XXXI.—A synthesis of hydrastine. Part I

Synthesis of Phthalideisoquinoline and Protoberberine Alkaloids and Indolo[2,1-a]isoquinolines in a Divergent Route Involving Palladium(0)-Catalyzed Carbonylation1

“…( ± )- β -Hydrastine (1c): 80% yield from 19c ; mp 135−137 °C (MeOH) (lit 12a. mp 135 °C; 136−140 °C;10c 135−137 °C; 137−138 °C; , 138−139 °C; 138−140 °C; 150−151 °C; 11b,c 151−152 °C). 1 H NMR (270 MHz) δ 2.22−2.32 (m, 2H), 2.42−2.65 (m, 2H), 2.85−2.94 (m, 1H), 2.55, 3.89, 4.06 (each s, each 3H), 3.99, (d, J = 3.6 Hz, 1H), 5.48 (d, J = 3.6 Hz, 1H), 5.90 (s, 2H), 6.38 (s, 1H), 6.58 (s, 1H), 6.52, 7.08 (AB type, J = 8.2 Hz, each 1H). 10c,, …”

“…( ± )- α -Hydrastine (2c): 74% yield, mp 152−154 °C (MeOH) (lit 12a. mp 150 °C; 150−151 °C; 150−154 °C; , 151−152 °C). 1 H NMR (270 MHz) δ 2.40−2.80 (m, 3H), 2.55 (s, 3H), 3.00−3.10 (m, 1H), 3.84 (s, 3H), 3.98 (s, 3H), 4.00, (d, J = 3.3 Hz, 1H), 5.54 (d, J = 3.3 Hz, 1H), 5.78, 5.83 (each d, J = 1.3 Hz, each 1H), 6.37 (s, 1H), 6.65 (s, 1H), 7.04, 7.29 (AB type, J = 8.3 Hz, each 1H) …”

Stereochemical Configuration of Some Phthalideisoquinoline Alkaloids

“…Synthetic hydrastine-a was shown to be the racemate of natural hydrastine (6). Aminohydrastine-a was easily converted t o hydrastine-a by the same reactions that coupled the aromatic rings in aminohydrastine-b, the other race~nic stereoisomer (7). A study of models shows that the ring coupling is easy for configuration A, but mould involve tremendous distortion for configuration B.…”

A new route to diarylisoquinolones

“…Robinson has described some experiments along these lines using stabilised carbaniom! Our route, employing relatively unstabilised phthalide carbanions, would only be effective provided the intermediate amide anion (4) was insufficiently nucleophilic to attack the lactone function of the phthalide (Scheme 1, path ii). Alternatively, if such attack were to occur, a route (path i) to isoquinolone derivatives would be opened.…”