Rasta Resin-TBD-Catalyzed γ-Selective Morita–Baylis–Hillman Reactions of α,γ-Disubstituted Allenones

Abstract

Rasta resin-TBD (RR-TBD) was found to be an efficient organocatalyst for γ-selective Morita–Baylis–Hillman reactions between α,γ-disubstituted allenones and aryl aldehydes. In these reactions the heterogeneous nature of RR-TBD greatly facilitated product isolation since the catalyst could be separated simply by filtration.

Key words

allenones - Morita–Baylis–Hillman reactions - organocatalysis - polymer-supported catalysts - rasta resin

• References and Notes


For selected reviews regarding MBH reactions and the utility of MBH products, see:
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For selected examples and reviews regarding the use of MTBD as a catalyst, see:
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For details regarding the rasta resin concept, see:
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For our previous research using rasta resin, see:
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• 14 General Procedure for the Synthesis of Allenones 3A–D: α-Bromo ketone 4A or 4B (20.0 mmol), Ph₃P (6.29 g, 24.0 mmol), and benzene (100 mL) were added to a 250-mL round-bottomed flask equipped with a magnetic stirrer and a condenser. The reaction flask was immersed in an oil bath, and the reaction mixture was refluxed for 2 d. After cooling to r.t., the solvent was removed under reduced pressure to afford the crude phosphonium salt 5A or 5B as a viscous oil. The crude salt dissolved in CHCl₃ (65 mL) was transferred to a 100-mL round-bottomed flask equipped with a magnetic stirrer. The reaction mixture was cooled to 0 °C with an ice-water bath and then Et₃N (6.1 mL, 44 mmol) was added dropwise. The ice-water bath was removed, and the reaction mixture was then stirred at r.t. for 3 h. The reaction mixture was cooled to 0 °C and the appropriate acid chloride (18.0 mmol) was added dropwise. After 1 h, the reaction mixture was warmed to r.t. and stirred for a further 10 h. The reaction mixture was transferred to a separation funnel and H₂O (100 mL) was added. The organic layer was separated and washed with brine (50 mL) and then dried over MgSO₄. The solvent was removed under reduced pressure to afford a yellow oil which was then purified by silica gel column chromatography using a mixture of CH₂Cl₂ and hexane as the eluent. 4-Methylhepta-4,5-dien-3-one (3A): ¹H NMR (400 MHz, CDCl₃): δ = 5.43–5.50 (m, 1 H), 2.59–2.71 (m, 2 H), 1.79 (d, J = 7.3 Hz, 3 H), 1.76 (d, J = 2.7 Hz, 3 H), 1.07 (t, J = 7.3 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 212.29, 202.88, 159.50, 138.13, 91.70, 88.92, 32.10, 13.49, 13.39, 8.99. HRMS: m/z calcd for C₈H₁₂O: 124.0883; found: 124.0881.
• 15 General Procedure for the MBH Reactions: Allenone 3A–D (0.8 mmol), aldehyde 6a–e (0.4 mmol), NMP (1.0 mL), and 1, 2 or 8 (0.08 mmol) were added to a 10-mL round-bottomed flask equipped with a magnetic stirrer. The reaction mixture was stirred either at r.t. (when 1 was used as the catalyst) or at 50 °C (when 2 or 8 was used as the catalyst) for the reaction times indicated in Table 2. When 1 was used as the catalyst, solid NH₄Cl (0.006 g, 0.1 mmol) was added to the reaction mixture to quench the reaction. The reaction mixture was then transferred to a separation funnel, and then H₂O (30 mL) and EtOAc (15 mL) were added. The organic layer was separated, washed with brine (30 mL), and dried over MgSO₄. The solvent was evaporated under reduced pressure to afford an oil, which was purified by silica gel column chromatography using a mixture of EtOAc and hexane as the eluent. When 2 was used as the catalyst, the reaction mixture was merely filtered, and the crude product was purified by silica gel column chromatography. 7-(4-Chlorophenyl)-7-hydroxy-4,6-dimethylhepta-4,5-dien-3-one (7Aa): ¹H NMR (400 MHz, CDCl₃): δ = 7.29–7.37 (m, 4 H, CH_Ar, major + minor), 5.26 (s, 1 H, CHOH, major), 5.24 (s, 1 H, CHOH, minor), 2.50–2.64 (m, 2 H, COCH ₂CH₃, major + minor), 2.43 (br s, 1 H, OH, major), 2.37 (s, 1 H, OH, minor), 1.78 [s, 3 H, (CH ₃)CCOEt, major + minor], 1.74 [s, 3 H, (CH ₃)CCHOH, major + minor], 1.05 (t, J = 7.4 Hz, 3 H, CH₂CH ₃, major + minor). ¹³C NMR (major diastereomer, 101 MHz, CDCl₃): δ = 208.73 (s, =C=), 202.80 (s, COEt), 140.12 (s, C _ArCHOH), 133.73 (s, C_ArCl), 128.62 (s, C_ArH), 127.67 (s, C_ArH), 106.43 (s, CCHOH), 105.04 (s, CCOEt), 74.48 (s, CHOH), 32.43 (s, CH₂CH₃), 8.92 (s, CH₂ CH₃). The signals for (CH₃)CCHOH and (CH₃)CCO (14.43, 14.20, 13.81) were not assigned due to overlapping signals. ¹³C NMR (minor diastereomer, 101 MHz, CDCl₃): δ = 208.67 (s, =C=), 202.86 (s, COEt), 140.09 (s, C _ArCHOH), 133.80 (s, C_ArCl), 128.67 (s, C_ArH), 127.74 (s, C_ArH), 106.42 (s, CCHOH), 105.32 (s, CCOEt), 74.39 (s, CHOH), 32.43 (s, CH₂CH₃), 8.88 (s, CH₂ CH₃). HRMS: m/z calcd for C₁₅H₁₇Cl₁O₂: 264.0912; found: 264.0724.
• 16 See reference 10 for details and a cartoon illustrating the structure of 8. The polystyrene support used in 8 is commercially available and is the typical material used in polystyrene-supported reagents and catalysts.

For research involving similar polystyrene-supported TBD reagents and catalysts, see:
• 17a Fringuelli F, Pizzo F, Vittoriani C, Vaccaro L. Chem. Commun. 2004; 2756
• 17b Fringuelli F, Pizzo F, Vittoriani C, Vaccaro L. Eur. J. Org. Chem. 2006; 1231
• 17c Lanari D, Ballini R, Bonollo S, Palmieri A, Pizzo F, Vaccaro L. Green Chem. 2011; 13: 3181
• 17d Lanari D, Ballini R, Palmieri A, Pizzo F, Vaccaro L. Eur. J. Org. Chem. 2011; 2874
• 17e Alonzi M, Bracciale MP, Broggi A, Lanari D, Marrocchi A, Santarelli ML, Vaccaro L. J. Catal. 2014; 309: 260