Aza-Diels—alder reactions

Catalytic enantioselective addition to imines, in particular, aza-Diels-Alder reaction 99CRV1069. 

Reaction of 2-aminopyridines with formaldehyde and electron rich styrenes 383 permitted the synthesis of 3,4-dihydro-2//-pyrido[l,2-n]pyr-imidines 384 (96TL2615). First imines 382 formed they are involved in a formal aza-Diels-Alder reaction to give compounds 384. 

Catalytic enantioselective hetero-Diels-Alder reactions are covered by the editors of the book. Chapter 4 is devoted to the development of hetero-Diels-Alder reactions of carbonyl compounds and activated carbonyl compounds catalyzed by many different chiral Lewis acids and Chapter 5 deals with the corresponding development of catalytic enantioselective aza-Diels-Alder reactions. Compared with carbo-Diels-Alder reactions, which have been known for more than a decade, the field of catalytic enantioselective hetero-Diels-Alder reactions of carbonyl compounds and imines (aza-Diels-Alder reactions) are very recent. 

In 1996, the first example of the catalytic enantioselective aza Diels-Alder reactions of azadienes using a chiral lanthanide catalyst was reported [4], In this article, successful examples of such catalytic reactions are surveyed. 

To achieve catalytic enantioselective aza Diels-Alder reactions, choice of metal is very important. It has been shown that lanthanide triflates are excellent catalysts for achiral aza Diels-Alder reactions [5]. Although stoichiometric amounts of Lewis acids are often required, a small amount of the triflate effectively catalyzes the reactions. On the basis of these findings chiral lanthanides were used in catalytic asymmetric aza Diels-Alder reactions. The chiral lanthanide Lewis acids were first developed to realize highly enantioselective Diels-Alder reactions of 2-oxazolidin-l-one with dienes [6]. 

Scheme 5.2 Catalytic enantiose-lective aza Diels-Alder reaction (1)...

Tab. 5.1 Effect of additives in the asymmetric aza Diels-Alder reaction...

Tab. 5.2 Catalytic enantioselective aza Diels-Alder reactions using azadienes...

Several examples of catalytic aza Diels-Alder reactions using the chiral zirconium catalyst are shown in Table 5.5 [18]. High chemical yields and good to high... 

Polymer-supported BINOLs thus prepared were treated with Zr(Ot-Bu)4 to form polymer-supported zirconium 20. In the presence of 20 mol% of various zirconium 20, the model aza Diels-Alder reactions of imine Id with Danishefsky s diene (7a) were performed results from selected examples are shown in Table 5.8. Whereas the 4-t-butylphenyl group resulted in lower enantiomeric excess (ee), higher ee were obtained when 3,5-xylyl, 4-biphenyl, 4-fluorophenyl, and 3-tri-... 

Several examples of catalytic asymmetric aza Diels-Alder reactions are shown in Table 5.10 [30]. The reaction always proceeded smoothly to afford the correspond-... 

Thus, a novel chiral zirconium complex for asymmetric aza Diels-Alder reactions has been developed by efficient catalyst optimization using both solid-phase and liquid-phase approaches. High yields, high selectivity, and low loading of the catalyst have been achieved, and the effectiveness of chiral catalyst optimization using a combination of solid-phase and liquid-phase methods has been demonstrated. 

Aza Diels-Alder Reactions of a-lmino Esters with Dienes... 

Tab. 5.n Aza Diels-Alder reaction ofa-imino esters OSiMea... 

Tab. 5.12 Aza Diels-Alder reactions using several dienes...

A chiral magnesium catalyst prepared from magnesium iodide and 1,2-diphenyl-ethylenediamine was also found to he effective in asymmetric aza Diels-Alder reaction of a-imino ester 21b with 7a (Scheme 5.12) [32]. The novel catalyst was discovered using parallel comhinatorial methods. 

Tab. 5.13 Catalytic asymmetric aza Diels-Alder reactions of 2-azadienes...

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