19.11 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
2 min read•may 7, 2024
The is a powerful tool for making carbon-carbon double bonds. It combines a phosphorus ylide with an aldehyde or ketone to create with specific structures. This reaction is crucial for building complex molecules in organic synthesis.
Understanding the Wittig reaction's mechanism and is key to predicting outcomes. It offers advantages over other alkene-forming reactions, making it a go-to method for creating diverse carbon frameworks in organic chemistry.
Wittig Reaction
Wittig reaction mechanism
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- of phosphorus ylide to carbonyl carbon of aldehyde or ketone forms
- Betaine intermediate cyclizes to give four-membered oxaphosphetane intermediate
- Oxaphosphetane decomposes through cycloelimination reaction yields alkene product and phosphine oxide byproduct
- Stereochemistry of alkene product depends on ylide structure and reaction conditions
- Unstabilized ylides (no conjugating groups) typically give (Z)-alkenes (cis)
- Stabilized ylides (conjugated with electron-withdrawing groups like carbonyl or cyano) typically give (E)-alkenes (trans)
- The reaction's is influenced by the stability of the ylide and its
Preparation of phosphorus ylides
- Alkyl halide (e.g., ) undergoes SN2 reaction with phosphine (typically ) forms
- Treatment of phosphonium salt with (, , ) deprotonates alpha carbon generates resonance-stabilized ylide
- Ylide is nucleophilic at alpha carbon due to negative charge and stabilizing effect of adjacent phosphonium group
- Base plays crucial role in generating ylide from phosphonium salt via deprotonation
- Ylides are important in organic synthesis
Wittig reaction vs other alkene syntheses
- Highly selective for synthesis of alkenes with defined stereochemistry and substitution patterns
- Can prepare highly substituted alkenes including
- Allows synthesis of and through sequential Wittig reactions
- Tolerates wide range of functional groups in both ylide and carbonyl compound
- Advantages over aldol condensation:
- Does not require strong acids or bases which can cause isomerization or rearrangement of sensitive substrates
- Aldol condensation may give mixtures of regioisomers with unsymmetrical
- Advantages over :
- Typically gives higher yields and more tolerant of steric hindrance
- Peterson olefination advantageous for synthesis of silyl-substituted alkenes
Carbonyl Chemistry and Related Reactions
- The Wittig reaction is a key transformation in
- It involves the conversion of carbonyl compounds to alkenes
- Related reactions include , which also form carbon-carbon double bonds
- Understanding of resonance structures is crucial for predicting reactivity and selectivity in these reactions
Key Terms to Review (38)
Aldehydes: Aldehydes are a class of organic compounds characterized by the presence of a carbonyl group (C=O) with a hydrogen atom attached to the carbon. They are important intermediates in many chemical reactions and have a wide range of applications in various industries, from pharmaceuticals to fragrances.
Alkenes: Alkenes are a class of unsaturated organic compounds characterized by the presence of a carbon-carbon double bond. They are an important functional group in organic chemistry, with a wide range of applications and reactivity. Alkenes are closely related to the topics of chirality, isomerism, electrophilic addition reactions, halogenation, hydration, the E2 reaction, infrared spectroscopy, 13C NMR spectroscopy, alcohol preparation, and the Wittig reaction.
Anti stereochemistry: Anti stereochemistry describes the spatial arrangement in a chemical reaction where two substituents are positioned on opposite sides of a double bond or ring structure after the reaction. It is particularly relevant in the halogenation of alkenes, resulting in products where the added atoms are located across from each other.
Aprotic Solvent: An aprotic solvent is a type of organic solvent that does not contain an active hydrogen atom and does not participate in hydrogen bonding. These solvents are commonly used in various organic chemistry reactions, including the E1 and E1cB reactions, the reduction of carbonyl compounds, the Wittig reaction, and the Claisen condensation reaction.
Benzyl Bromide: Benzyl bromide is an organic compound with the chemical formula C6H5CH2Br. It is a colorless liquid that is commonly used as a precursor in organic synthesis, particularly in the Wittig reaction, which is a key topic in the study of nucleophilic addition of phosphorus ylides.
Betaine Intermediate: The betaine intermediate is a key step in the Wittig reaction, a widely used organic reaction for the synthesis of alkenes from aldehydes or ketones and phosphorus ylides. The betaine intermediate is a zwitterionic species that forms as a result of the nucleophilic addition of the phosphorus ylide to the carbonyl carbon.
