Beyond the Tebbe Olefination: Direct Transformation of Esters into Ketones or Alkenes

Abstract

A direct, effective, and operationally simple transformation of esters into ketones or alkenes by the exclusive action of Tebbe’s reagent has been developed. The transformation utilizes the dual character of Tebbe’s reagent as both a methylenation agent and a rearrangement catalyst in the reaction of a wide range of substituted vinyl ethers. The resulting transformation involves sequential methylenation and rearrangement reactions and it offers a high degree of selectivity toward the synthesis of ketones or alkenes. The scope and limitations of the developed methods have been also examined.

Key words

vinyl ethers - rearrangement - Tebbe’s reagent - methylenation - alkenes - ketones

• References and Notes

• 1a Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
• 1b Bhunia A, Yetra RS, Biju AT. Chem. Soc. Rev. 2012; 41: 3140
• 2 Molecular Rearrangements in Organic Synthesis . Rojas CM. Wiley; Hoboken: 2015. DOI: 10.1002/9781118939901
• 3a Martín Castro AM. Chem. Rev. 2004; 104: 2939
• 3b Ilardi EA, Stivalaa CE, Zakarian A. Chem. Soc. Rev. 2009; 38: 3133
• 4a Zhang YD, Reynolds NT, Manju K, Rovis T. J. Am. Chem. Soc. 2002; 124: 9720
• 4b Nasveschuk CG, Rovis T. Angew. Chem. Int. Ed. 2005; 44: 3264
• 4c du Roizel B, Sollogoub M, Pearce AJ, Sinaÿ P. Chem. Commun. 2000; 1507
• 4d Paquette LA, Zhang Y. Org. Lett. 2005; 7: 511
• 5 Minbiole EC, Minbiole KP. C. J. Antibiot. 2016; 69: 213

For representative reviews, see:
• 6a Goethals EJ, Du Prez F. Prog. Polym. Sci. 2007; 32: 220
• 6b Cationic Polymerizations: Mechanisms, Synthesis, and Applications. Matyjaszewski K. Marcel Dekker; New York: 1996
• 7 Padwa A, Bur SK. Tetrahedron 2007; 63: 5341
• 8 Tietze LF, Beifuss U. Angew. Chem. Int. Ed. 1993; 32: 131
• 9 Maziarz E, Furman B. Tetrahedron 2014; 70: 1651
• 10 Domżalska A, Maziarz E, Furman B. Tetrahedron 2017; 73: 7030
• 11a Tebbe FN, Parshall GW, Reddy GS. J. Am. Chem. Soc. 1978; 100: 3611
• 11b Pine SH. Org. React. (N. Y.) 1993; 43: 1
• 11c Beadham I, Micklefield J. Curr. Org. Synth. 2005; 2: 231
• 12 Chung SW, Uccello DP, Choi H, Montgomery JI, Chen J. Synlett 2011; 2072
• 13a Effenberger F. Angew. Chem. Int. Ed. Engl. 1969; 8: 295
• 14 Manxzer LE, Deaton J, Sharp P, Schrock RR. In Inorganic Syntheses . Vol. 21, Fackler JP. Jr. Wiley; New York: 1982. Chap. 31, 135
• 15 Daub GW, McCoy MA, Sanchez MG, Carter JS. J. Org. Chem. 1983; 48: 3876
• 16 Stevenson JW. S, Bryson TA. Tetrahedron 1982; 23: 3143
• 17 Awale S, Miyamoto T, Linn TZ, Li F, Win NN, Tezuka Y, Esumi H, Kadota S. J. Nat. Prod. 2009; 72: 1631
• 18 Direct Formation of Alkenes 10; General ProcedureA 0.5 M solution of the Tebbe reagent in PhMe (1.4 equiv) and pyridine (1.4 equiv) were successively added to a cooled solution of the appropriate ester 7 in PhMe (4 mL/mmol) at –40 °C. The resulting mixture was allowed to warm to rt and stirred until the ester was completely consumed (TLC; 2–12h). The mixture was then poured into a cold 1:1 mixture of 10% aq NaOH and toluene at 0 °C and immediately filtered. The organic phase was washed with the dil aq NaOH and H₂O, dried ­(Na₂SO₄), concentrated, redissolved in the PhMe (6 mL/mmol), cooled to –40 °C, and treated with a second portion of Tebbe reagent (3.0 equiv). The resulting mixture was allowed to warm to rt and stirred until the vinyl ether disappeared (TLC). Pyridine (3.0 equiv) was added and the resulting mixture was stirred at rt for 2–4 h until the ketone was completely converted. The mixture was then poured into a cold 1:1 mixture of 10% aq NaOH and toluene at 0 °C. The precipitate that formed was filtered off and the organic phase was washed with the dil aq NaOH and H₂O (×2), then dried (Na₂SO₄) and concentrated. The residue was purified by flash column chromatography with an appropriate solvent system.1,1′-(2-Methylbut-1-ene-4,4-diyl)dibenzene (10a)¹⁵ Synthesized according to the general procedure, starting from ester 7a (226.1 mg, 1 mmol), as a colorless oil; yield: 128.6 mg (57%); R_f = 0.88 (20% EtOAc–hexane). ¹H NMR (400 MHz, C₆D₆): δ = 7.16–7.03 (m, 8 H), 7.02–6.92 (m, 2 H), 4.74–4.52 (m, 2 H), 4.06 (t, J = 7.9 Hz, 1 H), 2.64 (d, J = 7.9 Hz, 2 H), 1.52 (s, 3 H). ¹³C NMR (101 MHz, C₆D₆): δ = 144.8, 143.0, 128.2, 128.0, 126.0, 112.6, 49.4, 43.8, 22.3.