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The application of alkaline metal(Ca, Sr, Ba) complex as catalyst in organic chemistry
2010.12.04
张文全
1
introduction
Alkaline earth metals are very attractive because they are abundant and ubiquitous elements in nature and form safe compounds compared with other heavy transition metals. However, their positive use as catalysts in asymmetric synthesis is still limited. Their strong Brønsted basicity and mild Lewis acidity can influence their catalytic activity, as well as chiral modification of a complex in a positive manner.
2
calciumThe application of calcium complex in organic chemistry will showfollow
Baylis¨CHillman
Baylis¨CHillman
Mannich reaction
Friedel-Craft reaction
Hydroarylation of Alkenes
Hydroamination
Pictet-Spengler reaction
Tischenko ReactionHydrophosphination
Aldol Reaction
CaLn
Michael Reactions
3
O
PhCHO
1eq 1.5eq
CaL(16mol%)Bu3P(10mol%)
THF,rt, 7h
O
Ph
OH
O
O
Ca
First example of an optically active calcium catalyst
Shiro Ikegami, Tetrahedron Letters 41 (2000) 2165
Baylis–Hillman Reaction
62 yield%56 ee%
4
Ph
O
Ph
H3CO
O
OCH3
O Ph
O
Ph
CH(CO2Me)2
*
cat. 15mol%
toluene, -15oC24h
2eq KOH
1eqCaCl2absEtOH
2KClOH
OH
O
OCa
H3CO
O
OCH3
Ocat. 15mol%
toluene, -15oC24h
O
O
CH(CO2Me)2
75 yield%88 ee%
G. Kumaraswamy, Tetrahedron Letters 42 (2001) 8515
Michael Reactions
5
OO
OMe
O 10mol%(R)cat
toluene,-40oC 12h
O
CO2Me
O
*
OH
OH
*2eq KOH
1eqCaCl2absEtOH
O
O
* Ca 2KCl
R2
R2 R1
R1
OH
OH
R3
R3
OH
OH
OH
OH
OO
OMe
O 10mol%(R)cat
toluene,-40oC 12h
O
CO2Me
O
*88yield%80ee%
G. Kumaraswamy, Adv. Synth. Catal. 2005, 347, 867 6
R1O
O
OR1
O
R2 NO2
Ca(OAr)2(10mol%)ligand(10mol%)
toluene,-20oC24h, 0.2M,4AMS
R1O
O
OR1
O
R2
NO2
N
O
N
O
NH HN
PhPh
O2S SO2NO
N N
O
R1
R2R2
R1
NO
N N
O
Ph
PhPh
Ph
anti
Ca(OAr)2
Ar=p-MeOC6H4
18-96ee%50-quant yield%
NO
N N
O
Ph
PhPh
PhCaOAr ArO
Shu Kobayashi, Angew. Chem. Int. Ed. 2009, 48, 9117 7
MeO
O
OMe
O
N
NN CaArO OAr
*
ArOHN
NN Ca
*
MeO
O
OMe
O
MeO
O
OMe
O
Ph
N+
O O-
OAr
N
N NCa
*
ArO
MeO
O
OMe
O
Ph
NO2
PhNO2
*
*
8
upto 84ee%
NO
OR1
Ph
O
OR2
M(OiPr)2(10mol%)Pybox(10mol%)
Conditions, 34h, 0.2MMS 4A
N O
OR1
PhR2O
O
NO
N N
O
R1 R1
R2R2
R2R2
NO
N N
O
R1 R1
R2R2
R2R2
CaPrOi OiPr
Shu Kobayashi, Tetrahedron: Asymmetry 21 (2010) 1221
9
10
N
O
O
O
R
O
R1O OR1
O
OMe OH 10mol%
Ca(OR2)2(10mol%)PyBox(11mol%)
N
O
O
O
R
R1O
O
R1O O
almost>90ee%
NO
N N
O
Ph Ph
ligand
NO
N N
O
Ph PhCa
EtO OAr
real catalyst
Shu Kobayashi, J. AM. CHEM. SOC. 2010, 132, 789011
R1
R2
O
Ph N
Ph
OR3
Oligand(10mol%)Ca(Oi-Pr)2(10mol%)
-30oC,THF,0.2M,12hMS 4A
Ph N
Ph
