Use of (R)-Mandelic Acid as Chiral Co-Catalyst in
the Michael Addition Reaction Organocatalyzed
by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane
under Solvent-Free Conditions

• Authors: C. Gabriela Ávila-Ortiz , Manuel López-Ortiz , Alberto Vega-Peñaloza , Ignacio Regla , Eusebio Juaristi
• Languages of publication: EN

Abstracts

EN

This article describes a study on the Michael
addition reaction of cyclohexanone to nitroolefins
catalyzed by the chiral secondary amine (1S,4S)-2-tosyl-
2,5-diazabicyclo[2.2.1]heptane. Reactions were carried
out under solvent-free conditions to make them more
environmentally friendly. Initially, the observed diastereoand
enantioselectivities were moderate to good, but
were significantly improved by lowering the reaction
temperature. Furthermore, a variety of chiral acids were
also tested as co-catalysts in both of their enantiomeric
forms, which revealed that (R)-mandelic acid affords
excellent results in terms of yield and stereoselectivity.
Monitoring the reaction by MS-TOF allowed for the
detection of key reaction intermediates, and a reasonable
reaction mechanism in which both catalysts are involved
is proposed.

Keywords

EN

Asymmetric organocatalysis; chiralco-catalysts; Michael addition; solvent free reaction; diazabicyclo[2.2.1]heptane; mandelic acid

• Publisher: De Gruyter Open
• Journal: Asymmetric Catalysis
• Year: 2015
• Volume: 2
• Issue: 1

Dates

online

29 - 6 - 2015

received

5 - 5 - 2015

accepted

9 - 6 - 2015

Contributors

author

C. Gabriela Ávila-Ortiz

• Departamento de
  Química, Centro de Investigación y de Estudios Avanzados, Instituto
  Politécnico Nacional, Apartado Postal 14-740, 07000-México D.F.
  (Mexico)

author

Manuel López-Ortiz

• Facultad de Estudios Superiores
  Zaragoza, Universidad Nacional Autónoma de México (UNAM),
  Batalla del 5 de Mayo y Fuerte de Loreto, Iztapalapa, 09230, México,
  D.F. (Mexico)

author

Alberto Vega-Peñaloza

• Departamento de
  Química, Centro de Investigación y de Estudios Avanzados, Instituto
  Politécnico Nacional, Apartado Postal 14-740, 07000-México D.F.
  (Mexico)

author

Ignacio Regla

• Facultad de Estudios Superiores
  Zaragoza, Universidad Nacional Autónoma de México (UNAM),
  Batalla del 5 de Mayo y Fuerte de Loreto, Iztapalapa, 09230, México,
  D.F. (Mexico)

author

Eusebio Juaristi

• Departamento de
  Química, Centro de Investigación y de Estudios Avanzados, Instituto
  Politécnico Nacional, Apartado Postal 14-740, 07000-México D.F.
  (Mexico)

