Reactions Exam 1

resonance vs equilibrium

resonance:

• e- moves

• no bonds broken

• resonance forms avg single structure

equilibrium

• e- and atoms move

• bonds break

• structures exist separately

Ionic mechanisms

~90% org rxns

move 2e- at a time

from high e- density to low

Radical mechanisms

~10% org rxns

move 1e- at a time

3 types of radical mechanism steps

initiation

propagation

termination

Initiation and Termination energy differences

Initiation: takes energy to break bond (RDS)

Termination: generates energy bc forming bond

Proton Transfers need

some sort of base (anion or lone pair)

Intramolecular PT

favored for >5 ring T.S. (bc of ring stain)

faster than intermolecular (more favored)

Intermolecular PT

1,2 and 1,3 proton transfers

favored for <5 ring TS

Questions for Mechanism Intuition

where is most e- density?

what is most stable confirmation?

where are weakest bonds? (heteroatom bonds)

Ionic vs radical rxn?

Can a stable carbo - cation/anion be formed?

potential signs of radical mechanism

UV light or weak heteroatom bonds

(not always the case though)

Central Chirality/Point of Chirality

Localized on one atom

priority determined by atomic number

Axial Chirality

molecule viewed along axis

assign priority to front groups, then back

bonds along axis is twisted —> groups are not in same plane

Planar Chirality

results from arrangement of out-of-plane groups

When symmetry elements exist:

molecule is not chiral

axis, plane, etc

Regioselectivity

one direction of bond formation/break is preferential over other directions

Elements of regioselectivity

same starting funct groups

different reacting sites

different connectivity in products

Chemo selectivity

rxn takes place preferentially at one funct group

Elements of chemoselectivity

starting material had two diff funct groups

only one funct groups reacts (makes majority product)

Stereoselectivity

general term

formation of one stereoisomer over the other

*should always have one isomer in xs*

Enantioselective

when generated isomers are enantiomers

if selectivity results in only one enantiomer (100:0)

chiral, non-racemic compound

enantiomerically pure compound

if selectivity results in non-equimolar mix (99:1)

enantioenriched compound

ee

enantiomeric excess

%S-%R

er

enantiomeric ratio

diastereoselectivity

when generated isomers are diastereomers

when one stereocenter in products has changed, but others have not

stereospecificity

production of single isomer as result of mechanism of rxn and the stereochemistry

gives diff stereoisomer of product from each stereoisomer of starting material

Approaches to enantioenriched natural products

ideal: use one chiral building block to start and form stereocenters through rxn

Chiron Approach

Stereoselective Synthesis Approach

Chiron Approach

buy chirality

purchase building blocks

Stereoselective Synthesis Approach

create chirality

synthesize building block through disastereoselective or enationselective rxns

Chiron Approach Advantage

good/simple if it fits desired molecule structure

Chiron Approach Disad

limited # of natural starting materials (amino acids, carbohydrates, terpenes)

Stereoselective Synthesis Adv

more choice with materials and process

Stereoselective Synthesis Disad

enantio rxns: wasteful bc only need 50% product, requires extra steps to separate racemic mix

Oxidation of Alcohols

alcohol — > aldehyde/ketone

Oxidation of Alcohol steps

-install LG on alcohol oxygen

-base deprotonates a-hydrogen

-eliminate LG

-generate aldehyde/ketone

If aldehyde is generated and water is present

further oxidation to carboxy acid occurs

Oxidation to carboxy acid steps

-water adds to aldehyde (generates diol)

-add LG to one alcohol group

-base removes a-proton, elim LG

-generates carboxy acid

permanganate oxidation steps

-alcohol attacks Mn

-intermolecular PT (~H+) to neutralize charge

-LP on O- deprononates a-H

-manganate LG leaves —> generates aldehyde

-water adds —> generates equilib w/ diol

-repeat steps 1-4

Swern Ox Rxn

DMSO + C2O2Cl2 + NEt3 + ROH —> DMS + aldehyde

Swern Ox Steps

-charged DMSO attack carbonyl

-from intermediate, Cl is kicked out

-Cl- attacks S, breaks bonds to make CO2 and CO

-alcohol attack S, Cl- deprotonate alc H

-Cl leaves S complex (equilb)