OR3
O
R1
R2O
78-99ee%
with excellent diastereo- and enantioselectivities
R2
O
Ph N
Ph
OR3
Oligand(10mol%)Ca(Oi-Pr)2(10mol%)
-30oC,THF,0.2M,12hMS 4A N
HPh
Ph
OR2O
O
OR3
R2
O
Ph N
Ph
NR1R3
Oligand(10mol%)Ca(Oi-Pr)2(10mol%)
-30oC,THF,0.2M,12hMS 4A N
HPh
Ph
OR2O
O
NR1R3
N
O
N
O
Ph Phligand
Shu Kobayashi, J. AM. CHEM. SOC. 2007, 129, 5364Shu Kobayashi, J. AM. CHEM. SOC. 2008, 130, 13321Shu Kobayashi, O.L. 2008, Vol. 10, No. 5, 807
with excellent diastereo- and enantioselectivities
12
Catalytic cycle of the 1,4-addition reaction
13
Two Possible Reaction Mechanisms of the [3 + 2] Cycloaddition Reaction
14
O
OR2
O
R2Oconcerted pathway
Ph NOR1
O
NH
Ph
OR2O
O
OR1
O
OR2
trans
O
OR2 concerted pathway
Ph NOR1
O
NH
Ph
OR2O
O
OR1
O
OR2
cisO
OR2
NH
Ph
OR2O
O
OR1
O
OR2
trans
NH
Ph
OR2O
O
OR1
O
OR2
cis
so stepwise is possible
cis/trans=2/1
15
R1
Ar
R1
Ar
Ar
R1
R2
R1
OH
R1
OH
OH
R1
R2
ArH
R1
OHR2
R1
OHR2
OH
R1
R2
R2
R1
Ar
R1
Ar
Ar
R1
R2
R2
R2
R2
secondary tertiary
5mol% Ca(NTf2)2/Bu4NPF6 room temperature
Ca(NTf2)2+Bu4NPF6 CaNTf2PF6
more reactive
Meike Niggemann, Angew. Chem. Int. Ed. 2010, 49, 3684
Friedel-Craft Reaction
electrion-rich AromaticArH =
CaNN
F3CO2S
SO2CF3
SO2CF3
F3CO2S
16
HO
CaL
NuO O
ArH=H
17
Ar H
NBoc
R1
O
R2
O
R3cat(2-5mol%)
Ar
NH O
R1
O R3
R2
Boc
solvent
cat:
Kazuaki Ishihara, Angew. Chem. Int. Ed. 2010, 49, 3823
Mannich Reaction
18
Ar H
NBoc
R1
O
R2
O
R3cat(2-5mol%)
Ar
NH O
R1
O R3
R2
Boc
solvent
when R2=H, H(1b) is betterwhen R2=H and R1 or R3 =SR, Ca(1a)2 is better
19
N
HR1
Boc
R2O OR2
O O
Ca(OiPr)2
PyBox Ligand HN
R1
Boc
CO2R2
CO2R2
up to 77%ee
N
O
N
O
NO
N N
O
R1 R1
OH
I
OH
I
NO
N N
O
Bn Bn
Aliphatic N-Boc imine can react, good yield but low ee
Shu Kobayashi, J. Org. Chem. 2010, 75, 963 20
Ar1Ar2
Ocat.10mol%
tol. -10oC, MS4AtBuOOH,48h
Ar1Ar2
O
Oupto 91 yield%upto 80 ee%
O
O
* Ca
O
O
* CaO
O
O
Ar2Ar1
O
+HO
* CaO
O
tBuOOHAr1Ar2
O
O
Ar1Ar2
O
n
n
n
O
OCa
trime
ric
Ca
Ca
Ca
OO
O
O
O
O
* *
*
epoxidation
G. Kumaraswamy, Tetrahedron: Asymmetry 14 (2003) 379721
R1
R3 R4
R2Ar-H
Ca(NTf2)2/Bu4NPF6 r.t.
Ar
R1
R3
H
R3
R4
OH
OS
O
Arene electrion-rich Aromatic
R1
R3
R2etcolefinic
R1
R3
R2
CaNTf2PF6 R1
R3
R2CaPF6
Nu
path one:
Meike Niggemann, Chem. Eur. J. 2010, 16, 11246
path two:
Hydroarylation of Alkenes
HO
CaL
Nu
22
KN(SiMe3)2 BDICH CaI2N N
Ar ArCa(Me3Si)2N THF
THF
N HNBDIH
HNLCa
n
H2N n
HN
n
HNLCa n
H2N nHN(SiMe3)2
N NAr ArCa
(Me3Si)2N THF
Michael S. Hill, J. AM. CHEM. SOC. 2005, 127, 2042
Hydroamination
23
aminoalkene product Time(h) Temp.(oC) Conv.%
24
N NAr ArCa
(Me3Si)2N THF
1
Ph
H2N
NPh10mol%cat3
C6D6,r.t.
