PHD
  1. Inorganic chemistry  1.1. Coordination chemistry  1.1.1. Ligand field theory  1.1.2. Crystal field theory  1.1.3. Molecular Orbital Theory for Coordination Compounds  1.1.4. Stability of Coordination Compounds  1.1.5. Electronic spectra of coordination compounds  1.1.6. Isomerism in Coordination Compounds  1.1.7. Kinetics and mechanism of coordination reactions  1.2. Organometallic Chemistry  1.2.1. Metal Carbonyls  1.2.2. Metal alkyl and aryl  1.2.3. Fischer and Schrock carbonaceans  1.2.4. Oxidative Addition and Reductive Elimination  1.2.5. Metal Hydrides  1.2.6. Catalysis by organometallic compounds  1.2.7. Metallocenes and Sandwich Complexes  1.2.8. CH activation  1.3. Solid state chemistry  1.3.1. Crystal structures and lattices  1.3.2. Band theory and electrical properties  1.3.3. Defects in the crystal  1.3.4. Synthesis of solid state materials  1.3.5. Magnetic and optical properties of solids  1.3.6. Superconductivity  1.3.7. Solid state ionics  1.4. Bio-inorganic chemistry  1.4.1. Metalloproteins and enzymes  1.4.2. Metal ion transport and storage  1.4.3. The role of metals in medicine  1.4.4. Bioinspired catalysis  1.4.5. Metal–DNA interactions  1.4.6. Metal Complexes in Medical Science  1.5. Lanthanides and Actinides  1.5.1. Electronic configuration and oxidation states in lanthanides and actinides  1.5.2. Spectral and Magnetic Properties in Lanthanides and Actinides  1.5.3. Separation and Extraction of Lanthanides and Actinides  1.5.4. Coordination chemistry of f-block elements  1.6. Main Group Chemistry  1.6.1. Chemistry of boron compounds  1.6.2. Chemistry of Silicon and Germanium Compounds  1.6.3. Chemistry of Phosphorus and Sulfur Compounds  1.6.4. Organosilicon chemistry  1.6.5. Noble Gas Chemistry
  2. Organic chemistry  2.1. Reaction mechanism  2.1.1. Nucleophilic substitution reactions  2.1.2. Electrophilic addition and substitution reactions  2.1.3. Elimination reactions  2.1.4. Rearrangement reactions  2.1.5. Radical reactions  2.1.6. Pericyclic Reactions  2.1.7. Photochemical reactions  2.2. Stereoscopic  2.2.1. Chirality and optical activity  2.2.2. Structural analysis  2.2.3. Stereoelectronic effects  2.2.4. Asymmetric synthesis  2.2.5. Dynamic Stereochemistry  2.3. Organometallic Chemistry in Organic Synthesis  2.3.1. Organolithium and organomagnesium reagents  2.3.2. Transition metal catalyzed coupling reactions  2.3.3. Palladium-catalyzed reactions  2.3.4. Olefin Metathesis  2.3.5. Gold and silver catalysis  2.4. Natural products chemistry  2.4.1. Alkaloids and terpenoids  2.4.2. Steroids and Flavonoids  2.4.3. Total synthesis of natural products  2.4.4. Biosynthesis of natural products  2.5. Supramolecular Chemistry  2.5.1. Host-Guest Chemistry  2.5.2. Self-assembly and molecular recognition  2.5.3. Supramolecular Catalysis  2.5.4. Molecular Machines
  3. Physical Chemistry  3.1. Thermodynamics  3.1.1. Laws of Thermodynamics  3.1.2. Chemical Potential and Equilibrium  3.1.3. Statistical thermodynamics  3.1.4. Non-equilibrium thermodynamics  3.2. Quantum Chemistry  3.2.1. Schrödinger equation and its applications  3.2.2. Molecular orbital theory  3.2.3. Density functional theory  3.2.4. Post-Hartree–Fock methods  3.3. Chemical kinetics  3.3.1. Reaction rate theory  3.3.2. Mechanism and rate laws  3.3.3. Catalysis and enzyme kinetics  3.3.4. Reaction dynamics  3.4. Spectroscopy and molecular structure  3.4.1. Infrared Spectroscopy  3.4.2. UV-visible spectroscopy  3.4.3. Nuclear Magnetic Resonance Spectroscopy  3.4.4. Mass Spectrometry  3.4.5. Raman Spectroscopy  3.5. Surface and Colloid Chemistry  3.5.1. Absorption and Catalysis  3.5.2. Surfactants and micelles  3.5.3. Colloidal Stability  3.5.4. Nanomaterials and Interfaces
  4. Analytical chemistry  4.1. Chromatography  4.1.1. Gas Chromatography  4.1.2. High Performance Liquid Chromatography  4.1.3. Thin Layer Chromatography  4.1.4. Ion Chromatography  4.2. Electroanalytical techniques  4.2.1. Voltammetry and Polarography  4.2.2. Conductometry and potentiometry  4.2.3. Colometry  4.3. Spectroscopic Methods  4.3.1. Atomic absorption spectroscopy  4.3.2. Fluorescence Spectroscopy  4.3.3. X-ray diffraction  4.3.4. Electron paramagnetic resonance spectroscopy  4.4. Chemometrics  4.4.1. Data processing and statistical methods  4.4.2. Multidisciplinary analysis  4.4.3. Machine Learning in Analytical Chemistry
  5. Theoretical and Computational Chemistry  5.1. Molecular dynamics simulation  5.2. Quantum chemistry methods  5.3. Computational drug design  5.4. Machine Learning in Chemistry  5.5. Ab initio molecular dynamics
  6. Biophysics and Medicinal Chemistry  6.1. Drug discovery and design  6.2. Enzyme kinetics and inhibition  6.3. Chemical biology approach  6.4. Protein-ligand interactions  6.5. Bioorthogonal chemistry
  7. Materials chemistry  7.1. Polymer chemistry  7.1.1. Polymerization mechanism  7.1.2. Functional Polymers  7.1.3. Biodegradable Polymer  7.1.4. Conducting and semiconducting polymers  7.2. Nano Chemistry  7.2.1. Nanoparticles and nanostructures  7.2.2. Carbon-based nanomaterials  7.2.3. Quantum dots  7.3. Energy and Environmental Chemistry  7.3.1. Battery and Fuel Cell Chemistry  7.3.2. Green chemistry and sustainable materials  7.3.3. Photocatalysis

