The reaction of a stabilised carbon nucleophile with activated π-systems, to form a new carbon-carbon single bond via 1,4-conjugate addition is called a Michael Addition. This reaction is hugely important in organic synthesis, and was first discovered in 1883 by Komnenos, but was named after Arthur Michael, who performed systematic investigations into its mechanism in 1887.
This reaction is one that even the most junior chemists should know and understand as it is a very useful way of introducing new carbon-carbon bonds. This base catalysed reaction requires an α,ß-unsaturated target (e.g. an alkene or an alkyne) and a reactant with acidic protons which will enable, with the use of a base, the formation of a nucleophile).
The species with the π-system is known as the "Michael acceptor" as it accepts the electrons given by the nucleophile (the "Michael donor"). The products of the Michael addition are known as "Michael adducts". Today, nearly all 1,4-additions ("conjugate additions") are referred to as Michael additions.
Frequently carbonyls such as ß-ketoesters or diketones are used as Michael donors (in fact this reaction was originally discovered when working with malonates) which form enolates in the same way as the base catalysed mechanism in the aldol reaction.
1. General Scheme
Scheme M1: The Michael addition
Scheme M2: Michael addition mechanism
This reaction results in the loss of a double (π) bond and the formation of a new single (σ) bond, and as a result, any (Z)- or (E)- isomerism in the alkene is lost. However, when R1 and R2 on the Michael acceptor are not the same, a stereogenic centre is created. Diastereoselectivity can be obtained by carefully choosing reagents and conditions (e.g. selecting reagents with defined stereochemistry).
- Self condensation of the Michael donor is possible, in cases where the donor also contains conjugated systems (e.g. α,ß-unsaturated carbonyls).
- the Michael donor (the nucleophile) can be derived from the deprotonation of ketones (and aldehydes), nitriles or deprotonation of heteroatoms.
- Only catalytic amounts of base are required. When using a full equivalent, then the product carbanion may exist in the reaction solution for some time and may undergo further reaction with electrophiles.
- The reaction will proceed in both protic and aprotic solvents. In protic solvents, the Michael adduct may result from the resultant carbanion abstracting a proton from the solvent rather than recovering it from the base.
- In protic solvents, the reaction is reversible.
- Competing reactions (namely 1,2-additions) can occur when
using more complex Michael donors, but this competition, as well as
self-condensation, can be reduced by the careful selection of
reaction medium
and base.
The Michael addition is heavily documented in chemical journals, online resources and textbooks, however the following sources were useful for the creation of this resource.
(Oxford University Press, 1991)
Sykes; A Guidebook to Mechanisms in Organic Chemistry, 6th edn., 200-202.
(Longman Scientific & Technical, 1986)
Kürti and Czakó; Strategic Applications of Named Reactions in Organic Synthesis. 1st edn., 286-267.
(Elsevier Academic Press 2005)
Carey; Organic Chemistry. 4th edn., 724.
(McGraw Hill Publishing, 2000)
March and Smith; March's Advanced Organic Chemistry, Reactions, Mechanisms and Structure. 5th edn., 1022-1024.
(John Wiley & Sons, 2001)