Weiss-Cook Condensation
The Weiss-Cook Condensation is a named chemical reaction that involves the synthesis of bicyclic enones from cycloalkanones. This reaction is characterized by a cross-aldol condensation of 3-oxoglutarate with a 1,2-dione, which can have either aliphatic or aromatic moieties. The process typically results in the formation of a bridged bithiophene structure, which is useful in the synthesis of monomers and polymers[3][4].
The reaction was reported by Weiss and Edwards in 1968 and involves an α-dicarbonyl molecule and two equivalents of 3-oxoglutarate[16]. The mechanism of the Weiss-Cook Condensation is similar to that of the Knoevenagel condensation, which is a nucleophilic addition of an active hydrogen compound to a carbonyl group followed by a dehydration reaction[7]. However, the Weiss-Cook reaction specifically synthesizes cis-bicyclo[3.3.0]octane-3,7-dione using an acetonedicarboxylic acid ester and a diacyl (1,2 ketone)[7].
The reaction has been utilized in various studies and applications, including the synthesis of indole-based propellane derivatives[12] and the preparation of cis-1,5-dimethylbicyclo[3.3.0]octane-3,7-dione in undergraduate organic laboratories[15]. It has also been noted for its unusual condensation reactions, such as the condensation of dimethyl 2,3-dioxobutanedioate with two equivalents of dimethyl 3-oxoglutarate, which produces an "abnormal" product[9].
The Weiss-Cook Condensation is an example of a convenient annulation method that has been developed for the synthesis of bicyclic enones, and it can be catalyzed by palladium(0) in the presence of enol triflates[8]. The reaction has been subject to studies that explore its process development, experimental design, and optimization[15].
Citations:
[1] https://synarchive.com/named-reactions/weiss-cook-condensation
[2] https://onlinelibrary.wiley.com/doi/10.1002/9780470638859.conrr662
[3] https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/slct.201904180
[4] https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/slct.201904180
[5] https://cdnsciencepub.com/doi/pdf/10.1139/v94-148
[6] https://pubs.acs.org/doi/abs/10.1021/acs.jchemed.9b00653
[7] https://en.wikipedia.org/wiki/Knoevenagel_condensation
[8] https://www.researchgate.net/publication/301085455_Weiss-Cook_condensation
[9] https://www.researchgate.net/publication/237864170_Unusual_Weiss-Cook_condensation_of_dimethyl_23-dioxobutanedioate_and_dimethyl_3-oxoglutarate
[10] https://pubs.rsc.org/en/content/articlehtml/1997/p1/a605817e
[11] https://pubs.acs.org/doi/10.1021/jo00107a013
[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869257/
[13] https://pubs.rsc.org/doi/a605817e
[14] https://www.studocu.com/en-ca/document/douglas-college/organic-chemistry-part-ii/a-weiss-cook-condensation-reaction-part-b/14306882
[15] https://www.researchgate.net/publication/344009664_Process_Development_of_the_Weiss-Cook_Reaction_for_the_Preparation_of_cis_-15-Dimethylbicyclo330octane-37-dione_in_the_Undergraduate_Organic_Laboratory
[16] https://www.chemistry-online.com/organic-chemistry/named-reactions/weiss-cook-condensation/
[17] https://link.springer.com/chapter/10.1007/978-3-319-03979-4_284
[18] https://en.wikipedia.org/wiki/File:Weiss%E2%80%93Cook_reaction.png
[19] https://onelook.com/reverse-dictionary.shtml?s=Dieckmann+condensation