-NEt3 deprotinates methyl H, LP deprotonates a-H

Swern Mod Ox Rxn

DMSO + TFA + NEt3 + ROH —> DMS + aldehyde

Swern Mod Steps

-charged DMSO attacks TFA carbonyl

-e swing, kick out anhydride group

-alc attacks S, anhydride anion deprotinates alc H

-original carbonyl leaves (equilb), generates anion and S-alc group

-NEt3 deprotinates S-methyl H, LP deprotinates a-H

Pfitzner-Moffat Rxn

DMSO + R2N2C + HX + ROH —> DMS + aldehyde

Pfitzner-Moffat Steps

-N LP attacks HX

-charges DMSO attacks carbon in starting material

-alc O attacks S

-X- deprotinates alc H

-intramolecular PT w/ N double bond , grabs S-methyl H

-carbonyl N group leaves

-S=methyl bond grabs a-H

Corey-Kin Rxn

DMS + NC5O2CL + NEt3 + ROH —> DMS + aldehyde

Corey-Kim Steps

-S removes Cl from N-Cl complex

-N attacks S, removes Cl

-alc O attacks S

-Cl- removes alc H

-N group leaves (equilb)

-NEt3 removes a-H

Parikh-Doering rxn

DMSO + SO3 + ROH + NEt3 —> DMS + aldehyde

Parikh-Doering steps

-SO3 attacked by charges DMSO

-alc attacks DMSO sulfur

-O LP from SO3 grabs alc H

-HSO4 - leaves (equilb)

-NEt3 deprotonates S-methyl

-S-methyl anion deprotinates a-H

-generates aldehyde

Kornblum Ox rxn

R-OTS-R’ + DMSO + Na2CO3 —> ketone + DMS

Kornblum Ox steps

-charged DMSO attack OTS complex

-sodium bicarb deprotonate S-methyl

-S-methyl anion deprotinates a-H

-generaes ketone and DMS

DMP Ox rxn

DMP + ROH —> aldehyde

DMP ox steps

-OAc group of DMP leaves (equib)

-alc attacks I

-OAc - group deprotonates alc proton

-another OAc group leaves (equib)

-OAc - removes a-H

-generates aldehyde

Pinnick rxn

Na+ ClO2 - + NaH2PO4 + aldehyde —> carboxy acid

Pinnick steps

-ClO2 LP deprotonates H NaH2PO4

-aldehyde O deprotonates H on ClO2-H

-O on ClO2 attacks carbonyl

-O=Cl bond deprotonates a-H, kicks off Cl-OH

-generates carboxy acid

Ley Ox rxn

ROH + RuO4 (aka TPAP) —> aldehyde

Ley Ox steps

-alc attacks TPAP

-~H+ to neutralize charge

-O grabs a-H, generates aldehyde

Oppenauer Ox rxn

ROH + Al(OiPr)3 + acetone —> aldehyde + Al(OiPr)3 + iPr-alc

Oppenauer Ox steps

-alc attacks Al, kicks off OiPr

-OiPr deprotinates alc

-acetone attacks Al

-O-Al bond breaks, a-H goes to acetone double bond

-breaks Al-O bond, generates products

Activated DMSO to aldehyde ox rxn acronym

S.S.PM.CK.PD

S.S.PM.CK.PD stands for

Swern, Swern Mod, Pfitzner-Moffat, Corey-Kim, Parikh-Doering

S.S.PM.CK.PD reagents to look for

includes Cl, TFA, N=O, NCS, SO3

ox rxn: specific for aldehyde to carboxy acid

pinnick (NaClO2)

ox rxn: protect stereocenters

ley (N+ RuO4-)

ox agents: selective for benzylic/allylic/proporgylic

MnO2