Activation of 1,2- and 1,3-Ketoamides with Thiourea Organocatalyst for the Enantioselective Domino Synthesis of Functionalized Cyclohexanes

Abstract

Several reactive sites of 1,2- and 1,3-ketoamides were successively exploited in two complementary domino transformations for the synthesis of polysubstituted monocyclic or bridged bicyclic cyclohexanes, with the creation of up to six stereogenic centers. In both cases, a chiral bifunctional thiourea organocatalyst allowed efficient control of chirality in the final carbocycle.

Key words

domino reactions - ketones - amides - cyclizations - cycloalkanes - stereoselectivity - catalysis - thioureas

• References


For reviews on organocatalytic domino reactions, see:
• 1a Enders D, Grondal C, Hüttl MR. M. Angew. Chem. Int. Ed. 2007; 46: 1570
• 1b Yu X, Wang W. Org. Biomol. Chem. 2008; 6: 2037
• 1c Alba A.-N, Companyo X, Viciano M, Rios R. Curr. Org. Chem. 2009; 13: 1432
• 1d Grondal C, Jeanty M, Enders D. Nature Chem. 2010; 2: 167
• 1e Pellisier H. Adv. Synth. Catal. 2012; 354: 237
• 2 Name Reactions for Carbocyclic Ring Formations . Li JJ. John Wiley; Hoboken: 2010. Chap. 4 197

For selected examples of two-component approaches, see:
• 3a Halland N, Aburel PS, Jørgensen KA. Angew. Chem. Int. Ed. 2004; 43: 1272
• 3b Zhou J, List B. J. Am. Chem. Soc. 2007; 129: 7498
• 3c Reyes E, Jiang H, Milelli A, Elsner P, Hazell RG, Jørgensen KA. Angew. Chem. Int. Ed. 2007; 46: 902
• 3d McGarraugh PG, Brenner SE. Org. Lett. 2009; 11: 5654
• 3e Hayashi Y, Okano T, Aratake S, Hazelard D. Angew. Chem. Int. Ed. 2007; 46: 4922
• 3f Anwar S, Chang H.-J, Chen K. Org. Lett. 2011; 13: 2200

For selected examples of multicomponent approaches, see:
• 4a Ramachary DB, Chowdari NS, Barbas III CF. Angew. Chem. Int. Ed. 2003; 42: 4233
• 4b Enders D, Hüttl MR. M, Runsik Y, Raabe G, Wendt B. Angew. Chem. Int. Ed. 2007; 46: 467
• 4c Penon O, Carlone A, Mazzanti A, Locatelli M, Sambri L, Bartoli G, Melchiorre P. Chem. Eur. J. 2008; 14: 4788
• 4d Wang Y, Han RG, Zhao YL, Yang S, Xu PF, Dixon DJ. Angew. Chem. Int. Ed. 2009; 48: 9834
• 4e Jiang K, Jia Z.-J, Yin X, Wu L, Chen Y.-C. Org. Lett. 2010; 12: 2766
• 4f Jia Y, Mao Z, Wang R. Tetrahedron: Asymmetry 2011; 22: 2018
• 5a For the concept underlying this subject, see: Bonne D, Constantieux T, Coquerel Y, Rodriguez J. Chem. Eur. J. 2013; 19: 2218
• 5b For a review, see: Bonne D, Constantieux T, Coquerel Y, Rodriguez J. Tetrahedron: Asymmetry 2010; 21: 1085
• 6a Baslé O, Raimondi W, Sanchez Duque MM, Bonne D, Constantieux T, Rodriguez J. Org. Lett. 2010; 12: 5246
• 6b Sanchez Duque MM, Baslé O, Isambert N, Gaudel-Siri A, Génisson Y, Plaquevent J.-C, Rodriguez J, Constantieux T. Org. Lett. 2011; 13: 3296

For similar sequences with 1,2-keto esters and a chiral copper(II) complex, see:
• 7a Nakamura A, Lectard S, Hashizume D, Hamashima Y, Sodeoka M. J. Am. Chem. Soc. 2010; 132: 4036
• 7b Shi D, Xie Y, Zhou H, Xia C, Huang H. Angew. Chem. Int. Ed. 2012; 51: 1248

For a related three-component one-pot sequence, see:
• 7c Varga S, Jakab G, Drahos L, Holczbauer T, Czugler M, Soós T. Org. Lett. 2011; 13: 5416
• 8 Vakulya B, Varga S, Csámpai A, Soós T. Org. Lett. 2005; 7: 1967
• 9 Okino T, Hoashi Y, Furukawa T, Xu X, Takemoto Y. J. Am. Chem. Soc. 2005; 127: 119
• 10 Malerich JP, Hagihara K, Rawal VH. J. Am. Chem. Soc. 2008; 130: 14416

For recent reviews, see:
• 11a Presset M, Coquerel Y, Rodriguez J. ChemCatChem 2012; 4: 172
• 11b Presset M, Coquerel Y, Rodriguez J. Chem. Rev. 2013; 113: 525

For examples of N-heterocyclic carbene-catalyzed enolization and Michael additions, see:
• 12a Boddaert T, Coquerel Y, Rodriguez J. Adv. Synth. Catal. 2009; 351: 1744
• 12b Boddaert T, Coquerel Y, Rodriguez J. Chem. Eur. J. 2011; 17: 2266
• 13 For the method used to prepare the 1,3-ketoamides, see: Presset M, Coquerel Y, Rodriguez J. J. Org. Chem. 2009; 74: 415
• 14 HPLC analysis of the corresponding hemiaminal 10d after oxidation showed that it was obtained with an er of 84:1. See ref. 6b for details.

For reviews on the use of 1,2-dicarbonyls as pronucleophiles, see:
• 15a Raimondi W, Bonne D, Rodriguez J. Angew. Chem. Int. Ed. 2012; 51: 40
• 15b Raimondi W, Bonne D, Rodriguez J. Chem. Commun. 2012; 48: 6763