CTL Frustrated Lewis Pairs

The Chemistry of Frustrated Lewis Pairs
MacMillan Group Meeting

Tracy Liu
4 December 2013
RR
B
R
R
N
R
R
RR
B
R
R
N
R
R
RR
B
R
R
N
R
R
R
R
B
R
RR
B
R
N
RR
B
R
H2
R
R
B
R
R
B
R
RR
B
R
N
RR
B
R
H2
R
heat
R
R
B
R
Number of Publications
Rapid Emergence of FLP Chemistry
100
80
60
40
20
0
2000
2006
2009
2012
289 total publications in FLP chemistry

Leading Academics:
Douglas W. Stephan, University of Toronto, Canada
Gerhard Erker, Westflische Wilhelms-Universitt Mnster, Germany
Imre Ppai, Chemical Research Cent. of the Hungarian Acad. of Sciences, Hungary
The Advent of FLP Chemistry

1942 - Brown makes an
interesting observation
Me
N
Me
Me
BF 3
BF 3
BMe 3
No Reaction
Me
Brown, H. C.; Schlesinger, H. I. JACS, 1942, 64, 325-329.

Me
N
Me
Me
BF 3
BF 3
BMe 3
No Reaction
Me
Brown, H. C.; Schlesinger, H. I. JACS, 1942, 64, 325-329.

1959 - Wittig finds PPh 3 and BPh 3

does not form an adduct
Mg
PPh 3
Br
PPh 3
BPh 3
BPh 3
No formation of classical Lewis Acid/Base adduct
Wittig, G.; Benz, E. Chem. Ber., 1959, 92, 1999-2013.

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

coining of the term "FLP"
BPh 3
[Ph 3C-]Na+
Ph 3C
and
BPh 3
Ph 3C
BPh 3
no observation of polybutadiene
Tochtermann, W. ACIE, 1966, 5, 351-371.

2006 - Stephan finds FLPs
can reversibly split H 2


Me
F
F
Me
PH
B(C 6F 5)3
(Me 3C6H 2)2P
B(C 6F 5)2
H
Me 2
Me 2SiHCl
F
H
(Me 3C6H 2)2P
B(C 6F 5)2
H
F
Welch, G. C.; San Juan, R. R.; Masuda, J. D.; Stephan, D. W. Science, 2006, 314, 1124-1126.



F
H
(Me 3C6H 2)2P
heat
B(C 6F 5)2
(Me 3C6H 2)2P
B(C 6F 5)2
H2
H
F



F
H
(Me 3C6H 2)2P
heat
B(C 6F 5)2
(Me 3C6H 2)2P
B(C 6F 5)2
H2
H
F



2007 - FLPs catalytically

perform hydrogenations
B(C 6F 5)2
(tBu) 2P
N
tBu
(5 mol %)
1 atm H 2
Ph
HN
tBu
Ph
98%
(C 6F 5)Ph2P (20 mol %)
B(C 6F 5)3 (20 mol %)
Ph
Ph
5 bar H 2
Me
Ph
Ph
99%
Chase, P.A.; Welch, G. C.; Jurca, T.; Stephan, D. W. ACIE, 2007, 46, 8050-8053.
Greb, L.; Ona-Burgos, P.; Schirmer, B.; Grimme, S.; Stephan, D. W.; Paradies, J. ACIE, 2012, 51, 10164-10168.


2008 - FLPs reversibly

bind CO2

tBu 3P
B(C 6F 5)3

CO2, 25 C
(tBu) 3P
B(C 6F 5)3
O
-CO2, 80 C
vacuum, 5 hrs
Mmming, C. M.; Otten, E.; Kehr, G.; Frlich, R.; Grimme, S.; Stephan, D. W.; Erker, G. ACIE, 2009, 48, 6643-6646.



bind CO2


Me
Me
B(C 6F 5)2
OMe
Me
N
2010 - Asymmetric
hydrogenation
of imines with FLPs
Ph
OMe
HN
(5 mol %)
Me
tBu 3P (5 mol %)
25 bar H 2
Me
>99%
81% ee
Chen, D.; Wang, Y.; Klankermeyer, J. ACIE, 2010, 49, 9475-9578.




