A new route to the crinane skeleton via the low-valent titanium-mediated double reduction of cyclic sulfonamides

• Short route to multi-cyclic alkaloid skeleton. • Regioselectivity in alkene formation by elimination and in an intramolecular Heck reaction. • Sulfonamide group as both an amino protecting group and also as a temporary tether. • New application of low-valent titanium reduction. The construction of a benzo-fused tetracyclic sulfonamide, followed by its low-valent titanium-based reduction and subsequent conversion to racemic crinane is reported. The synthesis of the tetracyclic sulfonamide features a sulfonyl templated, regio- and diastereoselective intramolecular Heck reaction, which installs an all-carbon quaternary centre. Thereafter, a low-valent titanium reduction removes the sulfonyl group, liberating a 3-aryloctahydroindole. A Pictet-Spengler reaction then generates the targeted ethano-bridged phenanthridine core structure of the crinan alkaloids.