Imines hydroxyaniline derived

Enantiomerically pure Br0nsted acid catalysts are beginning to see application in the aza-Diels-Alder reaction. For example, the aza-Diels-Alder reaction of 2-hydroxyaniline-derived aromatic imines, including (8.151), with diene (8.123) proceeds with up to 91% ee in the presence of 10 mol% of the phosphoric acid (8.158). While the strong acidity of this catalyst precludes its use in reactions of labile substrates, the pyridinium salt of the related acid (8.159) catalyses the aza-Diels-Alder reaction with less stable dienes such as Brassard s diene (8.134) with ees between 92 and 99%. ... 

The catalytic asymmetric azadiene-Diels-Alder reaction has also received some recent attention. Initial work in this area used hydroxyaniline-derived imine... 

Phosphoric acid can catalyze electron-demanding aza-Diels-Alder reaction smoothly between hydroxyaniline-derived imine 10 and 2,3-dihydro-2//-furan 11 to afford enantioenriched 8-hydroxytetrahydroquinolines as reported by Akiyama et al. [6]. Interestingly, Rueping and Lin disclosed that in the presence of A-triflylphosphoramide... 

After Akiyama et al. reported the first organocatalzyed inverse electron-demand aza-Diels-Alder reaction (Povarov reaction) between o-hydroxyaniline-derived imines and alkyl vinyl ethers [6], Liu et al. developed a three-component Povarov reaction of aldehydes 3, anilines 7, and benzyl A-vinylcarbamates 8a that efficiently afforded enantioenriched (2,4-c )-4-amino-l,2,3,4-terahydroquinoline 35 with a wild substrate scope (Scheme 2.9) [15a], Subsequently, a full study of the mechanism, substrate scope, and catalyst loading of this transformation was made, which revealed that this type of three-component Povarov reaction underwent a stepwise mechanism [15b]. Very recently, He, Shi, and others proved independently that the hydroxystyrenes 8b or 8c can also act as good dienophiles in asymmetric three-component Povarov reactions, thus providing efficient methods to access structurally diverse multisubstituted tetrahydroquinolines 35a or 35b in high stereoselectivities [16]. 

In the Diels-Alder reaction between Danishefsky s diene and N-aryl imines derived from o-hydroxyaniline catalyzed by Ih, Akiyama observed substantial increases in chemical yield and enantioselectivty by the addition of stoichiometric amounts of acetic acid (Scheme 5.14) [27]. The authors concede that the role of the protic acid is unclear. 

Akiyama applied Im in the inverse-demand aza-Diels-Alder reaction of various acyclic and cyclic vinyl ethers with N-aryl imines derived from o-hydroxyaniline to provide ophcally active tetrahydroquinoline derivatives (Scheme 5.16) [29]. Since aldimines derived from p-methoxyaniline gave no cycloaddition product, a nine-membered cyclic TS (akin to that proposed for the author s Mannich reachon) was invoked to rationalize the high levels of enantio-control. 

Kobayashi has demonstrated that a chiral zirconium catalyst derived from 3,3 dibromo or 3,3 dichloro BINOL can catalyze the addition of substituted allyl stannanes to the imines derived from 2 hydroxyaniline and aryl or hetereoaryl substituted aldehydes (Scheme 1.25) [95]. The active catalyst is possibly generated by the bonding of the alcohol functionalities of the imine and of allylstarmane to the zirconium center. 

The HDA reaction can also be performed using imines as dienophiles to give piperidinone derivatives as the cycloadducts. This aza-Diels-Alder process has been performed in an asymmetric fashion using a variety of enantiomerically pure metal-based Lewis acids. Early work in this area was carried out by Kobayashi and coworkers using zirconium catalysts derived from BINOL (8.150) in the cycload-dition of diene (8.123) with aryl imines derived from 2-hydroxyaniline such as (8.151). ° More recently aryl imines derived from 2-methoxyaniline (o-anisidine)... 

The first enantioselective Povarov reactions were two-component processes catalyzed by chiral complex of Lewis acids, but gave only modest results in terms of conversion and diastereo- and enantioselectivities [63]. Better results were obtained by Akiyama using a chiral Brpnsted acid derived from (/ )-BINOL (79) to catalyze the reaction of alkyl vinyl ethers with aromatic imines derived from o-hydroxyanilines, which gave derivatives of 8-hydroxytetrahydroquinoline 80 in good yields, with excellent diastereoselectivities and enantiomeric excesses. The authors attribute these results to the formation of a cyclic transition state wherein the chiral catalyst coordinates with both the OH and imine nitrogen, driving the attack of the nucleophile by ih Re face of the imine (Schemes 3.22 and 3.24) [64]. 

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