Michael Addition Initiated Substrate- or Catalyst-Controlled Chemodivergent Three-Component Construction of Fused and Bridged Polycyclic Heterocycles

Abstract

The results on the multicomponent reaction between cyclic β-keto esters, enals, and simple primary aliphatic amines are reported. In thermal conditions in the presence of 4 Å molecular sieves, two different­ families of heterocyclic products (aminobicyclo[3.3.1]nonanones or cycloalka[b]piperidines) were obtained depending on the presence of a substituent in the α-position of the aldehyde. Moreover, preliminary results on the possibility to obtain these two bicyclic cores from the very same starting materials by introducing organocatalysts with different activation modes in the reaction are presented.

Key words

1,3-dicarbonyls - heterocycles - Michael addition - multicomponent reaction - organocatalysis

• References


For monographs and reviews on multicomponent reactions, see:
• 1a Zhu J, Bienaymé H. Multicomponent Reactions . Wiley-VCH; Weinheim: 2005
• 1b Touré BB, Hall DG. Chem. Rev. 2009; 109: 4439
• 1c Ruijter E, Scheffelaar R, Orru RV. A. Angew. Chem. Int. Ed. 2011; 50: 6234
• 1d Climent MJ, Corma A, Iborra S. RSC Adv. 2012; 2: 16
• 1e Dömling A, Wang W, Wang K. Chem. Rev. 2012; 112: 3083
• 1f Brauch S, van Berkel SS, Westermann B. Chem. Soc. Rev. 2013; 42: 4948
• 1g Cioc RC, Ruijter E, Orru RV. A. Green Chem. 2014; 16: 2958

For reviews on the application of multicomponent reactions to the synthesis of heterocycles, see:
• 2a Jiang B, Rajale T, Wever W, Tu S.-J, Li G. Chem. Asian J. 2010; 5: 2318
• 2b Bugaut X, Bonne D, Coquerel Y, Rodriguez J, Constantieux T. Curr. Org. Chem. 2013; 17: 1920

For reviews and book chapters, see:
• 3a Simon C, Constantieux T, Rodriguez J. Eur. J. Org. Chem. 2004; 4957
• 3b Liéby-Muller F, Simon C, Constantieux T, Rodriguez J. QSAR Comb. Sci. 2006; 25: 432
• 3c Bonne D, Coquerel Y, Constantieux T, Rodriguez J. Tetrahedron: Asymmetry 2010; 21: 1085
• 3d Sanchez Duque MM, Allais C, Isambert N, Constantieux T, Rodriguez J. Top. Heterocycl. Chem. 2010; 23: 227
• 3e Isambert N, Sanchez Duque MM, Plaquevent J.-C, Génisson Y, Rodriguez J, Constantieux T. Chem. Soc. Rev. 2011; 40: 1347
• 3f Bonne D, Constantieux T, Coquerel Y, Rodriguez J. Chem. Eur. J. 2013; 19: 2218
• 3g Rodriguez J, Bonne D, Coquerel Y, Constantieux T In Science of Synthesis – Multicomponent Reactions 2 . Müller TJ. J. Thieme; Stuttgart: 2014: 1-36
• 4a Simon C, Lieby-Muller F, Peyronel J.-F, Constantieux T, Rodriguez J. Synlett 2003; 2301
• 4b For preliminary studies using Dowex basic ion-exchange resins as promoters, see: Simon C, Peyronel J.-F, Clerc F, Rodriguez J. Eur. J. Org. Chem. 2002; 3359
• 4c For an early contribution using α-unsubstituted 1,3-dicarbonyls and α,β-unsaturated imines, see: Geirsson JK. F, Johannesdottir JF. J. Org. Chem. 1996; 61: 7320

For reviews on the construction of bicyclo[3.2.1]octanes, see:
• 5a Presset M, Coquerel Y, Rodriguez J. ChemCatChem 2012; 4: 172
• 5b Presset M, Coquerel Y, Rodriguez J. Chem. Rev. 2013; 113: 525

For selected examples, see:
• 6a Stork G, Landesman HK. J. Am. Chem. Soc. 1956; 78: 5129
• 6b Hendrickson JB, Boeckman RK. J. Am. Chem. Soc. 1971; 93: 1307
• 6c Murray DF, Baum MW, Jones M. J. Org. Chem. 1986; 51: 1
• 6d Ravishankar L, Trivedi GK. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1989; 28: 303
• 6e Hong X, France S, Mejía-Oneto JM, Padwa A. Org. Lett. 2006; 8: 5141
• 6f Hong X, France S, Padwa A. Tetrahedron 2007; 63: 5962
• 6g Corkey BK, Heller ST, Wang Y.-M, Toste FD. Tetrahedron 2013; 69: 5640
• 7a Sanchez Duque MM, Baslé O, Génisson Y, Plaquevent J.-C, Bugaut X, Constantieux T, Rodriguez J. Angew. Chem. Int. Ed. 2013; 52: 14143
• 7b Du H, Rodriguez J, Bugaut X, Constantieux T. Adv. Synth. Catal. 2014; 356: 851

