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

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Reaction Steps

The solution of succinaldehyde 8 (57.5 g, 668 mmol) in THF (334 ml) obtained in Example 1B was stirred at r.t. (S)-Proline (1.54 g, 13.4 mmol, 0.02 eq.) was added as a solid and the reaction stirred at r.t. for 20 h. THF (334 ml) was added, followed by [Bn2NH2][OCOCF3] (4.16 g, 13.4 mmol, 0.02 eq.). The reaction was stirred for a further 14 h. The volume of the reaction mixture was reduced by half under reduced pressure. tert-Butyl methyl ether (TBME) (334 ml) was added and the mixture stirred for 20 min before filtration of the resulting solids (through a sinter funnel). The solids were washed with TBME (3×50 ml) and the filtrate was concentrated under reduced pressure. (Note: During concentration of the filtrate, for the purposes of this example it is important not to heat the water bath of the rotary evaporator). The material was purified by column chromatography (˜350 g silica), eluting with petrol/EtOAc (6:4 to 4:6), to give the lactol 7 (as an approximately 2:1 mixture of diastereoisomers, 16%), as a brown oil. This material is of sufficient purity to take forward for the next transformation (see Example 3C). While it does contain some unreacted succinaldehyde and oligomeric side-products these do not interfere with the subsequent transformation and purification.

Provenance & Evidence