Download document 8195554

Chem 634 Fall 2014
Reduction of C–C π-Bonds (Continued)
Announcements
•  Midterms are not yet graded.
•  Presentations on Sat, Nov 22 (soon!).
•  Colloquium: Student-Invited Seminar!!!
Enantioselective Alkene Hydrogenation Using Ruthenium
•  L2Ru(II)(OAc)2 are very effective at hydrogenating functionalized alkene.
Unsaturated Carboxylic Acids:
CO2H
Me
cat. [Ru-(S)-BINAP(OAc)2]
MeOH, 13 atm H2
CO2H
MeO
MeO
97% ee
(S)-Naproxen
Me
Me
CO2H
Me
cat. [Ru-(R)-BIPHEMP(OAc)2]
MeOH, 180 atm H2
F
CO2H
F
Me
Me
CO2H
cat. [Ru-(S)-H8BINAP(OAc)2]
MeOH, 1.5 atm H2
Me
94% ee
Me
Me
CO2H
97% ee
Mechanism for Ruthenium Cat. Hydrogenation of Alkenes
O
Me
R
HO
O
O
H R
R
HO
P
*
R
O
Ru
O
O
P
P
O
Me
P
*
R
O
Ru
*
R
O
Ru
P
O
O
O
R
O
P
Me
R
H2
O
R
H
2 HOR
H
HO2CR
P
*
P
R
R
H
O R
Ru
R
O
O
P
P
*
R
O
H
*
H
HOR
P
H
O R
Ru
O
O
P
HOR
R
O
H H
O
Ru
O
O
Me
R
R
HO2CR
R
Halpern
Allylic Alcohols Also Effective Substrates
Me
Me
Me
cat. [Ru(S-BINAP)(CF3CO2)2]
OH
30 atm H2, rt
Me
Me
Me
OH
96% ee
Me
Me
cat. [Ru(S-TolBINAP)(OAc)2]
Me
30 atm H2, rt
OH
Me
Me
Me
OH
98 % ee
•  Homoallylic alcohols are also reasonable substrates, but not longer homologues.
Me
cat. [Ru(S-BINAP)(OAc)2]
Me
OH
Me
100 atm H2, rt
Me
Me
OH
Me
92 % ee
Me
Me
Me
cat. [Ru(S-BINAP)(OAc)2]
OH
no reaction
100 atm H2, rt
Noyori JACS 1987,109,1596.
Enantioselective Alkene Hydrogenation with Iridium
Me
cat. [Ir]BArf
Me
50 atm H2
97% ee
MeO
Me
Me
cat. [Ir]BArf
MeO
[Ir]BArf =
50 atm H2
Me
Me
Me
CF3
O
Me
otol2P
N
Ir
B
tBu
CF3
81% ee
cat. [Ir]BArf
CO2Et
Me
50 atm H2
CO2Et
Me
84% ee
Pfaltz ACIE 1998, 37, 2897
•  Tri-substituted alkenes work best.
•  First example of asymmetric tetra-substituted alkene hydrogenation.
4
Enantioselective Alkene Hydrogenation with Iridium
Me
Me
Me
cat. [Ir]BArf
Me
50 atm H2
MeO
MeO
AcO
Me
Me
Me
Me
93% ee
Me
[Ir]BArf =
Me
Me
cat. [Ir]BArf
50 atm H2
AcO
Me
Me
Me
Me
O
otol2P
Me
CF3
N
B
Ir
Ph
CF3
4
Me
Me
>98% de
Pfaltz Science 2006, 311, 642.
Other Reducing Agents
Transfer Hydrogenation
Organic source of "H2”
O
O
H
Me
H
O
H
O
HNEt3
H
Pd/C
Me
Me
Me
Also,
" -2H2"
" -H2"
Me
Me
Diimide
N N
H
H
H
H
Reagent Prepared In Situ From
1) KO2C-N=N-CO2K/ AcOH
2) H2N-NH2/ NaIO4/ EtOH
3) etc
Mech:
N N
H
H
N
H
N
H
Pros)
Cis > trans
Strained > non-Strained
tolerates NO2, C=O, cyclopropyl, Bn, Cbz, etc
Cons)
Can explode - use w/ caution
Alkyne Reductions
Pd/C/Pt/C etc
R
R'
H
H
R'
R
H
R' = H or alkyl, aryl
H
Lindlar Catalyst (Semi-hydrogenation)
Pd/CaSO4
R
R'
N
H
H
R
R'
Cis
•  Works best with non-sterically demanding systems.
