A Simple Entry to Yne-amides from Yne-oxazolidinones

Abstract

A convenient entry to yne-amides, useful building blocks for chemical synthesis whose synthesis can be rather difficult – especially in the acyclic series – is reported. They were found to be readily obtained by a simple ring opening of the corresponding, readily available yne-oxazolidinones with organolithium reagents. Surprisingly, no competitive carbolithiation of the highly reactive nitrogen-substituted alkyne or propargylic lithiation were observed, this method therefore providing a useful entry to yne-amides which can be obtained in fair to good yields.

Key words

ynamides - yne-oxazolidinones - organolithium - ring opening - alkynes

• References and Notes


For general reviews on ynamides, see:
• 1a Zificsak CA, Mulder JA, Hsung RP, Rameshkumar C, Wei L.-L. Tetrahedron 2001; 57: 7575
• 1b Evano G, Coste A, Jouvin K. Angew. Chem. Int. Ed. 2010; 49: 2840
• 1c DeKorver KA, Li H, Lohse AG, Hayashi R, Lu Z, Zhang Y, Hsung RP. Chem. Rev. 2010; 110: 5064
• 1d Evano G, Theunissen C, Lecomte M. Aldrichimica Acta 2015; 48: 59
• 2 Evano G, Jouvin K, Coste A. Synthesis 2013; 45: 17

For representative examples, see:
• 3a Witulski B, Stengel T. Angew. Chem. Int. Ed. 1998; 37: 489
• 3b Rainier JD, Imbriglio JE. Org. Lett. 1999; 1: 2037
• 4 Jouvin K, Heimburger J, Evano G. Chem. Sci. 2012; 3: 756
• 5 Mansfield SJ, Campbell CD, Jones MW, Anderson EA. Chem. Commun. 2015; 51: 3316
• 6a Dunetz JR, Danheiser RL. Org. Lett. 2003; 5: 4011
• 6b Zhang Y, Hsung RP, Tracey MR, Kurtz KC. M, Vera EL. Org. Lett. 2004; 6: 1151
• 7 Hamada T, Ye X, Stahl SS. J. Am. Chem. Soc. 2008; 130: 833
• 8 Coste A, Karthikeyan G, Couty F, Evano G. Angew. Chem. Int. Ed. 2009; 48: 4381
• 9 Jouvin K, Couty F, Evano G. Org. Lett. 2010; 12: 3272
• 10 Lu T, Hsung RP. ARKICOC 2014; (i): 127
• 11 Sueda T, Oshima A, Teno N. Org. Lett. 2011; 13: 3996
• 12 DeKorver KA, Walton MC, North TD, Hsung RP. Org. Lett. 2011; 13: 4862
• 13 Beveridge RE, Batey RA. Org. Lett. 2012; 14: 540
• 14a Laouiti A, Rammah MM, Rammah MB, Marrot J, Couty F, Evano G. Org. Lett. 2012; 14: 6
• 14b Laouiti A, Jouvin K, Bourdreux F, Rammah MM, Rammah MB, Evano G. Synthesis 2012; 44: 1491
• 15 Wang L, Huang H, Priebbenow DL, Pan F.-F, Bolm C. Angew. Chem. Int. Ed. 2013; 52: 3478
• 16 Nandi GC, Kota SR, Naicker T, Govender T, Kruger HG, Arvidsson PI. Eur. J. Org. Chem. 2015; 2681
• 17 Perrin FG, Kiefer G, Jeanbourquin L, Racine S, Perrotta D, Waser J, Scopelliti R, Severin K. Angew. Chem. Int. Ed. 2015; 54: 13393
• 18 Racine E, Monnier F, Vors J.-P, Taillefer M. Org. Lett. 2011; 13: 2818
• 19 Yields based on a Reaxys search (alkynylation of acyclic secondary amides with hypervalent alkynyl iodonium salts) performed on Feb. 10, 2016 and which furnished only 13 results.

