DOC PREVIEW
Pitt CHEM 2320 - Reductions

This preview shows page 1-2-3-4-27-28-29-30-56-57-58-59 out of 59 pages.

Save
View full document
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
View full document
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience
Premium Document
Do you want full access? Go Premium and unlock all 59 pages.
Access to all documents
Download any document
Ad free experience

Unformatted text preview:

I-Q. ReductionsI. Basic PrinciplesThe most important practical difference between oxidation and reduction is that thereduction of unsymmetrical ketones generates chiral secondary alcohols. Reduction istreated extensively in most organic text and reference books. More thorough treatises canbe 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.- Cho, B. T., "Recent advances in the synthetic applications of the oxazaborolidine-mediatedasymmetric reduction." Tetrahedron 2006, 62, 7621-7643.- Gladiali, S.; Alberico, E., "Asymmetric transfer hydrogenation: Chiral ligands andapplications." Chem. Soc. Rev. 2006, 35, 226-236.Dr. P. WipfPage 1 of 593/31/2008Hydrogen/Metal catalystsH2, Raney-NiH2, PtO2H2, RhH2, Pd/CH2, Lindlar-CatalystHydrides 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 • NH3LiBH4 (LBH)LiEt3BH (super hydride)K(i- PrO)3BH (KIPBH)Li, Na, K, LS-SelectrideBH-, K+3BH-, Li+3Dr. P. WipfPage 2 of 593/31/2008Hydrides 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)2Sia2BHBu3SnHDissolving Metal ReagentsNa/NH3/ROH (Birch)Li/NH3/ROHLi/NH3Zn/HOAcZn/HCl (Clemmensen)Na/HgZn/HgMiscellaneous ReductantsNH2NH2/KOHMeerwein-Ponndorf-Verley, i-PrOH, Al(i-Pro)3Diimide (H-N=N-H, prepared in situ from KOCON=NCOOK; adds to nonpolarizeddouble bonds)Et3SiH/BF3Dr. P. WipfPage 3 of 593/31/2008The 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).Dr. P. WipfPage 4 of 593/31/2008Diastereoselectivity of ReductionsOOH+OHcis17%25%90%>95%8%trans83%75%10%<5%92%LAHNaBH4L-SelectrideLS-SelectrideMAD/t-BuMgCleq. attack ax. attackDr. P. WipfPage 5 of 593/31/2008Dr. P. WipfPage 6 of 593/31/2008Me4NBH(OAc)3OOHinternal hydride delivery:HBOOOAcOAcOHOHantiOOHexternal hydride delivery:BOOOHOHsynOBHOOOH BNaBH4, Et3B,MeOH, orDr. P. WipfPage 7 of 593/31/2008Acid to Alcohol [LAH]Wipf, P.; Kim, Y.; Fritch, P. C. J. Org. Chem. 1993, 58, 7195.1. LiOH, H2O2, THF/H2O2. LAH, Et2O3. Oxalyl chloride, DMSO, Et3N4. Ph3P=C(CH3)CO2Et, CH2Cl2N OOBnOC6H13C6H13OOEt70%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.OtBuOOSiMe3O1. TBAF, CO2, -78 °C2. BH3•THF, 0 °C - rt, 42%OtBuOOOOHDr. P. WipfPage 8 of 593/31/2008Ester 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.BocNH CO2H BocNH CHO1. MeI, KHCO3, DMF2. NaBH4, LiCl, THF, EtOH3. DMSO, Py-SO3, Et3N 90% CH2OHNHHHOTBSOCHONHHHOTBSOCO2MeNHHHOHO(COCl)2, DMSO,CH2Cl2, NEt31. TBS-Cl, im., 89%2. LiCl, NaBH4, THF, EtOH, 