bind CO2
2010 - Asymmetric
hydrogenation
of imines with FLPs

I. Theories on the Mechanism of H 2 Activation

II. Applications of FLPs in Hydrogenation Reactions
and Storage of Small Molecules




bind CO2
2010 - Asymmetric
hydrogenation
of imines with FLPs


Two Competing Models on the Mechanism of H 2 Activation
H
A
R
R
D * donation
H
H
D
R
R
R
A donation
Electron Transfer Model
R 3P
BR 3
Electric Field Model
Initial Hypotheses on the Mechanism of H 2 Activation
tBu 3P
B(C 6F 5)3
Mes 3P
B(C 6F 5)3
H2
1 atm
H2
1 atm
[tBu 3PH][HB(C 6F 5)3]
[Mes 3PH][HB(C 6F 5)3]
Welch, C.; Stephan, D. W. JACS, 2007, 129 , 1880-1881.
Initial Hypotheses on the Mechanism of H 2 Activation
tBu 3P
B(C 6F 5)3
Mes 3P
B(C 6F 5)3
H2
[tBu 3PH][HB(C 6F 5)3]
1 atm
H2
[Mes 3PH][HB(C 6F 5)3]
1 atm
R 3P
H
BR 3
H
(H 2) p (B)
PR 3 + BR 3
R 3P
[R 3PH][HBR 3]
H
BR 3
LP (P) * (H 2)
Welch, C.; Stephan, D. W. JACS, 2007, 129 , 1880-1881.
First DFT Study on the Mechanism of H 2 Activation
tBu 3P ------ B(C 6F 5)3
Multiple H-bonds between CH---F groups give rise to a preorganized complex

Non-directional dispersion forces between tBu and C6F 5 groups render the complex flexible
Rokob, T. A.; Hamza, A.; Stirling, A.; Sos, T.; Ppai, I. ACIE, 2008, 120 , 2469-2472.
tBu 3P --- HH --- B(C 6F 5)3
Located T.S. features a nearly linear PHHB axis

H 2 bond elongated from 0.74 A to 0.79 A indicative of an early T.S.
10.4 kcal/mol higher than tBu 3P---B(C 6F 5)3 + H 2
tBu 3P --- HH --- B(C 6F 5)3
Discovered significant H 2 polarization

Electron transfer proceeds via simultaneous tBu 3P (H 2) and (H 2) B(C 6F 5)3 donation

The Electron Transfer Model
Non-bonding interactions between bulky substituents lead to a higher E frustrated complex


Frustration energy, Et, decreases the activation energy and renders hydrogen splitting
facile and highly exothermic via reactant state destabilization


Frustration energy, Et, decreases the activation energy and renders hydrogen splitting
facile and highly exothermic via reactant state destabilization
Non-bonding interactions between bulky substituents stabilizes both the T.S. and product
An Alternative Mechanism of H 2 Activation
Mes
C6F 5
C6F 5
B
C6F 5
Mes
H2
Mes
C6F 5
H
Mes
Ph
Ph
Mes
Mes
Mes
H2
B
Ph
Mes
B
H
Ph
H
Linear T.S. not possible for certain tethered FLPs
Grimme, S.; Kruse, H.; Goerigk, L.; Erker, G. ACIE, 2010, 49, 1402-1405.

Calculated T.S. employing a dispersion corrected DFT model:
(C 6F 5)3B ---- PtBu 3 + H 2
(C 6F 5)2B
PMes 2
H2
Calculated T.S. do not have a linear relationship along PHHB axis
incr. E
2 kcal/mol between
each line
2-D potential E surface for tBu 3P + B(C 6F 5)3 system
incr. E
peak
2 kcal/mol between
each line

artificial T.S.
peak
Ppai's non-dispersion corrected DFT model overestimated the PB bond distance

resulting in a T.S. that is otherwise not present

The Electric Field Model
R 3P
BR 3
Neglect the FLP as a molecular species

and replace it by an electric field
Polarization from electric field generated in
the interior of the FLP cavity allows for H 2 splitting

R 3P
BR 3
Neglect the FLP as a molecular species

and replace it by an electric field
Polarization from electric field generated in
the interior of the FLP cavity allows for H 2 splitting
F = Electric field strength (a.u.)

(1 a.u. = 5.1422 x 1011 Vm-1)
Critical field strength needed for H 2 splitting is 0.05 0.06 a.u.



(1 a.u. = 5.1422 x 1011 Vm-1)
Critical field strength needed for H 2 splitting is 0.05 0.06 a.u.
tBu
C6F 5
P
B
tBu C6F 5
C6F 5
tBu
0.04 - 0.06 a.u.
C6F 5
Mes
P
B
C6F 5
Mes
0.04 - 0.06 a.u.


