Catalytic asymmetric aza Diels-Alder reactions using a chiral lanthanide Lewis acid. Enantioselective synthesis of tetrahydroquinoline derivatives using a catalytic amount of a chiral source

The First Enantioselective Aza-Diels-Alder Reactions of Imino Dienophiles on Use of a Chiral Zirconium Catalyst

“…A typical experimental procedure is described for the reaction of the aldimine obtained from o-tolualdehyde and 2-aminophenol with 3: 6,6'-Dibromo-1,1'-bi-2-naphthol (0.088 mmol) in toluene (0.5 mL) and N-methylimidazole (0.12 mmol) in toluene (0.25 mL) were added to Zr(OtBu) 4 (0.04 mmol) in toluene (0.25 mL) at room temperature. The mixture was stirred for 1 h at the same temperature, and then cooled to À 45 8C.…”

“…[3] Quite recently, we reported the first example of a catalytic, enantioselective azaDiels ± Alder reaction of azadienes on using a chiral lanthanide catalyst. [4] While high diastereo-and enantioselectivities were attained in the reaction of azadienes with dienophiles, the products obtained were limited to 8-hydroxytetrahydroquinoline derivatives. Here we report the catalytic, enantioselective aza-Diels ± Alder reactions of aldimines (imino dienophiles) with Danishefskys diene for the synthesis of a wide variety of chiral piperidine derivatives; a chiral zirconium compound was used as catalyst.…”

Recent Advances in Asymmetric CC and C‐Heteroatom Bond Forming Reactions using Polymer‐Bound Catalysts

“…[183] In 1996, Kobayashi et al reported the first examples of catalytic asymmetric aza-Diels±Alder reactions using a chiral ytterbium catalyst. [184] The same authors disclosed reactions of azadienophiles (imino dienophiles) with Danishefsky×s diene using chiral zirconium-binaphthol complexes like 221 (Scheme 48). [185] While high yields and selectivities were obtained, the catalyst loading was rather high (10 ± 20 mol %).…”

Sodium Salts of Anionic Chiral Cobalt(III) Complexes as Catalysts of the Enantioselective Povarov Reaction

“…Thus,wedecided to test these catalysts in the challenging Povarov reaction [3] of simple 2-azadienes and dienophiles to generate structurally diverse 1,2,3,4-tetrahydroquinoline (THQ) derivatives with contiguous stereogenic centers,w hich are key structural motifs of numerous natural products and pharmacologically relevant molecules. [4] Thec atalytic enantioselective Povarov reaction has been intensively investigated [5][6][7] since the pioneering work by Ishitani and Kobayashi, who employed ac hiral ytterbium complex as the catalyst.[6a] In these cases,classical chiral Lewis acids [6] or chiral Brønsted acids [7] have generally been the catalysts of choice to promote asymmetric versions.Thus,the development of new chiral catalyst motifs that are principally distinct from traditional ones is still highly desirable.Herein, we show that the sodium salts of anionic chiral Co III complexes (CCC À Na + )a re able to act as promising chiral catalysts for the asymmetric Povarov reaction of aw ide variety of simple 2-azadienes and dienophiles,s uch as 2,3-dihydrofuran, ethyl vinyl ether, and an N-protected 2,3-dihydropyrrole,g iving rise to multiply substituted THQ derivatives in high yields and with excellent stereoselectivities (Scheme 1).Our initial investigation started with the reaction of N-phenyl benzaldimine (1a)with 2,3-dihydrofuran (2a)inthe presence of the Brønsted acids of various anionic chiral Co III complexes (CCC À H + , 4a-4e;5mol %), which are all derived from salicylaldehydes and l-amino acids (Table 1, entries 1-7).[2d] Among them, L-4e, [8] which bears a3 ,5-di-tert-butylsubstituted (R 1 ,R 2 )s alicylaldehyde and a tert-butyl group (R 3 )onthe amino acid moiety,gave the highest enantiomeric ratio of 75:25 (entry 7). Interestingly,t he use of sodium salt L-4f to replace its acidic form L-4e improved both the diastereo-and enantioselectivities (entry 8v s. entry 7).…”

“…[6a] In these cases,classical chiral Lewis acids [6] or chiral Brønsted acids [7] have generally been the catalysts of choice to promote asymmetric versions.Thus,the development of new chiral catalyst motifs that are principally distinct from traditional ones is still highly desirable.Herein, we show that the sodium salts of anionic chiral Co III complexes (CCC À Na + )a re able to act as promising chiral catalysts for the asymmetric Povarov reaction of aw ide variety of simple 2-azadienes and dienophiles,s uch as 2,3-dihydrofuran, ethyl vinyl ether, and an N-protected 2,3-dihydropyrrole,g iving rise to multiply substituted THQ derivatives in high yields and with excellent stereoselectivities (Scheme 1).…”