Total Syntheses of ( )-Kopsifoline D and ( ) …ccc.chem.pitt.edu/wipf/Current...
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Total Syntheses of (–)-Kopsifoline D and (–)-Deoxoapodine: Divergent Total Synthesis via Late- Stage Key Strategic Bond Formation Kiyoun Lee and Dale L. Boger The Scripps Research Institute La Jolla, Ca J. Am. Chem. Soc. 2014, 136, 3312. Joseph Salamoun Current Lit. 3/15/14 Wipf Group Joe Salamoun @ Wipf Group Page 1 of 10 4/12/2014
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Transcript of Total Syntheses of ( )-Kopsifoline D and ( ) …ccc.chem.pitt.edu/wipf/Current...
Total Syntheses of (–)-Kopsifoline
D and (–)-Deoxoapodine:
Divergent Total Synthesis via Late-
Stage Key Strategic Bond
Formation
Kiyoun Lee and Dale L. Boger The Scripps Research Institute
La Jolla, Ca J. Am. Chem. Soc. 2014, 136, 3312.
Joseph Salamoun Current Lit. 3/15/14
Wipf Group Joe Salamoun @ Wipf Group Page 1 of 10 4/12/2014
Kopsifolines and Related Compounds
• Common pentacyclic core structure.
• Allows for a common intermediate.
• Same synthetic strategy provides access to a number of natural products.
Joe Salamoun @ Wipf Group Page 2 of 10 4/12/2014
Synthesis of the Common Intermediate
J. Am. Chem. Soc., 2010, 132, 3009.
Indole
Ester
OTBS
O-Bridge
Simplified representation of A.
Joe Salamoun @ Wipf Group Page 3 of 10 4/12/2014
J. Am. Chem. Soc., 2010, 132, 3009. Org. Lett., 2013, 15, 868.
Synthesis of (+)-Fendleridine and Kopsinine
Joe Salamoun @ Wipf Group Page 4 of 10 4/12/2014
MacMillan’s Enantioselective Synthesis of (–)-Kopsinine
Nature, 2011, 475, 183. Joe Salamoun @ Wipf Group Page 5 of 10 4/12/2014
Synthesis of Kopsifoline H and Dihydrokopsifoline D
J. Am. Chem. Soc., 2014, 136, 3312. Joe Salamoun @ Wipf Group Page 6 of 10 4/12/2014
Synthesis of Kopsifoline D and Deoxoapodine
J. Am. Chem. Soc., 2014, 136, 3312. Joe Salamoun @ Wipf Group Page 7 of 10 4/12/2014
Overman Racemic Synthesis of Deoxoapodine
J. Am. Chem. Soc., 1991, 113, 2598. Joe Salamoun @ Wipf Group Page 8 of 10 4/12/2014
Key Step from Overman Synthesis
J. Am. Chem. Soc., 1991, 113, 2598. Joe Salamoun @ Wipf Group Page 9 of 10 4/12/2014
Conclusions
• Practical use of the same intermediate for the synthesis of a variety of natural products with the same core structure.
• The synthetic routes utilize similar chemistry
displaying reproducibility/usefulness of the reactions.
• Key steps are diastereoselective but not
enantioselective. It is a racemic synthesis with chiral separation of key intermediates. This invites questions about the true yields of the reactions when accounting for enantiomers.
Joe Salamoun @ Wipf Group Page 10 of 10 4/12/2014