H-bonding interactions form the FLP while non-directional dispersion forces instill
flexibility allowing H 2 entry termed the "preparation step"

Activation energy is the "preparation step"; after entrance H 2 splitting is barrierless

Activation energy is the "preparation step"; after entrance H 2 splitting is barrierless
No molecular orbitals arguments invoked; believe this accounts for the similar reactivity
of chemically different FLPs
The Electron Transfer Model Revisited
C6F 5
tBu
P
tBu
tBu
tBu
B
C6F 5
C
C6F 5
C6F 5
N
N
tBu
C6F 4H
B
C6F 5
C6F 5
Mes
B
C6F 4H
Rokob, T. A.; Bak, I.; Stirling, A.; Hamza, A.; Ppai, I. JACS, 2013, 135 , 4425-4437.
C6F 5
tBu
P
tBu
tBu
tBu
B
C6F 5
C
C6F 5
C6F 5
N
N
tBu
C6F 4H
B
C6F 5
C6F 5
Mes
B
C6F 4H

(1 a.u. = 5.1422 x 1011 Vm-1)
At the "critical field" of 0.06 a.u., the activation energy is 75 kcal/mol

(1 a.u. = 5.1422 x 1011 Vm-1)

Only at higher electric fields, 0.09 a.u. and above, does the activation energy lower
to a reasonable range (20 kcal/mol or lower)

(1 a.u. = 5.1422 x 1011 Vm-1)

Only at higher electric fields, 0.09 a.u. and above, does the activation energy lower
to a reasonable range (20 kcal/mol or lower)
Only at field strengths above 0.1 a.u., does H 2 splitting become "barrierless"
C6F 5
tBu
P
tBu
tBu
tBu
B
C6F 5
C
C6F 5
C6F 5
N
N
tBu
C6F 4H
B
C6F 5
C6F 5
Mes
B
C6F 4H
C6F 5
tBu
P
tBu
tBu
tBu
B
C6F 5
C
C6F 5
C6F 5
N
N
tBu
C6F 4H
B
C6F 5
C6F 5
Mes
B
C6F 4H
C6F 5
tBu
P
tBu
tBu
tBu
B
C6F 5
C
C6F 5
C6F 5
N
N
tBu
C6F 4H
B
C6F 5
C6F 5
Mes
B
C6F 4H
EFs within FLP cavities are not homogeneous and are not always strong enough to effect H 2 splitting
Me
tBu
P
tBu
tBu
tBu
C
N
tBu
Mes
N
+ B(C 6F 5)3
+ B(C 6F 5)3
+ B(C 6F 5)3
Mes
C6F 5
tBu
C6F 5
Me
C6F 5
C6F 5
P
Me
Me
tBu
Ph
P
Ph

0.09 a.u.
For none of the FLPs studied is the EF along the H 2 axis high enough to permit H 2 splitting
Me
tBu
P
tBu
tBu
tBu
C
N
tBu
Mes
N
+ B(C 6F 5)3
+ B(C 6F 5)3
+ B(C 6F 5)3
Mes
C6F 5
tBu
C6F 5
Me
C6F 5
C6F 5
P
Me
Me
tBu
Ph
P
Ph
H
A
D * donation
H
H
R
R
H
H
D
R
R
R
R
A donation
Use of dispersion corrected DFT basis set results in a generally bent DHHA geometry
explained by frontier orbitals aligning themselves for optimal orbital overlap
Deviation from ideal 180 D---H 2 angle and 90 H 2---A angle due to polarization of the
/ * orbitals of H 2




bind CO2
2010 - Asymmetric
hydrogenation
of imines with FLPs


The First Example of Catalytic Hydrogenations with FLPs

Hydrogenation of Imines, Nitriles, and Aziridines
F
PR 2
(C 6F 5)2B
F
1 R = Mes
2 R = tBu
N
Ph
tBu
5 mol % cat.
1 atm H 2
80 C
HN
tBu
Ph
79% (1)
98% (2)
Chase, P. A.; Welch, C.; Jurca, T.; Stephan, D. W. ACIE, 2007, 46, 8050-8053.

F
PR 2
(C 6F 5)2B
F
1 R = Mes
2 R = tBu
tBu
5 mol % cat.
1 atm H 2
80 C
Ph
HN
tBu
Ph
79% (1)
98% (2)
Ph
N
Ph
SO2Ph
Ph
97% (1)
87% (2)
Ph
Ph
N
Ph
88% (1)
Ph
98% (1)

Catalytic hydrogenation only possible for sterically hindered imines
F
Mes 2P
B(C 6F 5)2
F
N
Ph
Ph
F
HN
5 mol %
5 atm H 2
120 C
Ph
Ph
5%

