c vs o (c: soft, o: hard)furutalab/kougi/2016-aor/aor_no...ambident reactivity aor no5 (2016.6.03)...
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Ambident ReactivityAOR No5 (2016.6.03)
Ambident Electrophiles
Ambident Nucleophiles
O
O
Me
O
O
Me
O
O
Me
OEt
Br
EtO
BrCvsO(C:soft,O:hard)
hard
soft
4.3 Ambident Nucleophiles
Nucleophiles which have two sites at which an electrophile may attack are called ambident.
hard electrophiles reacting at the harder nucleophilic site soft electrophiles reacting at the softer site
4.3.1 Thiocyanate lon, Cyanide lon and Nitrite lon (and the NitroniumCation)
isomerizationkinetic thermodynamic
Reaction issofastthattheselectivity isnotcontrolled.
-O N O
CH3I
OMe3+
MeOTf
H3C O N O H3C NO-
O+
30 70
50 50
59 41
HSAB
SN2
4.3.2 Enolate lonsWhy does an enolate ion react with some electrophiles at carbon andwith others at oxygen?
Effect of Leaving Groups
The harder the leaving group, the lower the proportion of C-alkylation The softer the leaving group, the lower will be the energy of the LUMO.
4.3.3 Allyl Anions
4.3.3.1 X-substituted Allyl Anions
α/γ selectivity
thermodynamicallystable
Li vs Zn
6-memberedtransitionstate
α
γ
α
C-Substituted Allyl Anions - Pentadienyl Anions
Both α attack and γ attack
Birchreduction
Z-Substituted Allyl Anions - Dienolate lons
α attack
sec-isoamyl
dienolate
13CNMR:chargedensity
Dienol etherγ carbonismorenucleophilicsitetowardssoftelectrophile
X,Z-substituted------- α vsγ
4.3.4 Aromatic Electrophilic Substitution
Wheland intermediate
4.3.4.1 Molecular orbitals of the lntermediates in Electrophilic Attack on Monosubstituted Benzenes
Origin of o,p-regioselectivity
Curly arrows illustrate the electron distribution in the frontier orbital, and for reaction kinetics it is the frontier orbital that is most important.
But, for the thermodynamic argument, we need to know the energy of all of the filled orbitals, and not just one of them.
Morestable
Model for an X-substituted Benzene Ring
ψ3 in 4.87 does not lower the energy level (0β) because there are no π-bonding interactions between any of the adjacent atoms-it is a nonbonding molecular orbital.
2x3.50β 2x3.45β 2x3.08β≈ >>
1.4.3 Longer Conjugated System
Model for an Z-substituted Benzene Ring
m-regioselectivity
(Ψ1 +ψ2) of 4.91 is greater than those of 4.89 and 4.96.
relatively slow rate of meta- substitutionsrelatively fast rate of the ortho- and para-substitutions
The endothermicity of 1.28β on the right is not much greater than that forbenzene (1. 27β); however, the presence of two positive charges in theintermediate on the right has not been all0wed for, and this willobviously raise the energy of this intermediate.
4.3.4.2 The Frontier Orbitals of Monosubstituted Benzenes
C-substituents
Benzene
Benzylsystem
(1) Place a zero on the smaller number of alternate atoms: node
(2) the sum of the coefficients on all the unmarked atoms joined to anyone of the marked atoms must be zero
Rule of Orbital Coefficients Estimation
ESR
C,X,Z
Fukui’s frontier electron population
WhereC3 andC2 arethecoefficientsatthatsiteinthetwohighest-energyπorbitalsψ3 andψ2,respectively,withtheonelabelledψ3 havingarbitrarilythehigherenergy,Δλ.isthedifferenceinenergybetweenψ3 andψ2,andDisaconstant(3isusedinfact)representingsomekindofmeasureofthecontributionofψ2 totheoveralleffect.
K. Fukui, J. Chem. Phys. 1954, 22, 1433
4.3.4.3 Halogenobenzenes
AmixtureofthepropertiesoftheZ- andX-substituted benzenes
Slowreactionwitho/p directing
Theo /p orientationismainlydependent onthecoefficientsandoverallchargesateachoftheatoms,andthereducedratecouldbelargelydeterminedbytheenergiesofthehigheroccupiedorbitals.
