Asymmetric Organocatalytic Synthesis of Cyclopentane γ-Nitroketones

Dedicated to Professor Steven V. Ley CBE FRS on the occasion of his 70^th birthday

Abstract

This paper describes the use of bifunctional thiourea catalysts in the intramolecular reaction of a nitronate with conjugated ketones to generate the corresponding γ-nitroketones. In contrast to our previous studies in this area, we obtained the cis-functionalized systems as the major diastereoisomers in good yields and reasonable selectivities.

Key words

organocatalysis - nitronate - cyclization - Michael addition - γ-nitroketone

• References and Notes

• 1 For general reviews, see: Cobb AJ. A. In Enantioselective Organocatalyzed Reactions II: Asymmetric C–C Bond Formation Processes. Mahrwald R. Springer; Dordrecht: 2011. and other chapters within both volumes I and II
• 2a Nodes WJ, Nutt DR, Chippindale AM, Cobb AJ. A. J. Am. Chem. Soc. 2009; 131: 16016
• 2b Rajkumar S, Shankland K, Brown GD, Cobb AJ. A. Chem. Sci. 2012; 3: 584
• 2c Rajkumar S, Shankland K, Goodman JM, Cobb AJ. A. Org. Lett. 2013; 15: 1386
• 2d Aitken LS, Arezki NR, Dell’Isola A, Cobb AJ. A. Synthesis 2013; 45: 2627
• 2e Aitken LS, Hammond LE, Sundaram R, Shankland K, Brown GD, Cobb AJ. A. Chem. Commun. 2015; 51: 13558
• 3 Nodes WJ, Shankland K, Rajkumar S, Cobb AJ. A. Synlett 2010; 3011
• 4a Sato Y, Jacobs WA. J. Biol. Chem. 1949; 179: 623
• 4b Beisler JA, Sato Y. J. Chem. Soc. C 1971; 149
• 4c Heretsch P, Giannis A. The Veratrum and Solanum Alkaloids. In The Alkaloids: Chemistry and Biology . Vol. 74. Knölker Hans-Joachim. Chap. 4 Academic Press; London: 2015: 201-232
• 5 Elworthy TR, Kertesz DJ, Kim W, Roepel MG, Quattrocchio-Setti L, Smith DB, Tracy JL, Chow A, Li F, Brill ER, Lach LK, McGee D, Yang DS, Chiou S.-S. Bioorg. Med. Chem. Lett. 2004; 14: 1655

See:
• 6a Okino T, Hoashi Y, Takemoto Y. J. Am. Chem. Soc. 2003; 125: 12672
• 6b Okino T, Hoashi Y, Furukawa T, Xu X, Takemoto Y. J. Am. Chem. Soc. 2005; 127: 119
• 6c Vakulya B, Varga S, Csámpai A, Soós T. Org. Lett. 2005; 7: 1967
• 6d Li B.-J, Jiang L, Liu M, Chen Y.-C, Ding L.-S, Wu Y. Synlett 2005; 603
• 6e McCooey SH, Connon SJ. Angew. Chem. Int. Ed. 2005; 44: 6367
• 6f Ye J, Dixon DJ, Hynes PS. Chem. Commun. 2005; 4481
• 7 Sohtome Y, Tanatani A, Hashimoto Y, Nagasawa K. Tetrahedron Lett. 2004; 45: 5589
• 8 Representative Procedure To a solution of (E)-8-nitro-1-phenyloct-3-en-2-one (1, 150 mg, 0.6 mmol) in MeCN (5 mL) was added catalyst I (60.1 mg, 20 mol%) in one portion. The resulting mixture was stirred at r.t. for 7 d, whereupon the solvent was removed under reduced pressure, and the residue was purified by column chromatography (Et₂O–hexane, 1:3) to afford cis-1-(2-nitrocyclopentyl)-3-phenylpropan-2-one (2d) as a colorless oil (140 mg, 94%).
• 9 Analytical Data for Compound 2d The ee was determined by chiral HPLC analysis at 20 °C to be 65% {Chiralpak AD-H [0.46 cm × 25 cm]: t _R1 = 32.7 min, t _R2 = 39.2 min}. ¹H NMR (400 MHz, CDCl₃): δ = 1.45–1.48 (2 H, m, CH₂CH₂CHNO₂), 1.65–1.68 (2 H, m, CH₂CHRCHNO₂), 2.10 (1 H, m, CHHCHNO₂), 2.34 (1 H, m, CHHCHNO₂), 2.48 [2 H, m, cpCH₂C(O)], 2.70 (1 H, m, CHNO₂CHR), 3.80 (2 H, s, CH₂Ph), 5.04 (1 H, dt, J = 6.6, 2.2 Hz, CHNO₂), 7.17–7.30 (5 H, m, ArH). IR: 1260, 2973, 1714, 1544, 1458 cm^–1. HRMS: m/z calcd for C₁₄H₁₈O₃N [MH⁺]: 248.1132; found: 248.1133.
• 10 CCDC 1406015 contains 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.