Regio- and Diastereoselective Allenylation of Aldehydes in Aqueous Media: Total Synthesis of (+)-Goniofufurone(1).

The regio- and diastereoselectivities of metal-mediated allenylation of carbonyl compounds were investigated in aqueous media. Different metal mediators showed varied regioselectivities on product formation during propargylation-allenylation reactions of carbonyl compounds with simple propargyl bromide. Under the standard reaction conditions, the use of indium provided the highest regioselectivity, with a preference of formation of the homopropargyl alcohol. The use of tin and bismuth as the metal mediator provided slightly lower selectivities with the same preference. The use of zinc and cadmium as the mediators further lowered the product selectivity. The reactions of an aliphatic aldehyde with simple propargyl bromide showed a lower selectivity than the reaction of an aromatic aldehyde in most cases, except for the use of tin or zinc (where comparable selectivities were observed). On the other hand, the reaction of terminal-substituted propargyl bromides with aldehydes mediated by indium showed a high regioselectivity in forming allenylation products. The indium-mediated allenylation of carbonyl compounds bearing an alpha-hydroxyl group also proceeded with a high diastereoselectivity, forming syn-diols predominantly in aqueous ethanol. The high diastereoselectivity in allenylation of alpha-hydroxyl-substituted aldehydes was attributed to the chelation effect exhibited by the alpha-hydroxyl substitutent. Through the use of this highly diastereoselective allenylation, (+)-goniofufurone was synthesized from D-glucurono-6,3-lactone.