For contributions of other research groups, see:
• 8a A pseudo three-component reaction initiated by an organocatalytic enantioselective Michael addition of a 1,3-dicarbonyl compound: Bertelsen S, Johansen RL, Jørgensen KA. Chem. Commun. 2008; 3016
• 8b A three-component reaction involving the addition to an in situ generated α,β-unsaturated imine: Jiang J, Yu J, Sun X.-X, Rao Q.-Q, Gong L.-Z. Angew. Chem. Int. Ed. 2008; 47: 2458
• 8c An enantioselective Hantzsch synthesis of polyhydroquinolines: Evans CG, Gestwicki JE. Org. Lett. 2009; 11: 2957
• 8d A three-component reaction involving a conjugate addition to nitroolefins: Wang Y, Han R.-G, Zhao Y.-L, Yang S, Xu P.-F, Dixon DJ. Angew. Chem. Int. Ed. 2009; 48: 9834

For reviews on organocatalytic enantioselective multicomponent reactions, see:
• 9a Marson CM. Chem. Soc. Rev. 2012; 41: 7712
• 9b de Graaff C, Ruijter E, Orru RV. A. Chem. Soc. Rev. 2012; 41: 3969
• 9c Volla CM. R, Atodiresei I, Rueping M. Chem. Rev. 2014; 114: 2390
• 10 For a review on catalytic selective synthesis, see: Mahatthananchai J, Dumas AM, Bode JW. Angew. Chem. Int. Ed. 2012; 51: 10954
• 11 Filippini M.-H, Faure R, Rodriguez J. J. Org. Chem. 1995; 60: 6872
• 12 Erkkilä A, Majander I, Pihko PM. Chem. Rev. 2007; 107: 5416
• 13 Doyle AG, Jacobsen EN. Chem. Rev. 2007; 107: 5713
• 14a Marigo M, Wabnitz TC, Fielenbach D, Jørgensen KA. Angew. Chem. Int. Ed. 2005; 44: 794
• 14b Hayashi Y, Gotoh H, Hayashi T, Shoji M. Angew. Chem. Int. Ed. 2005; 44: 4212
• 14c Xu L.-W, Li L, Shi Z.-H. Adv. Synth. Catal. 2010; 352: 243
• 14d Jensen KL, Dickmeiss G, Jiang H, Albrecht Ł, Jørgensen KA. Acc. Chem. Res. 2012; 45: 248
• 14e Meninno S, Lattanzi A. Chem. Commun. 2013; 49: 3821
• 15a Wu L.-Y, Bencivenni G, Mancinelli M, Mazzanti A, Bartoli G, Melchiorre P. Angew. Chem. Int. Ed. 2009; 48: 7196
• 15b Melchiorre P. Angew. Chem. Int. Ed. 2012; 51: 9748
• 15c Cassani C, Martín-Rapún R, Arceo E, Bravo F, Melchiorre P. Nat. Protoc. 2013; 8: 325
• 16 Fuerst DE, Jacobsen EN. J. Am. Chem. Soc. 2005; 127: 8964
• 17 Yang W, Du D.-M. Adv. Synth. Catal. 2011; 353: 1241
• 18a Okino T, Hoashi Y, Takemoto Y. J. Am. Chem. Soc. 2003; 125: 12672
• 18b Okino T, Hoashi Y, Furukawa T, Xu X, Takemoto Y. J. Am. Chem. Soc. 2005; 127: 119
• 19a Vakulya B, Varga S, Csámpai A, Soós T. Org. Lett. 2005; 7: 1967
• 19b McCooey SH, Connon SJ. Angew. Chem. Int. Ed. 2005; 44: 6367
• 20a Malerich JP, Hagihara K, Rawal VH. J. Am. Chem. Soc. 2008; 130: 14416
• 20b Alemán J, Parra A, Jiang H, Jørgensen KA. Chem. Eur. J. 2011; 17: 6890
• 20c Storer RI, Aciro C, Jones LH. Chem. Soc. Rev. 2011; 40: 2330
• 21 Given the low enantiomeric excesses of products 5b and 9, no attempt was made to determine the absolute configuration of the major enantiomer.
• 22 Schmidt Y, Breit B. Chem. Eur. J. 2011; 17: 11780