Organocatalytic Diastereo‐ and Enantioselective Annulation Reactions—Construction of Optically Active 1,2‐Dihydroisoquinoline and 1,2‐Dihydrophthalazine Derivatives

Abstract

Good to high conversions (70–100 %) into optically active tri‐ or tetracyclic nitrogen‐containing compounds 1 based on 1,2‐dihydroisoquinolines and 1,2‐dihydrophthalazines proceed with high diastereoselectivity (d.r.≥15:1) and good to excellent enantioselectivity (85–96 % ee) in the presence of a chiral amine.

Alternative tandem cyclisation pathways in the reaction between imines and enones

“…23 Although L-proline provided cyclisation, there was no asymmetric induction, and indeed, a C2-symmetric chiral pyrrolidine was required in order to effect asymmetric induction.…”

A new era for organic synthesis—highlights of the recent progress

“…There are a number of research works on the proline-type organocatalysts, for example: Jørgensen et al reported the organocatalytic diastereo-and enantioselective annulation reactions in the construction of optically active 1,2-dihydroisoquinoline and 1,2-dihydrophthalazine derivatives [111]; Maruoka et al reported the design of an axially chiral amino acid with a binaphthyl backbone as an organocatalyst (Structure A) for a direct asymmetric aldol reaction [112]; Jørgensen et al reported organocatalytic conjugate addition of malonates to α,β-unsaturated aldehydes and finished the asymmetric formal synthesis of (−)-paraxetine [113]; Zhao et al reported organocatalytic enantioselective synthesis of α-hydroxy phosphonates via a proline-catalyzed asymmetric cross aldol reaction of activated ketones [114]; proline derivatives were reported to be involved into the organocatalytic direct Michael reaction of ketones and aldehydes with nitroalkenes [115,116]; Barbas, III explored 3-pyrrolidinecarboxylic acid (Structure B) for direct catalytic asymmetric Mannich-type reaction of unmodified ketone with anti-selectivity [117]; Palomo reported highly efficient asymmetric Michael addition of aldehyde to nitroalkene catalyzed by trans-4-hydroxyprolylamide (Structure C), with 4-hydroxy group involved in the reaction transition state [118]; Wang and Wang [119] reported the directly, highly enantioselective Michael addition of aldehyde to nitro styrene catalyzed with pyrrolidine sulfonamide (Structure D).…”

Aza‐Henry Reactions of 3,4‐Dihydroisoquinoline

“…The literature contains numerous examples of the reaction of imines with organometallic reagents, [6] or the reaction of alkylated or acylated (Reissert-like) isoquinolines with (frequently reactive, metallated) nucleophiles (5 to 6, see Scheme 1,B). [7][8][9] Recent examples of the reaction of isoquinolines with non-organometallic species include Shibasaki's catalytic, asymmetric cyanation of isoquinolines, [10] Jorgensen's intramolecular organocatalytic annulation reaction of an enamine with an alkyliminium ion in the synthesis of 1,2-dihydroisoquinoline derivatives, [11] and Jacobsen's organocatalyzed acyl nitro-Mannich reaction between isoquinolines and silyl ketene acetals. [12,13] Reports of similar reactions with dihydroisoquinolines rather than quinolines are fewer in number, but, besides the synthesis of Reisserttype compounds, [14] include intramolecular [15] and intermolecular [16] attack of enolates on alkyldihydroisoquinolinium salts, enolate addition to a chiral acyldihydroisoquinolinium salt, [17] enantioselective metal-catalyzed addition of malonates and alkenylzirconocenes to acyldihydroisoquinolinium salts, [18] and 1,3-dipolar cycloadditions of the azomethine ylides derived from Reissert compounds.…”