Intercepting the Nazarov Oxyallyl Intermediate with α-Formyl­vinyl Anion Equivalents to Access Formal Morita–Baylis–Hillman Alkylation Products

Abstract

A Lewis acid catalyzed cationic domino reaction involving sequential electrocyclization and polar addition of allenol ethers onto the resulting oxyallyl species is described. The overall sequence allows a highly stereoselective synthesis of densely substituted cyclopentanoid compounds containing α-formylvinyl functionality which is formally equivalent to products of a Morita–Baylis–Hillman alkylation process.

Key words

interrupted Nazarov cyclization - oxyallyl cation - allenol ethers - carbonyl umpolung - Morita–Baylis–Hillman alkylation

• References and Notes

• 1 Current location: Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan.
• 2 Tietze LF. Chem. Rev. 1996; 96: 115
• 3 Barton DH. R. Aldrichimica Acta 1990; 23: 3

For recent reviews, see:
• 4a Simeonov SP. Nunes JP. M. Guerra K. Kurteva VB. Afonso CA. M. Chem. Rev. 2016; 116: 5744
• 4b Jana N. Driver TG. Org. Biomol. Chem. 2015; 13: 9720
• 4c West FG. Scadeng O. Wu Y.-K. Fradette RJ. Joy S. In Comprehensive Organic Synthesis . Molander GA. Knochel P. Elsevier; Oxford: 2014. 2nd ed., Vol. 5 827
• 4d Tius MA. Chem. Soc. Rev. 2014; 43: 2979
• 4e Spencer WT. Vaidya T. Frontier AJ. Eur. J. Org. Chem. 2013; 3621
• 4f Shimada N. Stewart C. Tius MA. Tetrahedron 2011; 67: 5851
• 4g Vaidya T. Eisenberg R. Frontier AJ. ChemCatChem 2011; 3: 1531

Selected recent examples:
• 5a Williams CW. Shenje R. France S. J. Org. Chem. 2016; 81: 8253
• 5b William R. Wang S. Mallick A. Liu XW. Org. Lett. 2016; 18: 4458
• 5c William R. Leng WL. Wang S. Liu X.-W. Chem. Sci. 2016; 7: 1100
• 5d Shenje R. Williams CW. Francois KM. France S. Org. Lett. 2014; 24: 6468
• 5e William R. Wang S. Ding F. Arviana EN. Liu X.-W. Angew. Chem. Int. Ed. 2014; 53: 10742
• 5f Riveira MJ. Mischne MP. J. Org. Chem. 2014; 79: 8244
• 5g Chaplin JH. Jackson K. White JM. Flynn BL. J. Org. Chem. 2014; 79: 3659
• 5h Bonderoff SA. Grant TN. West FG. Tremblay M. Org. Lett. 2013; 15: 2888
• 5i Scadeng O. Ferguson MJ. West FG. Org. Lett. 2011; 13: 114

For a review, see:
• 5j Wenz DR. Read de Alaniz J. Eur. J. Org. Chem. 2015; 23
• 6 For a review, see: Grant TN. Rieder CJ. West FG. Chem. Commun. 2009; 5676
• 7a Wu Y.-K. Dunbar CR. McDonald R. Ferguson MJ. West FG. J. Am. Chem. Soc. 2014; 136: 14903
• 7b Wu Y.-K. West FG. Org. Lett. 2014; 16: 2534
• 7c Wu Y.-K. McDonald R. West FG. Org. Lett. 2011; 13: 3584
• 8a Schatz DJ. Kwon Y. Scully TW. West FG. J. Org. Chem. 2016; 81: 12494
• 8b Kwon Y. Scadeng O. McDonald R. West FG. Chem. Commun. 2014; 50: 5558
• 8c Kwon Y. McDonald R. West FG. Angew. Chem. Int. Ed. 2013; 52: 8616
• 9 Liu W. Khedkar V. Baskar B. Schürmann M. Kumar K. Angew. Chem. Int. Ed. 2011; 50: 6900

For reviews, see:
• 10a Satpathi B. Ramasastry SS. V. Synlett 2016; 27: 2178
• 10b Chandra Bharadwaj K. RSC Adv. 2015; 5: 75923
• 10c Wei Y. Shi M. Chem. Rev. 2013; 113: 6659
• 10d Basavaiah D. Veeraraghavaiah G. Chem. Soc. Rev. 2012; 41: 68
• 10e Basavaiah D. Reddy BS. Badsara SS. Chem. Rev. 2010; 110: 5447
• 11 Chinchilla R. Nájera C. Chem. Rev. 2000; 100: 1891

