Diastereocontrol in Cyclic systems 2

• Cyclobutane is slightly puckered to relieve torsional strain • Cyclobutene is planar

• Usually selective for attack on the C=O face opposite the C3 substituent, regardless of the nucleophile size - but selectivity higher for small nucs - alcohol on same side as substituent • Akin to intrinsic preference for axial attack in cyclohexanones (small nucs) • Less hindered than in the 6-ring case

• Strong preference for electrophile attack on the face opposite to a large substituent • Electrophile opposite direction in product

• Envelope and half chair • Envelope is slightly favoured • 5 atoms not equivalent unlike a cyclohexane chair - Rapid ring-flipping interconverts them

• A single substituent prefers pseudoequatorial position of the envelope flap • 1,3 cis more stable than 1,3 trans

• Carbonyl or exo C=C prefers flat position on half-chair • Tend to model as planar

• Can only be accommodated at the end of the envelope- where all the atoms can be coplanar • Alkenes, enolates and esters • Esters have C-O in planar bit of envelope as C-O had partial double bond character

• Less predictable than cyclohexanones dues to lack of well-defined conformation • Still tendency for small hydride donors to give axial reduction = equatorial alcohol and large to give equatorial = axial alcohol

• Cyclohexanones • Cyclopentanones experience an increase in torsional strain during sp2-sp3 rehybridization • Hexanones experience a decrease • So if cyclohexanone and pentanone are attached nucleophile will attack hexanone

• Occurs on opposite face to substituent • Not to do with sterics as pseudo equatorial groups don’t present an effective steric blockade to either C=C face • Reaction proceeds under torsional control with substituent pseudo equatorial and the electrophile adding to the top face to relieve torsional strain in the TS - Away from eclipse

• Tend to add to same face as substituent • Torsional steering again 3 Unless C3 group is very bulky then steric hindrance drives reaction to opposite face

• Relies on temporary stereogenic centre allowing the original stereo centre to be destroyed and then reset diastereoselectivity • Produces good selectivity where would be very hard otherwise

• In some reactions reagents preassociate with polar functional groups in the vicinity of the reaction centre • Such reactions which are attractive rather than repulsive frequently provide a stereochemical outcome which is opposite to that predicted on steric effects alone

• Hydrogen bonding • Covalent • Lewis acid-base interactions • Maintained in the TS for the reaction

• hydroxyl-directed cyclopropanation • hydroxyl-directed epoxidation

• A zinc carbenoid species reacts initially at the hydroxyl group of an allylic alcohol • Followed by intramolecular carbene delivery • Results in product where alcohol and carbon triangle thing are on same side

• Epoxidation of cyclic allylic alcohols by peracids • hydroxyl group delivers the oxidant to the syn face of the alkene via hydrogen bonding

• One with pseudoequatorial hydroxyl group • When OH is axial, the anomeric interaction in the pseudoaxial isomer renders the C=C bond less reactive • It stabilises the molecule but loses energy of Pi-bond so makes it less reactive to electrophiles

• For O-protected substrates • Under steric control • Selectivity can be moderate

• Cyclic allylic amines undergo hydrogen bond-directed epoxidation • First need to be protonated on nitrogen to give corresponding ammonium salt • This also suppresses competing N-oxidation

• Homogenous hydrogenations of alkenes can be substrate-directed by using cationic irdium (or rhodium) catalysts • These associate with a wide range of polar functionality by Lewis acid-base interactions • Hydrogens added syn to each other and to DG?

• Methoxy • free esters • Alcohol • amides • All give v good selectivity

• Hydroxyl-directed cyclopropanation of allylic alcohols • hydroxyl-directed epoxidation of allylic alcohols • Epoxidation of cyclic allylic amines by H-bonding • Hydrogenation of alkenes by Lewis-base interactions - Rh or Ir catalyst

• Spiro bicycle • Fused bicycle • Bridged bicylce