Professor Scott E. Denmark University of Illinois, Urbana-Champaign - IASOC
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Professor Scott E. Denmark
University of Illinois, Urbana-Champaign
Activating Acids with Bases: Theory and Applications
An Homage to G. N. Lewis
Ischia Advanced School
of Organic Chemistry 2006
Ischia, Italy
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
19-23 September 2006
G. N. Lewis (1875-1946)(Asymmetric) Catalysis: The Chemical Evergreen reagents
catalystsOpportunities for Catalysis in the Main Group? • Lewis Acidity: – B(+3), Al(+3), Ga(+3), In(+3) – Si(+4), Sn(+2, +4), Pb(+4) – P(+5), Sb(+3, +5), Bi(+3, +5) – O(+2), S(+2, +4, +6), Se(+2, +4, +6), Te(+2, +4, +6) – F(+1), Cl(+1, +3, +5, +7), Br(+1, +3, +5, +7), l(+1, +3, +5, +7) • Catalyzed Chemical Processes – Carbonyl addition reactions (aldol, allylation, ene) – Acetal addition reactions – Friedel-Crafts reactions – Conjugate addition reactions – Azomethine addition reactions – Epoxide opening reactions – Cycloadditions ([4+2], hetero [4+2], [3+2]), Electrocyclic reactions – Sigmatropic (and other) rearrangements
Strategies for Modulating Lewis Acidity: Structural
structural perturbations (“strain-release Lewis acidity”)
p orbital spn hybrid
distort ΔH0 = -22.7 kcal/mol N
R B B
+
R
M R M
R R N
R
(Mihkailov)
F3C CF
3
F3C CF3
R R θ = 90Þ O
θ = 109Þ distort O LB
Si Si LB
O
R M R M Si 94Þ
R R O
R CF3
R F3C F3C CF3
(J. C. Martin)
θ = 77Þ Me
Si O Si Me Si
O Me intramolecular O O
+ O O H silicon transfer
MeO H MeO
Me MeO Me
Ph
MeStrategies for Modulating Lewis Acidity: Electronic
electronic perturbations (electrophilic)
LB X X
X LB LB X
X M M X
X
M X X M X
X
X X X
LB
Binding equilibrium becomes more favorable as
electron deficiency at M increases: X = NR2 < OR < halide < TfO ~Tf2N
electronic perturbations (nucleophilic?) Gutmann’s Fourth Rule “spillover effect”
_
F "…although a donor-acceptor
- Cl
F F interaction will result in a net transfer of Cl Cl
B F B electron density from a donor species Sb net decrease
F F
F Cl
F to an acceptor species, it will, in the Cl
electron deficient more electron
case of polyatomic species, actually O net increase
MP2: q(au) +0.990
deficient!! lead to a net increase of electron C
MP2: q(au) +1.070
density at the donor atom of the donor O O
species and to a net decrease of Cl C C Cl
C. Cramer, private communication electron density at the acceptor atom
of the acceptor species."
Cl ClStructure, Bonding and Charge Distribution in Hypercoordinate
Silicon Compounds
(3c-4e) p (3c-4e) p
X L L
Lewis base (L) X Lewis base (L)
X L
X Si X X Si X Si
X X X
X X
sp3 sp2 sp
tetrahdral (Td) tbp (C3v) octahedron (D4h or C2v)
formal bond order: 1.0 formal bond order (apical): 0.75 formal bond order: 0.66
Si-Cl 2.039 Å formal bond order (basal): 0.83 Si-Cl 2.273 Å
X Si charge X charge X L Si charge X charge X L Si charge X charge
Cl +0.178 - 0.045 Cl Cl +0.279 -0.430(a), -0139(b) Cl Cl +0.539 -0.423
1.
1. Coordination
Coordinationbybyboth
bothneutral
neutraland
andanionic
anionicligands
ligandsresults
resultsininaadecrease
decreaseininthe
theelectron
electron
density
densityat
atthe
thecentral
centralsilicon
siliconatom
atomand
andan
anincrease
increaseininelectron
electrondensity
densityon
onthe
theligands.
ligands.
