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1,4-Addition

1.  1,4-Addition is an electrophilic addition reaction of conjugate dienes.

eg:  Two electrophilic addition reactions could occur between 1,3-butadiene (1) and hydrogen chloride.



In Reaction 1, the net reaction is addition of a hydrogen atom to C-1 and a chlorine atom to C-4 in 1.  Hence, Reaction 1 is called 1,4-addition and its product (2) 1,4-adduct.



In Reaction 2, the net reaction is addition of a hydrogen atom to C-1 and a chlorine atom to C-2 in 1.  Hence, Reaction 2 is called 1,2-addition and its product (3) 1,2-adduct.



The regioselectivity of the overall reaction depends on the temperature.  At low temperature (eg: –78°C), the major product is 3; at high temperature (Δ), it is 2.  The carbon-carbon double bond in 2 is more highly substituted than the one in 3, so 2 is more stable than 3.  That the less stable 3 is the major product at low temperature implies that at low temperature the system is under kinetic control and 3 is the faster-forming product.  That the more stable 2 is the major product at high temperature the system is under thermodynamic control.

mechanism at low temperature:



The first step is reversible; the second step is irreversible.  Thus, the overall reaction is irreversible, i.e, the system is under kinetic control and the major product is the faster-forming product.  The first step, an acid-base reaction, generates the allylic carbocation 4 and the chloride ion.  In the second step, 4 reacts with the chloride ion.  In the two resonance forms (4a, 4b) of 4, 4a has the more stable carbocation center and, therefore, is more stable than 4b.  Thus, in the hybrid the partial positive charge on C-2 is more intense than that on C-4.



In the second step, the chloride ion reacts faster with the more electrophilic C-2, leading to 3.  Thus, 3 is the faster-forming product and, since the system is under kinetic control, major product.

mechanism at high temperature:



Notice that, at high temperature, 2 and 3 interconvert via 4.



Since 2 is more stable than 3, the equilibrium lies toward 2 and the equilibrium constant, K, is greater than 1.



Hence, 2 is the major product.

2.  1,4-Addition, also known as conjugate addition, is a nucleophilic addition reaction of α, β–unsaturated carbonyl compounds and α, β–unsaturated nitriles.

eg:  Two nucleophilic addition reaction could occur between methylvinyl ketone (1) and methanethiol in basic medium.



mechanism of Reaction 1:



The net reaction from 1 to 4 is the addition of two ligands to atoms 1 and 4 in 1.  Hence, the reaction is called 1,4-addition, or conjugate addition, and its product (2) 1,4-adduct.



mechanism of Reaction 2:



The net reaction from 1 to 3 is the addition of two ligands to atoms 1 and 2 in 1.  Hence, the reaction is called 1,2-addition, or direct addition, and the product (3) 1,2-adduct.



The overall reaction between an α, β–unsaturated compound and a nucleophile is regioselective.  Whether the dominant process is 1,4-addition or 1,2-addition depends on several factors, such as α, β–unsaturated compound, nucleophile, solvent, concentration, temperature, reaction time, and catalyst, if any, making if difficult to make a generalization.  Most resonance-stabilized carbon nucleophiles, such as enolate ions and enamines overwhelmingly prefer 1,4-addition to 1,2-addition. (See Michael addition)

1,4-Addition: Mastery Check 1,2-Addition: Mastery Check