Stereoselectivity in the organoiron-mediated synthesis of (±)-mesembrine

Electrophilic C12 Building Blocks for Alkaloids: 1,1 Iterative Organoiron‐Mediated Routes to (±)‐Lycoramine and (±)‐Maritidine

“…Traces of the eneone of oxomaritidine were identified in the NMR spectrum of the crude product before purification. The mechanism of this unusual oxidative dehydrogenation is not known, but we have similarly observed traces of the mesembrenone in the final product of our iron-mediated synthesis of mesembine, [53] suggesting the process is general in the decomplexation of this type of tricarbonyliron complex. A more efficient route to maritidine 2, however, was achieved by a formal total synthesis linking to the Guillou route [48] by BOC protection of the amine before removal of the Fe(CO) 3 group from 20.…”

“…The corresponding intermediate for maritidine extends the (1-arylcyclohexadienyl)iron building block with a benzylic substituent adjacent to the point of attachment of the arene. Compared to our earlier 1,1 iterative syntheses of the simple target molecules O-methyljoubertiamine [50] and mesembrine, [53] the corresponding step for lycoramine is more challenging because an ortho oxygen substituent is present on the arene, and this may block the approach of the nucleophile by the ipso pathway. However, crystallographic studies [5] have shown that ether substituents can be accommodated below the plane of the dienyl system (and thus out of the path of the incoming nucleophile).…”

Asymmetric organic synthesis with stoichiometric transition metal complexes

“…Particularly notable are methodologies designed by Stephenson 25,26 for the installation of the quaternary carbon stereocenter in applications to racemic syntheses of Amaryllidaceae alkaloids (Scheme 18).…”

Stereochemical Requirements of Oxidative Cyclizations in Extended Iterative Organoiron-Mediated Routes to Alkaloids

“…The combined organics were dried (MgSO 4 ), filtered, and evaporated under reduced pressure to give crude product (30 mg) as a yellow oil. The crude oil was purified by column chromatography over silica gel (eluting with a gradient from 2:1 to 1:1 hexanes−EtOAc) to give (4,5-dimethoxybiphenyl-2-yl) (±)-Tricarbonyl[ (1,2,3,4-η)-5β-(2′-(tert-butyldiphenylsilanyloxymethyl)-4′,5′-dimethoxyphenyl)-2-methoxy-1,3-cyclohexadiene]iron(0) (18b) and (±)-Tricarbonyl[ (1,2,3,4 (1,2,3,4,5-η)-1-(4′,5′dimethoxy-2′-(tert-butyl-diphenylsilanyloxymethylphenyl)-4methyoxycyclohexadienyl]iron(1+) tetrafluoroborate(1−) 16b 1b (1200 mg, 270 μmol) was dissolved in dry CH 3 CN (9 mL) at 0 °C. Sodium borohydride (41 mg, 1.08 mmol) was added.…”