2.2.Hypervalent
Hypervalentbonding
bondingisishighly
highlyionic
ionicinincharacter
characterand
anddissociation
dissociationcan
canbe
befacile.
facile.
3.3.Hypervalent
Hypervalentbonds
bondsfavor
favorelectronegative
electronegativeligands,
ligands,sp
spbonds
bondsfavor
favorelectropositive
electropositiveligands
ligands
M. Gordon, J. Phys. Chem. 1990, 94, 8125The Hypervalent 3-Center/4 Electron Bond
σ∗ (LUMO)
Si Si Si
Si
n (NB)
hypervalent bonds covalent bonds from sp-hybrids
formed from the py obtained from px and s-orbitals
and pz orbitals
σ (HOMO)
Cl Si Cl
L
N(2)
L L' binding site for s-donors N(1)
Si
C(11)
L' L binding site for s-acceptors C(12) O(2) O(1)
L
Cl(1)
Cl(2) Si
hypervalent (3c-4e) bonds covalent bonds
(px and pz orbitals) (py and s orbitals) Cl(3) Cl(4)
Si-Cl(1)/Cl(2): 2.180 Å
Si-Cl(3)/Cl(4): 2.197 ÅLewis Base Activation of Lewis Acids
+
δ+ XX XX
L X L L
δ− δ+ δ−
D + D A X D A X-
L X A X LL
L X LL X X
Lewis base Lewis acid increased increased
negative positive
charge charge
•• The
Thekinetically
kineticallysignificant
significant(strong)
(strong)Lewis
Lewisacid
acidisisgenerated
generatedonly
onlyininthe
thepresence
presenceof
ofthe
the
Lewis
Lewisbase
basethus
thusnegating
negatingthe theachiral
achiralbackground
backgroundreaction.
reaction.
•• Reactions
Reactionscancanbeberun
runwith
withaastoichiometric
stoichiometricamount
amountof ofthe
theweak
weakLewis
Lewisacid
acid
•Increased rates
•Increased rates
•Product
•Productinhibition
inhibitionisisminimized
minimized
+ O +
Cl
L Cl Cl
L Cl Cl – Si DL3
R H O
D + D Si Cl Cl–
L Cl Si Cl LL Cl
L Cl Cl
R H
Lewis base Lewis acid
Other
Otherelectrophiles:
electrophiles:enals,
enals,enones,
enones,azomethines,
azomethines,epoxides,
epoxides,nitrones,
nitrones,nitroalkenes
nitroalkenes
Pro
ProNucleophiles:
Nucleophiles: Nu-SiR
Nu-SiR3 ==allylsilanes
allylsilanes(stannanes)
(stannanes)enol
enolsilanes,
silanes,silyl
silylketene
keteneacetals,
acetals,etc.
etc.
3Catalytic Enantioselective Passerini Reaction
Ugi O Passerini
O
R3 H O 2C 2C O R2 H
R H R H
R3 N C R R1 N C
C* N 1
C* N 1 R3 O C R
O H O H
R2 R3NH2 O
O C
R3 OH
C H
R3 OH O
R2 H
multicomponent
multicomponentreactions
reactionsfor
for R2
molecular
moleculardiversity
diversity R2 C N
HO C R1
HO C H
N O O
R1
O R3
O R3
Isocyanide
Isocyanidebears
bearsdivalent
divalentcarbon
carbonatom
atomwith
withelectrophilic
electrophilicand
andnucleophilic
nucleophilicproperties
properties
Up
Upto
tofour
fournew
newbonds
bondsand
andone
onestereocenter
stereocentercreated
createdininvery usefulα−acyloxy
veryuseful α−acyloxyamides
amides
Auxiliary-based
Auxiliary-basedapproaches
approachesbut
butno
noexamples
examplesofofcatalytic
catalyticenantioselective
enantioselectiveprocess!!