PHD → Organic chemistry → Stereoscopic ↓


Asymmetric synthesis


Asymmetric synthesis, also known as chiral synthesis, is a fundamental process in organic chemistry that focuses on generating compounds with a specific arrangement of atoms, thereby achieving a particular spatial configuration. This type of synthesis is important in the production of enantiomerically pure compounds, which is often important in pharmaceuticals due to their interactions with biological systems. Understanding asymmetric synthesis broadly involves exploring innovation in stereochemistry, reaction mechanisms, catalyst use, and chiral technology.

Understanding stereochemistry

Stereochemistry is a subdiscipline of chemistry that deals with the three-dimensional arrangement of atoms in molecules, particularly important for chiral molecules with non-superimposable mirror images, known as enantiomers. These enantiomers can have quite different effects in biological systems - thalidomide is a historical example where one enantiomer was therapeutic and the other teratogenic.

Visualize stereochemistry with this basic carbon molecule example. In the tetrahedral configuration:

The diagram above shows a tetrahedral carbon found in nature, with four substituents arranged in space. Depending on the substituents, it can form a chiral center.

Mechanism of asymmetric synthesis

The primary purpose of asymmetric synthesis is to selectively produce the desired enantiomer. This involves using chiral catalysts or auxiliaries that induce a chiral environment and control the stereochemical outcome of reactions. Mechanisms typically include:

  1. Formation of a chiral intermediate that guides the path of the reaction.
  2. The use of chiral catalysts to provide a preferential pathway increases the reaction rate for one enantiomer compared to the other.
  3. The use of enantioselective reactions, where a particular conformation is stabilized, leading to a predominant enantiomer.

