Conjugate Addition Routes to 2-alkyl-2,3-dihydroquinolin-4(1H)-ones and 2-alkyl-4-hydroxy-1,2-dihydroquinoline-3-carboxylates

Kingsbury, Alex; Brough, Steve; Pedrina McCarthy, Antonio; Lewis, William; Woodward, Simon

Abstract

Under CuBr·SMe2/PPh3 catalysis (5/10 mol-%) RMgCl (R = Me, Et, nPr, CH=CH2, nBu, iBu, nC5H11, cC6H11, Bn, CH2Bn, nC11H23) readily (-78 oC) undergo 1,4-addition to Cbz or Boc protected quinolin-4(1H)-ones to provide 2-alkyl-2,3-dihydroquinolin-4(1H)-ones (14 examples, 54-99% yield). Asymmetric versions require AlEt3 to Boc-protected ethyl 6substituted 4(1H)-quinolone-3-carboxylates (6-R group = all halogens, n/i/t-alkyls, CF3) and provide 61-91% yield, 30-86% ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76-86% ee). Additions of AlMe3 or Al(nC8H17)3 provide ~45 and ~75% ee on addition to the parent (6-R = H). Ligand (S)-(BINOL)P-N(CHPh2)(cC6H11) provides the highest ee values engendering addition to the Si face of the 4(1H)-quinolone-3-carboxylate. Allylation and deprotection of a representative 1,4-addition product example confirm the facial selectivity (X-ray).

Citation

Kingsbury, A., Brough, S., Pedrina McCarthy, A., Lewis, W., & Woodward, S. (2020). Conjugate Addition Routes to 2-alkyl-2,3-dihydroquinolin-4(1H)-ones and 2-alkyl-4-hydroxy-1,2-dihydroquinoline-3-carboxylates. European Journal of Inorganic Chemistry, 2020(11-12), 1011-1017. https://doi.org/10.1002/ejic.201901036

• Journal Article Type: Article
• Acceptance Date: Nov 28, 2019
• Online Publication Date: Nov 29, 2019
• Publication Date: Mar 27, 2020
• Deposit Date: Dec 3, 2019
• Publicly Available Date: Nov 30, 2020
• Journal: European Journal of Inorganic Chemistry
• Print ISSN: 1434-1948
• Electronic ISSN: 1099-0682
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 2020
• Issue: 11-12
• Pages: 1011-1017
• DOI: https://doi.org/10.1002/ejic.201901036
• Public URL: https://nottingham-repository.worktribe.com/output/3464963
• Publisher URL: https://doi.org/10.1002/ejic.201901036
• Additional Information: This is the peer reviewed version of the following article: Kingsbury, A., Brough, S., McCarthy, A.P., Lewis, W. and Woodward, S. (2019), Conjugate Addition Routes to 2‐Alkyl‐2,3‐dihydroquinolin‐4(1H)‐ones and 2‐Alkyl‐4‐hydroxy‐1,2‐dihydroquinoline‐3‐carboxylates. Eur. J. Inorg. Chem., which has been published in final form at https://doi.org/10.1002/ejic.201901036. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.