F
Mes 2P
B(C 6F 5)2
F
N
Ph
Ph
F
HN
5 mol %
5 atm H 2
120 C
Ph
Ph
5%
F Bn
H
N
Mes 2P
Bn
B(C 6F 5)2
F
adduct formation between Lewis Basic product

and FLP shuts down catalytic activity

F
Mes 2P
B(C 6F 5)2
F
Ph
F
HN
5 mol %
5 atm H 2
120 C
Ph
Ph
Ph
5%
Protecting Imine with B(C 6F 5)3 recovers catalytic activity

F
Mes 2P
(C 6F 5)3B
Ph
B(C 6F 5)2
F
Ph
5 mol %
5 atm H 2
120 C
(C 6F 5)3B
Ph
Ph
57%

Catalytic hydrogenation only possible for B(C 6F 5)3 protected nitriles
Mes 2P
B(C 6F 5)2
B(C 6F 5)3
5 mol %
5 atm H 2
120 C
F
HN
B(C 6F 5)3
R = Me, 75%
R = Ph, 84%
Only the amine is isolated (cannot isolate imine)

F
Mes 2P
B(C 6F 5)2
F
H2
F
H
Mes 2P
B(C 6F 5)2
H
F

F
Mes 2P
B(C 6F 5)2
F
F
H
H2
H
Mes 2P
H
Mes 2P
B(C 6F 5)2
B(C 6F 5)2
Ph
F
proton transfer
Ph

F
HN
Mes 2P
F
N
B(C 6F 5)2
F
Ph
H2
H
Mes 2P
H
Mes 2P
B(C 6F 5)2
B(C 6F 5)2
Ph
F
proton transfer
Ph

F
HN
Mes 2P
F
N
B(C 6F 5)2
F
Ph
H2
H
Mes 2P
H
Mes 2P
B(C 6F 5)2
B(C 6F 5)2
Ph
F
proton transfer
Ph
Proton transfer precedes hydride delivery

Increased rates with electron rich imines (R = tBu, 1 hr vs. R = SO2Ph, >10 hrs)

F
Mes 2P
B(C 6F 5)2
F
H2
F
H
Mes 2P
B(C 6F 5)2
H
F

F
Mes 2P
B(C 6F 5)2
F
F
(C 6F 5)3B
Ph
H2
H
Mes 2P
Mes 2P
B(C 6F 5)2
B(C 6F 5)2
H
F
hydride delivery
(C 6F 5)3B
Ph

F
(C 6F 5)3B
H
N
Mes 2P
Ph
B(C 6F 5)2
F
Ph
(C 6F 5)3B
H2
H
Mes 2P
Mes 2P
B(C 6F 5)2
B(C 6F 5)2
H
F
hydride delivery
(C 6F 5)3B
Ph

F
(C 6F 5)3B
H
N
Mes 2P
Ph
B(C 6F 5)2
F
Ph
(C 6F 5)3B
H2
H
Mes 2P
Mes 2P
B(C 6F 5)2
B(C 6F 5)2
H
F
hydride delivery
(C 6F 5)3B
Ph
Hydride delivery precedes proton transfer
An Improved FLP
Hydrogenation of Ketimines and Enamines
H2
Mes 2P
B(C 6F 5)2
B(C 6F 5)3
Mes 2P
H
N
Ph
tBu
Mes 2P
B(C 6F 5)2
HN
20 mol %
2.5 bar H 2
r.t.
tBu
Ph
87%
Spies, P.; Schwendemann, S.; Lange, S.; Kehr, G.; Frhlich, R.; Erker, G. ACIE, 2008, 47, 7543-7546.
An Improved FLP
Hydrogenation of Ketimines and Enamines
H2
Mes 2P
B(C 6F 5)2
B(C 6F 5)3
Mes 2P
H
Mes 2P
tBu
B(C 6F 5)2
HN
20 mol %
2.5 bar H 2
r.t.
Ph
tBu
Ph
87%
O
N
N
Ph
tBu
70%
(5 mol %)
70%
(3 mol %)
Me
70%
(5 mol %)
70%
(10 mol %)
Spies, P.; Schwendemann, S.; Lange, S.; Kehr, G.; Frhlich, R.; Erker, G. ACIE, 2008, 47, 7543-7546.
Catalytic Hydrogenations Using only B(C6F 5 )3

Hydrogenation of Imines
N
Ph
tBu
B(C 6F 5)3 (cat.)

4 atm H 2
toluene, 25 C
(C 6F 5)3B
Ph
tBu
H 2N
4 atm H 2
toluene, 80 C
tBu
HB(C 6F 5)3
Ph
Chase, P. A.; Jurca, T.; Stephan, D. W. Chem. Comm., 2008, 1701-1703.

N
Ph
tBu
B(C 6F 5)3 (cat.)