An example of a basic asymmetric synthesis mechanism is as follows:

1. Reaction of prochiral substrate CH 3 CH=CH 2 with chiral catalyst.
2. Asymmetric interaction of hydrogen donor affects the sum of C=C bonds.
3. Preferential formation of CH 3 CH 2 CH 2 OH over its enantiomer due to the presence of chiral catalyst.

Main approaches in asymmetric synthesis

There are generally three approaches to asymmetric synthesis:

1. Use of chiral auxiliaries

Chiral auxiliaries are temporary appendages that are added to substrate molecules to induce chirality and are later removed. Their application is common in reactions where chirality is imperative for selectivity. The auxiliaries confer their chirality on the product by controlling which enantiotopic face of the molecule the reaction occurs on. An example is:

1. Addition of a chiral oxazolidinone to an aldehyde.
2. Oxazolidinone controls the ensuing reactions in favor of one stereoisomer.
3. After synthesis, removal of the auxiliary gives the pure enantiomer.

2. Chiral catalyst

Chiral catalysts offer the advantage of being used in small quantities and act by preferentially catalyzing the formation of one enantiomer. These typically involve transition metal complexes or organocatalysts. For example:

1. The use of a rhodium (Rh)-based complex allows asymmetric hydrogenation.
2. Rhodium catalyst coordinates asymmetric molecules thereby promoting enantioselectivity.

3. Asymmetric induction

Asymmetric induction refers to the creation of a new stereocenter from an existing chiral center within the molecule. The existing stereochemistry of the molecule determines the form of the new chiral center. An example includes:

1. Formation of =CH-NHR substituent from chiral aldehyde.
2. The chiral centre restricts the groups from rotating about the double bond, producing asymmetry.

Important reactions in asymmetric synthesis

A variety of reactions play an important role in asymmetric synthesis, including:

  • Asymmetric hydrogenation: This involves reactions where molecular hydrogen (H2) is added to unsaturated organic compounds to give chiral products with chiral catalysts.
  • Sharpless epoxidation: A well-known reaction developed by K. Barry Sharpless that uses diethyltartrate and titanium isopropoxide to catalyze the formation of epoxides from allylic alcohols.
  • Diels-Alder reaction: A chiral catalyst can direct the conformation of the diene and dienophile to selectively form one enantiomer.

The role of computational chemistry and modern advances

With advances in computational chemistry, predictions of energy configurations, simulations of molecular rotations, and stability calculations support the development of asymmetric synthesis processes. Computational models can provide detailed insight into the steric and electronic factors that affect the selectivity of reactions.

Modern advancements include:

  • High-throughput screening: Rapid testing of catalysts or reaction conditions to increase efficiency.
  • In-situ spectroscopy: immediate observation of reaction progress, providing insight into the mechanism.
  • Machine learning algorithms: Using a data-driven approach to predict outcomes and increase selectivity.

Challenges and future directions

Despite the progress, asymmetric synthesis faces challenges such as the scalability of chiral catalysts for industrial applications, the cost of chiral auxiliaries, and environmental concerns. Future improvements aim to design more sustainable catalysts, expand automation technologies, and refine precision.

Key possibilities include:

  • Green chemistry integration: Developing environmentally friendly methods using renewable resources for catalysts.
  • Bio-orthogonal reactions: Facilitating reactions in living systems, so that desired compounds can be produced in situ.
  • Microreactor technologies: allowing precise control of the reaction environment in asymmetric synthesis.

In summary, asymmetric synthesis remains a powerful tool in synthetic chemistry, with a broad application area in pharmaceuticals, agrochemicals and materials science. By manipulating molecular interactions in a chiral manner, chemists can create enantiomerically pure compounds required for biological activity while adhering to the principles of efficiency and stability. Continuing innovations in catalyst technology, computational modelling and reaction engineering will likely define the next era of asymmetric synthesis.


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Asymmetric synthesis

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