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Pitt CHEM 2320 - Chem 2320 NOTES

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1Hydroxamate to Aldehyde [LAH]Wipf, P.; Kim, H. Y. J. Org. Chem. 1993, 58, 5592.Isocyanate to FormamideTaber, D. F.; Yu, H.; Incarvito, C. D.; Rheingold, A. L., "Synthesis of (-)-isonitrin B." J. Am.Chem. Soc. 1998, 120, 13285.Nitro to AnilineBlaser, H.-U., "A golden boost to an old reaction." Science 2006, 313, 312-313.Dr. P. WipfChem 23203/28/20072Ester to Alcohol [DIBAL-H]Wipf, P.; Lim, S. J. Am. Chem. Soc. 1995, 117, 558; Wipf, P.; Lim, S. Chimia 1996, 50, 157.Enone 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.Dr. P. WipfChem 23203/28/20073Woodward, R. B. et al. J. Am. Chem. Soc. 1952, 74, 4223. Enone transposition.Epoxide to AlcoholDr. P. WipfChem 23203/28/20074Alkyne to (E)-Alkene [LAH]Martin, T.; Soler, M. A.; Betancort, J. M.; Martin, V. S. J. Org. Chem. 1997, 62,1570.Consider also: Boeckman, R. K.; Thomas, E. W. J. Am. Chem. Soc. 1977, 99, 2805.Reductive Dethionation [Et3SiH/Pd]Smith, A. B.; Chen, S. S.-Y.; Nelson, F. C.; Reichert, J. M.; Salvatore, B. A. J. Am.Chem. Soc. 1997, 119, 10935 (Fukuyama’s method).Dr. P. WipfChem 23203/28/20075Asymmetric Reductions-LAH modified reagents: Mosher: LAH + darvon alcoholMukaiyama: LAH + chiral diamineNoyori: Binal-H- LAH modified reagents: Seebach: TADDOLDr. P. WipfChem 23203/28/20076- NaBH4 modified reagents: Tartaric acidProlineFarina, V.; Reeves, J. T.; Senanayake, C. H.; Song, J. J., "Asymmetricsynthesis of active pharmaceutical ingredients." Chem. Rev. 2006, 106,2734-2793.Dr. P. WipfChem 23203/28/20077- Borane modified reagents: Alpine borane:The boat-TS conformation minimizes steric hindrance.DIP-Cl: (Ipc2B-Cl; better Lewis acid than Alpine borane, and more reactive).B-Chlorodiisopinocampheylborane (Ipc2BCl or DIP-chloride) is an excellentreagent for the asymmetric reduction of aryl alkyl ketones. (-)-DIP-chloride isdIpc2BCl, derived from (+)-pinene.For an in situ protocol, see: Zhao, M.; King, A. O.; Larsen, R. D.; Verhoeven, T. R.;Reider, P. J. Tetrahedron Lett. 1997, 38, 2641-4.Ramachandran, P. V. et al. Tetrahedron Lett. 1996, 37, 2205; Tetrahedron Lett.1997, 38, 761Dr. P. WipfChem 23203/28/20078Farina, V.; Reeves, J. T.; Senanayake, C. H.; Song, J. J., "Asymmetricsynthesis of active pharmaceutical ingredients." Chem. Rev. 2006, 106,2734-2793.Oxazaborolidines: The systematic studies of Hirao, Itsuno, and coworkersrevealed the catalytic nature of the aminoalcohol-borane system. Corey and co-workers identified the catalyst as oxazaborolidine (CBS = Corey-Bakshi-Shibata,diphenyloxazaborolidine). The transition state model shown below was proposedby Liotta (J. Org. Chem. 1993, 58, 799; Ph or alkene substituents occupy RLpositions).Preparation of the catalyst: Xavier, L. C.; Mohan, J. J.;Mathre, D. J.; Thompson, A. S.; Carroll, J. D.; Corley, E.G.; Desmond, R. Org. Syn. 1996, 74, 51.Corey, E. J.; Helal, C. J. Angew. Chem. Int. Ed. 1998, 37,1986 (review).Dr. P. WipfChem 23203/28/20079Corey, E. J.; Weinshenker, N. M.; Schaaf, T. K.; Huber, W. J. Am. Chem. Soc.1969, 91, 5675.• Corey, E. J. et al. J. Am. Chem. Soc.1987, 109, 7925. Asymmetric reductionto achieve diastereoselectivity.Corey, E. J.; Helal, C. J. Tetrahedron Lett. 1997, 38, 7511. Enantioselective:Corey, E. J.; Helal, C. J. Angew. Chem. Int. Ed. 1998, 37, 1986 (review).Wipf, P.; Lim, S. J. Am. Chem. Soc. 1995, 117, 558; Wipf, P.; Lim, S. Chimia 1996, 50, 157.Wipf, P.; Weiner, W. J. Org. Chem. 1999, 64, 5321-5324.Dr. P. WipfChem 23203/28/200710Enzymatic reductions: Baker’s yeast, lactate dehydrogenase (both L- and D-LDH are available). Review: Roberts, S. M., "Preparative biotransformations." J.Chem. Soc., Perkin Trans. 1 2001, 1475-1499.Noyori: BINAP-Ru(II)Cl2BINAP-Ru diacetate catalystDr. P. WipfChem 23203/28/200711The history ofenantioselectivehydrogenationChiral environment of the (R)-BINAP-transition metal complexDr. P. WipfChem 23203/28/200712Access to enantiomerically pure BINAPAsymmetric hydrogenation of ketones by BINAP–rutheniumcomplexesHalogen-containing BINAP–Ru(II) complexes are efficient catalysts for theasymmetric hydrogenation of a range of functionalized ketones.Coordinative nitrogen, oxygen, and halogen atoms near C=O functions direct thereactivity and stereochemical outcome in an absolute sense.(S)-BINAP–Ru(II)catalystDr. P. WipfChem 23203/28/200713Asymmetric hydrogenation of ketones by BINAP–rutheniumcomplexesAsymmetric hydrogenation of β-keto estersDr. P. WipfChem 23203/28/200714Armstrong, 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.Ali, S. M.; Georg, G. I. Tetrahedron Lett. 1997, 38, 1703.Fine-tuned reactivity and stereoselectivity is a factor of the steric (bulkiness andchirality) and electronic properties of the auxiliaries.Diamine-free BINAP–Ru complexes are totally ineffective.Asymmetric hydrogenation of simple ketones byBINAP/diamine–ruthenium complexesDr. P. WipfChem 23203/28/200715Asymmetric synthesis of various important pharmaceuticalsAsymmetric hydrogenation of simple ketones byBINAP/diamine–ruthenium complexesExcellent enantioselectivity (90-100% ee).Wide scope of substrates (C=O, C=C, C=N).Rivals or exceeds enzymes: e.g. 2,400,000(TON), 228,000 h-1, 63 s-1 (TOF).Development of pharmaceuticals and syntheticintermediates.Successful industrial applications.An enormous scientific or technological impactand even more general social benefits.Significance of BINAP ChemistryDr. P. WipfChem 23203/28/200716Asymmetric transfer hydrogenation catalyzed by RuH[(S,S)-YCH(C6H5)CH(C6H5)NH2](η6-arene)R = alkyl or D; Y = O or NTsNewer developmentsMatsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R., "Asymmetric transferhydrogenation of α,β-acetylenic ketones." J. Am. Chem. Soc. 1997, 119, 8737.The use of chiral Ru(II) catalysts and 2-propanol as the hydrogen donor allowshighly selective reduction of structurally diverse acetylenic ketones to propargylicalcohols with ee’s approaching 99%. The 16-electron


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