Application of new methodologies using principles of green chemistry in organic synthesis

Electrochemical methods represent an attractive and sustainable alternative to traditional synthetic methods. These conditions are attractive in that they are an inexpensive and direct means of supplying the electrons and protons required for the desired transformation. A strong case can be made that, by its very nature, electrosynthesis can directly address 10 of the 12 principles of green chemistry. The aldol reaction is of fundamental importance to organic synthesis that, in its current form, is decidedly not green. Most aldol-type reactions require the use of stoichiometric amounts of base at some point. Reductions of γ, δ-epoxy-α, β-unsaturated esters and amides will provide access to the corresponding δ-hydroxy-β, γ-unsaturated carbonyl compounds. Current methods for reductions of epoxy carbonyl compounds typically involve using stoichiometric amounts of highly reactive, toxic and expensive reagents such as SmI2 and titanium(III) complex. Existing examples of cathodic reductions of epoxy carbonyls compounds are few and have only been demonstrated with a very limited substrate scope and most of their work employed a mercury cathode or included seemingly unnecessary reagents. In this case, we designed an alternative route to vinylogous aldol-type products that relies on a combination of enantioselective catalysis and electrosynthesis. The interest in enantioselective γ-allylation of α, β-unsaturated aldehydes came from the total synthesis of fragment C of Biselyngbyaside B. We proposed a new method of enantioselective γ-allylation of α, β-unsaturated aldehydes under palladium and dienamine catalysis and mechanistic hypotheses. Even the direct γ-allylation was unsuccessful after efforts, the γ-allylation product of α, β-unsaturated aldehydes can be synthesized via α-allylation through Tsuji allylation, then Cope rearrangement via microwave irradiation. The enantioselective Tsuji allylation has been tried with several chiral phosphorus ligands and the result has been presented.

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