A concise synthesis of (-)-hamigeran B and (-)-4-bromohamigeran B is presented. The key reactions include a Suzuki coupling of enol triflate 15 with arylboronic ester for efficient synthesis of the densely 1,2,3-trisubstituted cyclopentene 23, a coordination-controlled intramolecular Friedel-Crafts cyclization of free phenol 13 for highly regioselective construction of tricyclic core 12, and a LiOH/O-promoted hydrolysis and concomitant aerobic oxidation of 31 for atom- and step-economic accessing of diketone 32. The application of these key transformations allowed for a rapid and efficient synthesis of (-)-hamigeran B and (-)-4-bromohamigeran B in 13 steps from the readily available chiral material 18.
The
details for the synthetic studies on enantioselective total
synthesis of cyathane diterpenoids cyrneine A (1) and
B (2), glaucopine C (3), and (+)-allocyathin
B2 are presented. We established a mild Suzuki coupling
for heavily substituted nonactivated cyclopentenyl triflates using
a phosphinamide-derived palladacycle as precatalyst and a chelation-controlled
highly regioselective Friedel–Crafts cyclization. The utilization
of these two key reactions enabled a rapid construction of the 5-6-6
tricyclic skeleton. In the middle stage of the synthesis, a Birch
reductive methylation, a modified Wolff–Kishner–Huang
reduction, and a carbenoid-mediated ring expansion were employed as
the key reactions to furnish the 5-6-7 tricyclic core bearing two
antiorientated all-carbon quaternary stereocenters at the C6 and C9 ring junctions. By applying these key transformations,
a more efficient total synthesis of cyrneine A and allocyathin B2, and the first total synthesis of cyrneine B and glaucopine
C, were accomplished through a collective manner. The late-stage conversions
involving a base-mediated double bond migration and a double bond
migration/aerobic γ-CH oxidation cascade for the stereoselective
synthesis of cyrneine B and glaucopine C were interesting.
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