4 atm H 2
toluene, 25 C
(C 6F 5)3B
Ph
tBu
H 2N
4 atm H 2
toluene, 80 C
tBu
HB(C 6F 5)3
Ph
Isolation of zwitterion suggests adduct formation with the product is reversible

and that the B(C 6F 5)3 catalyst can be recycled

N
Ph
tBu
B(C 6F 5)3 (cat.)

4 atm H 2
toluene, 25 C
(C 6F 5)3B
tBu
H 2N
4 atm H 2
toluene, 80 C
Ph
tBu
HB(C 6F 5)3
Ph

N
Ph
tBu
5 mol % B(C 6F 5)3

5 atm H 2
120 C
HN
tBu
Ph
89%

N
Ph
tBu
B(C 6F 5)3 (cat.)

4 atm H 2
toluene, 25 C
(C 6F 5)3B
tBu
H 2N
4 atm H 2
toluene, 80 C
Ph
tBu
HB(C 6F 5)3
Ph

B(C 6F 5)3
H2 +
N
R'
H
HB(C 6F 5)3
R'

N
Ph
tBu
B(C 6F 5)3 (cat.)
(C 6F 5)3B
4 atm H 2
toluene, 25 C
tBu
H 2N
4 atm H 2
toluene, 80 C
Ph
tBu
HB(C 6F 5)3
Ph

B(C 6F 5)3
H2 +
N
R'
H
R N B(C 6F 5)3
H
R'
H
HB(C 6F 5)3
R'

N
Ph
tBu
B(C 6F 5)3 (cat.)
(C 6F 5)3B
4 atm H 2
toluene, 25 C
tBu
H 2N
4 atm H 2
toluene, 80 C
Ph
tBu
HB(C 6F 5)3
Ph

NH
B(C 6F 5)3
H2 +
R'
N
R'
H
R N B(C 6F 5)3
H
R'
H
HB(C 6F 5)3
R'
Expanding the Scope to Oxygenated Substrates

Hydrogenation of Silyl Enol Ethers
PPh 2 PPh 2
H 2, r.t.
PPh 2 PPh 2
HB(C 6F 5)3
H 2, 60 C
Wang, H.; Frhlich, R.; Kehr, G.; Erker, G. Chem. Comm., 2008, 5966-5968.

PPh 2 PPh 2
H 2, r.t.
PPh 2 PPh 2
HB(C 6F 5)3
H 2, 60 C
OTMS
R
OTMS
20 mol % cat.
2 bar H 2, r.t.
R'

B(C 6F 5)3
H 2, r.t.
PPh 2 PPh 2
PPh 2 PPh 2
HB(C 6F 5)3
H2, 60 C
OTMS
R
2 bar H 2, r.t.
OTMS
OTMS
OTMS
OTMS
20 mol % cat.
R
OTMS
93%
OTMS
Me
tBu
Ph
R'
89%
86%
85%
>99%
Studies of Hantzsch Ester with B(C6F 5 )3 Unveils New Substrates

Hydrogenation of N-heterocycles
EtO
O
OEt
Me
N
H
Me
B(C 6F 5)3
-40 C
EtO
OEt
Me
N
H
Me
60%
EtO
HB(C 6F 5)3
-20 C
OEt
H
Me
B(C 6F 5)3
N
H
Me
55%
(70% at r.t.)
Webb, J. D.; Laberge, V. S.; Geier, S. J.; Stephan, D. W.; Crudden, C. M. Chem. Eur. J., 2010, 16 , 4895-4902.
Geier, S. J.; Chase, P. A.; Stephan, D. W. Chem. Comm., 2010, 46, 4884-4886.

EtO
O
OEt
Me
N
H
Me
B(C 6F 5)3
-40 C
EtO
OEt
Me
N
H
Me
EtO
HB(C 6F 5)3
-20 C
60%
OEt
H
Me
B(C 6F 5)3
N
H
Me
55%
(70% at r.t.)
Observation of hydride delivery into pyridinium inspired

experimentation with N-heterocycle substrates

EtO
O
OEt
Me
N
H
Me
B(C 6F 5)3
-40 C
EtO
OEt
Me
N
H
EtO
HB(C 6F 5)3
-20 C
Me
60%
OEt
H
Me
B(C 6F 5)3
N
H
Me
55%
(70% at r.t.)

5 mol % B(C 6F 5)3

N
4 atm H 2, 2 hrs, r.t.

