γ-Selective Vinylogous Aza-Morita–Baylis–Hillman Reaction with N-Carbamoylimines

Abstract

Vinylogous aza-Morita–Baylis–Hillman (aza-MBH) reactions of a vinylcyclopentenone with N-Boc imines provide the corresponding γ-adducts in high regioselectivity (10 examples). While the corresponding reactions with N-Ts imines give the α-adducts and γ-adducts depending on the catalyst, those with N-Boc imines proceed in a γ-selective manner, irrespective of the promoter. The nature of the protecting groups on the nitrogen of the aldimines is found to play a key role in the regiochemical course of vinylogous aza-MBH reactions.

Key words

regioselectivity - vinylogous aza-Morita–Baylis–Hillman reaction - DABCO - N-Boc imine - N-Ts imine

• References and Notes

• 1a Wei W, Shi M. Chem. Rev. 2013; 113: 6659
• 1b Declerck V, Martinez J, Lamaty F. Chem. Rev. 2009; 109: 1
• 2a Back TG, Rankic DA, Sorbetti JM, Wulff JE. Org. Lett. 2005; 7: 2377
• 2b Sorbetti JM, Clary KN, Rankic DA, Wulff JE, Parvez M, Back TG. J. Org. Chem. 2007; 72: 3326
• 2c Shi Y.-L, Shi M. Tetrahedron 2006; 62: 461
• 2d Clary KN, Back TG. Synlett 2007; 2995
• 2e Duvvuru D, Betzer J.-F, Retailleau P, Frison G, Marinetti A. Adv. Synth. Catal. 2011; 353: 483
• 2f Shuler M, Duvvuru D, Rateilleau P, Betzer J.-F, Marinetti A. Org. Lett. 2009; 11: 4406
• 3 It was reported that the γ-adduct of an α,β,γ,δ-unsaturated lactone (a 4-alkenylcoumarin derivative) was obtained under aza-MBH conditions with concomitant reduction of the γ,δ-double bond, see: Duvvuru D, Retailleau P, Betzer J.-F, Marinetti A. Eur. J. Org. Chem. 2012; 897
• 4 γ-Selective MBH reactions of α,γ-dialkylallenoates have been reported, see: Selig P, Turočkin A, Raven W. Synlett 2013; 24: 2535
• 5 Ueda Y, Kawabata T. Top. Curr. Chem. 2015; 372: 203
• 6 Hyakutake R, Gondo N, Ueda Y, Yoshimura T, Furuta T, Kawabata T. Tetrahedron Lett. 2016; 57: 1321
• 7a Heasley B. Eur. J. Org. Chem. 2009; 1477
• 7b Parr BT, Davies HM. L. Nat. Commun. 2014; 5: 4455
• 8 Kobayashi S, Mori Y, Fossey JS, Salter MM. Chem. Rev. 2011; 111: 2626
• 9 Mayer H, Lakhdar S, Maji B, Ofial AR. Beilstein J. Org. Chem. 2012; 8: 1458
• 10 Appel R, Mayr H. J. Am. Chem. Soc. 2011; 133: 8240
• 11a Buskens P, Klankermayer J, Leitner W. J. Am. Chem. Soc. 2005; 127: 16762
• 11b Raheem IT. Adv. Synth. Catal. 2005; 347: 1701
• 11c Roy D, Patel C, Sunoj RB. J. Org. Chem. 2009; 74: 6936
• 11d Yukawa T, Seelig B, Xu Y, Morimoto H, Matsunaga S, Berkessel A, Shibasaki M. J. Am. Chem. Soc. 2010; 132: 11988
• 11e Saunders LB, Cowen BJ, Miller SJ. Org. Lett. 2010; 12: 4800
• 11f Regiani T, Santos V, Godoi MN, Vaz BG, Eberlin MN, Coelho F. Chem. Commun. 2011; 47: 6593
• 11g Lindner C, Liu Y, Karaghiosoff K, Maryasin B, Zipse H. Chem. Eur. J. 2013; 19: 6429
• 11h Verma P, Verma P, Sunoj RB. Org. Biomol. Chem. 2014; 12: 2176
• 12 γ-Selective Vinylogous Aza-MBH Reaction; General Procedure DABCO (60 μmol, 1.0 equiv) was added to a solution of diene 1 (60 μmol, 1.0 equiv) and N-Boc imine 2b (0.18 mmol) in anhydrous DMF (0.24 mL) at room temperature and the resulting mixture was heated to 50 °C. After stirring for 36 h, the reaction mixture was partitioned between EtOAc and 1 N HCl. The layers were separated and the aqueous phase was extracted with EtOAc (×3). The combined organic layer was dried over Na₂SO₄, filtered and concentrated in vacuo. The crude residue was purified by preparative thin-layer chromatography to obtain the roughly separated product including the α- and γ-adducts. The ratio of α- and γ-adducts was determined by ¹H NMR spectroscopy. The α- and γ-adducts were separated carefully by preparative thin-layer chromatography to afford the pure γ-adduct. tert-Butyl [2-(3-Oxocyclopent-1-en-1-yl)-1-phenylallyl]carbamate (4ba) Colorless oil; yield: 8.0 mg (46%). IR (neat): 3328, 2978, 2929, 1701, 1681, 1516, 1366, 1246, 1168, 866 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.35–7.24 (m, 5 H), 5.98 (s, 1 H), 5.90 (s, 1 H), 5.66 (s, 1 H), 5.61 (d, J = 7.6 Hz, 1 H), 4.95–4.87 (m, 1 H), 2.92–2.73 (m, 2 H), 2.46–2.32 (m, 2 H), 1.44 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 209.75, 170.79, 154.74, 143.97, 139.49, 129.79, 129.20, 128.35, 127.53, 119.49, 80.32, 57.04, 34.54, 28.57, 28.47. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₂₃NO₃Na: 336.1570; found: 336.1540. tert-Butyl [1-(4-Chlorophenyl)-2-(3-oxocyclopent-1-en-1-yl)allyl]carbamate (4bb) White amorphous powder; yield: 12 mg (57%). IR (neat): 3323, 2978, 1702, 1575, 1492, 1366, 1248, 1167, 888, 732 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.35–7.27 (m, 2 H), 7.24–7.17 (m, 2 H), 5.97 (s, 1 H), 5.89 (s, 1 H), 5.60 (s, 2 H), 4.89 (s, 1 H), 2.92–2.72 (m, 2 H), 2.41 (t, J = 5.1 Hz, 2 H), 1.44 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 209.52, 170.44, 154.69, 143.81, 138.16, 134.19, 129.84, 129.35, 128.84, 120.13, 80.58, 56.35, 34.55, 28.56, 28.46. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₂₂NO₃ClNa: 370.1180; found: 370.1182.