Diastereocontrol in Acyclic systems 2

• A C-H bond eclipses the C=C group (inside position- where torsion angle =0 degrees to C=C)

• Gives the best orbital alignment for two stabilising sigmaC-H –>piC-C hyperconjugative interactions (seen in acetaldehyde) • C=C bond is electron-rich, so also get piC-C –>sigma*C-H negative hyperconjugative interaction (similar to anomeric effect) • Electrons end up lower in energy overall- fill lower energy MO.

• Allylic H lies in the outside position 180 Degrees from C=C • Destabilising sigma C-H –> pi C-C interactions occur between the C-H bonds and the pi-orbital of the C=C group putting energy at a maximum.

• Hyperconjugation is the stabilising interaction that results from the interaction of the electrons in a σ-bond (usually C-H or C-C) with an adjacent empty or partially filled p-orbital or a π-orbital • Gives an extended molecular orbital that increases the stability of the system.

• A conformation with hydrogen in the inside position is lower in energy than that with methyl • Then conformation where ME is in inside position • Then conformation where H or Me are in outside position

• Same explanation as propene • Additional steric interaction known as 1,3-allylic strain (A^1,3 strain) • An energy raising effect • If methyl was in inside position it would interact with the H on opposite side of C=C- sterics not good • Small effect

• Where the Me is perpendicular- 90 degrees to the C=C • Then where H is in inside position 3 Then where Me is in inside position - very high compared to the other 2

• Increasing the size of the eclipsing substituent on the alkene massively increases the effect of the 1,3-allylic strain • Now 2 Me groups interacting when Me in inside position as Me on otherside of C=C as well - big strain • No strain when Me in 90 degrees so most stable

• When H is in the inside position and Me facing up • Then Me in inside position- slight A^ 1,3 • Then when Me is in outside position • Highest energy is H in outside position

• Same reasons as previously • Me in inside- slight sterics • H in outside- 1,2-allylic strain A^1,2 strain • Me in outside- Destabilising sigma C-H –> pi C-C - 1,2-allylic strain A^1,2 strain • This strain severely destabilises conformation - 2 Me groups interacting

• Not always

• A sigma bond at the allylic position is aligned antti to the forming bond in order to stabilise the TS • Not single transition state as with C=O additions with nucleophiles as approach trajectories depend on both electrophile and alkene

• Steric interactions as like simple F-A model for C=O additions • TS with the least allylic strain and minimal steric interactions between the alkene and electrophile will be the lowest in energy

• Epoxidation • Hydroboration • Iodolactonisation • Substrate-directed reactions

• Small group is in inside position of alkene to minimise the A^1,3 strain and larger group pointing upish • m-CPBA approaches anti to large group • Epoxide group forms same side to small group and opposite to large • In general Z-substituted alkene is required for high diastereoselectivity as A^1,3 strain is much more severe • dr increases when R group on opposite side of C=C is larger

• Large group in anti position (90 degrees to C=C) - avoid clash with electrophile • Small group in inside position to minimise A^1,3 strain • BH3 approaches anti to large group • B adds to the less substitutes end of the alkene (anti-Markovnikov)

• Small group in inside position to minimise A^1,3 strain • Get rapid and reversible iodonium ion formation - only productive when reacts on top face • Iodolactonization via SN2 - forms 6 ring intermediate • All groups in chair like TS should be equatorial

• Same process as hydroxyl-directed epoxidation of cyclic allylic alcohols • Z-substituted alkene generally required for high diastereoselectivity • OH in same side as O e.g both pointing forward

• Using cationic iridium or rhodium catalysts • Addition on top face • Small group in inside position OH pointing up to allow interaction with Rh

• When 2 non-hydrogen substituents attached to atoms 1 and 2 • Hydroboration

• Hydroboration of chiral allylic alcohols is reagent-dependent • For BH3- original OH will be on same side as R group • 9-BBN-H opposite sides

• Medium sized OH is in inside position minimises A^1,2 strain to methyl on opposite side • L group is anti- borane approaches anti to this group • B adds to less-substituted end of the alkene

• Borane is so large that it encounters severe non-bonded steric interactions with the inside substituent so it is preferable to put the smallest group (H) in this position despite the increase in A^1,2 strain

• Essentially opposite to nucleophilic additions to C=O • Donor groups (electropositive) prefer anti position • Acceptor groups prefer inside position (electronegative) - but exceptions