Diastereoselective Synthesis of 1-Benzyltetrahydroisoquinoline Derivatives from Amino Acids via 1,4 Chirality Transfer. Part 1

Abstract

L-(−)-Phenylalanine, L-(+)-valine, and L-(−)-proline were used in the diastereoselective synthesis of benzyltetrahydroisoquinoline derivatives.The search for methods for the asymmetric synthesis of chiral compounds has been an area of intense study over the past two decades. 1 The need for the preparation of chiral compounds in enantiomerically pure form has increased lately as a result of several factors, mainly connected with a stereodiscrimination of chiral compounds by most biological systems and therefore the pressure on the pharmaceutical industry to develop nonracemic drugs. Tetrahydroisoquinolines still attract considerable interest in the modern chemistry of biologically active compounds, and consequently several new effective approaches for their stereocontrolled synthesis have recently been developed. 2 Special attention has been devoted to the asymmetric synthesis using enantiospecific processes proceeding from the chiral pool to gain access to this broad class of compounds. 3 Of all the members of chiral

Cyclizations of N-Acyliminium Ions

“…There is a large body of practical synthetic chemistry involving cyclic N -acyliminium ions that contain additional heteroatoms. − A notable example is the hydantoin-based N -acyliminium ion cyclization illustrated in eq 108 . In the bromination of the 5-phenyl derivative 326 ( n = 2), the tricyclic product 327 forms spontaneously in 90% yield; there is no need for a Lewis acid such as tin(IV) chloride to generate the requisite N -acyliminium ion.…”

“…Piperazinones cyclize to isoquinoline tricycles generally with excellent yields. ,− For instance, treatment of 333 with 12 N HCl at 0 °C affords the drug praziquantel, 334 , in 95% yield . An unprotected nitrogen is well tolerated in this type of cyclization (eq 110) .…”

Variety of natural products derived from tryptophan and stereoselective synthesis of tetrahydro-β-carboline derivatives of pharmacological importance

“…Recently, we proposed a general method for the construction of isoquinoline and β-carboline systems, which utilized natural amino acids as the source of chirality [23][24][25].…”

Diastereoselective Decarboxylation of Cyclopentene Dicarboxylic Acid Derivatives

“…first reported the successful diastereoselective addition of alcohols to diastereotopic silyenes . Additionally, diquinanes from acyclic precursors, 4-phenyl-1,2,3,4-tetrahydroisoquinolines from chiral lactam enolates, and 1-benzyltetrahydroisoquinolines from amino acids have been synthesized diastereoselectively. The diastereoselective products were also achieved by Evans asymmetric alkylation of oxazolidinone glycolates and by Grignard addition to 2-acylindoline .…”