Carbon-Carbon Double Bond: A carbon-carbon double bond is a covalent chemical bond in which two carbon atoms share four electrons, with two pairs of electrons forming the bond. This type of bond is a fundamental structural feature in many organic compounds and is central to understanding the properties and reactivity of alkenes, a class of unsaturated hydrocarbons.
Carbonyl Chemistry: Carbonyl chemistry refers to the study of organic compounds containing a carbonyl group, which is a carbon-oxygen double bond. This functional group is central to many important reactions and properties in organic chemistry, including nucleophilic addition, alpha halogenation, and the Wittig reaction.
Carbonyl group: A carbonyl group is a functional group characterized by a carbon atom double-bonded to an oxygen atom, represented as C=O. This group is pivotal in organic chemistry as it forms the backbone of various important classes of compounds, influencing their chemical properties and reactivity.
Conjugated Dienes: Conjugated dienes are organic compounds with two carbon-carbon double bonds that are separated by a single carbon-carbon bond. This arrangement of alternating double and single bonds creates a system of delocalized pi electrons, which gives conjugated dienes unique stability and reactivity properties.
E/Z Isomers: E/Z isomers, also known as geometric isomers, are a type of stereoisomers that arise when two identical substituents are located on opposite sides (trans, Z) or the same side (cis, E) of a carbon-carbon double bond. The E/Z designation is determined by the relative positions of the higher priority substituents around the double bond.
Elimination reactions: Elimination reactions are a type of organic reaction where two atoms or groups are removed from a molecule, resulting in the formation of a double bond. These reactions often involve the loss of small molecules like water or hydrogen halides from larger organic molecules.
Elimination Reactions: Elimination reactions are a class of organic reactions where two atoms or groups are removed from a molecule, typically resulting in the formation of a new carbon-carbon double bond. These reactions are an important aspect of organic chemistry, as they allow for the conversion of various functional groups and the synthesis of alkenes and other unsaturated compounds.
Georg Wittig: Georg Wittig was a German chemist who is best known for developing the Wittig reaction, a powerful method for the synthesis of alkenes from aldehydes or ketones and phosphorus ylides. The Wittig reaction is a key tool in organic synthesis and has had a significant impact on the field of organic chemistry.
Ketones: Ketones are organic compounds characterized by a carbonyl group (C=O) bonded to two other carbon atoms within the molecule. They are formed by the oxidation of secondary alcohols.
Ketones: Ketones are a class of organic compounds containing a carbonyl group (C=O) bonded to two alkyl or aryl groups. They are characterized by the presence of a carbonyl carbon flanked by two carbon atoms. Ketones are important in various organic chemistry topics, including chirality, oxidation reactions, mass spectrometry, infrared spectroscopy, and NMR spectroscopy.
N-butyllithium: n-Butyllithium is an organolithium compound with the formula $C_4H_9Li$. It is a highly reactive and versatile reagent used in organic synthesis, particularly in the alkylation of acetylide anions and the Wittig reaction.
Nucleophilic Addition: Nucleophilic addition is a fundamental organic reaction in which a nucleophile, a species that donates electrons, adds to an electrophilic carbon center, typically a carbonyl carbon, to form a new product. This reaction is central to understanding many important topics in organic chemistry, including functional groups, polar reactions, carbocation stability, reaction stereochemistry, and the chemistry of aldehydes, ketones, alcohols, and other carbonyl-containing compounds.
Nucleophilic addition reaction: A nucleophilic addition reaction is a chemical process where a nucleophile forms a bond with an electrophilic carbon atom of a compound, typically found in aldehydes and ketones. This reaction results in the conversion of the carbonyl group into a more complex, often larger, molecule.
Organophosphorus Compounds: Organophosphorus compounds are a class of organic molecules that contain at least one phosphorus-carbon bond. They are widely used in various applications, including as pesticides, nerve agents, and intermediates in organic synthesis, particularly in the context of the Wittig reaction.
Oxaphosphetane Formation: Oxaphosphetane formation is a key step in the Wittig reaction, a widely used method for the synthesis of alkenes from carbonyl compounds and phosphorus ylides. This four-membered cyclic intermediate is formed through the nucleophilic addition of a phosphorus ylide to a carbonyl group, and its subsequent rearrangement is crucial for the overall success of the Wittig reaction.
Peterson Olefination: The Peterson olefination is a method for the synthesis of alkenes from carbonyl compounds and stabilized phosphorus ylides. It is a variation of the well-known Wittig reaction, which involves the nucleophilic addition of phosphorus ylides to carbonyl groups.
