Intramolecular Hydroaminations Mediated by Reductive Mercuration or n‐Butyllithium To Afford 3‐Methyl‐ and 3,4‐Dimethyl‐1,2,3,4‐tetrahydroisoquinolines

Abstract

The synthesis of 3‐methyl‐ and 3,4‐dimethyltetrahydroisoquinolines from aromatic aminoalkenes using intramolecular hydroamination reactions is described. This reaction was achieved by way of a reductive aminomercuration using mercuric acetate followed by sodium borohydride, or by using sub‐stoichiometric amounts of n‐butyllithium. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Isomerization of Allylbenzenes

“…van Otterlo and co-workers modified the Beller approach to provide 3-methyl- and 3,4-dimethyl-1,2,3,4-tetrahydroisoquinolines 258 from precursors 257 , by way of an intramolecular hydroamination promoted by substoichiometric amounts of n -butyllithium. , To prove that an isomerization was critical to the success of the reaction, compound 259 could readily be isolated after treatment of 257a with n -butyllithium at room temperature, which was subsequently converted into the corresponding tetrahydroisoquinoline 258a with n -butyllithium at higher temperatures (Scheme ). For an interesting aside, involving the synthesis of 1,2,3,4-tetrahydroisoquinolines from ortho -allyl arylaziridines using sec -butyl lithium in a flow-microreactor system, see the work by Yoshida, Luisi, and co-workers .…”

Synthesis of 2-substituted tetrahydroisoquinolin-6-ols: potential scaffolds for estrogen receptor modulation and/or microtubule degradation

“…Based on our own interest in the synthesis and utilization of the THIQ skeleton, [28][29][30][31][32] it was thus decided to synthesize some tetrahydroisoquinolin-6-ol-based libraries. To this end, 6-methoxy-1,2,3,4-tetrahydroisoquinoline was synthesized as the hydrobromide or hydrochloride salt 14 from commercially available 2-(3'methoxyphenyl)ethylamine 13 according to the reliable procedure of Zhong and co-workers (Scheme 1).…”

4.05 Addition of HX Reagents to Alkenes, Alkynes, and Allenes without Transition Metal

“…Mark et al found that tetraalkyl ammonium iodide react with α,β-unsaturated enones in trifluoroacetic acid at room temperature to produce β-iodoketones as the only detectable product (equation 70 …”

“…69 The ortho-allylated benzylamines were treated with a stoichiometric amount of mercury(II) acetate in a water/THF (1:1) solvent mixture (equation 103). 70 Sodium borohydride reduction of the in situ-formed organomercury intermediate under basic conditions led to formation of the corresponding tetrahydroisoquinolines in 63-90% yields with moderate diastereoselectivity. The reaction can also be achieved by utilizing the n-butyllithium-mediated approach (equation 104).…”