Novel DBU-MeOH-Promoted One-Pot Stereoselective γ-Functionalization of 1,3-Dicarbonyls: An Easy Access to γ-Arylidene, γ-Alkylidene and γ-Allylidene α-Ketoesters and -amides

Abstract

Cyclic β-ketoesters and β-ketoamides undergo, in a one-pot process, an unprecedented DBU-MeOH-promoted regio- and stereoselective γ-functionalization with aldehydes, by a directed γ-aldol reaction and dehydration sequence, to afford synthetically valuable alkylidene (or arylidene) cycloalkanones in good yields. While β-ketoesters give good results only with aromatic aldehydes, β-ketoamides react smoothly either with aromatic, aliphatic, or α,β-unsaturated aldehydes following a totally regioselective 1,2-addition. The overall sequence, probably initiated by a reversible α-aldol reaction, allows the formation of hitherto unknown and stereodefined γ-functionalized cycloalkanones having three reactive centers, such as two electrophilic and one nucleophilic site.

Key words

β-ketoesters - β-ketoamides - γ-functionalization - aldol reaction - alkylidene (or arylidene) cycloalkanones

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35

While 1c was totally unreactive, 1a gave methyl adipate resulting from a retro-Dieckmann ring cleavage, see ref. 33.

36

The dimethoxy acetal function resulted from a trans-acetalization of the ethoxy enol ether under the reaction conditions. Methyl adipate (35 %) resulting from a retro-Dieckmann ring cleavage of 1a was also formed.

44

Attempts to extend the Robinson annulation using various experimental conditions including the use of MeONa⁺-MeOH, K₂CO₃-MeOH or acetone, and pyrrolidine in refluxing benzene or toluene, were unsuccessful due to the retro-Michael reaction.