process!!Passerini Reaction: Lewis Base Activation of Lewis Acid
Cl3 catalyst turnover
product release Si
O
Lewis base
R2 N 1.5 SiCl4
R catalyst
H Cl (LB*)
activation of Lewis acid
Ln*Cl3SiO
N
R2 R1 [LB2*SiCl3] 0.5 (SiCl6)2–
H Cl
chloride capture 0.5 SiCl4 O
R2 H
SiCl3LB2* SiCl3LB2*
O O
2
0.5 (SiCl6)2–
R R2 H
H N 1
R
Cl
0.5 (SiCl5)2– binding to aldehyde
1
C NR
addition
•activated
•activatedsilyl
silylcation
cationpreferentially
preferentiallybinds
bindscarbonyl
carbonylsubstrate,
substrate,instead
insteadofofthe
theisocyanide
isocyanide
•attenuated
•attenuatedLewis
Lewisacidity
acidityof
ofthe
thesilicon
siliconcenter
centerininimidoyl
imidoylchloride
chlorideresults
resultsfacile
facileturnover
turnover
•catalyst
•catalystturnover
turnoverbecomes
becomesthe therelease
releaseofofthe
theLewis
Lewisbase,
base,instead
insteadofofthe
theLewis
Lewisacid
acidCatalytic Enantioselective Passerini Reaction: Aldehyde Survey
OH
O t-BuNC (1.2 equiv) SiCl3 NaHCO3 (aq) NHt-Bu
+ SiCl4 + catalyst O R
or
R H (1.1 equiv) (5 mol %) CH2Cl2 / -78 °C
R
N
t-Bu 1. MeOH O OH
4h or OMe
Cl 2. NaHCO3 (aq) R
O
OH OH OH OH OH
NHt-Bu OMe NHt-Bu NHt-Bu NHt-Bu
O O O O O
MeO F3C
yield 96% yield 95% yield 89% yield 89% yield 93%
er: > 99/1 er: > 99/1 er: 98.3/1.7 er: 96.5/3.5 er: > 99/1
OH OH OH OH OH
NHt-Bu OMe O NHt-Bu NHt-Bu NHt-Bu
O O O O O
yield 81% yield 71% yield 83% yield 53% yield 76%
er: 97.8/2.2 er: 97.9/2.1 er: 95.9/4.1 er: 87.1/12.9 er: 77.0/23.0
OH OH
NHt-Bu OMe Me Me
O O N O O N
P P
yield 92% yield 88% N N N N
er: 81.9/18.1 er: 81.8/18.2 Me Me Me Me
cat.Cast and Sponsors
Xiping
XipingSu John
Su JohnHeemstra,
Heemstra,Jr.
Jr.
Robert
RobertA.A.Stavenger Won-jin
Stavenger Won-jinChung
Chung
Son
SonPham William
Pham WilliamCollins
Collins
Jiping
JipingFu Tyler
Fu TylerWilson
Wilson
Yu
YuFan Peter
Fan PeterYao
Yao
Greg
GregBeutner
Beutner
Tommy
TommyBui Dr.
Bui Dr.Brian
BrianEklov
Eklov
Dr.
Dr.Moballigh
MoballighAhmad
Ahmad
Dr.
Dr.Diane
DianeCoe
Coe
Dr.
Dr.Brian
BrianGriedel
Griedel
Dr.
Dr.Stephen
StephenB. B.D.
D.Winter
Winter Funding
Funding
Dr.
Dr.Ken-Tsung
Ken-TsungWong
Wong
Prof.
Prof.Yutaka
YutakaNishigaichi
Nishigaichi National
NationalScience
ScienceFoundation
Foundation
Dr.
Dr.Sunil
SunilK.
K.Ghosh
Ghosh Eastman
EastmanKodak
KodakCompany
Company
Dr.
Dr.Thomas
ThomasWynn
Wynn Boehringer
BoehringerIngelheim
IngelheimPharmaceuticals
Pharmaceuticals
Dr.
Dr.Steven
StevenMacNeil
MacNeil Ministry
MinistryofofScience
Scienceand
andEducation
Education(Japan)
(Japan)
Dr.
Dr.Marcel
MarcelSchleusner
Schleusner GlaxoSmithKline
GlaxoSmithKline(UK)
(UK)
Dr.
Dr.Martin
MartinEastgate
Eastgate Pharmacia Corporation
Pharmacia Corporation
Dr.
Dr.Michael
MichaelEdwards
Edwards Abbott
AbbottLaboratories
LaboratoriesYou can also read
