Methane → (3aR,6aS)-2-Hydroxy-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-5-carbaldehyde

참여 물질

반응 단계

The solution of succinaldehyde 8 from the first step (50.6 g, 0.588 mol) in 2-MeTHF was stirred at r.t. (S)-Proline (1.35 g, 11.8 mmol, 0.02 eq.) was added as a solid (Note: The reaction turns from a colourless suspension to a pink suspension over 10 min) and the reaction stirred at r.t. for 20 h. THF (294 ml) was added, followed by [Bn2NH2][OCOCF3] (3.67 g, 11.8 mmol, 0.02 eq.). The reaction was stirred for a further 20 h. Note: The reaction turns to a dark maroon suspension over 20 h. Activated charcoal (100 g) was added to the reaction and the volume of the reaction mixture was reduced by ½ under reduced pressure (˜300 mL). tert-Butyl methyl ether (TBME) (an equal volume to the volume of THF/2-MeTHF removed; 300 mL) was added slowly (over ˜15 mins) and with vigorous stirring of the mixture. Note: For the purposes of this example, slow addition of TBME helps to avoid the formation of oligomer aggregates. The mixture was stirred for 60 min before filtration of the resulting solids (through a sinter funnel; diameter: ˜10 cm). The solids were washed with 2-MeTHF (3×120 ml or until the product was not observed in the filtrate by TLC, 1:1 petroleum ether/EtOAc) and the filtrate was concentrated under reduced pressure. Note: For the purposes of this example, the filtrate should not be concentrated to complete dryness to help avoid solidifying the oligomers on the column, thereby clogging the column during the purification process. The material was purified by column chromatography (˜400 g silica), eluting with petroleum ether/EtOAc (8:2 to 5:5), to give the lactol 7 (as an approximately 2:1 mixture of diastereoisomers), as a brown oil.

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