Abstract
Reduction of α,β-unsaturated ketones generally can give rise to a variety of products, of which chiral allylic alcohols (1,2-reduction) and saturated ketones (1,4-reduction) are the most useful from the synthetic point of view. With the appropriate substitution pattern these processes generate new stereogenic centres, where copper hydride coordinated to chiral ligand provided useful level of enantioselectivity. Attractiveness of the catalytic systems based on Cu(I) owes it to their high catalytic activity, low cost and ability to employ hydrogen or ubiquitous hydrosilanes as stoichiometric reducing reagents. This overview is focused on the efforts directed at developing and refining practical methods to tackle the issues of regio- and enantioselectivity with a particular focus on selective 1,2- and 1,4-manifolds, it mostly covers research published in 2010–2015 referring to earlier works for maintaining continuity.
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References
Hudlicky M (1984) Reductions in organic chemistry. Ellis Horwood, Chichester
Rendler S, Oestreich M (2007) Polishing a diamond in the rough: “Cu–H” catalysis with silanes. Angew Chem Int Ed 46:498–504. doi:10.1002/anie.200602668
Deutsch C, Krause N, Lipshutz BH (2008) CuH-catalyzed reactions. Chem Rev 108:2916–2927. doi:10.1021/cr0684321
Lipshutz B (2009) Rediscovering organocopper chemistry through copper hydride. It’s all about the ligand. Synlett 2009:509–524. doi:10.1055/s-0028-1087923
Moritani Y, Appella DH, Jurkauskas V, Buchwald SL (2000) Synthesis of β-alkyl cyclopentanones in high enantiomeric excess via copper-catalyzed asymmetric conjugate reduction. J Am Chem Soc 122:6797–6798. doi:10.1021/ja0009525
Lipshutz BH, Servesko JM (2003) CuH-catalyzed asymmetric conjugate reductions of acyclic enones. Angew Chem Int Ed 42:4789–4792. doi:10.1002/anie.200352313
Lipshutz BH, Servesko JM, Petersen TB, Papa PP, Lover AA (2004) Asymmetric 1,4-reductions of hindered β-substituted cycloalkenones using catalytic SEGPHOS–ligated CuH. Org Lett 6:1273–1275. doi:10.1021/ol0400185
Lipshutz BH, Amorelli B, Unger JB (2008) CuH-catalyzed enantioselective intramolecular reductive aldol reactions generating three new contiguous asymmetric stereocenters. J Am Chem Soc 130:14378–14379. doi:10.1021/ja8045475
Yun J, Buchwald SL (2001) One-pot synthesis of enantiomerically enriched 2,3-disubstituted cyclopentanones via copper-catalyzed 1,4-reduction and alkylation. Org Lett 3:1129–1131. doi:10.1021/ol015577f
Chae J, Yun J, Buchwald SL (2004) One-pot sequential Cu-catalyzed reduction and Pd-catalyzed arylation of silyl enol ethers. Org Lett 6:4809–4812. doi:10.1021/ol048313c
Liu H, Zhang W, He L, Luo M, Qin S (2014) Computational investigations on the phosphine-ligated CuH-catalyzed conjugate reduction of α-β unsaturated ketones: regioselectivity and stereoselectivity. RSC Adv 4:5726. doi:10.1039/c3ra44015j
Chen JX, Daeuble JF, Brestensky DM, Stryker JM (2000) Highly chemoselective catalytic hydrogenation of unsaturated ketones and aldehydes to unsaturated alcohols using phosphine-stabilized copper (I) hydride …. Tetrahedron 56:2153–2166. doi:10.1016/s0040-4020(99)01098-4
Moser R, Bošković ZV, Crowe CS, Lipshutz BH (2010) CuH-catalyzed enantioselective 1,2-reductions of α, β-unsaturated ketones. J Am Chem Soc 132:7852–7853. doi:10.1021/ja102689e
