An enone, also known as an alkenone, is a type of organic compound that contains both alkene and ketone functional groups within its structure. In the case of an α,β-unsaturated ketone, the alkene is positioned in a conjugated arrangement with the carbonyl group of the ketone. The simplest example of an enone is methyl vinyl ketone, also known as butenone.
Cyclic enones encompass a diverse group of compounds, including cyclopropenone, cyclobutenone, cyclopentenone, cyclohexenone, and cycloheptenone. These compounds share the characteristic feature of having a cyclic structure along with the enone functionality.
Synthesis of Enones
Aldol condensation & Knoevenagel condensation
The synthesis of enones is typically achieved through methods such as Aldol condensation or Knoevenagel condensation. Some commercially significant enones, like mesityl oxide (a dimer of acetone), phorone, and isophorone (trimers), are produced through condensation reactions involving acetone.
Another method involves the Meyer–Schuster rearrangement, which starts with propargyl alcohol. An additional approach to obtain α,β-unsaturated carbonyls is through Selenoxide elimination. Cyclic enones can be prepared using the Pauson–Khand reaction.
Selenoxide Elimination
Selenoxide elimination, also known as α-selenation, is a chemical synthesis method used to create alkenes from selenoxides. Its primary application is in the synthesis of α,β-unsaturated carbonyl compounds from their saturated counterparts. This process shares a mechanistic relationship with the Cope reaction.
The Meyer–Schuster rearrangement
The Meyer–Schuster rearrangement is a chemical reaction characterized by an acid-catalyzed rearrangement of secondary and tertiary propargyl alcohols. When the alkyne group is located internally, this reaction leads to the formation of α,β-unsaturated ketones.
On the other hand, when the alkyne group is terminal, it results in the production of α,β-unsaturated aldehydes.
The Pauson–Khand (PK) reaction
The Pauson–Khand (PK) reaction is a chemical reaction that can be described as a [2+2+1] cycloaddition. In this reaction, an alkyne, an alkene, and carbon monoxide come together to form an α,β-cyclopentenone, facilitated by the presence of a metal-carbonyl catalyst.
The Robinson annulation
The Robinson annulation is a versatile method for synthesizing cyclic enones. It begins with a β-ketoester or β-diketone precursor, containing a carbonyl group and an adjacent C=C double bond.
Strong bases like sodium ethoxide generate enolate ions from these precursors. These enolates then undergo intramolecular Michael additions, where they attack their own C=C double bonds, forming new carbon-carbon bonds.
Recent Advancements
Allyl-nickel catalysis represents a breakthrough in chemical synthesis, allowing for the selective α,β-dehydrogenation of carbonyl compounds. Furthermore, a novel oxidative cycloalkenylation reaction has been developed, offering a versatile approach to creating bicycloalkenones.
This innovative method enables the synthesis of bicyclo alkenones with a wide range of fused, bridged, and spirocyclic ring systems, utilizing unactivated ketone and alkene precursors. These advancements in catalysis expand the possibilities for complex molecule synthesis in organic chemistry.
The catalytic process involving triphenylphosphine oxide facilitates the reductive halogenation of an α,β-unsaturated ketone. This reaction employs trichlorosilane as the reducing agent and an N-halo succinimide as the electrophilic source of halogen.
It enables the selective synthesis of unsymmetrical α-halo ketones, demonstrating its utility in chemical transformations.
A skeletal reorganization of silyl enol ethers, mediated by I(III), allows for a formal enone α-arylation. This metal-free transformation provides favorable conditions, yielding good results and exhibiting high stereoselectivity, particularly for β-substituted enones.
Reactions of Enones
Michael additions
The Michael addition reaction of enones is a versatile chemical process in which a nucleophile is added to the β-carbon of α,β-unsaturated carbonyl compounds (enones). It involves the formation of Michael adduct intermediates, subsequently yielding various organic compounds.
Enones can be conjugated or non-conjugated, and the reaction’s regioselectivity and stereoselectivity depend on the specific reactants and conditions. Widely employed in organic synthesis, the Michael addition enables the construction of complex molecules, including pharmaceuticals and natural products.
Nazarov cyclization
The Nazarov cyclization reaction, often referred to as the Nazarov cyclization, is a chemical reaction widely used in the field of organic chemistry to synthesize cyclopentenones.
This reaction is commonly categorized into classical and modern variants, depending on the specific reagents and substrates used. It was first identified by Ivan Nikolaevich Nazarov (1906–1957) in 1941 during his investigations into the rearrangements of allyl vinyl ketones.
Rauhut–Currier reaction
The Rauhut–Currier reaction, also known as the vinylogous Morita–Baylis–Hillman reaction, is an organic reaction initially focused on the dimerization or isomerization of electron-deficient alkenes, such as enones. This transformation is achieved through the use of an organophosphine compound, typically of the R3P type.
In a broader sense, the Rauhut–Currier reaction involves coupling one active alkene or latent enolate with a second Michael acceptor, resulting in the formation of a new C–C bond. This bond forms between the alpha-position of one activated alkene and the beta-position of the second alkene, under the influence of a nucleophilic catalyst.
The reaction mechanism of the Rauhut–Currier reaction closely resembles that of the more well-known Baylis–Hillman reaction, except that the former employs phosphine catalysts instead of DABCO and deals with carbonyl compounds rather than enones.
Notably, the Rauhut–Currier reaction predates the Baylis–Hillman reaction by several years. When compared to the Morita–Baylis–Hillman (MBH) reaction, the Rauhut–Currier (RC) reaction exhibits differences in substrate reactivity and regioselectivity.
The original 1963 study of this reaction involved the dimerization of ethyl acrylate to produce the ethyl diester of 2-methylene-glutaric acid, using tributylphosphine as the catalyst in an acetonitrile solvent.
Diels−Alder reaction
The enantioselective Diels−Alder reaction involving straightforward α,β-unsaturated ketones, and a catalyst based on cinchona alkaloid has been explored.
Conjugate reduction
A system consisting of nickel(II) chloride, lithium metal, a catalytic polymer-supported arene, and ethanol has proven to be highly effective for the conjugate reduction of diverse α,β-unsaturated carbonyl compounds, all conducted under exceptionally mild reaction conditions.
Concepts Berg
What are enones?
Enones are organic compounds that contain a carbon-carbon double bond (C=C) and a carbonyl group (C=O) on adjacent carbon atoms within the same molecule.
How are enones different from ketones?
Enones are ketones with a C=C double bond in the molecule, making them a subclass of ketones.
Can enones participate in conjugate addition reactions?
Yes, enones are known for their reactivity in conjugate addition reactions, which involve the addition of nucleophiles to the β-carbon of the C=C double bond.
What is the significance of enones in organic synthesis?
Enones are important intermediates in organic synthesis and serve as versatile building blocks for the construction of complex molecules.
Can you give an example of a natural product containing an enone functional group?
Curcumin, a compound found in turmeric, contains an enone moiety and is known for its potential health benefits.
What is the reactivity of enones in Michael’s addition reactions?
Enones can undergo Michael addition reactions, which involve the addition of nucleophiles to the β-carbon of the C=C double bond. This reaction is valuable in organic synthesis for forming carbon-carbon bonds.
Reference link
- An Article (pubs.acs.org)
- An Article (en.wikipedia.org)
- An Article (organic-chemistry.org)
