Nucleophilic conjugate addition

Reaction mechanism

A Keto-enol tautomerism to the saturated carbonyl compound.

Reactions

• Conjugated carbonyls react with secondary amines to 1,4-keto-amines. For example the conjugate addition of methylamine to 2-cyclohexenone gives the compound 3-(N-methylamino)-cyclohexanone.
• Conjugated carbonyls react with diethylaluminum cyanide.
• The Gilman reagent is an effective nucleophile for 1,4-additions to conjugated carbonyls.
• The enolates to conjugated carbonyls.
• The enamines to conjugated carbonyls.

Scope

Conjugate addition is effective in the formation of new carbon-carbon bonds with the aid of organometallic reagents such as the organo zinc iodide reaction with methylvinylketone.^[1]

An example of an BINAP.^[2]

In another example of asymmetric synthesis the α,β-unsaturated carbonyl compound first reacts with a enantiomeric excess.^[3]

This principle is also applied in an enantioselective DEAD.^[4]

References

1. ^  Asymmetric Synthesis of exo-Isobrevicomin and exo-Brevicomin via Conjugated Addition of Primary Alkyl Iodides to a, b-Unsaturated Ketones Andréa L. de Sousa and Inês S. Resck J. Braz. Chem. Soc. vol.13 no.2 São Paulo 2002 Online Article
2. ^  (R)-3-phenyl-cyclohanone Tamio Hayashi, Makoto Takahashi, Yoshiaki Takaya, and Masamichi Ogasawara Organic Syntheses, Coll. Vol. 10, p.609 (2004); Vol. 79, p.84 (2002). Online article
3. ^  Enantioselective Organo-Cascade Catalysis Yong Huang, Abbas M. Walji, Catharine H. Larsen, and David W. C. MacMillan J. Am. Chem. Soc.; 2005; 127(43) pp 15051 - 15053; (Communication) DOI: 10.1021/ja055545d Abstract
4. ^  Asymmetric Multicomponent Domino Reactions and Highly Enantioselective Conjugated Addition of Thiols to ,α,β-Unsaturated AldehydesMauro Marigo, Tobias Schulte, Johan Franzén, and Karl Anker Jorgensen J. Am. Chem. Soc.; 2005; 127(45) pp 15710 - 15711; (Communication) DOI: 10.1021/ja055291 Abstract