Diastereomerically Pure Morita–Baylis–Hillman (MBH) Acetates and Carbonates from Allenic α- and γ-MBH Alcohols

Abstract

Diastereomerically pure allenic Morita–Baylis–Hillman (MBH) acetates and carbonates have been prepared from their corresponding α- and γ-MBH alcohols. Derivatizations proceeded under standard conditions without epimerization. Both α- and γ-MBH derivatives were shown to be suitable substrates for further transformations.

Key words

allenes - catalysis - nucleophiles - protecting groups - esterification

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• 12 α-Selective MBH Reaction; Typical Procedure: γ-(tert-Butyl)allenoate 2 (640 mg, 3.80 mmol, 1.1 equiv) and furan-2-carbaldehyde (3d; 332 mg, 3.46 mmol, 1.0 equiv) were dissolved in DMF (7.0 mL) and the solution was cooled to –60 °C. TBD (96.3 mg, 692 μmol, 20 mol%) dissolved in DMF (1.0 mL) was added and the mixture was stirred at –60 °C for 2.0 h. Solid NH₄Cl (excess) was added, the mixture was diluted with aq LiCl (5% w/w, 30 mL) and extracted with Et₂O (3 × 25 mL). The combined organic extracts were washed with LiCl (5% w/w, 25 mL), sat. aq NaCl (25 mL), dried over MgSO₄, filtered, and the solvent was evaporated. Column chromatography (silica gel; 3.0 × 20 cm; petroleum ether–Et₂O, 80:20) gave the apolar isomer 5d-ap (90 mg, 340 μmol, 10%) and the polar isomer 5b-po (637 mg, 2.41 mmol, 69%) as colorless oils. Overall yield: 727 mg (2.75 mmol, 79%); dr (ap/po) = 12:88.
• 13a Synthesis of Allenic MBH Acetates; Typical Procedure: Apolar γ-MBH alcohol 4b-ap (180 mg, 641 μmol) was dissolved in CH₂Cl₂ (3.0 mL) and the solution was cooled to 0 °C. Pyridine (77 μL, 75 mg, 961 μmol, 1.5 equiv) and AcCl (77 μL, 75 mg, 961 μmol, 1.5 equiv) were added dropwise, and the solution was stirred at 0 °C for 1.0 h. The reaction was quenched with dilute HCl (10% aq, 10 mL) and extracted with CH₂Cl₂ (3 × 20 mL). The combined organic extracts are washed with H₂O (25 mL), sat. aq NaCl (25 mL), dried over MgSO₄, filtered, and the solvent was evaporated. Column chromatography (silica gel; 1.0 × 18 cm; petroleum ether–EtOAc, 91:9) of the residue gave diastereomerically pure γ-MBH acetate 6b-ap (167 mg, 515 μmol, 80%) as a colorless oil.
• 13b Synthesis of Allenic MBH Carbonates; Typical Procedure: Polar γ-MBH alcohol 4b-po (84 mg, 298 μmol) was dissolved in CH₂Cl₂ (4.0 mL) and the solution was cooled to 0 °C. Boc₂O (72 mg, 328 μmol, 1.1 equiv) and DMAP (7.3 mg, 59 μmol, 20 mol%) were added, and the solution was stirred at 0 °C for 1.0 h. The mixture was evaporated to dryness, and the residue was directly purified by column chromatography (silica gel; 2.0 × 16 cm; petroleum ether–EtOAc, 91:9) to give the diastereomerically pure γ-MBH carbonate 8b-po (105 mg, 277 μmol, 93%) as a colorless oil.

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