Synthesis of the Kopsia alkaloids (±)-pauciflorine B, (±)-lahadinine B, (±)-kopsidasine, (±)-kopsidasine-N-oxide, (±)-kopsijasminilam and (±)-11-methoxykopsilongine

Pictet–Spengler condensation of with tryptamine gave , which was converted into . Treatment of with phenyl chloroformate resulted in , which underwent transannular cyclization to give . The more stable cyano-analog was made by treating with Tf2O/DMAP to generate , and quenching the reaction with trimethylsilyl cyanide. Treatment of with acryloyl chloride (excess) at 75°C gave , which was directly treated with N-hydroxy-2-thiopyridone/Et3N to give . Irradiation of in the presence of t-BuSH resulted in reductive decarboxylation to give and a small amount of the 2-thiopyridyl ether . Protection of the aniline nitrogen in required the use of triphosgene/pyridine followed by methanol. The final step for the conversion of into required conjugate reduction of the α,β-unsaturated ester followed by α-hydroxylation and gave (11,12-demethoxy lahadinine B). Exposure of to PhI(OAc)2/MeOH cleanly gave , which was directly reduced with Zn/AcOH to . Conversion of into proceeded as before, and when was treated with AgBF4/THF followed by aqueous NaHCO3 it was converted into (±)-kopsidasine , completely characterized as its derived N-oxide . Treatment of with AgBF4/THF followed by aqueous NaHCO3, gave . Oxidation of with m-chloroperoxybenzoic acid resulted in the N-oxide which underwent fragmentation to give when exposed to trifluoroacetic anhydride. When the diene was treated with Mn(dpm)3 (cat)/PhSiH3/O2 in isopropyl alcohol at 0°C, it was converted into kopsijasminilam . Peracetic acid in EtOAc (10%) was used to quench the AgBF4/THF conversion of into , and resulted in / (4:1, 65%) along with small amounts of and . Application of these procedures, with some modifications, to the 11,12-dimethoxy substituted systems gave (±)-lahadinine B . Treatment of with triethylsilane in the presence of trifluoroacetic acid cleanly converted it into 11-methoxykopsilongine (93%). Treatment of (±)-lahadinine B with AgBF4/THF followed by work-up with EtOAc/MeCO3H (10%) gave (±)-pauciflorine and the double bond isomer .