Studies on the syntheses of heterocyclic compounds. Part CCCXCII. An alternative total synthesis of petaline

2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands

“…This phenylethylamine (1) Next, the phenylacetamide (2) was converted into the corresponding 1-benzyltetrahydroisoquinoline (BTHIQ) (3) using the Bischler-Napieralski cyclodehydration reaction. The use of a POCl 3 and P 2 O 5 mixture in dry toluene followed by NaBH 4 reduction was required since the presence of a halogen in position 3 of the phenylacetamide can inactivate the Bischler-Napieralski cyclodehydration reaction due to the electro-attractive properties of the halogen [8,[31][32][33]. Once obtained, the BTHIQ 6-chloro-7-methoxy-1-(3'-methoxybenzyl)-1,2,3,4-THIQ hydrochloride (3) was subjected to Mannich cyclization conditions using 37% aqueous formaldehyde [34] to generate the corresponding 2,11-dimethoxy-3-chloro-THPB (3a) with high yield (86%).…”

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

“…Finally, 7,8-substituted-1,2- DHIQ 2k , representative of the cularine alkaloids, could be synthesized in 88% yield with complete regioselectivity. This has been a difficult substitution pattern to prepare by more conventional Pictet–Spengler or Bischler–Napieralski syntheses because they preferentially cyclize to the undesired 6,7-isomers (not shown) …”

Alkaloids

“…Simple 1-benzylisoquinolines have also been prepared from isoquinolines devoid of a substituent in the 1-position by application of the Grignard reaction [89], the Reissert reaction [90], or the Stevens rearrangement [91], [92].…”