.alpha.-Alkylation and stereochemistry of cis- and trans-decahydroquinolines mediated by the formamidine and Boc activating groups. Synthesis of pumiliotoxin C

Total Synthesis of (±)‐Pumiliotoxin C: An Electrochemical Approach

“…Conversely, Booth et al [27] have observed that when the nitrogen atom is substituted by larger groups, conformer B is preferred. These findings were confirmed by Meyers et al, [4] who showed that in the case of N-formamidines and N-Boc derivatives, the cis-decahydroquinoline system exists predominantly in conformation B. These results agree with our observations, and support the fact that 10 would exist in conformation B with selectivity greater than 99 %, as determined by 1 H NMR spectroscopy.…”

“…The outlet solution was concentrated under reduced pressure and the crude material was taken-up in water. The aqueous phase was extracted with dichloromethane (50 mL × 3) and the organic layers were dried with MgSO 4 …”

“…The crude material was taken-up with a 15 % ammonia solution (50 mL) and extracted with diethyl ether (50 mL × 3). The aqueous layer was removed and the combined organic phases were dried with anhydrous MgSO 4 Phenyl-2,3,6,7,8,8a-hexahydroquinolin-4(1H)-one (9): THF (5 mL) containing 8 (0.76 g, 2.63 mmol) and 50 mL of 1.5 m H 2 SO 4 were added, under an argon atmosphere, to a flask equipped with a reflux condenser. The solution was refluxed under an argon atmosphere for 5 h. The reaction mixture was made basic by the addition of 50 mL of a saturated solution of Na 2 CO 3 .…”

“…For this, one has to deal with the construction of the cis-decahydroquinoline ring and should also correctly orient the substituents borne by the C-2 and C-5 carbon atoms. These synthetic routes have included alkylation of N-formamidine derivatives, [4] aminocyclization reactions, [5] Haller-Bauer cleavage, [6] ni-atom during the elaboration of aminonitriles 4 and 15. The oxygen atom of the keto carbonyl group in octahydroquinolinone 10 was removed by an unprecedented two-step method involving a Shapiro reaction and a palladium-catalyzed reduction of the intermediate alkene 13.…”

Efficient Asymmetric Synthesis of Pumiliotoxin Cvia Intramolecular [4+2] Cycloaddition

“…Chromatography of the free bases obtained from the mother liquor gave a second amount of 1 (3.5%) and a more-polar fraction isolated as the hydrochloride in 14% yield. The structure of the latter was deduced on the basis of the 1 H-NMR spectrum of the free base [8] and by comparison with literature data of the racemic compound [9] to be the isomer 11, which has the inverse absolute configurations at C(4a), C(5), and C(8a). The third isomer present in the crude mixture could not be obtained in pure form.…”