heterocyclic systems embrace a very broad variety of compounds ranging from cyclic ethers and imines to highly labile analogs of cyclooctatetraene, and the properties and chemical behavior of these compounds of course depend entirely on the extent and location of unsaturation. For this reason, preparative methods and reactions are treated together for each ring system and oxidation level. 

Three-component reactions of aldehydes, amines, and allyltributyltin also proceeded smoothly in micellar systems with Sc(OTf)3 as Lewis acid catalyst, to afford the corresponding homoallylic amines in high yields (Eq. 19) [68]. Not only aromatic aldehydes but also aliphatic, unsaturated, and heterocyclic aldehydes worked well. The procedure is very simple—merely mixing an aldehyde, an amine, and allyltributyltin in the presence of Sc(OTf)3 and SDS in water no homoallylic alcohol (an adduct between an aldehyde and allyltributyltin) was produced. It was suggested that imine formation from aldehydes and amines was very fast under these conditions, and that the selective activation of imines rather than aldehydes was achieved. 

In 2013, the first successful generation of ds-homoenolate equivalents from ds-enals under the catalysis of N-heterocyclic carbene D4 was developed by the Chi group. The ds-homoenolate intermediates I undergo effective reaction with a,p-unsaturated imines to afford chiral cyclic ketones 62. Compared to the trans-enals, ds-enals show different stereoselectivities and new reactivity patterns (Scheme 20.29). 

Catalytic asymmetric formal [4-1-2] cycloaddition reactions offer a versatile and elegant approach to the asymmetric synthesis of six-membered heterocycles. In 2006, Bode and coworkers demonstrated NHC-catalysed generation of enolate equivalents from enals for enantioselective Diels-Alder reactions. Reaction with a,p-unsaturated imine 100 provided the dihy-dropyridinones 101 in good yield and with remarkable enantioselectivities (Scheme 20.44). 

A commercially available polystyryldiphenylphosphine has been used to convert 3 -azido-3 -deoxy-nucleosides into the corresponding 3 -amino-3 deoxy-nucleosides, by formation and hydrolysis of phosphine imine intermediates. The formation of heterocyclic compounds on photolysis of glycosyl azides is covered in Section 6, and the formation of unsaturated sugars by radical elimination of vicinal phenyl selenide and xanthate azides from i ropriate saturated compounds is covered in Chapter 13. 

The enantioselective intramolecular formal 2+4-cycloaddition of acrylates and a, -unsaturated imines (99) catalysed by chiral phosphines (100), derived from amino acids, produced A-heterocycles (101) (Scheme 31). Chiral dirhodium(II) carboxamidates (102) catalysed the hetero-Diels-Alder reactions between 2-aza-3-silyloxy-l,3-butadienes and aldehydes to yield all cw-substituted l,3-oxazinan-4-ones in high yields and high enantioselectivity (98% ee)P The nickel-catalysed 4 + 2-cycloaddition of a, -unsaturated oximes with alkynes yielded 2,3,4,6-tetrasubstituted pyridine derivatives. The reaction of isoquinoline, an activated alkyne, and 4-oxo-4//-l-benzopyran-3-carboxaldehyde (103), in ionic solvents, produced 9a//,15//-benzo[a][l]benzopyrano[2,3-/t]quinolizine derivatives (105) via the zwitterion (104) selectively and in good yields (Scheme 32).The Diels-Alder cycloaddition of ethyl 3-(tetrazol-5-yl)-l,2-diaza-l,3-butadiene-l-carboxylates with -rich heterocycles, nucleophilic olefins, and cumulenes formed 3-tetrazolyl-l,4,5,6-tetrahydropyridazines regioselectively. The silver-catalysed formal inverse-electron-demand Diels-Alder... 

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