Module 8 - Asymmetric Hydrosilylation and Related Reactions Notes | EduRev

: Module 8 - Asymmetric Hydrosilylation and Related Reactions Notes | EduRev

 Page 1


NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 1 of 58 
Module 2    Asymmetric Carbon-Carbon Bond Forming 
Reactions 
Lecture 5  
2.1 Enantioselective Ene and Cycloaddition Reactions 
Alder-ene and Diels-Alder reactions are six electron pericyclic processes 
between a “diene” or an alkene bearing an allylic hydrogen and an electron-
deficient multiple bond to form two bonds ? ? bond. 
The lecture covers the examples of recent developments in enantioselective 
intermolecular Alder-ene glyoxylates with alkenes. Few studies on intra- and 
intermolecular Diels-Alder type reactions are also covered in the latter part of 
the lecture.  
2.1.1 Carbonyl-Ene Reaction 
Chiral Lewis acid catalyzed enantioselective ene reaction is one of the efficient 
methods for atom economical carbon-carbon bond formation. For example, Ti-
BINOL prepared in situ catalyzes efficiently the carbonyl-ene reaction of 
glyoxylate with ?-methylstyrene in the presence of molecular sieves with high 
enantioselectivity (Scheme 1). 
Page 2


NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 1 of 58 
Module 2    Asymmetric Carbon-Carbon Bond Forming 
Reactions 
Lecture 5  
2.1 Enantioselective Ene and Cycloaddition Reactions 
Alder-ene and Diels-Alder reactions are six electron pericyclic processes 
between a “diene” or an alkene bearing an allylic hydrogen and an electron-
deficient multiple bond to form two bonds ? ? bond. 
The lecture covers the examples of recent developments in enantioselective 
intermolecular Alder-ene glyoxylates with alkenes. Few studies on intra- and 
intermolecular Diels-Alder type reactions are also covered in the latter part of 
the lecture.  
2.1.1 Carbonyl-Ene Reaction 
Chiral Lewis acid catalyzed enantioselective ene reaction is one of the efficient 
methods for atom economical carbon-carbon bond formation. For example, Ti-
BINOL prepared in situ catalyzes efficiently the carbonyl-ene reaction of 
glyoxylate with ?-methylstyrene in the presence of molecular sieves with high 
enantioselectivity (Scheme 1). 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 2 of 58 
Scheme 1 
Besides the early transition metal based Lewis acid catalysts, square planar 
dicationic late transition metal complexes bearing C
2
-symmetric diphosphine 
ligands have also been considerably studied as chiral Lewis acids for carbonyl-
ene reactions. For example, the isolated MeO-BIPHEP-Pd complex 1a bearing 
electron withdrawing benzonitrile as the labile, stabilizing ligands has been 
used for the ene reaction of ethyl glyoxylate with up to 81% ee (Scheme 2). The 
isolated 1a exhibits more catalytic activity compared to that 1b which is in situ 
generated although both offer similar enantioselectivity. 
Page 3


NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 1 of 58 
Module 2    Asymmetric Carbon-Carbon Bond Forming 
Reactions 
Lecture 5  
2.1 Enantioselective Ene and Cycloaddition Reactions 
Alder-ene and Diels-Alder reactions are six electron pericyclic processes 
between a “diene” or an alkene bearing an allylic hydrogen and an electron-
deficient multiple bond to form two bonds ? ? bond. 
The lecture covers the examples of recent developments in enantioselective 
intermolecular Alder-ene glyoxylates with alkenes. Few studies on intra- and 
intermolecular Diels-Alder type reactions are also covered in the latter part of 
the lecture.  
2.1.1 Carbonyl-Ene Reaction 
Chiral Lewis acid catalyzed enantioselective ene reaction is one of the efficient 
methods for atom economical carbon-carbon bond formation. For example, Ti-
BINOL prepared in situ catalyzes efficiently the carbonyl-ene reaction of 
glyoxylate with ?-methylstyrene in the presence of molecular sieves with high 
enantioselectivity (Scheme 1). 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 2 of 58 
Scheme 1 
Besides the early transition metal based Lewis acid catalysts, square planar 
dicationic late transition metal complexes bearing C
2
-symmetric diphosphine 
ligands have also been considerably studied as chiral Lewis acids for carbonyl-
ene reactions. For example, the isolated MeO-BIPHEP-Pd complex 1a bearing 
electron withdrawing benzonitrile as the labile, stabilizing ligands has been 
used for the ene reaction of ethyl glyoxylate with up to 81% ee (Scheme 2). The 
isolated 1a exhibits more catalytic activity compared to that 1b which is in situ 
generated although both offer similar enantioselectivity. 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 3 of 58 
H CO
2
Et
O
OH
CO
2
Et
MeO
MeO
Pd
Ph
2
P
P
Ph
2
NCAr
NCAr
2+
MeO
MeO
Pd
Ph
2
P
P
Ph
2
2+
2SbF
6
Pd cat. (2 mol %)
CH
2
Cl
2
, 0 °C, 5 h
1a 81% ee (70 ? 10% conv.)
1b 81% ee (55% conv.)
1a: Ar = 3,5-CF
3
C
6
H
3
2SbF
6
1b
J. J. Becker, et al., Org. Lett. 2002, 4, 727.
Scheme 2 
MeO-BIPHEPs-Pt complexes 3 with OTf
-
 as counter anion also exhibit similar 
catalytic activity and selectivity in the asymmetric glyoxylate ene reaction 
(Scheme 3). The addition of phenol facilitates the reaction by trapping the OTf 
anion and traces of water. 
H CO
2
Et
O
MeO
MeO
Ar
2
P
P
Ar
2
OTf
OTf
Pt
2+
CO
2
Et
OH
Pt cat. (2 mol %)
C
6
F
5
OH
CH
2
Cl
2
, -50 °C, 5 h
3a  Ar = Ph
3b  Ar = p-CF
3
-C
6
H
4
3c  Ar = p-
t-
Bu-C
5
H
4
3d  Ar = p-OMe-C
6
H
4
H
O OEt
O
Pt
P
P
*
H
O
H
H H
RfO ORf
S CF
3
O
O
O
H
H
ORf
RfO
H
ORf
 
2+
Catalyst Conv. (%) ee (%)
3a
3b
3c
3d
77
63
79
78
77
68
85
83
J. H. Koh, et al., Org. Lett. 2001, 3, 1233.
Scheme 3 
 