Junge K, Wendt B, Addis D, Zhou S, Das S, Beller M (2010) Copper-catalyzed enantioselective hydrosilylation of ketones by using monodentate binaphthophosphepine ligands. Chem Eur J 16:68–73. doi:10.1002/chem.200902442
Voigtritter KR, Isley NA, Moser R, Aue DH, Lipshutz BH (2012) Regioselective reductions of β, β-disubstituted enones catalyzed by nonracemically ligated copper hydride. Tetrahedron 68:3410–3416. doi:10.1016/j.tet.2011.10.056
Brunner H, Miehling W (1984) Asymmetrische katalysen: XXII. Enantioselektive hydrosilylierung von ketonen mit CuI-katalysatoren. J Organomet Chem 275:c17–c21. doi:10.1016/0022-328X(84)85066-4
Lipshutz BH, Noson K, Chrisman W (2001) Ligand-accelerated, copper-catalyzed asymmetric hydrosilylations of aryl ketones. J Am Chem Soc 123:12917–12918. doi:10.1021/ja011529e
Wu J, Chan ASC (2006) P-Phos: a family of versatile and effective atropisomeric dipyridylphosphine ligands in asymmetric catalysis. Acc Chem Res 39:711–720. doi:10.1021/ar0680015
Wu J, Ji J-X, Chan ASC (2005) A remarkably effective copper(II)-dipyridylphosphine catalyst system for the asymmetric hydrosilylation of ketones in air. Proc Natl Acad Sci 102:3570–3575. doi:10.1073/pnas.0409043102
Zhang X-C, Wu F-F, Li S, Zhou J-N, Wu J, Li N, Fang W, Lam KH, Chan ASC (2011) Copper-dipyridylphosphine-polymethylhydrosiloxane: a practical and effective system for the asymmetric catalytic hydrosilylation of ketones. Adv Synth Catal 353:1457–1462. doi:10.1002/adsc.201100105
Yu F, Zhou J-N, Zhang X-C, Sui Y-Z, Wu F-F, Xie L-J, Chan ASC, Wu J (2011) Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols. Chem Eur J 17:14234–14240. doi:10.1002/chem.201102157
Zhou J-N, Fang Q, Hu Y-H, Yang L-Y, Wu F-F, Xie L-J, Wu J, Li S (2014) Copper(II)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine. Org Biomol Chem 12:1009–1017. doi:10.1039/c3ob42214c
Qi S-B, Li M, Li S, Zhou J-N, Wu J-W, Yu F, Zhang X-C, Chan ASC, Wu J (2013) Copper-dipyridylphosphine-catalyzed hydrosilylation: enantioselective synthesis of aryl- and heteroarylcycloalkyl alcohols. Org Biomol Chem 11:929–937. doi:10.1039/C2OB27040D
Schmidt F, Stemmler RT, Rudolph J, Bolm C (2006) Catalytic asymmetric approaches towards enantiomerically enriched diarylmethanols and diarylmethylamines. Chem Soc Rev 35:1–17. doi:10.1039/b600091f
Lee C-T, Lipshutz BH (2008) Nonracemic diarylmethanols from CuH-catalyzed hydrosilylation of diaryl ketones. Org Lett 10:4187–4190. doi:10.1021/ol801590j
Sui Y-Z, Zhang X-C, Wu J-W, Li S, Zhou J-N, Li M, Fang W, Chan ASC, Wu J (2012) Cu II-catalyzed asymmetric hydrosilylation of diaryl- and aryl heteroaryl ketones: application in the enantioselective synthesis of orphenadrine and neobenodine. Chem Eur J 18:7486–7492. doi:10.1002/chem.201200379
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Malkov, A.V., Lawson, K. (2015). 1,2- Versus 1,4-Asymmetric Reduction of Ketones. In: Harutyunyan, S. (eds) Progress in Enantioselective Cu(I)-catalyzed Formation of Stereogenic Centers. Topics in Organometallic Chemistry, vol 58. Springer, Cham. https://doi.org/10.1007/3418_2015_157
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DOI: https://doi.org/10.1007/3418_2015_157
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