•  Quinoline is a poison.
•  Also lead can be used.
Dissolving Metal Reduction of Alkynes
Li/NH3
R
R'
must not have aryl's
R
R'
trans is major
Red-Al Reduction of Propargyl Alcohols
H
H2O
Red-Al
R'
OH
Must be propargylic alcohol
R'
Al O
R2
H
R
OH
H
Thermodynamic Product
Radical Mechanism
Denmark JOC, 1982, 47, 4595
A Twist
Red-Al
R'
OH
OH
I
NIS
H
R
O
N I
H
O
R'
Al O
Diimide With Alkynes
R
H
+
R
H
N
N
fast
R
H
N2H2
R
R
H
slow
R
Birch Reduction
H
H
R
Na/NH3
R
H
or Li/NH3
H
1,4 diene
Mechanism:
Na/NH3
R
or Li/NH3
R
H
H
H
R
H-NH2
M+
M
H
R
R
H
H
-MNH2
R
H
H
R
RO-H
or
R-X
H
H
R
H
H
1,4 diene
Regiochemistry - Stability of First Radical
H
OMe
H
H
H
OMe
OMe
Li
then H-NH2
H H
or other EDG
Extended Radical
O
O
OMe
or other EWG
OMe
Li
then H-NH2
O
H
H
H
captodatively stabilized
(push-Pull)
H
H
OMe
Arene Hydrogenation
Pt/C, Rh/C, Ru/C
R
High Pressure
H2
forcing conditions
H
H
H
H
H
H
R
H
H H
H
Hydroboration
R
NaOH
R
R'
retension
Br2
R
NaOH
R
R
R'2BH
R'
R
R
R
H
BR2
R'
OH
H2O2
O
H2N S OH
O
Br
R'
R
NH2
R
R'
retension
TPAP/NMO
R
O
R
R'
Hydroboration
Regiochemistry:
Hydridic
δ−
H B R
δ+
R
R
Me
H
R
1) B2H6
2) H2O2
BR2
Me H
OH
Other Hydroboration Reagents
HBCl2
BH
9-BBN =
O
catechol borane (BCat) =
B H
O
pinicol borane (BPin) =
Me
Me
O
B H
Me
Me
O
Stereoselectivity
Small Hydroborating Agent:
Me
RL
Me
1) B2H6
RL
2) H2O2 /NaOH
RM
OH
RM
RL
RM
H
Me
Vs
RL
Me
H
H
RM
BH2
Favored
RL
Me
H
BH2
H
RM
Stereoselectivity
Large Hydroborating Agent:
Me
Me
1) 9BBN
RL
RL
2) H2O2 /NaOH
RM
H
RM
RL
Vs
Favored
H
H
B
Me
RL
Me
RM
H
RL
RM
RM
B
H
Me
OH
H
B
Asymmetric Hydroboration
H
(-) IPC2B-H
Me
B H
1.
2
Me
Me
2) H2O2 /NaOH
HO
Me
Me
98% ee
Asymmetric Hydroboration
O
OH
B H
O
Me
Rh(I)/L*
Major
Me
N
BINAP 98% ee
PPh2
92% ee
Fe
PCy2
PPh2
92% ee
Hydroboration of Alkynes
Terminal:
O
B H
H
O
Me
O
B
Me
O
H
Pd(0) PhI
H
Ph
Me
H
Hydroboration of Alkynes
Internal - Steric Control:
Me
Me
(Sia)2BH
Me
Me
BR2
Me
Me
Me
BH
Me
2
disamylborane
Me
Hydroboration of Alkynes
Note:
R1
R2
H
Cy2BH
BCy2
BCy2
R1
+
H
R1
R2
R2
AcOH 1 equiv required
H
H
R1
R2
Good way to get selective reduction