88% Dr. P. WipfPage 9 of 593/31/2008Lactone to LactolCorey, 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.THPOHOOOTHPDIBAl-H, toluene-60 °CTHPOHOOHOTHP OHHOOONHOOC6H13OOOHNHOOC6H13OO55%1. NaBH4, CeCl3•7H2O, EtOH/H2O, -25 °C2. NaIO4, MeOH/H2Oaranorosin Dr. P. WipfPage 10 of 593/31/2008Amide to AmineArmstrong, 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.NBocHSOHNHMeOHNHHSOHNHMeH1. BH3•SMe2 (2.4 equiv) 18 h, 35 °C2. HCl/MeOH workup (removes Boc) 80%•2HCl NOHONSia2BH or Chx2BHTHF, 25 °C9-BBNTHF, 25 °C76% 75% Dr. P. WipfPage 11 of 593/31/2008Amide 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.HHNOOO1. Lawesson's reagent2. Raney-Ni, EtOH 73% HHNOO Amide to AldehydeOOOHCONMe2OONHBocOOOHCHOOONHBocNa[(MeO(CH2)2O)2AlH2]morpholine, -45 °C, THF72% Dr. P. WipfPage 12 of 593/31/2008Hydroxamate to Aldehyde [LAH]Wipf, P.; Kim, H. Y. J. Org. Chem. 1993, 58, 5592.CO2HBocHNOHOHOBocHNOTIPSCON(Me)OMeBocHNOH1. NMM, ClCO2-i-Bu1. TIPS-Cl, im., DMAP CH2Cl2, 88%2. LAH, THF, -50oC2. MeNH(OMe), Et3N 92%3. (EtO)2P(O)CH2- CO2Si(Me)3, n-BuLi, THF; H2O/H+, 66%Isocyanate to FormamideTaber, D. F.; Yu, H.; Incarvito, C. D.; Rheingold, A. L., "Synthesis of (-)-isonitrin B." J. Am.Chem. Soc. 1998, 120, 13285.1. NaClO22. NaH, (PhO)2P(O)N33. heat4. NaBH4, t-BuOH, H2O52%OOTBSOTBSOHNOOTBSOTBSOHDr. P. WipfPage 13 of 593/31/2008Nitro to AnilineBlaser, H.-U., "A golden boost to an old reaction." Science 2006, 313, 312-313.DisproportionationRNO2NitroDirect route+H2-H2ORNO+H2RNHOH+H2-H2ONitrosoHydroxylamineRNH2AnilineCondensation-H2ORNNRO-Azoxy+H2-H2ORNNRAzo+H2RNHHNRHydrazo+H2Condensation routeDr. P. WipfPage 14 of 593/31/2008Ester to Alcohol [DIBAL-H]Wipf, P.; Lim, S. J. Am. Chem. Soc. 1995, 117, 558; Wipf, P.; Lim, S. Chimia 1996, 50, 157.SCH3OOOTIPSHOEtOOHOHOTIPSOCH3O1. DiBAL-H, THF92%2. Sharpless-Epox. Dr. P. WipfPage 15 of 593/31/2008Enone to Allylic Alcohol or KetoneHard metal hydrides, e.g. LAH, add predominantly 1,2-, whereas softer hydrides,e.g. LiAl(t-BuO)3H, prefer 1,4-. 1,2-Addition also is the major pathway forreductions with electrophilic hydrides such AlH3.Luche reduction: Wipf, P.; Kim, Y.; Goldstein, D. M. J. Am. Chem. Soc. 1995, 117,11106.Wipf, P.; Lim, S. J. Am. Chem. Soc. 1995, 117, 558; Wipf, P.; Lim, S. Chimia1996, 50, 157.OOTBDMSOH89%NaBH4, CeCl3,


View Full Document

Pitt CHEM 2320 - Reductions

Documents in this Course
SYNTHESIS

SYNTHESIS

32 pages

Load more
Download Reductions
Our administrator received your request to download this document. We will send you the file to your email shortly.
Loading Unlocking...
Login

Join to view Reductions and access 3M+ class-specific study document.

or
We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view Reductions 2 2 and access 3M+ class-specific study document.

or

By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?