Bis(2-ethylhexyl)amine as an Effective Organocatalyst for the Racemic Reactions of α,β-Unsaturated Aldehydes Involving an Iminium Ion

This letter is dedicated to Prof. Hisashi Yamamoto on the occasion of his 80th birthday.

Abstract

Bis(2-ethylhexyl)amine is shown to be a suitable organocatalyst to prepare racemic compounds in the reactions of α,β-unsaturated aldehydes involving an iminium ion, whereas diphenylprolinol silyl ether is a well-known chiral organocatalyst for the asymmetric versions of the same reactions. The generality and limitations of bis(2-ethylhexyl)amine are disclosed.

Key words

organocatalysis - racemate - diphenylprolinol silyl ether - bis(2-ethylhexyl)amine - α,β-unsaturated aldehyde - iminium ion

Publication History

Received: 23 June 2023

Accepted after revision: 21 September 2023

Accepted Manuscript online:
21 September 2023

Article published online:
31 October 2023

• References and Notes


Selected reviews on organocatalysis:
• 1a Asymmetric Organocatalysis 1 . List B. Thieme; Stuttgart: 2012
• 1b Comprehensive Enantioselective Organocatalysis: Catalysts, Reactions, and Applications. Dalko PI. Wiley-VCH; Weinheim: 2013
• 2a Palomo C, Mielgo A. Angew. Chem. Int. Ed. 2006; 45: 7876
• 2b Mielgo A, Palomo C. Chem. Asian J. 2008; 3: 922
• 2c Xu L.-W, Li L, Shi Z.-H. Adv. Synth. Catal. 2010; 352: 243
• 2d Jensen KL, Dickmeiss G, Jiang H, Albrecht L, Jørgensen KA. Acc. Chem. Res. 2012; 45: 248
• 2e Gotoh H, Hayashi Y. Diarylprolinol Silyl Ethers: Development and Application as Organocatalysts. In Sustainable Catalysis: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries. Dunn J, Hii KK, Krische MJ, Williams MT. John Wiley & Sons; Hoboken: 2013: 287
• 2f Donslund BS, Johansen TK, Poulsen PH, Halskov KS, Jørgensen KA. Angew. Chem. Int. Ed. 2015; 54: 13860
• 2g Reyes-Rodriguez GJ, Rezayee NM, Vidal-Albalat A, Jørgensen KA. Chem. Rev. 2019; 119: 4221
• 3 Hayashi Y, Gotoh H, Hayashi T, Shoji M. Angew. Chem. Int. Ed. 2005; 44: 4212
• 4 Marigo M, Wabnitz TC, Fielenbach D, Jørgensen KA. Angew. Chem. Int. Ed. 2005; 44: 794
• 5 Mukherjee S, Yang J.-W, Hoffmann S, List B. Chem. Rev. 2007; 107: 5471
• 6 Erkkilä A, Majander I, Pihko PM. Chem. Rev. 2007; 107: 5416
• 7 Hayashi Y, Han X, Mori N. Chem. Eur. J. 2023; 29: e202301093
• 8 Amine I is a mixture of meso- and dl-isomers, but their ratio could not be determined by NMR analysis or by HPLC analysis after Cbz protection.
• 9a Gotoh H, Ishikawa H, Hayashi Y. Org. Lett. 2007; 9: 5307
• 9b Zu L.-S, Xie H.-X, Li H, Wang J, Wang W. Adv. Synth. Catal. 2007; 349: 2660
• 9c Wang Y.-C, Li P.-L, Liang X.-M, Zhang TY, Ye J.-X. Chem. Commun. 2008; 1232

The 1,4-addition reaction of an amine to α,β-unsaturated carbonyl compounds is a key step of the Baylis–Hillman reaction:
• 10a Baylis AB, Hillman ME. D. German Patent 2155113, 1972 , Chem. Abstr. 1972, 77, 34174q.

For selected reviews, see:
• 10b Basavaiah D, Rao A, Satyanarayana T. Chem. Rev. 2003; 103: 811
• 10c Masson G, Housseman C, Zhu J. Angew. Chem. Int. Ed. 2007; 46: 4614
• 10d Declerck V, Martinez J, Lamaty F. Chem. Rev. 2009; 109: 1
• 11 Landge VG, Shrestha KK, Grant AJ, Young MC. Org. Lett. 2020; 22: 9745 ; as for the mechanism, see the Supporting Information
• 12 In eq. 5, a small amount of the Michael addition product of CD₃OD might be generated, but we were unable to isolate it after reduction.
• 13 Hayashi Y, Toyoshima M, Gotoh H, Ishikawa H. Org. Lett. 2009; 11: 45
• 14 Umekubo N, Han X, Mori N, Hayashi Y. Eur. J. Org. Chem. 2022; e202200603
• 15a Gotoh H, Masui R, Ogino H, Shoji S, Hayashi Y. Angew. Chem. Int. Ed. 2006; 45: 6853
• 15b Gotoh H, Ogino H, Ishikawa H, Hayashi Y. Tetrahedron 2010; 66: 4894
• 16 Hayashi Y, Obi K, Ohta Y, Okamura D, Ishikawa H. Chem. Asian J. 2009; 4: 246
• 17 Sundén H, Ibrahem I, Córdova A. Tetrahedron Lett. 2006; 47: 99
• 18 Marigo M, Franzén J, Poulsen TB, Zhuang W, Jørgensen KA. J. Am. Chem. Soc. 2005; 127: 6964
• 19 Hayashi Y, Umekubo N. Angew. Chem. Int. Ed. 2018; 57: 1958
• 20 Umekubo N, Iwata R, Hayashi Y. Chem. Lett. 2020; 49: 867
• 21a Umekubo N, Suga Y, Hayashi Y. Chem. Sci. 2020; 11: 1205
• 21b Hayashi Y. J. Org. Chem. 2021; 86: 1
• 22 Umekubo N, Hayashi Y. ACS Org. Inorg. Au 2022; 2: 245
• 23a Patora-Komisarska K, Benohoud M, Ishikawa H, Seebach D, Hayashi Y. Helv. Chim. Acta 2011; 94: 719
• 23b Seebach D, Sun X.-Y, Ebert M.-O, Schweizer WB, Purkayastha N, Beck AK, Duschmalé J, Wennemers H, Mukaiyama T, Benohoud M, Hayashi Y, Reiher M. Helv. Chim. Acta 2013; 96: 799