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Diastereoselective Synthesis and Diversification of Highly Functionalized CyclopentanonesWe gratefully acknowledge funding by the Royal Society (M.B. and I.R.B.).
Received: 30 October 2017
Accepted after revision: 01 December 2017
21 December 2017 (online)
An efficient entry into highly substituted cyclopentanones is presented based on functionalizing cyclopentenones by means of an aza-Michael reaction with different aniline nucleophiles. The excellent diastereoselectivity of this process is ascribed to H-bonding between a tertiary alcohol and the incoming nucleophiles. Additionally, the functionalization of the parent cyclopentenones via the Baylis–Hillman reaction is demonstrated. Together, these transformations showcase the elaboration of a simple precursor by installation of versatile functionalities at either the α- or β-position of the embedded enone and thus represent valuable methods for the construction of diversely functionalized cyclopentanones.
Key wordscyclopentanone - aza-Michael reaction - Baylis–Hillman reaction - diastereoselectivity - H-bonding
- Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591745.
- Supporting Information
- 1a Lovering F. Bikker J. Humblet C. J. Med. Chem. 2009; 52: 6752
- 1b Lovering F. Med. Chem. Commun. 2013; 4: 515
- 1c Bajorath J. Expert Opin. Drug Discovery 2016; 11: 825
- 1d Kirkpatrick P. Nat. Rev. Drug Disc. 2003; 2: 948
- 2a Li C.-J. Trost BM. Proc. Natl. Acad. Sci. U.S.A. 2008; 105: 13197
- 2b Varma RS. ACS Sustainable Chem. Eng. 2016; 4: 5866
- 2c Sheldon RA. Green Chem. 2016; 18: 3180
- 3a Anastas PT. Warner JC. Green Chemistry Theory and Practice . Oxford University Press; New York: 1998
- 3b Anastas P. Eghbali N. Chem. Soc. Rev. 2010; 39: 301
- 3c Li C.-J. Anastas PT. Chem. Soc. Rev. 2012; 41: 1413
- 4 Baumann M. Baxendale IR. Filipponi P. Hu T. Org. Process Res. Dev. 2017; 21: 2052
- 5a Veits GK. Wenz DR. Palmer LI. St Amant AH. Hein JE. de Alaniz JR. Org. Biomol. Chem. 2015; 13: 8465
- 5b Shu T. Ni Q. Song X. Zhao K. Wu T. Puttreddy R. Rissanen K. Enders D. Chem. Commun. 2016; 52: 2609
- 5c Liu G. Shirley ME. Van KN. MacFarlin RL. Romo D. Nat. Chem. 2013; 5: 1049
- 6 CCDC 1581502 (9e), and CCDC 1581503 (9g), and CCDC 1581504 (11) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
- 7 Although separation of these diastereoisomers was found challenging by silica gel chromatography, fractional crystallization from solutions of structures 11 in Et2O was found possible.6