Asymmetric Electrophilic a-Amidoalkylation 6: Syntheses of Tetrahydroisoquinolines of High Enantiomeric Purity

A General Methodology for the Enantioselective Synthesis of 1‐Substituted Tetrahydroisoquinoline Alkaloids

“…Similarly, the usefulness of this methodology in the synthesis of 1‐phenethyltetrahydroisoquinolines was demonstrated by the preparation of 7g 20 from α‐amidoalkylation product 5g .…”

Preparation of β-Amido Ketones and Aldehydes via Amidoalkylation of Enamines, Enol Silyl Ethers, and Vinyl Ethers

“…Amidoalkylations, which have been used widely in organic synthesis, 11a,b have provided many β-amidocarbonyl compounds. 12a-e Our previous work has demonstrated N -(1-benzotriazol-1-ylalkyl)amides to be versatile reagents for the amidoalkylation of malonates and acetoacetates, reactive aromatics, cyanide anion, mercaptans, alcohols, ammonia, ethyl diphenylphosphinite anion, primary and secondary amines, and triallylstannanes 22a,b giving in each case the expected products. We have previously reported one example that used an N -(benzotriazol-1-ylmethyl)benzamide to react with isopropenyl acetate to afford a β-amido ketone in relatively poor yield .…”

Aza‐Henry Reactions of 3,4‐Dihydroisoquinoline

“…[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. [19] It is typical for the dihydroisoquinoline to be covalently "activated" by alkylation or acylation (or via formation of the N-oxide [20] ) prior to nucleophilic attack, but in some cases this is not necessary.…”