References

• [1] Buckley B.R., Organocatalysis, Annu. Rep. Prog. Chem., Sect.B: Org. Chem., 2013, 109, 189-206.
• [2] Alemán J., Cabrera S., Applications of asymmetric organocatalysisin medicinal chemistry, Chem. Soc. Rev., 2013, 42,774-793.
• [3] Woods P.A., Smith A.D., Supramolecular Organocatalysis,Supramolecular Chemistry: From Molecules to Nanomaterials,2012, John Wiley & Sons, UK.
• [4] Marques-Lopez E., Herrerabc R.P., Christmann M., Asymmetricorganocatalysis in total synthesis-a trial by fire, Nat. Prod.Rep., 2010, 27, 1138-1167.
• [5] Bertelsen S., Jørgensen K.A., Organocatalysis-after the goldrush, Chem. Soc. Rev., 2009, 38, 2178-2189.
• [6] Melchiorre P., Marigo M., Carlone A., Bartoli G., Asymmetricaminocatalysis-Gold rush in organic chemistry, Angew. Chem.Int. Ed., 2008, 47, 6138-6171.
• [7] MacMillan D.W.C., The advent and development of organocatalysis,Nature, 2008, 455, 304-308.
• [8] Enders D., Grondal C., Hüttl M.R.M., Asymmetric organocatalyticdomino reactions, Angew. Chem. Int. Ed., 2007, 46,1570-1581.
• [9] de Figueiredo R.M., Christmann M., Organocatalytic synthesisof drugs and bioactive natural products, Eur. J. Org. Chem.,2007, 2575-2600.
• [10] List, B., The ying and yang of asymmetric aminocatalysis,Chem. Commun., 2006, 819-824.
• [11] Seayad J., List B., Asymmetric organocatalysis, Org. Biomol.Chem., 2005, 3, 719-724.
• [12] Dalko P.I., Moisan L., In the golden age of organocatalysis,Angew. Chem. Int. Ed., 2004, 43, 5138-5175.
• [13] Ahrendt K.A., Borths C.J., MacMillan D.W.C., New strategiesfor organic catalysis: the first highly enantioselective organocatalyticDiels-Alder reaction, J. Am. Chem. Soc., 2000, 122,4243-4244.
• [14] List B., Lerner R.A., Barbas III C.F., Proline-catalyzed directasymmetric aldol reactions, J. Am. Chem. Soc., 2000, 122,2395-2396.
• [15] Hernández J.G., Avila-Ortiz C.G., Juaristi E., Useful chemicalactivation alternatives in solvent-free organic reactions. In:Molander G.A., Knochel P. (eds.), Comprehensive OrganicSynthesis, 2nd edition, Vol 9, Oxford: Elsevier; 2014. pp.287-314.
• [16] Hernández J.G., Juaristi E., Recent efforts directed to thedevelopment of more sustainable asymmetric organocatalysis,Chem. Commun., 2012, 48, 5396-5409.
• [17] Sheldon R.A., Green solvents for sustainable organic synthesis:state of the art, Green Chem., 2005, 7, 267-278.
• [18] Cao C.-L., Ye M.-C., Sun X.-L, Tang Y., Pyrrolidine−thiourea as abifunctional organocatalyst: Highly enantioselective Michaeladdition of cyclohexanone to nitroolefins, Org. Lett., 2006, 8,2901-2904.
• [19] Chua P.J., Tan B., Zeng X., Zhong G., Prolinol as a highly enantioselectivecatalyst for Michael addition of cyclohexanone tonitroolefins, Med. Chem. Lett., 2009, 19, 3915-3918.
• [20] Luo C., Du D.-M., Synthesis, 2011, 1968-1973.
• [21] Vega-Peñaloza A., Sánchez-Antonio O., Ávila-Ortiz C.G.,Escudero-Casao M., Juaristi E., An alternative synthesis of chiral(S)-proline derivatives that contain a thiohydantoin moiey andtheir application as organocatalyts in the asymmetric Michaeladdition reaction under solvent-free conditions, Asian J. Org.Chem., 2014, 3, 487-496.
• [22] Hernández J.G., Juaristi E., Asymmetric aldol reaction organocatalyzedby (S)-proline-containing dipeptides: Improvedstereoinduction under solvent-free conditions, J. Org. Chem.,2011, 76, 1464-1467.
• [23] Hernández J.G., Juaristi E., Efficient ball-mill procedure inthe ‘green’ asymmetric aldol reaction organocatalyzed by(S)-proline-containing dipeptides in the presence of water,Tetrahedron, 2011, 67, 6953-6959.
• [24] Seebach D., Golińsky J., Synthesis of open-chain 2,3-disubstituted4-nitroketones by diastereoselective Michael-addition of(E)-enamines to (E)-nitroolefins. A topological rule for C-C bondforming processes between prochiral centres, Helv. Chim. Acta,1981, 64, 1413-1423.