Peter W. Roesky, Organometallics 2007, 26, 4392
25
HO
R1
NH2
H R3
OHO
R1NH
R3
R1-H or OMe aldehydes
3AMS, DCM23oC
10mol%Ca[OCH(CF3)2]2
HO
R1
NH2
R2 R3
O cat. 20mol%HO
R1 NH
R2 R3
R1-H or OMe ketones
3AMS, tol.100oC
regioselective products in most cases, giving rise to only the A-ol isomer.However, when a nitrogen functionality is present, the isomeric ratio of products is altered to give mixtures of the favored 6-ol isomer and the disfavored B-ol regioisomer.
such as:
HO NH2HO
NH3AMS, tol.100oC
N
ON
NH
NOH
A-ol B-ol
10mol%Ca[OCH(CF3)2]2
Pictet-Spengler Reaction
26
O
NN Ca
OROR
CaRO
NCa
ORN
OCa
RO
James P. Stambuli, ORGANIC LETTERS, 2008, Vol. 10, No. 22, 5289James P. Stambuli, J. Org. Chem. XXXX, XXX, 000
HO
R1
NH2
R2 R3
O cat. 20mol%HO
R1 NH
R2 R3
R1-H or OMe ketones
3AMS, tol.100oC
O
O
OMe
O
O
O
Ketone:
27
HO
R1
NH2
HO
N
R1
HO
N
R1
CaOR
OR
HO
N
R1
Ca
ORH
-OR
HO
N
R1
Ca
OR
HO
NH
R1
R1CHO
Ca(OR)2
Ca(OR)2
ROH
28
R H
O 0.1-10mol%cat
C6D6, rt R O
O
R
NCa
NAr Ar
(Me3Si)2N THF
Ar=2,6-diisopropylphenyl
10-96yield%
O
O
CF3
O
OMe
O O
Anthony G. M. Barrett, Michael S. Hill, O. L. 2007, Vol. 9, No. 2, 331
Tischenko Reaction
CaL
O
O
R
R
R
O
H
How to start the catalic cycle?being continuing to study
29
R HPPh210mol%cat
C6D6,25-75oC13-36h
RPPh2 78-95conv%
Anthony G. M. Barrett, Michael S. Hill, Organometallics 2007, 26, 2953
Hydrophosphination
30
Anthony G. M. Barrett, Michael S. Hill, Organometallics 2008, 27, 497
R1N C NR1 HP(R3)2catalyst
R1
NH
NR2
P(R3)2
C6D6, r.t.
31
Ca[(H3C)3Si]2N
[(H3C)3Si]2N L
L
R
R
OH
OHL=THF, DME
R= H, OCH3
R
R
O
O
CaLn
O
H
O
R
O
R
OH
cat3mol%
CH3CN mix THF-20oC
O O
Ocat3mol%
CH3CN mix THF -20oC
O
R
OH
76 yield%91 ee%
Ryoji Noyorib, Tetrahedron Letters 42 (2001) 4669
Aldol Reaction
32
NHAc
R1
R
N
N
CO2i-Pr
i-PrO2C
cat. 10mol%4A MS, -35oC
then HBr, EtOH
cat. 10mol%4A MS, -35oC
then NaBH4, MeOH
O
NNH
CO2i-Pr
R1
CO2i-Pr
Ree: 85-95%
NHAc
NNH
CO2i-Pr
R1
CO2i-Pr
Rdr: >95:5; ee: 88-96%
O
OP
O
OCa
n
Jieping Zhu, O. L. XXXX, Vol. xx, No. x 33
strontium
HO
O
HO
ArAr
Z
O2S NH HN SO2
Ph Ph
Need to develop new ligand
34
Ph
NHN
OiPr
O2S
Ar
catalyst(10mol%)
MS 4A, DMFRT, 17h
NBoc O2S
Ar
Me
OiPrPh
NBoc
N
OiPr
O2S
Ar
cat.DMF
N-
OiPr
O2S
Ar
+ML(dmf)m
THF
N
OiPr
O2S
Ar
ML(dmf)m
S. Kobayashi, Angew. Chem. Int. Ed. 2009, 48, 5927S. Kobayashi ,Bull. Chem. Soc. Jpn. Vol. 82, No. 9, 1083
Mannich Mg(OtBu)2
Sr(HMDS)2
35
solvent effect
Conditions A: DMF, RT, 17 h, Ar=2,5-xylyl.Conditions B: Ligand 4 (11 mol%), THF, RT, 24 h, Ar=p-NO2-C6H4.
