Cyclic

• Hyperconjugation

  Overlap of 𝛔 orbital with 𝛔* orbitals

  Stabilises staggered conformations - conformation with the correct orbital overlap
• Pitzer (Torsional) Strain

  Repulsion of sigma electron orbitals

  Destabilises the eclipsed conformations
• Sterics

  Repulsion between substituents

  Destabilises the eclipsed conformations
• Hydrogen bonding

  • Stabilises cynical + synperiplanar conformations
• A Values

  The energy difference (kcal mol-1) between the lowest energy conformation of a system and the highest energy conformation of a mono-substitubed cyclohexane

  Gives a value to the size of a substituent

  Can calculate the equilibrium concentrations of axial + equatorial
• Baeyer (angle) strain

  Atoms are distorted from their ideal bond angles to form a ring
• Small rings - 3/4 membered rings

  Normal rings - 5-7

  Medium rings - 8-14

  Large rings - >14
• Anomeric effect

  Electronegative groups in the 2-position in an O or N-containing ring will adopt an axial position, despite the 1,3-diaxial interactions - allowed by hyperconjugation

  Lone pair is able to donate into the vacant 𝛔* orbtial

  The effect is reduced in other ring sizes - poor orbital overlap 🠆 sterics dominate
• Substituents with a larger A values (more bulky) are more stable in the equatorial position

  1,3-diaxial interactions are minimised
• Conformational locking

  The prevention of ring flipping

  Caused by bulky substituents (t-butyl)

  Fused rings with trans substituents are conformationally locked
• Karplus curve


  Relates the 3J coupling constant to the dihedral angle between protons

  Larger J values = larger dihedral angle

  
• Irreversible cyclisation

  formation of small + normal rings

  the aliphatic molecule will contain both an electrophile + nucleophile

  the nucleophile must be able to reach the C-LG 𝛔* orbtial for ring closure
• 3-memerbered rings form via irreversible cyclisation the fastest 3>5>6>>4

  the entropic cost increases with ring size - more order is required of chain arrangement

  the enthalpic cost decreses withn ring size - small rings are more strained
• Revisible cylcisation cannot happen for small rings
• Conformations

  The different spatial arrangements that a molecule can adopt due to rotation about single bonds
• Conformational analysis

  The study of the energy changes that occur during rotations
• Conformers

  Molecular structures that differ only by virtue of rotation of bonds
• Conformations

  Changes the reactivity of the molecule
• Carbenes

  • a carbon with a lone pair and 2 bonds
  • forms cyclopropane on addition to an alkene
  • very reactive (formed in situ)
  • a singlet carbene if the R group is a halogen
  • a triplet carbene if the R group is an alkyl

  
• Singlet carbenes are generated by alpha-elimination

  • stereochemistry of alkene is maintained in the cylcopropane
  • favour electron rich location in the molecule

  Triplet carbenes are generated via decomposition of diazo compounds

  • stereochemistry of the alkene is not necessarily retained in the cyclopropane
  • spin inversion of an alkyl electron must occur in order to close the ring
  • electrons cannot form the bond if they have the same spin
  • inversion is slow
• Carbenoids

  • metal-bound species that exhibit carbene-like reactivity
  • can form cyclopropane on addition of diiodomethane + Zn(Cu)
  • are more stable + selective than carbenes
  • alkene geometry is conserved in the product
• Epoxide synthesis

  1. Weitz-Scheffer reactions
  2. an alkene bound to an EWG + H2O2 + NaOH
  3. peroxy ion is a nucleophilic oxidant - an electron deficient alkene is required
  4. Alkene + peracid
  5. peracid - R-O-O-H
  6. are electrophilic oxidants - react with electronrich/neutral alkenes
  7. alkene geometry is maintained
• Epoxides

  • have high ring strain (Baeyer + Pitzer)
  • C-O bond is polarised + weak due to high p-orbital character

  
• periplanar - in the same plane

  clinal - out of plane

  syn - same

  anti - opposite

  
• Staggered conformations are lower energy

  Antiperiplanar is most favourable

  Energy is activation energy

  
• Transannular strain

  the repulsion of the orbitals of atoms on opposite sides of the ring

  effects medium rings only (8-14 MRs)
• Epoxide opening

  • basic conditions
  • Sn2 mechanism - inversion of stereochemistry at the reacting centre
  • attack via the least hindered site
  • requires a reactive nucleophile
  • regioselectivite + stereoselective
  • acidic conditions
  • Sn2 mechanism with Sn1 character
  • attack via the site which can best support a +ve charge (usually most hindered positions)
  • regioselective

  
• Cyclobutanes

  • synthesied by [2+2] cycloaddition
  • UV light provides the energy
  • may occur at carbonyl groups - oxetanes

  
• Carbacycles - 6MRs

  • synthesised by irreversible, reversible cyclisation
  • Robinson annulation([2+2 addition])
  • Diels-Alder reaction ([4+2] cycloadiition. the diene must adopt the s-cis conformation)
  • Birch reduction - Na in liquid NH3. Removes a double bond from a fully conjugated system

  
• Cyclic acetals

  a ring containing 2 Os

  
• Cyclohexane SN2 substitution - inversion

  anti distereoisomer - slow - nucleophile must pass between two axial Hs to attack the sigma* orbital

  syn diastereoisomer - fast - LG is axial so sigma* orbital is more easily accessed by the lone pair on the nucleophile

  
• Cyclohexanones (cyclohexane + ketone (one sp2 centre)) - 1,2-addition

  adopts a chair conformation - can undergo either equatorial or axial attack

  axial attack - nucleophile takes axial position - low steric hinderance for small nucleophiles

  equatorial attack - nucleophile takes equatorial position

  
• 6MRs with 2 sp2 centres (e.g. an enolate) adopt a half-chair conformtation

  can also ring flip

  • electrophile can be attacked from above or below
  • above - high energy twist-boat TS - minor product
  • below - low energy chair-like TS - major product

  
• Irreversible cylisation - kinetically controlled

  • SN2 reactions
  • carbene additions
  • alkene oxidation
  • cycloadditions
• Reversible cyclisation - thermodynamically controlled

  • acetal formation
  • some additions to carbonyl compounds
  • additions to conjugate double bonds