Practical total synthesis of RS-15385

Synthesis of Lamellarin G Trimethyl Ether by von Miller–Plöchl‐Type Cyclocondensation

“…Enone 10 was obtained in 82 % yield by aldol condensation of veratraldehyde ( 11 ) with 1,1‐dimethoxypropan‐2‐one (see Scheme ) . The key step of the sequence, the modified von Miller–Plöchl reaction of the deprotonated α‐amino nitrile 7 to enone 10 , . produced pyrrolo[2,1‐ a ]isoquinoline 12 in 75 % yield .…”

“…[48] The key step of the sequence, the modified von Miller-Plöchl reaction of the deprotonated α-amino nitrile 7 to enone 10. [47,49] produced pyrrolo[2,1-a]isoquinoline 12 in 75 % yield. [41] To introduce the aryl substituent in 2-position, a bromination [28] with NBS was carried out.…”

“…6,7‐Dimethoxy‐3,4‐dihydroisoquinoline (9): The title compound was prepared according to a modified procedure of J. C. Rohloff et al Homoveratrylamine ( 8 ) (14.3 mL, 15.0 g, 82.8 mmol) was dissolved in ethyl formate (23 mL) and the mixture was heated to reflux for 23 h. Excess ethyl formate was removed under reduced pressure. The solid residue was dissolved in DCM (100 mL) and the resulting solution was added dropwise to a solution of PCl 5 (20.68 g, 99.3 mmol, 1.2 equiv.)…”

“…The combined organic layers were dried with Na 2 SO 4 . The solvent was removed under reduced pressure to obtain the product as a red oil (15. [49] 6,7-Dimethoxy-3,4-dihydroisoquinoline-1-carbonitrile (7): The title compound was prepared according to a modified procedure of Werner et al [47] To an ice-cooled solution of dihydroisoquinoline 9 (4.00 g, 20.9 mmol) in methanol (10 mL) was added a solution of KCN (4.90 g, 65.12 mmol, 3.6 equiv.) in water (22 mL).…”

Highly Regioselective Synthesis of Ethyl 2-(N-Methylformate-1,4,5,6-tetrahydropyridin-2-yl) Acetate and Its Conversion into Corresponding ( R )-Ethyl Homopepicolate by Asymmetric Hydrogenation

“…[4][5][6][7] For example, the ethyl 2-(N-acyl-1,4,5,6-tetrahydro-pyridin-2-yl)-acetate 2b (Scheme 1) described by Lhommet et al was obtained as a secondary product of the reaction of acid chlorides with the enaminoester 1 (Table 1, entry 2). [4] The reaction of 1 with dicarboxylic acid dichloride produces the C-acylated enaminoester 2c and keeps N unprotected as previously reported (Table 1, entry 3).…”