Efficient Organocatalytic Hetero-Diels-Alder Reactions of Activated Ketones under High Pressure for Direct Access to δ-Lactones [¹]

Abstract

A general and efficient protocol for the high-pressure-promoted hetero-Diels-Alder reactions of activated ketones has been developed. The reactions are successfully achieved by thiourea-derived organocatalysts, and the desired adducts, convenient precursors of δ-lactones, are obtained in good to high yields.

Key words

Hetero-Diels-Alder reaction - activated ketones - δ-lactones - thiourea catalyst - high pressure

References and Notes

• 1 High-Pressure Organic Chemistry, Part 35. For Part 34, see: Azad S. Kobayashi T. Nakano K. Ichikawa Y. Kotsuki H. Tetrahedron Lett.  2009,  50:  48 
• 2 Istvan ES. Deisenhofer J. Science  2001,  292:  1160 
• Reviews:
• 3a Collins I. J. Chem. Soc., Perkin Trans. 1  1999,  1377 
• 3b Boucard V. Broustal G. Campagne JM. Eur. J. Org. Chem.  2007,  225 
• Selected recent examples:
• 4a Perez LJ. Micalizio GC. Synthesis  2008,  627 
• 4b Habel A. Boland W. Org. Biomol. Chem.  2008,  6:  1601 
• 4c Evans DA. Burch JD. Hu E. Jaeschke G. Tetrahedron  2008,  64:  4671 
• 4d Jung W.-H. Guyenne S. Riesco-Fagundo C. Mancuso J. Nakamura S. Curran DP. Angew. Chem. Int. Ed.  2008,  47:  1130 
• 4e Crimmins MT. Dechert A.-MR. Org. Lett.  2009,  11:  1635 
• 4f Su Y. Xu Y. Han J. Zheng J. Qi J. Jiang T. Pan X. She X. J. Org. Chem.  2009,  74:  2743 
• Selected recent examples:
• 5a Wu F. Hong R. Khan J. Liu X. Deng L. Angew. Chem. Int. Ed.  2006,  45:  4301 
• 5b Pichlmair S. de Lera Ruiz M. Vilotijevic I. Paquette LA. Tetrahedron  2006,  62:  5791 
• 5c Kumar I. Rode CV. Tetrahedron: Asymmetry  2007,  18:  1975 
• 5d Hanessian S. Auzzas L. Org. Lett.  2008,  10:  261 
• Selected recent examples:
• 6a Shibahara S. Fujino M. Tashiro Y. Takahashi K. Ishihara J. Hatakeyama S. Org. Lett.  2008,  10:  2139 
• 6b Akaike H. Horie H. Kato K. Akita H. Tetrahedron: Asymmetry  2008,  19:  1100 
• 6c Chandrasekhar S. Rambabu Ch. Reddy AS. Tetrahedron Lett.  2008,  49:  4476 
• 6d Ding F. Jennings MP. J. Org. Chem.  2008,  73:  5965 
• Selected recent examples:
• 7a Lucas BS. Gopalsamuthiram V. Burke SD. Angew. Chem. Int. Ed.  2007,  46:  769 
• 7b Jensen KH. Sigman MS. Angew. Chem. Int. Ed.  2007,  46:  4748 
• 7c Dilger AK. Gopalsamuthiram V. Burke SD. J. Am. Chem. Soc.  2007,  129:  16273 
• 7d Yu Z. Liu X. Dong Z. Xie M. Feng X. Angew. Chem. Int. Ed.  2008,  47:  1308 
• 7e Yang X.-B. Feng J. Zhang J. Wang N. Wang L. Liu J.-L. Yu X.-Q. Org. Lett.  2008,  10:  1299 
• 7f Lin L. Chen Z. Yang X. Liu X. Feng X. Org. Lett.  2008,  10:  1311 
• 7g Tiseni PS. Peters R. Org. Lett.  2008,  10:  2019 
• Reviews of HDA reactions:
• 8a Cycloaddition Reactions in Organic Synthesis   Kobayashi S. Jørgensen KA. Wiley-VCH; Weinheim: 2002. 
• 8b Jørgensen KA. Angew. Chem. Int. Ed.  2000,  39:  3558 
• 8c Carmona D. Lamata MP. Oro LA. Coord. Chem. Rev.  2000,  200-202:  717 
• 8d Jørgensen KA. Eur. J. Org. Chem.  2004,  2093 
• 8e Gouverneur V. Reiter M. Chem. Eur. J.  2005,  11:  5806 
• 8f Lin L. Liu X. Feng X. Synlett  2007,  2147 
• Recent examples:
• 9a Moreau X. Bazán-Tejeda B. Campagne J.-M. J. Am. Chem. Soc.  2005,  127:  7288 
• 9b Broustal G. Ariza X. Campagne J.-M. Garcia J. Georges Y. Marinetti A. Robiette R. Eur. J. Org. Chem.  2007,  4293 
• 9c Chen I.-H. Oisaki K. Kanai M. Shibasaki M. Org. Lett.  2008,  10:  5151 
• 10a Fuji K. Chem. Rev.  1993,  93:  2037 
• 10b Corey EJ. Guzman-Perez A. Angew. Chem. Int. Ed.  1998,  37:  388 
• 10c Christoffers J. Mann A. Angew. Chem. Int. Ed.  2001,  40:  4591 
• 10d Denissova I. Barriault L. Tetrahedron  2003,  59:  10105 
• 10e Quaternary Stereocenters: Challenges and Solutions for Organic Synthesis   Christoffers J. Baro A. Wiley-VCH; Weinheim: 2005. 
• 10f Cozzi PG. Hilgraf R. Zimmermann N. Eur. J. Org. Chem.  2007,  5969 
• 10g Riant O. Hannedouche J. Org. Biomol. Chem.  2007,  5:  873 
• 10h Hatano M. Ishihara K. Synthesis  2008,  1647 
• 10i Shibasaki M. Kanai M. Chem. Rev.  2008,  108:  2853 
• 11a Schreiner PR. Chem. Soc. Rev.  2003,  32:  289 
• 11b Takemoto Y. Org. Biomol. Chem.  2005,  3:  4299 
• 11c Akiyama T. Itoh J. Fuchibe K. Adv. Synth. Catal.  2006,  348:  999 
• 11d Taylor MS. Jacobsen EN. Angew. Chem. Int. Ed.  2006,  45:  1520 
• 11e Connon SJ. Chem. Eur. J.  2006,  12:  5418 
• 11f Doyle AG. Jacobsen EN. Chem. Rev.  2007,  107:  5713 
• 11g Miyabe H. Takemoto Y. Bull. Chem. Soc. Jpn.  2008,  81:  785 
• 11h Connon SJ. Chem. Commun.  2008,  2499 
• 11i Connon SJ. Synlett  2009,  354 
• 12 Schreiner PR. Wittkopp A. Org. Lett.  2002,  4:  217 
• 13a Organic Synthesis at High Pressures   Matsumoto K. Acheson RM. Wiley; New York: 1990. 
• 13b For a huge compilation of high-pressure reactions, see: Matsumoto K. Hamana H. Iida H. Helv. Chim. Acta  2005,  88:  2033 
• 14 Review of DA reactions of 1-alkoxydienes, see: Maddaluno J. Synlett  2006,  2534 
• 16a Under uncatalyzed conditions, much higher pressures (2.0 GPa) are necessary to gain satisfactory results: Jurczak J. Chmielewski M. Filipek S. Synthesis  1979,  41 
• 16b For Eu(fod)₃-catalyzed reactions at 1.0 GPa and 50 ˚C, see: Jurczak J. Golebiowski A. Bauer T. Synthesis  1985,  928 
• 17 For a formal synthesis of the 4k-type compound, see: Alcaide B. Almendros P. Rodríguez-Acebes R. J. Org. Chem.  2006,  71:  2346 