80%
N
H
HB(C 6F 5)3
N
H

EtO
OEt
Me
N
H
B(C 6F 5)3
-40 C
Me
EtO
OEt
Me
N
H
EtO
HB(C 6F 5)3
-20 C
Me
OEt
H
Me
60%
B(C 6F 5)3
N
H
Me
55%

5 mol % B(C 6F 5)3

2 hrs, r.t.
N
H
80%
N
H
80%
Ph
N
H
74%
Me
Me
N
H
88%
N
H
84%
Aromatic Hydrogenation
Hydrogenation of Anilines to Cyclohexylamines
tBu
tBu
NH
Ph
B(C 6F 5)3
H 2, 25 C
tBu
NH 2
Ph
HB(C 6F 5)3
H2
NH 2
HB(C 6F 5)3
110 C
93%
Mahdi, T.; Heiden, Z. M.; Grimme, S.; Stephan, D. W. JACS, 2012, 134 , 4088-4091.
tBu
tBu
NH
Ph
B(C 6F 5)3
tBu
H 2, 25 C
NH 2
NH 2
H2
HB(C 6F 5)3
HB(C 6F 5)3
110 C
Ph
93%
iPr
NH 2
iPr
NH 2
iPr
NH 2
NH 2
Me
OMe
Me
Me
HB(C 6F 5)3
HB(C 6F 5)3
HB(C 6F 5)3
HB(C 6F 5)3
65%, 96 hrs
77%, 36 hrs
61%, 36 hrs
48%, 72 hrs
tBu
tBu
NH
Ph
B(C 6F 5)3
tBu
H 2, 25 C
NH 2
NH 2
H2
HB(C 6F 5)3
HB(C 6F 5)3
110 C
Ph
93%
iPr
iPr
NH 2
NH 2
iPr
NH 2
NH 2
Me
Me
OMe
Me
HB(C 6F 5)3
HB(C 6F 5)3
HB(C 6F 5)3
HB(C 6F 5)3
65%, 96 hrs
77%, 36 hrs
61%, 36 hrs
48%, 72 hrs
Ph
5 mol % B(C 6F 5)3
N
Ph
Ph
H 2, 110 C
H 2N
Ph
HB(C 6F 5)3
Ph
50%, 96 hrs
Hydrogenation of Non-Polar Substrates

Hydrogenation of Olefins
(C 6F 5)Ph2P
B(C 6F 5)3
H2
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
cation posseses much greater bronsted acidity

(C 6F 5)Ph2P
B(C 6F 5)3
H2
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
Ph
20 mol % (C 6F 5)Ph2P
20 mol % B(C 6F 5)3
Ph
Me
Ph
5 bar H 2, r.t.
Ph
99%

(C 6F 5)Ph2P
H2
B(C 6F 5)3
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
Ph
20 mol % (C 6F 5)Ph2P
20 mol % B(C 6F 5)3
Ph
Me
5 bar H 2, r.t.
Ph
Ph
99%
Ph
HB(C 6F 5)3
Me
Ph
Ph N
Ph
Me
Ph
hydride delivery
H HB(C 6F 5)3
69%
Ph
Me
Ph
Ph
NMePh
Ph 2NMe
Friedel Crafts
Ph
Ph
Me
31%

R
R
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
proton transfer
R
Me
HB(C 6F 5)3
hydride delivery
Me
R

R
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
proton transfer
Me
R
Me
HB(C 6F 5)3
hydride delivery
Me
R
Me
Me
96%
85%

R
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
proton transfer
Me
R
Me
HB(C 6F 5)3
Me
Me
96%
hydride delivery
Me
R
Me
MeO
85%
30%

R
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
proton transfer
Me
R
Me
HB(C 6F 5)3
Me
Me
96%
Me
MeO
85%
hydride delivery
Me
R
Me
Cl
30%
10%

R
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
proton transfer
Me
R
Me
HB(C 6F 5)3
Me
Me
hydride delivery
Me
Me
Me
TMS
Me
96%
MeO
85%
Cl
30%
10%
95%

R
[(C 6F 5)Ph2PH] [HB(C 6F 5)3]
Me
proton transfer
Me
R
HB(C 6F 5)3
Me
Me
hydride delivery
Me
Me
Me
TMS
Me
96%
MeO
85%
Cl
30%
10%
95%
99%
Me
Me
Me
Me
Me
99%

Hydrogenation of Alkynes to Cis-Alkenes
NMe 2
B
C6F 5
R'
NMe 2
H
R'
B
C6F 5
Chernichenko, K.; Madarsz, A.; Ppai, I.; Nieger, M.; Leskela, M.; Repo, T. Nat. Chem., 2013, 5, 718-723.