Page 4


NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 1 of 58 
Module 2    Asymmetric Carbon-Carbon Bond Forming 
Reactions 
Lecture 5  
2.1 Enantioselective Ene and Cycloaddition Reactions 
Alder-ene and Diels-Alder reactions are six electron pericyclic processes 
between a “diene” or an alkene bearing an allylic hydrogen and an electron-
deficient multiple bond to form two bonds ? ? bond. 
The lecture covers the examples of recent developments in enantioselective 
intermolecular Alder-ene glyoxylates with alkenes. Few studies on intra- and 
intermolecular Diels-Alder type reactions are also covered in the latter part of 
the lecture.  
2.1.1 Carbonyl-Ene Reaction 
Chiral Lewis acid catalyzed enantioselective ene reaction is one of the efficient 
methods for atom economical carbon-carbon bond formation. For example, Ti-
BINOL prepared in situ catalyzes efficiently the carbonyl-ene reaction of 
glyoxylate with ?-methylstyrene in the presence of molecular sieves with high 
enantioselectivity (Scheme 1). 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 2 of 58 
Scheme 1 
Besides the early transition metal based Lewis acid catalysts, square planar 
dicationic late transition metal complexes bearing C
2
-symmetric diphosphine 
ligands have also been considerably studied as chiral Lewis acids for carbonyl-
ene reactions. For example, the isolated MeO-BIPHEP-Pd complex 1a bearing 
electron withdrawing benzonitrile as the labile, stabilizing ligands has been 
used for the ene reaction of ethyl glyoxylate with up to 81% ee (Scheme 2). The 
isolated 1a exhibits more catalytic activity compared to that 1b which is in situ 
generated although both offer similar enantioselectivity. 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 3 of 58 
H CO
2
Et
O
OH
CO
2
Et
MeO
MeO
Pd
Ph
2
P
P
Ph
2
NCAr
NCAr
2+
MeO
MeO
Pd
Ph
2
P
P
Ph
2
2+
2SbF
6
Pd cat. (2 mol %)
CH
2
Cl
2
, 0 °C, 5 h
1a 81% ee (70 ? 10% conv.)
1b 81% ee (55% conv.)
1a: Ar = 3,5-CF
3
C
6
H
3
2SbF
6
1b
J. J. Becker, et al., Org. Lett. 2002, 4, 727.
Scheme 2 
MeO-BIPHEPs-Pt complexes 3 with OTf
-
 as counter anion also exhibit similar 
catalytic activity and selectivity in the asymmetric glyoxylate ene reaction 
(Scheme 3). The addition of phenol facilitates the reaction by trapping the OTf 
anion and traces of water. 
H CO
2
Et
O
MeO
MeO
Ar
2
P
P
Ar
2
OTf
OTf
Pt
2+
CO
2
Et
OH
Pt cat. (2 mol %)
C
6
F
5
OH
CH
2
Cl
2
, -50 °C, 5 h
3a  Ar = Ph
3b  Ar = p-CF
3
-C
6
H
4
3c  Ar = p-
t-
Bu-C
5
H
4
3d  Ar = p-OMe-C
6
H
4
H
O OEt
O
Pt
P
P
*
H
O
H
H H
RfO ORf
S CF
3
O
O
O
H
H
ORf
RfO
H
ORf
 
2+
Catalyst Conv. (%) ee (%)
3a
3b
3c
3d
77
63
79
78
77
68
85
83
J. H. Koh, et al., Org. Lett. 2001, 3, 1233.
Scheme 3 
 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 4 of 58 
The glyoxylate ene reaction is also effective using tropox dicationic DPPF-Ni 
complex 4 with enantioselectivity up to 90% ee (Scheme 4). 
Ph
H CO
2
Et
O
Ph CO
2
Et
OH
5 mol % 4
5.5 mol % (R)-DABN
CH
2
Cl
2
, rt, 24 h
4a: X = SbF
6
4b: X = ClO
4
Ni[(R)-DABN]SbF
6
90% ee (84%)
76% ee (52%)
75% ee (87%)
Ph
2
P
Fe
P
Ph
2
Ni
2+
4
2X
-
NH
2
NH
2
(R)-DABN
K. Mikami, K. Aikawa, Org. Lett. 2002, 4, 99.
Scheme 4 
The glyoxylate-ene reaction can also be carried out using chiral C
2
-symmetric 
bisoxazolinyl copper(II) complexes 5 and 6 as Lewis acid catalysts (Scheme 5).  
The aqua complex is air and water stable and exhibits only slight decrease in 
the reaction rate compared to the anhydrous complex 6. The sense of 
asymmetric induction depends on the oxazoline ring substituents, which can be 
rationalized by the tetrahedral and square-planer intermediates to account for 
the absolute configuration of the products. 
N N
Me Me
t-Bu t-Bu
Cu
2+
2SbF
6
N N
Me
Me
Ph Ph
Cu
2+
2OTf
R
H
O
CO
2
Et
R CO
2
Et
OH
R CO
2
Et
OH
R = Me, Ph, CH
2
OBn
       CH
2
OTBDPS
6
5 (1 mol %)
CH
2
Cl
2
, 0-25 °C
6(10 mol %)
93-98% ee (62-97%)
76%-99% (85-99%)
CH
2
Cl
2
, 0-25 °C
5
D. A. Evanes, et al., J. Am. Chem. Soc. 2000, 122, 7936.
Scheme 5 
In addition, chiral C
2
-symmetric trivalent pybox-Sc complex 7 is studied for the 
carbonyl-ene reactions with N-phenyl glyoxamides (Scheme 6). The ene 
products are obtained with excellent diastereo- and enantioselectivity. 
Presumably, the products are formed via proton transfer from the ?-cis 
substituent through an exo-transition state. 
Page 5


NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 1 of 58 
Module 2    Asymmetric Carbon-Carbon Bond Forming 
Reactions 
Lecture 5  
2.1 Enantioselective Ene and Cycloaddition Reactions 
Alder-ene and Diels-Alder reactions are six electron pericyclic processes 
between a “diene” or an alkene bearing an allylic hydrogen and an electron-
deficient multiple bond to form two bonds ? ? bond. 
The lecture covers the examples of recent developments in enantioselective 
intermolecular Alder-ene glyoxylates with alkenes. Few studies on intra- and 
intermolecular Diels-Alder type reactions are also covered in the latter part of 
the lecture.  
2.1.1 Carbonyl-Ene Reaction 
Chiral Lewis acid catalyzed enantioselective ene reaction is one of the efficient 
methods for atom economical carbon-carbon bond formation. For example, Ti-
BINOL prepared in situ catalyzes efficiently the carbonyl-ene reaction of 
glyoxylate with ?-methylstyrene in the presence of molecular sieves with high 
enantioselectivity (Scheme 1). 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 2 of 58 
Scheme 1 
Besides the early transition metal based Lewis acid catalysts, square planar 
dicationic late transition metal complexes bearing C
2
-symmetric diphosphine 
ligands have also been considerably studied as chiral Lewis acids for carbonyl-
ene reactions. For example, the isolated MeO-BIPHEP-Pd complex 1a bearing 
electron withdrawing benzonitrile as the labile, stabilizing ligands has been 
used for the ene reaction of ethyl glyoxylate with up to 81% ee (Scheme 2). The 
isolated 1a exhibits more catalytic activity compared to that 1b which is in situ 
generated although both offer similar enantioselectivity. 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 3 of 58 
H CO
2
Et
O
OH
CO
2
Et
MeO
MeO
Pd
Ph
2
P
P
Ph
2
NCAr
NCAr
2+
MeO
MeO
Pd
Ph
2
P
P
Ph
2
2+
2SbF
6
Pd cat. (2 mol %)
CH
2
Cl
2
, 0 °C, 5 h
1a 81% ee (70 ? 10% conv.)
1b 81% ee (55% conv.)
1a: Ar = 3,5-CF
3
C
6
H
3
2SbF
6
1b
J. J. Becker, et al., Org. Lett. 2002, 4, 727.
Scheme 2 
MeO-BIPHEPs-Pt complexes 3 with OTf
-
 as counter anion also exhibit similar 
catalytic activity and selectivity in the asymmetric glyoxylate ene reaction 
(Scheme 3). The addition of phenol facilitates the reaction by trapping the OTf 
anion and traces of water. 
H CO
2
Et
O
MeO
MeO
Ar
2
P
P
Ar
2
OTf
OTf
Pt
2+
CO
2
Et
OH
Pt cat. (2 mol %)
C
6
F
5
OH
CH
2
Cl
2
, -50 °C, 5 h
3a  Ar = Ph
3b  Ar = p-CF
3
-C
6
H
4
3c  Ar = p-
t-
Bu-C
5
H
4
3d  Ar = p-OMe-C
6
H
4
H
O OEt
O
Pt
P
P
*
H
O
H
H H
RfO ORf
S CF
3
O
O
O
H
H
ORf
RfO
H
ORf
 
