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CBS Reduction
Christine Beshay
CHE 676
Dr.Totah
12/1/2016
Overview
• History of COREY-BAKSHI-SHIBATA reduction and selectivity
• General features
• Mechanism
• Organic synthesis applications
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History of CBS reduction and selectivity
• In 1981 Itsuno et al reduced achiral ketones to chiral alcohols using
alkoxy-amine-borane complexes in enantioselectivity and in high
yield.
• In 1987 E.J. Corey, with his co-workers, used oxazaborolidines to
rapidlly reduce ketones in the presence of BH3-THF to give 2o alcohol
in enantioselectivity and in high yield.
• The enantioselective reduction of ketones using oxazaborolidine is
called the CBS reduction.
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General features
Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109 (18), 5551–5553.
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Mechanism
Quallich, G. J.; Blake, J. F.; Woodall, T. M. J. Am. Chem. Soc. 1994, 116 (19), 8516–8525.
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Organic synthesis application
B.W.Spur synthesis of prostaglandin E1
Rodríguez, A.; Nomen, M.; Spur, B. W.; Godfroid, J.-J. European J. Org. Chem. 1999, 1999 (10), 2655–2662.
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Organic synthesis application
E.J. Corey and co-workers synthesis protein phosphatase(Dysidiolide)
Corey, E. J.; B. E.; Roberts, J. Am. Chem. Soc. 1997, 119, 12425-12431.
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Organic synthesis application
C.J. Forsyth et al. synthesis of okadic acid
Sabes, S. F.; Urbanek, R. A.; Forsyth, C. J. J. Am. Chem. Soc. 1998, 120, 2534-2542.
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Optical yield
• In a chemical reaction, if the reaction is stereospecific and no
racemization occurs, the optical yield is 100%.
% Optical yield = (ee product / ee starting material) x 100%
Seeman, J. I.; Eliel, E. L. 1921.
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Recent organic synthesis
Synthesis of (+)-pseudohygroline and (+)-hygroline
Bhoite, S. P.; Kamble, R. B.; Suryavanshi, G. M. Tetrahedron Lett. 2015, 56 (32), 4704–47
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Recent paper 2016
• Sanderson and coworkers developed flow process for CBS asymmetric
reduction of ketones , using chip-microreactors.
• They used BH3 , (85% 2-MeTHF, 15% THF) and oxazaborolidine for
reduction.
• Under such reaction conditions, the reaction was complete in 10
minutes and alcohol was produced with 95% yield and a 91 : 9
enantiomeric ratio (highly enantioselectivety).
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CBS reduction using chip-microreactor
De Angelis, S.; De Renzo, M.; Carlucci, C.; Degennaro, L.; Luisi, R. Org. Biomol. Chem. 2016, 14 (18), 4304–4311.
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Conclusion
• This method of reduction using CBS catalyst achieved higher
enantioselectivity and yield.
• CBS reduction used not only in natural product synthesis, but also in
industry.
• This method is more effective to reduce ketones in stereoselective
and chemoselective way depending on the substituents, catalyst type,
and temperature.
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Refrences
1- Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109 (18), 5551–5553.
2- Quallich, G. J.; Blake, J. F.; Woodall, T. M. J. Am. Chem. Soc. 1994, 116 (19), 8516–
8525.
3- Rodríguez, A.; Nomen, M.; Spur, B. W.; Godfroid, J.-J. European J. Org. Chem. 1999,
1999 (10), 2655–2662.
4- Corey, E. J.; B. E.; Roberts, J. Am. Chem. Soc. 1997, 119, 12425-12431.
5- Sabes, S. F.; Urbanek, R. A.; Forsyth, C. J. J. Am. Chem. Soc. 1998, 120, 2534-2542.
6- Seeman, J. I.; Eliel, E. L. 1921.
7- Bhoite, S. P.; Kamble, R. B.; Suryavanshi, G. M. Tetrahedron Lett. 2015, 56 (32),
4704–47
8- De Angelis, S.; De Renzo, M.; Carlucci, C.; Degennaro, L.; Luisi, R. Org. Biomol.
Chem. 2016, 14 (18), 4304–4311.
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