Total Synthesis of New 8‐(Arylmethyl)berbines

Abstract

The total synthesis of the natural compound (8S*,14S*)‐8‐(4′‐hydroxybenzyl)‐2,3‐dimethoxyberbin‐10‐ol and its C‐8 epimer has been conveniently developed by making use of the diastereoselective Stevens rearrangement of the corresponding N‐(arylmethyl)berbinium salts as the key step.

Synthesis of New Dopamine D1 Antagonist SCH 23390 Analogues by the Stereoselective Stevens Rearrangement

“…Clear differences in the chemical shift of the signals arising from the N-Me group were observed for the two diastereoisomers. The NMe signal arising from the cis isomer appeared at a higher shift than that of the trans isomer by 1 H NMR spectroscopy (δ cis = 3.80 Ͼ δ trans = 3.51 ppm), and the opposite effect was observed in the 13 C NMR spectra (δ cis = 45.5 Ͻ δ trans = 48.1 ppm). These data are in accordance with those previously described for similar isoquinolinium salts.…”

“…[16] Similarly, the enantiomerically pure 4e was prepared from (+)-romneine (3e), a natural tetrahydroisoquinoline isolated in our laboratory from Romneya coulteri. [17] Given the satisfactory results attained in preceding work, [13] the (methoxycarbonyl)methyl group was chosen as the model alkylating agent. This procedure normally yielded a unique trans configured salt in excellent yields, except for 4h and 4i, which bear thienyl and furyl substituents at the C-1 position, respectively.…”

“…1 Isopropyl-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline (3c): [29] Benzyl-6,7-dimethoxy-N-methyl-1,2,3,4 [28] Isoquinoline 3h (1.4 g, 98 %) was obtained from the salt 2h (2.1 g, 5.0 mmol) as a yellow oil. 1 13 C NMR (100 MHz, CDCl 3 , 25°C): δ = 147.6, 146.9, 144.6 (C-6, C-7, C-2Ј), 127.5, 125.9, 125.8 (C-3Ј, C-4Ј, C-5Ј), 127.4, 124.7 (C-4a, C-8a -1-(2-pyridyl)-1,2,3,4-tetrahydroisoquinoline (7): [30] Tetrahydroisoquinoline 7 (1.2 g, 91 %) was obtained from the dihydroisoquinoline 6 (1.3 g, 5.0 mmol) as a yellow oil. 1 …”

Diastereoselective Synthesis of 1,2‐Disubstituted 2,3,4,5‐Tetrahydro‐1H‐3‐benzazepines by Means of the Stevens Rearrangement

“…[13] This treatment gave a mixture of 1a and 4 in a ratio 1:1, due to the initial salt dealkylation ( Table 1, Entry 1). To improve this result a variety of bases were tried.…”

“…In previous work we have made use of the Stevens rearrangement for the synthesis of 8-(arylmethyl)berbine. [13] As a continuation of our exploratory study of the Stevens rearrangement as a highly efficient reaction to synthesize nitrogen-containing compounds, we have now extended this methodology to the synthesis of 1H-3-benzazepines.…”