For representative contributions of our group to the chemistry of ynamides, see:
• 20a Fadel A, Legrand A, Evano G, Rabasso N. Adv. Synth. Catal. 2011; 353: 263
• 20b Gati W, Rammah MM, Rammah MB, Couty F, Evano G. J. Am. Chem. Soc. 2012; 134: 9078
• 20c Compain G, Jouvin K, Martin-Mingot A, Evano G, Marrot J, Thibaudeau S. Chem. Commun. 2012; 48: 5196
• 20d Gati W, Couty F, Boubaker T, Rammah MM, Rammah MB, Evano G. Org. Lett. 2013; 15: 3122
• 20e Laub HA, Evano G, Mayr H. Angew. Chem. Int. Ed. 2014; 53: 4968
• 20f Laouiti A, Couty F, Marrot J, Boubaker T, Rammah MM, Rammah MB, Evano G. Org. Lett. 2014; 16: 2252
• 20g Theunissen C, Metayer B, Henry N, Compain G, Marrot J, Martin-Mingot A, Thibaudeau S, Evano G. J. Am. Chem. Soc. 2014; 136: 12528
• 20h Lecomte M, Evano G. Angew. Chem. Int. Ed. 2016; 55: 4547 ; also see ref. 4, 8, 9, and 14

For representative examples of carbometallation of ynamides, see:
• 21a Chechik-Lankin H, Livshin S, Marek I. Synlett 2005; 2098
• 21b Gourdet B, Lam HW. J. Am. Chem. Soc. 2009; 131: 3802
• 21c Gourdet B, Rudkin ME, Watts CA, Lam HW. J. Org. Chem. 2009; 74: 7849
• 21d Das JP, Chechik H, Marek I. Nat. Chem. 2009; 1: 128
• 21e Minko Y, Pasco M, Lercher L, Botoshansky M, Marek I. Nature (London, U.K.) 2012; 490: 522
• 21f Lhermet R, Ahmad M, Hauduc C, Fressigné C, Durandetti M, Maddaluno J. Chem. Eur. J. 2015; 21: 8105
• 22 Jones S, Norton HC. Synlett 2004; 338
• 23 Bensa D, Coldham I, Feinäugle P, Pathak RB, Butlin RJ. Org. Biomol. Chem. 2008; 6: 1410
• 24 General Procedure for the Ring-Opening of Yne-oxazolidinones An oven-dried 10 mL round-bottom flask was charged with the corresponding yne-oxazolidinone (0.50 mmol). The flask was fitted with a rubber septum, evacuated under high vacuum and backfilled with argon. Freshly distilled THF (5 mL) was next added, and the solution was cooled to –78 °C before adding dropwise the organolithium reagent (0.65 mmol, 1.3 equiv). The reaction mixture was stirred for 20 min at this temperature, and the corresponding electrophile (0.75 mmol, 1.5 equiv) was then added. The reaction mixture was slowly warmed to room temperature, stirred for an additional 30 min, and quenched with a sat. aq solution of NH₄Cl (5 mL). The layers were separated, the aqueous layer was extracted thrice with Et₂O (3 × 5 mL), and the combined organic layers were washed with brine, dried over MgSO₄, filtered, and concentrated under reduced pressure. The crude product was finally purified by flash column chromatography using mixtures of EtOAc and PE as eluents. N-(2-Benzoyloxyethyl)-N-pentanoyl-oct-1-ynamine (16b) Yield 55% (98 mg, 0.27 mmol); yellow oil. ¹H NMR (300 MHz, CDCl₃): δ = 8.04 (d, J = 7.4 Hz, 2 H), 7.54 (t, J = 7.4 Hz, 1 H), 7.41 (t, J = 7.6 Hz, 2 H), 4.49 (t, J = 5.2 Hz, 2 H), 3.89 (t, J = 5.2 Hz, 2 H), 2.62 (t, J = 7.5 Hz, 2 H), 2.21 (t, J = 6.8 Hz, 2 H), 1.70–1.55 (m, 2 H), 1.51–1.15 (m, 10 H), 0.95–0.85 (m, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 175.2, 166.4, 133.0, 130.0, 129.8, 128.4, 75.1, 72.4, 62.0, 46.6, 34.1, 31.3, 28.9, 28.6, 27.0, 22.6, 22.4, 18.5, 14.1, 13.8. IR (ATR): ν_max = 2958, 2932, 2255, 1723, 1690, 1452, 1379, 1316, 1268, 1203, 1112, 1098, 1070, 1029, 737, 711 cm^–1. ESI-HRMS: m/z calcd for C₂₂H₃₁NO₃ [M + H]⁺: 358.2377; found: 358.2378.