CHEM 352, wk 2-3 (exam 2)

How to make OH a good leaving group?

1) Activate as a sulfonate (O-S-R, plus two double bonds from S to 2 O’s)

2) Convert to hydrogen halide

Thermodynamic enolate uses what base?

less reactive base, alkoxide

Kinetic enolate uses what base?

more reactive, lithium diisopropylamide (LDA) and cold temperatures (-78C)

Enolate

result from the removal of a proton on the carbon adjacent to a carbonyl (the “alpha carbon”). They are stable due to inductive effects 

• can be formed from aldehydes and ketones, but also from esters, amides, nitriles and many other carbonyl-containing compounds

• nucleophiles

• basic conditions

Enol

hydroxyl group (-OH) attached to a carbon-carbon double bond (C=C-OH).

• functional group or intermediate

• acidic conditions

Regioselectivity

preference of chemical bonding or breaking in one direction over all other possible directions

• one reaction site is preferred over another

Alkylation

transfer of an alkyl (alkane missing one hydrogen atom) substituent from one molecule to another via an alkyl carbocation, a free radical, etc

Alkyl Group

alkane missing one hydrogen atom

• formed by removing one hydrogen from the alkane chain

Halogenation

chemical reaction which replaces one or more (poly) hydrogens with halogens in a compound

Williamson Reaction

uses reactive alkoxide nucleophile and alkyl halide that can react via SN2

• way to form symmetric or unsymmetric ether (ROR)

• 1) Use a strong base to deprotonate alc 2) perform sn2 reaction with alkyl halides

Alkoxide

conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom (-OR)

Epoxide

cyclic ether, where the ether forms a three-atom ring: two atoms of carbon and one atom of oxygen

• Technically has two alpha carbons

Epoxides under acidic conditions

has SN2 inversion of stereochemistry but attacks the more substituted carbon to alleviate ring strain (SN1 influence)

Epoxides under basic and neutral conditions

nucleophile attacks epoxide at less alkyl substituted C of the ring (SN2), sterics matter

• strong nuc (small negative)

Alpha Carbon

carbon that is one carbon away from an aldehyde or ketone group

Carbocation Rearrangement

in sn1 and e1, if carbocation is next to more stable conformation

• allylic > 3 degree > 2 > 1

• Methyl shift, hydride (H-) shift

If you have a non-six memebered ring

• ring change by one step

Alcohol reactions

acid activation of 2/3 degree alcohals can lead to rearrangments

1/2 degree alcohals go through conversions to alkyl halides using PBr₃/PCl₃ (sn2 reagents)

intramolecular reactions

are fastest reactions and will occur if a nuc and electrophile are on the same molecule

• faster to tie your own shoe

What to know about conjugated diene

• Kinetic control, reactions under cold conditions at -80C, means that we are favoring the 1,2 addition product formation which always occurs faster

• Thermodynamic control, at higher temperatures, always favors the alkene that is most stable
  

Good Nucleophile

small, negatively charged, with a conjugate acid pka greater than 30

Good base

have a conjugate acid with a pka less than 12

Alcohol electrophile reacts with PBr3/PCl3

transforms alcohol into better leaving group

• react with a 1 or 2nd degree alcohol to perform SN2

alcohol electrophile reacting with a base who’s conjugate acid has a pka less than 16-18

proton transfer will result in a good oxygen nuc

• Creates an ether when reacting with 1 degree alc halide

Alcohol electrophile reacting with HX

• degree 1 —> SN2, creates alkyl halide

• degree 2/3 —> SN1, creates alkyl halide

alkyl halide electrophile reacted with a good base results in

a new pi bond forming

• 1 degree = only E2 with good base

• 2 & 3 degree = E1 or E2

alkyl electrophile reacting with a nuc results in

• 1 degree = only SN2 with good nuc

• 2 degree = SN2 with a strong nuc, or SN1 with weak polar protic nuc

• 3 degree = only SN1 with weak polar protic nuc

alcohol reacting with TsCl and pyridine follows this reactivity

epoxide electrophile results in

• acidic conditions = SN2 reaction (inverts stereochem) with SN1 influence (attacks more sub alpha C), attacked by nuc after protonating oxygen

• basic conditions = SN2, alpha C attacked by good nuc and then protonation occurs

alpha carbon of the C=O bond electrophile results in

• acidic conditions = after proton transfer, enol intermediate reacts with Br2 or Cl2 for alpha halogenation

• basic conditions = after proton transfer, enolate intermediate reacts with Br2 or Cl2 for poly alpha halogenation

• basic conditions = after proton transfer, enolate intermediate reacts with alkyl halides (alkylation)

  • kinetic enolate:

  • thermodyanmic enolate: