Catalysis of the Michael Reaction and the Vinylogous Michael Reaction by Ferric Chloride Hexahydrate

Abstract

Ferric chloride hexahydrate catalyzes the Michael reaction of 1,3-dicarbonyl compounds with a,b-unsaturated ketones under mild and non-basic conditions with extraordinary efficiency. The chemoselectivity of this Fe(III)-catalyzed process is superior to that of the classic base-mediated Michael reaction, since the latter suffers from various side and subsequent reactions, namely drawbacks such as aldol cyclizations and retro-Claisen reactions. Excellent yields and chemoselectivities together with the environmentally friendly nature of the Fe(III) catalysis make this an important alternative to established methods. An enone-dienol tautomerization of 2-acceptor substituted cycloalkenones is the precondition for the iron-catalyzed vinylogous Michael reaction. Herein a g-donor formally undergoes conjugate addition to a b-acceptor to furnish products with 1,7-dioxo constitutions. Actually, this process is a sequence initiated by the tautomerization followed by a [4+2]-cycloaddition and a retro-aldol reaction. When benzoquinone derivatives are employed as acceptors, the products of the vinylogous Michael reactions are highly functionalized biaryl precursor compounds.

Bijvoet in Solution Reveals Unexpected Stereoselectivity in a Michael Addition

“…The conjugated addition to a,b-unsaturated compounds (Michael reaction) is one of the most important reactions in C À C bond formation. [13] A few examples that use metallic enolates prepared from chiral and achiral oxazolidinones in conjugated addition reactions have been described to prepare versatile intermediates in the synthesis of compounds with interesting pharmacological activities. [14][15][16][17][18][19] By using the new methodology we determine the relative configuration of the reaction product, reveal with this an unexpected stereoselectivity and provide an insight into mechanistic organic chemistry.…”

Copper-Catalyzed Asymmetric Michael Reactions with α-Amino Acid Amides: Synthesis of an Optically Active Piperidine Derivative

“…[1Ϫ3] Metal-catalyzed Michael reactions are an important alternative to base catalysis, since the chemoselectivity is improved in most cases. [4,5] In the field of metal-catalyzed enantioselective Michael reactions the heterobimetallic catalysts developed by Shibasaki are presently defining the state-of-the-art. [6,7] Applying Shibasaki's method tertiary stereocenters are generally formed with excellent selectivities at ambient temperature, whereas low temperatures are required for the generation of quaternary stereocenters.…”

Direct asymmetric vinylogous Michael addition of cyclic enones to nitroalkenes via dienamine catalysis

“…In contrast, little progress has been reported in the corresponding enantioselective carbon-carbon bond formation γ to a carbonyl group (15). Among the few useful approaches devised to date, the concept of vinylogous nucleophilicity is the most powerful (16)(17)(18)(19). Formulated by Fuson in 1935 as the transmission of electronic effects through a conjugated π system (20), this principle accounts for the use of γ-enolizable α,β-unsaturated carbonyl compounds as precursors of nucleophilic dienolate equivalents, formally inverting the usual reactivity of this compound class.…”

“…In general, the critical regiochemical issue can be addressed by judiciously preparing preformed, stable dienolate equivalents. This strategy has been successfully applied to asymmetric vinylogous aldol (17,21), Mannich (18,22), and Michael reactions (19,23). Avoiding the stoichiometric preactivation of the vinylogous nucleophilic components would logically improve this approach, particularly from the standpoint of atom economy (24).…”