Transformation of (+)-thiomicamine into a new ligand for the enantioselective addition of methyllithium to prochiral imines

The asymmetric synthesis of (R)-(+)- and (S)-(−)-O-methylbharatamine

“…For this purpose chiral amines, commercially available, enantiomerically pure, (+)-thiomicamine 6 and (R)-and (S)-phenylalaninol 7, ent-7 have been chosen. Thiomicamine 6, an industrial waste product, has been used successfully by our research group, as a source or promoter of stereochemistry in many types of organic synthesis, including the enantioselective synthesis of isoquinoline alkaloids [21][22][23][24][25] and diastereoselective synthesis of protoberberine alkaloid, 26 as well. Our initial synthesis started with optically active amide 5a, prepared from thiomicamine 6 and o-toluoyl chloride 8 as according to literature procedure.…”

“…Recently, an efficient enantioselective synthesis of lactam 3 based upon the (À)-sparteine-mediated addition of nonchiral o-toluamides to 3,4-dihydroisoquinoline has been reported by Liu. 20 To continue our study on stereoselective syntheses of isoquinoline alkaloids, [21][22][23][24][25] including protoberberine system, 26 based on the addition of carbon nucleophiles to imines, we have performed the first asymmetric synthesis of (R)-(+)-and (S)-(À)-O-methylbharatamine 2. Our concept of the asymmetric synthesis is based on Tetrahedron: Asymmetry the lateral metallation methodology involving the addition of a carbon nucleophile derived from optically active o-toluamide 5 to 3,4-dihydroisoquinoline 4.…”

Synthesis of 1,2-Dihydroisoquinolines by a Modified Pomeranz–Fritsch Cyclization

“…1 H NMR (500 MHz, CDCl 3 ): δ 6.89 (d, J = 1.4 Hz, 1H), 6.83 (dd, J = 8.2, 1.6 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 4.43 (t, J = 5.5 Hz, 1H), 3.89 (s, 3H), 3.86 (s, 3H), 3.71 (q, J = 6.6 Hz, 1H), 3.36 (s, 3H), 3.31 (s, 3H), 2.63 (dd, J = 12.1, 5.6 Hz, 1H), 2.56 (dd, J = 12.1, 5.3 Hz, 1H), 1.63 (br s, 1H), 1.35 (d, J = 6.6 Hz, 3H); 13 C­{ 1 H} NMR (126 MHz, CDCl 3 ): δ 149.2, 148.1, 138.1, 118.9, 111.1, 109.6, 104.0, 58.2, 56.0, 56.0, 54.2, 53.8, 49.2, 24.6. The characterization data match the data that have been reported previously …”

Enantioselective addition of methyllithium to a prochiral imine—the substrate in the Pomeranz–Fritsch–Bobbitt synthesis of tetrahydroisoquinoline derivatives mediated by chiral monooxazolines

“…Spectral characteristics of the oily base 3, corresponded to the literature data. 12 The (S)-configuration of major enantiomer of amine 3 was established by HPLC comparison with a sample of (S)-(À)-3, after transformation into (S)-salsolidine 4 of known absolute stereochemistry. 15 …”

“…6 In this regard, the design and synthesis of new and efficient chiral ligands plays a crucial role. For enantioselective addition of organometallic reagents to the C@N bond, a variety of chiral ligands, most of which contained nitrogen and/ or oxygen functional groups, such as (À)-sparteine, 7,8 bisoxazolines, [8][9][10] aminoethers, [11][12][13] and diol ethers, 13 have been recently developed. A number of monooxazolines derived from (1S,2S)-2-amino-1-aryl-1,3-propandiols have been synthesized and tested as ligands in enantioselective additions of organometallic reagents to imines, cyclic 14 and Schiff base-type.…”