4.3.4.4 Frontier Orbitals of Polycyclic Aromatic Molecules. 4.3.4.5 ortho/para Ratios
3.50β 3.45βStericeffect
3.08β(3.05β) (2.93β)
Soft-soft interaction 4.3.4.6 Pyrrole, Furan and Thiophen
Morestable
4.3.4.7 Pyridine N-oxide Estimation by the Salem-Klopman Equation
G.Klopman,JACS 1968,90,223
HardestSO3:C3NO2
+:C4SoftestHgOAc+:C2
4.4 Electrophilicity
Characterised by having a low-energy LUMO and electron deficiency, either as a full positive charge or as a polarised bond with a partial positive charge at one or more sites
4.4.1 Trigonal Electrophile
Carbonyl groups
acid chlorides > aldehydes > ketones > esters > amides > carboxylate
strong weakelectrophilicity
Acid chlorides:
(i) the π stabilisation is small, because chlorine is electronegative, andconsequently the energy match is poor
(ii) the π stabilisation is offset by strong inductive electron withdrawalalong the C-Cl bond, raising the electrophilicity of the carbonyl group
(iii) anomeric stabilisation in the tetrahedral intermediate is greater-conjugation of the oxyanion with the C�Cl σ* orbital pulls down theenergy of the transition structure.
Stabilisation in the intermediate plays a larger role in determiningelectrophilicity than the differences in the energy of the startingmaterials
electrophilicity in alkyl halides in SNl , SN2, E1 and E2 reactions (I- > Br-> Cl->> F-)
X=FvsCl(I)600(3100)timesfaster
Oppositeorderinaromatichalides (F- > Cl-> Br-> I-)
Anomericeffect
2.2.3.3 The Anomeric Effect 4.4.2 Tetrahedral Electrophiles
electrophilicity of alkyl halides in SN2 reactions:methyl > ethyl > isopropyl > tert-butyl.
Steric effect andhyperconjugation which lowers the energy of the LUMO of the C�Br bondin tert-butyl bromide more than that in methyl bromide also reduces thecoefficient on, and at the same time lowers the overall energy of thestarting material.
8000:1
SN2
4edelocalization inallylicoverlap
ρ+ =-2.9
XacceleratesSN2
4.4.3 Hard and Soft Electrophiles
thehardestelectrophiles aresmall,chargedandhavearelativelyhigh-energyLUMO,andsoftelectrophiles arelarge,havelittlechargeandhaveaconspicuouslylow-energyLUMO.
RXvsC=O
SN2:exothermic----earlytransitionstructure—orbital interactionRX:softelectrophile
Addition:endothermic--- latetransitionstructureC=O:hardelectrophilewithlowLUMO
Evenwithinagroupofverysimilarelectrophiles, allsoftlikeprimaryalkylhalidesundergoingSN2displacement, thescaleofelectrophilicity isnotconstant.
4.5 Ambident Electrophile
LargeLUMOCoefficient
4.5.1 Aromatic Electrophiles
Pyridinium Cation
“H-”
hard
Soft
thermodynamicallystable
LUMO
Charge
4.5.1.2 ortho-and para-Halogenonitrobenzenes.
Linear-conjugated
faster
Cross-conjugated
Coulombic
4.5.2 Aliphatic Electrophiles
4.5.2.1 α,β-Unsaturated Carbonyl Compounds
α-fast
Thermodynamicallystable
+Li+:98:2
- Li+:23:77
softer 4.5.2.2 Allyl Hallides
InPolarsolvent SN1,SN1’
4.5.2.3 Unsymmetrical Anhydrides
LiAlH4 100:0(R=MeO)88:12(R=Me)
Elimination vs. Substitution
G.Biale,JACS 1971,93,4735
Singlet carbene Triplet carbene
concerted stepwise
Reactivity Carbene HOMO: high LUMO: low High ReactivityNucleophilic and electrophilic
Nucleophilic Carbenes Electrophilic Carbenes Cycloaddition,insertion intoC-H
Aromatic Carbene
nucleophilic
Cyclopentadienylidene
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Report No6 (6/03)
The dipole of pyrrole points in the direction 4.120. The explanation usuallyoffered is that the orbitals are polarised in the sense illustrated by thecanonical structures 4.121 and 4.122. This cannot be the reason, because thisis only one of the π orbitals, the HOMO. We can see on the drawing 4.104 thatthe total π charge, is higher on the nitrogen atom and lower on the carbon
atoms. The same must be true in the σ framework. Why then is the dipolepointing in the other direction?