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Aliphatic Alcohols
Caitlin McMahon
Alexanian Group Meeting
June 12, 2014
Importance of Deoxygenation
Ubiquitous in total synthesis & modification of natural products
Deoxygenation in synthesis of potent insecticide (functional group tolerant)
Importance of Deoxygenation
Carbohydrate & aminoglycoside chemistry
Enzymes deactivate hydroxy-group of antibiotics
Deoxygenation of nucleosides
Outline
Overview of historical methods of deoxygenation
Barton-McCombie Deoxygenation & Variations
Photochemical Deoxygenation
Direct Deoxygenation
Areas for exploration
Methods of Deoxygenation
Challenge: Strong C-O bond (85-91 kcal/mol)
Dehydration
reduction
reduction
hydrogenation
(or unhindered 2)
Rearrangements and undesired eliminations common
Hartwig, W. Tetrahedron 1983, 39, 26092645.
Benchmark Discovery
Barton-McCombie Deoxygenation (1975)
Widely utilized
Radical mechanism avoids elimination and
rearrangement pathways
Barton, D. H. R.; McCombie, S. W. J. Chem. Soc. [Perkin 1] 1975, 15741585.
Stuart W. McCombie
Imperial College
(Post-doc)
Solution
Make it catalytic in tin
Solution
Use different H-source
Phosphines
Hypophosphorous acid
Borane/H2O
Jang, D.; HyanCho, D.; Kim, J. Synth. Commun. 1998, 28, 35593565.
Wood, J. L. et al J. Am. Chem. Soc. 2005, 127, 1251312515.
Toluates:
Jordan, P. A.; Miller, S. J. Angew. Chem. Int. Ed. 2012, 51, 29072911.
Electrochemical Deoxygenation
Reduction of phosphinate derivatives
Probable mechanism:
Photo-catalyzed Deoxygenation
Early example:
Proposed mechanism
Photo-catalyzed Deoxygenation
Batch to flow deoxygenation via iodide intermediate
Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J.-X.; Yamamoto, Y. J. Org. Chem. 2000, 65, 61796186.
Denanc, M.; Guyot, M.; Samadi, M. Steroids 2006, 71, 599602.
Chemoselectivity:
Proposed mechanism:
Conclusions
Deoxygenation is important in chemical synthesis,
and functionalization.