Enantioselective Synthesis of Tetrahydroprotoberberines and Bisbenzylisoquinoline Alkaloids from a Deprotonated α-Aminonitrile

Abstract

Under controlled conditions, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile can be quantitatively deprotonated in the α-position. Its alkylation directly furnishes 3,4-dihydroisoquinolines which can serve as starting materials for the preparation of various alkaloids. Here, the preparation of the benzylisoquinolines (+)-laudanidine, (+)-armepavine, and (+)-laudanosine as well as the tetrahydroprotoberberines (-)-corytenchine and (-)-tetrahydropseudoepiberberine using Noyori's asymmetric transfer hydrogenation are described. The dimeric alkaloids (+)-O-methylthalibrine and (+)-tetramethylmagnolamine were obtained from nonracemic precursors in Ullmann diaryl ether syntheses.

A High‐Yielding Modular Access to the Lamellarins: Synthesis of Lamellarin G Trimethyl Ether, Lamellarin η and Dihydrolamellarin η

“…The required precursor could in turn be obtained from a-aminonitrile building block 4 and stilbene carbaldehyde 3 in a onepot 1,4-addition/cycloaromatization procedure (path A) [7e, 8] or by Hantzsch-type reaction of a suitably substituted phenacyl bromide (5) with dihydroisoquinoline 7, which can be readily prepared from the same aminonitrile by C-benzylation and spontaneous dehydrocyanation (path B, Scheme 1). [9] The latter method for the construction of the pyrrole ring has been employed by Ruchirawat and coworkers for the synthesis of numerous lamellarins. [7b, 10] The synthesis of pyrroles from deprotonated a-aminonitriles and a,b-unsaturated carbonyls requires an N-mono-or N-unsubstituted pronucleophile and was first reported by von Miller and Plçchl in 1898.…”

Chromatographically separable rotamers of an unhindered amide

“…Compound 4 was prepared by C-alkylation of the potassium salt of α-aminonitrile 1 with benzyl bromide 2 utilizing methodology established by our group for the syntheses of various isoquinoline alkaloids [5–7]. Spontaneous dehydrocyanation afforded the 1-benzylated 3,4-dihydroisoquinoline which was subsequently reduced in situ to tetrahydroisoquinoline 3 in a one-pot procedure with sodium borohydride in 63% yield.…”

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

“…As a starting point, N , N -dimethylglycine ( L1 ) introduced by Ma et al [22,25] in combination with copper iodide as the Cu-source was chosen, as this ligand has been successfully applied by us in a synthesis of two dimeric benzylisoquinoline alkaloids [26]. This model system was optimized with respect to the influence of different bases, molecular sieves, solvents, and temperatures (Table 1).…”