R'
NMe 2
NMe 2
B
H
R'
B
C6F 5
C6F 5
Me
Me
H2
N
H H
R'
B
C6F 5 H

R'
NMe 2
NMe 2
B
C6F 5
Me
Me
H H
R'
R
H2
R'
C6F 5
R'
B
C6F 5 H

NMe 2
C6F 5
C6F 5
R'
H2
Me
N
Me
H F
B
C6F 5 H
F
NMe 2
NMe 2
80 C
H
R'
B
C6F 5
C6F 5
Me
Me
H2
H H
R'
R
R'
B
C6F 5 H

NMe 2
C6F 5
C6F 5
R'
H2
Me
N
Me
H F
B
C6F 5 H
F
NMe 2
NMe 2
80 C
R'
B
C6F 5
C6F 5
NMe 2
D2
C6F 5
H
D
Me
Me
H2
H H
R'
R
R'
R'
B
C6F 5 H
Asymmetric Catalytic Hydrogenation

Me
Me
B(C 6F 5)2
OMe
Me
OMe
Ph
HN
(5 mol %)
Me
Me
tBu 3P (5 mol %)
25 bar H 2
>99%
81% ee
Me
Me C6F 5F
B
Me
H F
N
Ph
Me
favored approach
Me
F
Me F
F
F
F
C6F 5
OMe
H
Me
Me
disfavored approach
Chen, D.; Wang, Y.; Klankermeyer, J. ACIE, 2010, 49, 9475-9578.
Applications in Green Chemistry

Reversible CO 2 Binding
tBu 3P
B(C 6F 5)3
CO2, 25 C
(tBu) 3P
B(C 6F 5)3
O
80 C
vacuum, 5 hrs
-CO2
87%
B(C 6F 5)3
Mes 2P
CO2, 25 C
Mes 2P
B(C 6F 5)3
O
CH2Cl2, > -20 C

-CO2
Mes 2P
B(C 6F 5)3
79%
Mmming, C. M.; Otten, E.; Kehr, G.; Frhlich, R.; Grimme, S.; Stephan, D. W.; Erker, G. ACIE, 2009, 48, 6643-6646.

SO 2 and N 2O Binding
SO2 is a major air pollutant, precursor to acid rain
tBu 3P
B(C 6F 5)3
SO2, 25 C
(tBu) 3P
B(C 6F 5)3
S
80%
B(C 6F 5)3
Mes 2P
SO2, -75 C
Mes 2P
S* O
B(C 6F 5)3
O
Mes 2P
B(C 6F 5)3
83%
Sajid, M. et. al. Chem. Sci., 2013, 4, 213-219.

SO 2 and N 2O Binding
SO2 is a major air pollutant, precursor to acid rain
tBu 3P
B(C 6F 5)3
SO2, 25 C
(tBu) 3P
B(C 6F 5)3
S
80%
B(C 6F 5)3
Mes 2P
SO2, -75 C
Mes 2P
S* O
B(C 6F 5)3
O
Mes 2P
83%
B(C 6F 5)3
N 2O is a minor constituent in the atmosphere, but ~300x more potent as a greenhouse gas
tBu 3P
B(C 6F 5)3
N 2O, 25 C
(tBu) 3P
B(C 6F 5)3
76%
Sajid, M. et. al. Chem. Sci., 2013, 4, 213-219.

Otten, E.; Neu, R. C.; Stephan, D. W. JACS, 2009, 131 , 9918-9919.

Converting CO 2 to Fuels
Addition of Et 3SiH to CO2 in the presence of an FLP efficiently reduces CO2 to CH4
Me
Me
NH 2
Me
HB(C 6F 5)3
Me
Berkefeld, A.; Piers, W. E.; Parvez, M. JACS, 2010, 132 , 10660-10661.

B(C 6F 5)3
TMPH
O
H
CO2
Me
Me
NH 2
Me
HB(C 6F 5)3
Me

Et 3SiH + B(C 6F 5)3
B(C 6F 5)3
TMPH
O
Et 3Si
H
B(C 6F 5)3
CO2
O
O
H
SiEt 3
Me
Me
NH 2
Me
HB(C 6F 5)3
Me

B(C 6F 5)3
TMPH
O
H
Et 3Si
H
B(C 6F 5)3
CO2
O
SiEt 3
O
H
Me
Me
NH 2
Me
Et 3Si
B(C 6F 5)3
B(C 6F 5)3
O
O
Et 3Si
HB(C 6F 5)3
Me
SiEt 3
H

B(C 6F 5)3
TMPH
O
H
Et 3Si
H
B(C 6F 5)3
CO2
O
SiEt 3
Me
Me
NH 2
Me
Et 3Si
O
O
Et 3Si
Me
B(C 6F 5)3
B(C 6F 5)3
SiEt 3
HB(C 6F 5)3
Et 3Si
B(C 6F 5)3
H
Et 3Si
H
H
(Et 3Si)2O
+ B(C 6F 5)3

