Related Experiment Video
Updated: May 14, 2026
08:56
Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions
Published on: November 30, 2022
Suzuki-miyaura cross-coupling in acylation reactions, scope and recent developments.
Marco Blangetti1, Heléna Rosso, Cristina Prandi
1Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland. marco.blangetti@ucd.ie
Molecules (Basel, Switzerland)
|January 25, 2013
Summary
The Suzuki-Miyaura (SM) cross coupling reaction is a versatile tool, but its use for introducing acyl groups is less explored. This review covers methods for acyl SM coupling, including novel boronates and applications in natural product synthesis.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Catalysis
Background:
- The Suzuki-Miyaura (SM) cross-coupling reaction is a widely adopted methodology in synthetic organic chemistry.
- Despite its broad applicability, the SM reaction's utility for introducing acyl functionalities remains underexplored compared to other cross-coupling reactions.
- Acyl group introduction is crucial for synthesizing various organic molecules, including pharmaceuticals and natural products.
Purpose of the Study:
- To review and consolidate the various literature approaches for acyl Suzuki-Miyaura coupling reactions.
- To highlight recent advancements in SM reactions for acyl group introduction, focusing on novel coupling partners.
- To discuss the significance of acyl SM reactions in the synthesis of complex natural products.
Main Methods:
- Literature review of acyl Suzuki-Miyaura coupling strategies.
- Analysis of direct SM acylative coupling methods.
- Examination of cross-coupling reactions involving boronates and acylating agents (acyl chlorides, anhydrides).
- Investigation of masked acyl boronates and specific alkoxy boronates (styryl, dienyl) as coupling partners.
Main Results:
- The review systematically categorizes different methods for performing acyl SM couplings.
- It details the use of various boronates, including masked and alkoxy-functionalized variants, as effective acylating agents.
- The application of acyl SM reactions as a key step in synthesizing complex natural products is demonstrated.
Conclusions:
- The Suzuki-Miyaura reaction offers a valuable, yet underutilized, pathway for acyl group introduction.
- Recent developments have expanded the scope of acyl SM coupling through innovative boronates.
- Acyl SM coupling is a powerful synthetic strategy with significant potential in natural product synthesis.
Related Concept Videos
01:11Electrophilic Aromatic Substitution: Friedel–Crafts Acylation of Benzene
The Friedel–Crafts acylation reactions involve the addition of an acyl group to an aromatic ring. These reactions proceed via electrophilic aromatic substitution by employing an acyl chloride and a Lewis acid catalyst such as aluminum chloride to form aryl ketone.
01:04Crossed Aldol Reactions: Overview
Crossed aldol addition is the reaction between two different carbonyl compounds under acidic or basic conditions. Here, both the carbonyl compounds function as nucleophiles and electrophiles. As shown in Figure 1, such a reaction yields a mixture of products, two of which are formed via self-condensation, while the remaining two are formed via crossed-condensation. Without adjustment, the reaction's usefulness in organic chemistry is decreased.
01:19Amines to Amides: Acylation of Amines
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
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.
01:22Alkenes via Reductive Coupling of Aldehydes or Ketones: McMurry Reaction
The radical dimerization of ketones or aldehydes gives vicinal diols through a pinacol coupling reaction. However, the behavior of titanium metals used for the reaction as a source of electrons is unusual. When the reaction is carried out in the presence of titanium, diols can be isolated at low temperatures. Else titanium further reacts with diols, forming alkenes through the McMurry reaction.
01:16Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.