15

General Procedure A mixture of diene (2, 1.0 mmol) and ketone (3, 0.25 mmol) in the presence of 1a (0.1 mmol) in toluene or CH₂Cl₂ (ca. 2.5 mL) was placed in a Teflon reaction vessel, and the mixture was allowed to react at 1.0 GPa and r.t. for 10 h. After the pressure was released, the mixture was concentrated and purified by silica gel column chromatog-raphy (elution with hexane-Et₂O) to afford the pure adduct 4.

18

Typically, treatment of 4a with excess Jones’ reagent in acetone (0 ˚C, 3 h) gave the corresponding dihydropyranone 5 in 60% yield: colorless needles (Scheme  [²] ); mp 104-105 ˚C (hexane-CH₂Cl₂). FTIR (KBr): ν = 1745, 1718 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 2.85 (1 H, dt, J = 18.2, 2.5 Hz), 3.49 (1 H, ddd, J = 18.2, 5.8, 1.0 Hz), 3.73 (3 H, s), 6.12 (1 H, ddd, J = 9.8, 2.5, 1.0 Hz), 6.91 (1 H, ddd, J = 9.8, 5.8, 2.5 Hz), 7.33-7.44 (3 H, m), 7.60-7.63 (2 H, m). ^¹³C NMR (100 MHz, CDCl₃): δ = 33.0, 53.4, 84.2, 121.8, 124.9 (2×), 128.7 (2×), 128.9, 137.1, 143.6, 162.2, 171.0. Anal. Calcd for C₁₃H₁₂O₄: C, 67.23; H, 5.21. Found: C, 67.13; H, 5.35.

Scheme 2