Highly Enantioselective Synthesis of Polysubstituted Tetrahydroquinolines via Organocatalytic Michael/Aza-Henry Tandem Reactions

Abstract

Highly enantioselective chiral bifunctional thiourea catalyzed asymmetric tandem reactions for synthesis of substituted tetrahydroquinolines are described. Substituted tetrahydroquinolines were given in good yields (up to 98%), high enantioselectivities (up to >99% ee), and diastereoselectivities (up to 20:1 dr).

Organocatalytic Aza‐Michael–Michael Cascade Reactions: A Flexible Approach to 2,3,4‐Trisubstituted Tetrahydroquinolines

“…Recently, we communicated a new method for the two‐component, two‐step synthesis of polysubstituted tetrahydroquinoline derivatives through an organocatalytic asymmetric tandem Michael addition and aza‐Henry reaction [Eq. (1)] 7. This type of reaction yields the cis ‐isomer at the 2,3‐positions.…”

A New Henry/Michael/Retro‐Henry/Henry Domino Sequence Promoted by Bifunctional Organocatalysts

“…In all cases the reactions smoothly proceeded under very mild conditions, and the desired functionalized products (6)(7)(8)(9)(10)(11)(12)(13)(14) were obtained in good yield and diastereoselectivity and excellent enantioselectivity (up to 99% ee).…”

“…In more detail, we planned a new two-component cascade, in which nitromethane acted as a double-donor towards two differently reactive acceptors present in the same molecule. [12] Only Xu and co-workers [13] reported a similar tandem double addition of nitromethane, but they employed an imine and an a,b-unsaturated ketone as acceptors, thus carrying out a Michael/Henry sequence [Scheme 1, Eq. [12] Only Xu and co-workers [13] reported a similar tandem double addition of nitromethane, but they employed an imine and an a,b-unsaturated ketone as acceptors, thus carrying out a Michael/Henry sequence [Scheme 1, Eq.…”

Recent Developments in Asymmetric Organocatalytic Domino Reactions

“…[95] The authors have shown that installing an electron-withdrawing sulfone group on the amino group of 2-aminobenzaldehydes allowed for their activation, since the corresponding sulfonated 3-nitro-1,2-dihydroquinolines were generally obtained in better yields (75-92%), and enantioselectivities (70-90% ee). More recently, Xu et al developed an access to 2,3,4-trisubstituted tetrahydroquinolines 188a-g on the basis of asymmetric domino Michaelaza-Henry reactions involving nitromethane and chalcones 189a-g. [96] When these reactions were catalyzed with bifunctional thiourea 190, they furnished the potential biologically active polysubstituted tetrahydroquinolines 188a-g in generally both excellent yields (94-98%) and enantioselectivities (98 to > 99% ee) combined with moderate to high diastereoselectivities of up to 90% de, as shown in Scheme 51.…”