Regio- and Diastereoselective Allenylation of Aldehydes in Aqueous Media:  Total Synthesis of (+)-Goniofufurone¹

Abstract

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.

Electrochemical Regeneration of Low-Valent Indium(I) Species as Catalysts for C−C Bond Formations

“…Further support for the involvement of indium species and not aluminum-derived C À C bond formation is provided by the electrochemical reaction of propargyl bromide with benzaldehyde, which gives, under electrochemical conditions, a mixture of the corresponding homopropargylic alcohol and the allenylic alcohol in a ratio of 3:1 (Scheme 6), while an electrolysis in the absence of indium gave no desired product. [12] When the analogous propargylation was performed starting from metallic indium in aqueous methanol a similar product distribution was found (6:1), [13] but when we changed the solvent system to THF, the propargylation with metallic indium gave a complex mixture of products. These findings indicate that in the case of propargylation, the reaction does not proceed via aluminum species or via indium sesquibromides, but that reactive low-valent indium species are formed by a combination of chemical redox processes with metallic aluminum and electrochemical reactions at the anode.…”

Use ofN-Methylformamide as a Solvent in Indium-Promoted Barbier Reactions en Route to Enediyne and Epoxy Diyne Formation: Comparison of Rate and Stereoselectivity in C−C Bond-Forming Reactions with Water

“…1,2 New solvents in Diels−Alder(2) and Barbier 3,4 reactions have been sought to help streamline the one-pot transformations further, reducing synthetic steps and organic waste. Polar media often accelerate reactions of this type which has led to the use of water as an acceptable solvent for such organic conversions.…”

Asymmetric Synthesis of Styryl-Lactones

“…Li et al [57] also proposed a synthesis of (+)-goniofufurone (27), starting from D-glucurono-3,6-lactone 108, using an highly diastereoselective allenylation. Intermediate 112, obtained in four steps from 108, was subjected to an indium-mediated allenylation reaction, in aqueous medium, to generate a mixture of compounds in which the allene 113 was the major component (32%) with a high syn diastereoselectivity (> 91:9) " Fig.…”