Related Experiment Video
Updated: May 15, 2026
19:58
Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions
Published on: July 30, 2017
Achieving control over the branched/linear selectivity in palladium-catalyzed allylic amination
Igor Dubovyk1, Iain D G Watson, Andrei K Yudin
1Davenport Research Laboratories, Department of Chemistry, The University of Toronto, 80 St George Street, Toronto, Canada M5S 3H6.
The Journal of Organic Chemistry
|January 19, 2013
Summary
Branched allylic amines can be selectively synthesized by controlling palladium-catalyzed reactions. Acid promotes isomerization to linear products, while base addition isolates branched amines, offering tunable synthesis of allylic amines.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Palladium-catalyzed allylic amination of unsymmetrical electrophiles yields regioisomeric allylic amines.
- Controlling regioselectivity in these reactions is crucial for targeted synthesis.
Purpose of the Study:
- To investigate the factors controlling regioselectivity in palladium-catalyzed allylic amination.
- To develop methods for the selective synthesis of branched allylic amines.
- To explore the combination of isomerization and other reactions for novel synthetic routes.
Main Methods:
- Palladium-catalyzed reactions utilizing unsymmetrical allylic electrophiles and amines.
- Investigation of reaction conditions including acid/base additives and solvents.
- Kinetic and thermodynamic control studies.
- Combination with ring-closing metathesis.
Main Results:
- Initially formed branched allylic amines isomerize to linear products under thermodynamic control.
- Isomerization is facilitated by protic acid and active palladium catalysts.
- Addition of base suppresses isomerization, enabling isolation of branched products.
- Solvent choice significantly impacts kinetic regioselectivity and isomerization rates.
- A combined approach with ring-closing metathesis allows synthesis of exocyclic allylic amines from endocyclic precursors.
Conclusions:
- Regioselectivity in palladium-catalyzed allylic amination can be controlled through careful manipulation of reaction conditions.
- The isomerization pathway offers a route to linear products, while base addition favors branched products.
- This work provides a versatile platform for synthesizing diverse allylic amine structures, including exocyclic variants.
Related Concept Videos
01:27Radical Substitution: Allylic Bromination
In organic synthesis, the formation of products can be altered by changing the reaction conditions. For example, a dibromo addition product is formed when propene is treated with bromine at room temperature. In contrast, propene undergoes allylic substitution in non-polar solvents at high temperatures to give 3-bromopropene. In order to avoid the addition reaction, the bromine concentration must be kept as low as possible throughout the reaction. This can be achieved using N-bromosuccinimide...
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
02:27Preparation of Alkynes: Alkylation Reaction
Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
02:35Regioselectivity of Electrophilic Additions-Peroxide Effect
In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov’s rule. For example, the addition of hydrogen bromide to 2-methylpropene in the presence of peroxides gives 1-bromo-2-methylpropane. This addition reaction proceeds via a free radical mechanism, which reverses the regioselectivity. The free radical reaction mechanism involves three stages: initiation, propagation, and termination.
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...