Phosphonium Salt: A phosphonium salt is a positively charged species containing a phosphorus atom with four covalently bonded substituents. These salts are important intermediates in the Wittig reaction, a powerful method for the synthesis of alkenes from carbonyl compounds and phosphorus ylides.
Phosphonium Ylide: A phosphonium ylide is a reactive species containing a positively charged phosphorus atom and a negatively charged carbon atom. These ylides are key intermediates in the Wittig reaction, a powerful organic transformation that allows for the synthesis of alkenes from aldehydes or ketones.
Phosphorus Ylides: Phosphorus ylides are a class of highly reactive organic compounds containing a positively charged phosphorus atom bonded to a negatively charged carbon atom. They are central to the Wittig reaction, a powerful method for the synthesis of alkenes from aldehydes or ketones.
Polar aprotic solvents: Polar aprotic solvents are solvents that have a net dipole moment but do not possess hydrogen atoms capable of forming hydrogen bonds. They are used in organic reactions to dissolve electrolytes and facilitate reactions without participating in them.
Polyenes: Polyenes are organic compounds that contain multiple carbon-carbon double bonds arranged in a conjugated system. These types of compounds are particularly important in the context of interpreting ultraviolet spectra, the Wittig reaction, and the molecular orbitals of conjugated pi systems.
Resonance Structures: Resonance structures are a set of contributing structures that describe the delocalization of electrons in a molecule. They represent the different ways in which the atoms in a molecule can be bonded to satisfy the octet rule and create the most stable arrangement of electrons.
Sodium Ethoxide: Sodium ethoxide is an alkoxide compound with the chemical formula C₂H₅ONa. It is a strong nucleophile and base used in various organic reactions, including the preparation of alkenes, the Wittig reaction, and Claisen condensations.
Sodium Hydride: Sodium hydride (NaH) is a chemical compound consisting of a sodium cation (Na+) and a hydride anion (H-). It is a strong reducing agent and a powerful nucleophile, making it a versatile reagent in organic chemistry.
Stereochemistry: Stereochemistry is the study of the three-dimensional arrangement of atoms in molecules and how this arrangement affects the chemical and physical properties of the substance. It examines the spatial orientation of atoms and their relationship to one another, which is crucial in understanding many organic chemistry concepts.
Stereoselectivity: Stereoselectivity refers to the preference of a chemical reaction to form one stereoisomeric product over another. It is a crucial concept in organic chemistry that describes the ability of a reaction to control the spatial arrangement of atoms in the final product.
Strong Base: A strong base is a type of chemical compound that completely dissociates into its constituent ions in an aqueous solution, resulting in a high concentration of hydroxide ions (OH-) and a high pH. Strong bases are important in various organic chemistry reactions, such as the preparation of alkynes via elimination reactions and the Wittig reaction involving phosphorus ylides.
Tetrasubstituted Alkenes: Tetrasubstituted alkenes are organic compounds containing a carbon-carbon double bond where all four substituents attached to the double-bonded carbons are different. These unique alkenes are of particular interest in the context of alkene stereochemistry, the stability of alkenes, and the Wittig reaction.
Triphenylphosphine: Triphenylphosphine is an organophosphorus compound with the chemical formula PPh3, where Ph represents the phenyl group. It is a widely used reagent in organic synthesis, particularly in the Wittig reaction, which involves the nucleophilic addition of phosphorus ylides.
Wittig Reaction: The Wittig reaction is a chemical transformation that involves the nucleophilic addition of a phosphorus ylide to a carbonyl compound, resulting in the formation of an alkene. This reaction is a powerful tool in organic synthesis for the construction of carbon-carbon double bonds.
Ylide Resonance: Ylide resonance refers to the delocalization of electrons in a phosphorus-containing compound, known as a phosphorus ylide, which allows for the stabilization of the positive charge on the phosphorus atom and the negative charge on the adjacent atom. This resonance phenomenon is crucial in understanding the reactivity and behavior of phosphorus ylides, particularly in the context of the Wittig reaction.
Ylide Stability: Ylides are neutral, dipolar compounds containing a positively charged atom (typically phosphorus or sulfur) bonded to a negatively charged carbon atom. The stability of ylides is a crucial factor in determining their reactivity, particularly in the context of the Wittig reaction, a powerful tool for the formation of carbon-carbon double bonds.