• [25] Seebach D., Beck A.K., Golińsky J., Hay J.N., Laube T., Überden sterischen Verlauf der Umsetzung von Enaminen ausoffenkettigen Aldehyden und Ketonen mit Nitroolefinen zu2,3-disubstituierten 4-Nitroketonen, Helv. Chim. Acta, 1985, 68,162-172.
• [26] List B., Pojarliev P., Martin H.J., Efficient proline-catalyzedMichael additions of unmodified ketones to nitro olefins, Org.Lett., 2001, 3, 2423-2425.
• [27] Betancort J.M., Barbas III C.F., Catalytic direct asymmetricMichael reactions: Taming naked aldehyde donors, Org. Lett.,2001, 3, 3737-3740.
• [28] Enders, D., Seki, A., Proline-catalyzed enantioselective Michaeladditions of ketones to nitrostyrene, Synlett, 2002, 26-28.
• [29] For a recent review on (S)-proline-based chiral organocatalysts,see: Albrecht L., Jiang H., Jørgensen K.A., Hydrogen-bonding inaminocatalysis: From proline and beyond, Chem. Eur. J., 2014,20, 358-368.
• [30] Ishikawa H., Suzuki T., Hayashi Y., High-yielding synthesis ofthe anti-influenza neuramidase inhibitor (−)-Oseltamivir bythree “one-pot” operations, Angew. Chem. Int. Ed., 2009, 48,1304-1307.
• [31] Piovesana S., Scarpino Schietroma D.M., Bella M., Multiplecatalysis with two chiral units: An additional dimensionfor asymmetric synthesis, Angew. Chem. Int. Ed., 2011, 50,6216-6232.
• [32] Hanessian S., Pham V., Catalytic asymmetric conjugateaddition of nitroalkanes to cycloalkenones, Org. Lett., 2000, 2,2975-2978.
• [33] Tsogoeva S.B., Jagtap S.B., Dual catalyst control in the chiraldiamine-dipeptide-catalyzed asymmetric Michael addition,Synlett, 2004, 14, 2624-2626.
• [34] Mayer S., List B., Asymmetric counteranion-directed catalysis,Angew. Chem. Int. Ed., 2006, 45, 25, 4193-4195.
• [35] Bartoli G., Bosco M., Carlone A., Pesciaioli F., Sambri L.,Melchiorre P., Organocatalytic asymmetric Friedel-Craftsalkylation of indoles with simple α,β-unsaturated ketones, Org.Lett., 2007, 9, 1403-1405.
• [36] Carlone A., Bartoli G., Bosco M., Pesciaioli F., Ricci P., Sambri L.,Melchiorre P., Organocatalytic asymmetric β-hydroxylation ofα,β-unsaturated ketones, Eur. J. Org. Chem., 2007, 5492-5495.
• [37] Pesciaioli F., De Vincentiis F., Galzerano P., Bencivenni G., BartoliG., Mazzanti A., Melchiorre P., Organocatalytic asymmetricaziridination of enones, Angew. Chem. Int. Ed., 2008, 47,8703-8706.
• [38] De Vincentiis F., Bencivenni G., Pesciaioli F., Mazzanti A.,Bartoli G., Galzerano P., Melchiorre P., Asymmetric catalyticaziridination of cyclic enones, Chem. Asian J., 2010, 5,1652-1656.
• [39] Ricci P., Carlone A., Bartoli G., Bosco M., Sambri L., MelchiorreP., Organocatalytic asymmetric sulfa-Michael addition toα,β-unsaturated ketones, Adv. Synth. Catal., 2008, 350, 49-53.
• [40] Xia A.-B., Xu D.-Q., Luo S.-P., Jiang J.-R., Tang J., Wang Y.-F., XuZ.-Y., Dual organocatalytic ion-pair assemblies: A highly efficientapproach for the enantioselective oxa-Michael-Mannich reactionof salicylic aldehydes with cyclohexenones, Chem. Eur. J., 2010,16, 801-804.
• [41] Stiller J., Kowalczyk D., Jiang H., Jørgensen K.A., AlbrechtL., Novel organocatalytic activation of unmodified Morita-Baylis-Hillman alcohols for the synthesis of bicyclicα-alkylidene-ketones. Chem. Eur. J., 2014, 20, 13108-13112.
• [42] Melgar-Fernández R., González-Olvera R., Olivares-RomeroJ.L., González-López V., Romero-Ponce L., Ramírez-Zárate M.R.,Demare P., Regla I., Juaristi E., Synthesis of novel derivatives of(1S,4S)-2,5-diazabicyclo[2.2.1]heptane and their evaluation aspotential ligands in asymmetric catalysis, Eur. J. Org. Chem.,2008, 655-672.
• [43] Bächle F., Duschmalé J., Ebner C., Pfaltz A., Wennemers H.,Organocatalytic asymmetric conjugate addition of aldehydesto nitroolefins: Identification of catalytic intermediates and thestereoselectivity-determining step by ESI-MS, Angew. Chem. Int.Ed., 2013, 52, 12619-12623.

Identifiers

DOI

10.1515/asorg-2015-0004