User:Benjah-bmm27/degree/3/VKA

=Orbitals, VKA= "Orbitals in Organic Chemistry"
 * Neighbouring group participation in SN2 reactions: faster with allyl, benzyl and α-carbonyl halides due to stabilisation of the carbon 2p orbital in the transition state
 * Stereochemistry of E2 eliminations (requirement that acidic hydrogen and leaving group are antiperiplanar) arises due orbital geometry
 * Order of stability of carbocations (3° > 2° > 1° > methyl) is due to hyperconjugation of C-H σ bonds with empty 2pz orbital of the cationic trigonal planar carbon
 * Grob fragmentation
 * C-C σ bond donates its electron pair into a C-OMs σ* orbital, breaking the C-C and C-OMs σ bonds
 * OH lone pair donates its electrons into C-C σ*, forming C=O π bond and breaking the C-C σ bond
 * See also Eschenmoser fragmentation and this 2010 review: Synthetic Applications of the Carbonyl Generating Grob Fragmentation
 * Orbital effects on conformation
 * C-H σ → C-H σ* hyperconjugation as a contributory factor in the preference of ethane for a staggered conformation
 * C-H σ → C-F σ* hyperconjugation is much better than C-F σ → C-F σ*, so 1,2-difluoroethane prefers a gauche conformation. This is called the gauche effect.
 * Anomeric effect — pyrans
 * Important in carbohydrate conformation
 * Esters prefer the conformation that allows the non-carbonyl oxygen to donate a lone pair into the carbonyl C-O σ* orbital
 * Lactones normally cannot access this conformation, so they are more reactive

Cycloadditions

 * Diels-Alder reaction (regio- and stereoselectivity)
 * Cyclopentadiene > furan (often reacts reversibly because aromaticity is lost) > pyrrole (poor diene for DA)
 * Acyclic dienes (e.g. 1,3-butadiene) need to adopt the s-cis conformation to react, although the equilibrium lies heavily in favour of s-trans
 * Isoprene reacts better as its methyl group sterically clashes with a methylene H in both s-trans and s-cis conformations, pushing the equilibrium further towards s-cis than usual
 * 4-methylpenta-1,3-diene reacts very poorly as its s-cis conformation is heavily sterically crowded
 * 3-methylenecyclohex-1-ene does not react at all, as it is locked in the s-trans conformation
 * Dienophiles with electron withdrawing groups work best (lowest LUMO)
 * Maleic anhydride and maleate esters are excellent, methyl acrylate very good, 1,3-butadiene OK
 * Dienes with electron donating groups work best (highest HOMO)
 * Danishefsky's diene is exceptionally good
 * Woodward–Hoffmann rules
 * for an allowed thermal cycloaddition process, (4n+2) π electrons are required
 * [2+2] cycloadditions are symmetry forbidden, fail thermally, proceed photochemically
 * Endo rule
 * Lewis acid catalysis (e.g. SnCl4) lowers LUMO of dienophile, increasing rate and selectivity
 * Nitrone, ozone and nitrile oxide [3+2] cycloadditions
 * Nitrone + alkene → isoxazolidine
 * Ozonolysis: first step is O3 + alkene → molozonide
 * Nitrile oxide + alkene → isoxazoline

Sigmatropic rearrangements

 * Sigma (σ bonds), tropic (movement)
 * The main class is [3,3] sigmatropic rearrangements
 * Cope rearrangement (all carbon in the cyclic TS)
 * Claisen rearrangement (oxygen in the cyclic TS)
 * Industrial synthesis of citral (BASF)
 * oxy-Cope rearrangement (oxygen present, but outside the all-carbon cyclic TS)

Exo-tet and exo-trig

 * All exo-tet cyclisations are favoured
 * All exo-trig cyclisations are favoured

Endo-tet and endo-trig

 * 5- and 6-endo-tet cyclisations are disfavoured
 * 3-, 4-, and 5-endo-trig cyclisations are disfavoured; 6- and 7-endo-trig are favoured

Dig

 * All endo-dig cyclisations are favoured
 * 3- and 4-exo-dig are disfavoured; 5-, 6- and 7-exo-dig are favoured

Workshop questions

 * PreWS2: diazoalkane 1,3-dipolar cycloaddition (phenyldiazomethane + ethyl acrylate → a pyrazoline)