B(C 6F 5)3
TMPH
O
H
Et 3Si
H
B(C 6F 5)3
CO2
O
SiEt 3
Me
Me
NH 2
Me
Et 3Si
O
O
Et 3Si
Me
B(C 6F 5)3
B(C 6F 5)3
SiEt 3
HB(C 6F 5)3
Et 3Si
B(C 6F 5)3
H
Et 3Si
H
(Et 3Si)2O
+ B(C 6F 5)3
Et 3Si
B(C 6F 5)3
HCH 3
H
(Et 3Si)2O
+ B(C 6F 5)3
Limitations and Future Directions
Currently cannot hydrogenate aldehydes or ketones catalytically

O
H
Me
Me
N
H2
Me
Me
HB(C 6F 5)3
Me
20 C, 1hr
Me
N
H2
Me
B(C 6F 5)3
Me
95%
Discovery of better FLP catalysts for asymmetric induction; expanding the scope
to olefin hydrogenations
Hydrogen gas storage - currently FLPs can achieve 0.25 wt % H 2; whereas to be practical
need 6 - 9 wt % H 2 (i.e. ammonia-borane)
Sumerin, V.; Schulz, F.; Nieger, M.; Leskel, M.; Repo, T.; Rieger, B. ACIE, 2008, 47, 6001-6003.
Summary
Electron Transfer Model that Invokes Frontier Molecular Orbitals
Electric Field Model that disregards Frontier Molecular Orbitals
Secondary non-covalent interactions play key role in lowering H 2 activation barrier
II. Applications of FLPs in Hydrogenation Reactions and Storage of Small Molecules

Catalytic hydrogenation of imines, enamines, nitriles, aziridines, silyl enol ethers,
cyclic ethers, alkenes, alkynes, ynones
Stoichiometric hydrogenations of aldehydes, ketones
Asymmetric imine hydrogenations
Advances in area of green chemistry

CTL Frustrated Lewis Pairs

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CTL Frustrated Lewis Pairs

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The Chemistry of Frustrated Lewis Pairs

MacMillan Group Meeting

Rapid Emergence of FLP Chemistry

289 total publications in FLP chemistry

The Advent of FLP Chemistry

Brown, H. C.; Schlesinger, H. I. JACS, 1942, 64, 325-329.

The Advent of FLP Chemistry

Brown, H. C.; Schlesinger, H. I. JACS, 1942, 64, 325-329.

The Advent of FLP Chemistry

1959 - Wittig finds PPh 3 and BPh 3

No formation of classical Lewis Acid/Base adduct

Wittig, G.; Benz, E. Chem. Ber., 1959, 92, 1999-2013.

The Advent of FLP Chemistry

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

Tochtermann, W. ACIE, 1966, 5, 351-371.

The Advent of FLP Chemistry

1942 - Brown makes an

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

(Me 3C6H 2)2P

(Me 3C6H 2)2P

The Advent of FLP Chemistry

1942 - Brown makes an

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

(Me 3C6H 2)2P

(Me 3C6H 2)2P

The Advent of FLP Chemistry

1942 - Brown makes an

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

(Me 3C6H 2)2P

(Me 3C6H 2)2P

The Advent of FLP Chemistry

1942 - Brown makes an

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

2007 - FLPs catalytically

The Advent of FLP Chemistry

1942 - Brown makes an

2008 - FLPs reversibly

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

2007 - FLPs catalytically

The Advent of FLP Chemistry

1942 - Brown makes an

2008 - FLPs reversibly

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

2007 - FLPs catalytically

Chen, D.; Wang, Y.; Klankermeyer, J. ACIE, 2010, 49, 9475-9578.

The Advent of FLP Chemistry

1942 - Brown makes an

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

2008 - FLPs reversibly

2007 - FLPs catalytically

I. Theories on the Mechanism of H 2 Activation

The Advent of FLP Chemistry

1942 - Brown makes an

1966 - Tochtermann reports Ph 3Cand BPh 3 trap across olefins;

2008 - FLPs reversibly

2007 - FLPs catalytically

I. Theories on the Mechanism of H 2 Activation

Two Competing Models on the Mechanism of H 2 Activation

Electron Transfer Model

Electric Field Model

Initial Hypotheses on the Mechanism of H 2 Activation

[tBu 3PH][HB(C 6F 5)3]

[Mes 3PH][HB(C 6F 5)3]

Welch, C.; Stephan, D. W. JACS, 2007, 129 , 1880-1881.