i. basic principles i-q. reductions -...
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I-Q. Reductions
I. Basic Principles
The most important practical difference between oxidation and reduction is thatthe reduction of unsymmetrical ketones generates chiral secondary alcohols.Reduction is treated extensively in most organic text and reference books. Morethorough treatises can be found in:
- Comprehensive Organic Synthesis (Trost, B. M.; Fleming, I.; Eds.); Pergamon Press, Oxford1991, volume 8.- Paderes, G. D.; Metivier, P.; Jorgensen, W. L. J. Org. Chem. 1991, 56, 4718.- Sinclair, S.; Jorgensen, W. L. J. Org. Chem. 1994, 59, 762.- Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis.;VCH: New York, 1991.-Reductions in Organic Synthesis; Abdel-Magid, A. F., Ed.; ACS: Washington, DC, 1996.- Daverio, P.; Zanda, M., "Enantioselective reductions by chirally modified alumino- andborohydrides." Tetrahedron: Asymmetry 2001, 12, 2225-2259.
Hydrogen/Metal catalystsH2, Raney-NiH2, PtO2
H2, RhH2, Pd/CH2, Lindlar-Catalyst
Hydrides and Mixed HydridesAlH3 (LAH+AlCl3)LAHDIBAL-HLi(OMe)3AlH (LTMA)Li(O-t-Bu)3AlH (LTBA)NaH2Al(O(CH2)2OMe)2 (Red-Al, vitride, SMEAH; with CuBr→1,4-reductions)B2H6; BH3SMe2, BH3•THF, BH3 • NH3
LiBH4 (LBH)LiEt3BH (super hydride)K(i- PrO)3BH (KIPBH)Li, Na, K, LS-Selectride
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Hydrides and Mixed Hydrides (cont.)NaBH4 (SBH)NaCNBH3 (stable at pH 3-4)NaBH4, CeCl3 (Luche reagent, 1,2-reduction of enones)NaBH(OAc)3Zn(BH4)2Sia2BHBu3SnH
Dissolving Metal ReagentsNa/NH3/ROH (Birch)Li/NH3/ROHLi/NH3Zn/HOAcZn/HCl (Clemmensen)Na/HgZn/Hg
Miscellaneous ReductantsNH2NH2/KOHMeerwein-Ponndorf-Verley, i-PrOH, Al(i-Pro)3Diimide (H-N=N-H, prepared in situ from KOCON=NCOOK; adds to nonpolarized
double bonds)Et3SiH/BF3
The reduction of hindered halides with LAH proceeds predominantly by a single electrontransfer pathway (Ashby, E. C.; Welder, C. O. J. Org. Chem. 1997, 62, 3542).
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Diastereoselectivity of Reductions
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Acid to Alcohol [LAH]
Wipf, P.; Kim, Y.; Fritch, P. C. J. Org. Chem. 1993, 58, 7195.
Acid to Alcohol [BH3]
Dymock, B. W.; Kocienski, P. J.; Pons, J.-M., "A synthesis of the hypocholesterolemic agent1233A via asymmetric [2+2] cycloaddition." Synthesis 1998, 1655.
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Ester to Alcohol [LiBH4]
Hamada, Y.; Shibata, M.; Sugiura, T.; Kato, S.; Shioiri, T. J. Org. Chem. 1987, 52,1252.
Wipf, P.; Xu, W. J. Org.Chem. 1996, 61, 6556.
Lactone to Lactol
Corey, E. J.; Weinshenker, N. M.; Schaaf, T. K.; Huber, W. J. Am. Chem. Soc.1969, 91, 5675.
Wipf, P.; Kim, Y.; Fritch, P. C. J. Org. Chem. 1993, 58, 7195.
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Amide to Amine
Armstrong, J. D.; Keller, J. L.; Lynch, J.; Liu, T.; Hartner, F. W.; Ohtake, N.; Ikada,S.; Imai, Y.; Okamoto, O.; Ushijima, R.; Nakagawa, S.; Volante, R. P. TetrahedronLett. 1997, 38, 3203.
Godjoian, G.; Singaram, B. Tetrahedron Lett. 1997, 38, 1717.
Tertiary amides require two equivalents of 9-BBN to give tertiary amines. Sterically morehindered dialkylboranes react in a 1:1 stoichiometry to give aldehydes.
Amide to Amine [Raney-Nickel]
Wipf, P.; Kim, Y.; Goldstein, D. M. J. Am. Chem. Soc. 1995, 117, 11106.
Tian, X.; Hudlicky, T.; Königsberger, K. J. Am. Chem. Soc. 1995, 117, 3643.
Amide to Aldehyde
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