2+
Catalyst Conv. (%) ee (%)
3a
3b
3c
3d
77
63
79
78
77
68
85
83
J. H. Koh, et al., Org. Lett. 2001, 3, 1233.
Scheme 3 
 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 4 of 58 
The glyoxylate ene reaction is also effective using tropox dicationic DPPF-Ni 
complex 4 with enantioselectivity up to 90% ee (Scheme 4). 
Ph
H CO
2
Et
O
Ph CO
2
Et
OH
5 mol % 4
5.5 mol % (R)-DABN
CH
2
Cl
2
, rt, 24 h
4a: X = SbF
6
4b: X = ClO
4
Ni[(R)-DABN]SbF
6
90% ee (84%)
76% ee (52%)
75% ee (87%)
Ph
2
P
Fe
P
Ph
2
Ni
2+
4
2X
-
NH
2
NH
2
(R)-DABN
K. Mikami, K. Aikawa, Org. Lett. 2002, 4, 99.
Scheme 4 
The glyoxylate-ene reaction can also be carried out using chiral C
2
-symmetric 
bisoxazolinyl copper(II) complexes 5 and 6 as Lewis acid catalysts (Scheme 5).  
The aqua complex is air and water stable and exhibits only slight decrease in 
the reaction rate compared to the anhydrous complex 6. The sense of 
asymmetric induction depends on the oxazoline ring substituents, which can be 
rationalized by the tetrahedral and square-planer intermediates to account for 
the absolute configuration of the products. 
N N
Me Me
t-Bu t-Bu
Cu
2+
2SbF
6
N N
Me
Me
Ph Ph
Cu
2+
2OTf
R
H
O
CO
2
Et
R CO
2
Et
OH
R CO
2
Et
OH
R = Me, Ph, CH
2
OBn
       CH
2
OTBDPS
6
5 (1 mol %)
CH
2
Cl
2
, 0-25 °C
6(10 mol %)
93-98% ee (62-97%)
76%-99% (85-99%)
CH
2
Cl
2
, 0-25 °C
5
D. A. Evanes, et al., J. Am. Chem. Soc. 2000, 122, 7936.
Scheme 5 
In addition, chiral C
2
-symmetric trivalent pybox-Sc complex 7 is studied for the 
carbonyl-ene reactions with N-phenyl glyoxamides (Scheme 6). The ene 
products are obtained with excellent diastereo- and enantioselectivity. 
Presumably, the products are formed via proton transfer from the ?-cis 
substituent through an exo-transition state. 
NPTEL – Chemistry and Biochemistry  – Catalytic Asymmetric Synthesis 
 
Joint initiative of IITs and IISc – Funded by MHRD                                    Page 5 of 58 
N
Sc N
O O
N
OTf TfO
OTf
Ph Ph
Me
Et
Me
H
O
H
N
O
Ph Et
Me
H
N
Ph
OH
O
Me
Me
H
N
Ph
OH
O
Me
Et
Me
Me
5 mol % 7
CH
2
Cl
2
, rt
95% ee (83%)
syn/anti 10/1
99% ee (75%)
syn/anti 20/1
H
R
Me
H
O Sc
O
NHPh
H
+
+
H
O
H
N
O
Ph
5 mol % 7
CH
2
Cl
2
, rt
exo TS
7
D. A. Evans, J. Wu, J. Am. Chem. Soc. 2005, 127, 8006.
Scheme 6 
Co and Cr-based chiral complexes have also been explored for the carbonyl-ene 
reaction with glyoxylates. For example, chiral ?-ketoiminato complex 8 
catalyzes efficiently the reaction of 1,1-disubstiuted alkene and glyoxyl 
derivative in high enantioselectivity (Scheme 7). Similar to the earlier described 
Pd, Pt and Ni-based catalysts, hexafluoroantimonate as a counter anion is found 
to be the most effective. 
O
N N
Co
O O O
Ph Ph
SbF
6
Ph H
O
COPh
Ph
OH
COPh
X mol %  8
CHCl
3
, -21°C
X = 5      (3 h)   93% ee (93%)
X=  0.5 (45 h)   95% ee (80%)
X = 0.2 (80 h)   94% ee (80%)
8 S. Kzuka et al., Bull. Chem. Soc. Jpn. 2003, 76, 49.
Scheme 7 
Chiral Cr(III)-salen complex 9 bearing adamantyl group in the salen ligand has 
been used for the reaction of ethyl glyoxylate with 1,2-disubstituted alkenes 
(Scheme 8). The catalyst can be prepared in multigram scale and the ene 
products are obtained with up to 92% ee. The presence of adamantyl substituent 
essential for the enhancement in the enantioselectivity 
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