Selected examples:
• 12a Satpathi B. Ramasastry SS. V. Angew. Chem. Int. Ed. 2016; 55: 1894
• 12b Li Y.-Q. Wang H.-J. Huang Z.-Z. J. Org. Chem. 2016; 81: 4429
• 12c Cran JW. Krafft ME. Seibert KA. Haxell TF. N. Wright JA. Hirosawa C. Abboud KA. Tetrahedron 2011; 67: 9922
• 12d Webber P. Krische MJ. J. Org. Chem. 2008; 73: 9379
• 12e Shi M. Liu X.-G. Org. Lett. 2008; 10: 1043
• 12f Krafft ME. Haxell TF. N. Seibert KA. Abboud KA. J. Am. Chem. Soc. 2006; 128: 4174
• 12g Krafft ME. Seibert KA. Haxell TF. N. Hirosawa C. Chem. Commun. 2005; 5772
• 12h Krafft ME. Haxell TF. N. J. Am. Chem. Soc. 2005; 127: 10168
• 12i Koech PK. Krische MJ. J. Am. Chem. Soc. 2004; 126: 5350
• 12j Jellerichs BG. Kong J.-R. Krische MJ. J. Am. Chem. Soc. 2003; 125: 7758

Selected examples:
• 13a Trost BM. Luan X. Miller Y. J. Am. Chem. Soc. 2011; 133: 12824
• 13b Reynolds TE. Binkley MS. Scheidt KA. Org. Lett. 2008; 10: 5227
• 13c Reynold TE. Binkley MS. Scheidt KA. Org. Lett. 2008; 10: 2449
• 13d Reynold TE. Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 7806
• 13e Mueller AJ. Jennings MP. Org. Lett. 2007; 9: 5327
• 13f Yoshizawa K. Shioiri T. Tetrahedron 2007; 63: 6259
• 13g Gudimalla N. Fröhlich R. Hoppe D. Org. Lett. 2004; 6: 4005
• 13h Li G. Wei H.-X. Phelps BS. Purkiss DW. Kim SH. Org. Lett. 2001; 3: 823
• 13i Stergiades IA. Tius MA. J. Org. Chem. 1999; 64: 7547
• 13j Reich HJ. Eisenhart EK. Olson RE. Kelly MJ. J. Am. Chem. Soc. 1986; 108: 7791
• 13k Fleming I. Perry DA. Tetrahedron 1981; 37: 4027
• 13l Kuwajima I. Kato M. Tetrahedron Lett. 1980; 21: 623
• 14 Ishikawa T. Mizuta T. Hagiwara K. Aikawa T. Kudo T. Saito S. J. Org. Chem. 2003; 68: 3702
• 15 Representative Procedures Preparation of 3h via Method A Dienone 1d (41.5 mg, 0.14 mmol) and allenol ether 2c (61.9 mg, 0.29 mmol, 2.0 equiv) were dissolved in CH₂Cl₂ (2 mL, 0.1 M in dienone) under argon and cooled to –78 °C (acetone/dry ice bath). TMSOTf (27.8 μL, 0.15 mmol, 1.1 equiv) was added dropwise. The reaction mixture was stirred at the same temperature for 15 min, then was quenched with sat. aq NaHCO₃ (5 mL) and warmed to r.t. The aqueous layer was extracted with CH₂Cl₂ (2 × 10 mL), the combined organic layers were washed with brine solution (1 × 15 mL) and dried over anhydrous MgSO₄. After filtration, the solvent was removed by rotary evaporation providing a crude residue that was purified by flash column chromatography (silica gel, 8:1 hexane–EtOAc) to give 29.9 mg (51%) of 3h as a colorless oil. IR (film): 3060, 3028, 2958, 1737, 1670, 1601, 1498, 1452 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 9.86 (s, 1 H), 7.43–7.40 (m, 3 H), 7.40–7.36 (m, 2 H), 7.33–7.28 (m, 2 H), 7.25–7.21 (m, 3 H), 7.21–7.16 (m, 2 H), 7.15–7.10 (m, 2 H), 7.06–7.02 (m, 2 H), 3.97 (d, J = 11.9 Hz, 1 H) 3.59 (app. t, J = 11.8 Hz, 1 H), 3.23 (app. p, J = 5.8 Hz, 1 H), 1.77–1.68 (m, 1 H), 1.68–1.58 (m, 1 H), 1.47–1.35 (m, 1 H), 1.29–1.17 (m, 1 H), 0.93 (s, 3 H), 0.83 (t, J = 7.3 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 218.6, 192.5, 149.5, 143.3, 141.9, 136.5, 133.9, 130.0, 129.3, 128.5, 128.5, 128.0, 127.8, 126.8, 126.7, 56.0, 56.0, 55.9, 48.8, 31.5, 20.1, 16.0, 14.3 [one sp² carbon signal is missing due to peak overlap]. HRMS (EI, M⁺): m/z calcd for C₃₀H₃₀O₂: 422.2246; found: 422.2253. Preparation of 3b via Method B Dienone 1b (47.8 mg, 0.148 mmol) and allenol ether 2a (41.6 mg, 0.296 mmol, 2.0 equiv) were dissolved in DCE (2 mL, 0.1 M in dienone) under argon at r.t. Sc(OTf)₃ (14.5 mg, 0.029 mmol, 0.2 equiv) was added. The reaction mixture was stirred at the same temperature for 30 min then was quenched with sat. aq NaHCO₃ (5 mL). The aqueous layer was extracted with CH₂Cl₂ (2 × 10 mL), the combined organic layers were washed with brine (1 × 15 mL) and dried over anhydrous MgSO₄. After filtration, the solvent was removed by rotary evaporation providing a crude residue that was purified by flash column chromatography (silica gel, 8:1 hexane–EtOAc) to give 30.6 mg (55%) of 3b as a colorless oil. IR (film): 3034, 2958, 1739, 1689, 1612, 1583, 1514, 1463 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 9.60 (s, 1 H), 7.25–7.21 (m, 2 H), 6.91–6.87 (m, 2 H), 6.80–6.75 (m, 2 H), 6.74–6.70 (m, 2 H), 6.28 (s, 1 H), 6.10 (s, 1 H), 3.84 (d, J = 12.1 Hz, 1 H), 3.73 (s, 3 H), 3.72 (s, 3 H), 3.27 (app. t, J = 11.9 Hz, 1 H), 3.03 (dq, J = 11.7, 7.1 Hz, 1 H), 1.17 (d, J = 7.1 Hz, 3 H), 0.86 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 218.8, 194.0, 158.4, 158.4, 152.1, 138.3, 133.0, 130.1, 128.7, 128.4, 114.0, 113.3, 55.1, 55.1, 54.8, 53.8, 51.9, 50.7, 16.2, 13.6. HRMS (EI, M⁺): m/z calcd for C₂₄H₂₆O₄: 378.1831; found: 378.1831.
• 16a He W. Herrick IR. Atesin TA. Caruana PA. Kellenberger CA. Frontier AJ. J. Am. Chem. Soc. 2008; 130: 1003
• 16b He W. Sun X. Frontier AJ. J. Am. Chem. Soc. 2003; 125: 14278

For selected recent examples, see:
• 17a Shirinian VZ. Lvov AG. Yadykov AV. Yaminova LV. Kachala VV. Markosyan AI. Org. Lett. 2016; 18: 6260
• 17b Takeda T. Harada S. Nishida A. Org. Lett. 2015; 17: 5184
• 17c Jolit A. Walleser PM. Yap GP. A. Tius MA. Angew. Chem. Int. Ed. 2014; 53: 6180
• 17d Xi ZG. Zhu L. Luo S. Cheng JP. J. Org. Chem. 2013; 78: 606
• 17e Hutson GE. Türkmen YE. Rawal VH. J. Am. Chem. Soc. 2013; 135: 4988
• 17f Malona JA. Cariou K. Spencer WT. Frontier AJ. J. Org. Chem. 2012; 77: 1891

For early reports on catalytic interrupted Nazarov reactions, see:
• 18a Giese S. West FG. Tetrahedron 2000; 56: 10221
• 18b Wang Y. Arif AM. West FG. J. Am. Chem. Soc. 1999; 121: 876
• 18c Giese S. West FG. Tetrahedron Lett. 1998; 39: 8393