The addition of ligand 4 generally increased the syn selectivity
N
O O
N
ligand 4
36
NHN
OiPr
O2S
Sr(OiPr)2 (10mol%)ligand (12mol%)Et3N(10mol%)
THF,MS 4A,20oC48h, 85%yieldsyn/anti 83:1757% ee(syn)
NBoc O2S
Me
OiPr
NBoc
NO2NO2
O2S NH HN SO2
Ph Ph
this is the first example of a catalytic asymmetric Mannich-type reaction of a sulfonylimidate
37
EtO2C
EtO2C Ph Ph
OSr(OiPr)2(0.5-5mol%)Ligand(0.6-6mol%)
MS 4A(100mg)toluene,25oC,
EtO2C
CO2Et
Ph
Ph
O
O2S NH HN SO2
Ph Ph
Ligand:
Sr(O-i-Pr)2 ligand 2i-PrOHO2S N N SO2
Ph Ph
Sr
O2S N N SO2
Ph Ph
Sr
MeO
O
OMe
O
>90 yield%>90 ee%
Shuj Kobayashi, J. AM. CHEM. SOC. 2008, 130, 2430
Michael Reactions
38
n-PrO2C
n-PrO2C
Sr(HMDS)2(5mol%)Ligand(6mol%)
MS 4Atoluene,25oC,
O
Ph
OPhn-PrO2C
n-PrO2C
donor acceptor
O2S NH HN SO2
Ph Ph
ligand
Shu Kobayashi, Chemistry Letters Vol.38, No.3 (2009)
39
Ph
O
catalystTMSCN(2eq)2,6-dimethylphenol(2eq)
THF, 40oC Ph
O NC
HO
O
P
HO
O
PhPh
HO
O
HO
ArAr
ZAr= Ph, p-tolZ= OH, OMe, OiBu, H
Sr(OiPr)2 (0.5 mol%) + ligand (0.8 mol%)
HO
O
HO
p-tollot-p
BuOi 100yield%97ee%
Motomu Kanai, Masakatsu Shibasaki, J. AM. CHEM. SOC. 2010, 132, 886240
41
42
barium
Barium has the largest ionic radius, which often form oligomerLike:
43
44
OTMSCO2Me
MeO2C
Ba(OiPr)2 ligand
CH2Cl2
YCO2Me
Z
CO2Me
Y = OTMS (and OH), Z = HZ = OTMS (and OH), Y = H
HO
O
HO
ArAr
Z
F
F
64 yield%3:1 d.r88 ee%
additive CsF, the same mol% as Ba/ligand91 yield%4:1 d.r97 ee%
Motomu Kanai, Angew. Chem. 2009, 121, 1090
Diels–Alder-type reaction
OTMS
45
RCHOO
Ph
(R)-BaN-M(5mol%)
DME, -20oC R
OH
Ph
O
Ba(O-i-Pr)2OMe
OH
2.5 eq
DMErt
evap.
i-PrOH
DME (R)-BaB-M
MeO
O OMe
OBa
X
X
X = BINOL-Me or DME
Masakatsu Shibasaki, Tetrahedron Letters 39 (1998) 5561
Aldol Reaction First example of an optically active alkaline meta catalyst
up to 70 ee%
46
MeO
O OMe
OHBa
X
O
R
HO
BaO
O
O
O
X
X* *
BaO
O
O
OX
* *
O
R
HRCHO
R
OH
Ph
O
O
Ph
X
X
catalytic cycle
47
Ba(OtBu)2O
HOphenol good yield and dr value
RCHON
Boc
OBa alkoxide (10 mol%) phenol (22mol%)
NH
O
R
OBoc
0oC, THF, 0.2M, 24h
O
Shu Kobayashi, J. AM. CHEM. SOC. 2006, 128, 8704 48
O
HR
O
OBn
Ba(O-iPr)2 (5-10 mol%) ligand (5-10mol%)
DME
O
OBnR
OH
y-adduct
upto 99 ee%
Masakatsu Shibasaki, J. AM. CHEM. SOC. 2009, 131, 10842
49
N
HR
PPh2
O
N
Boc
O
R'
O Ba(O-t-Bu)2(10mol%)ligand(22mol%)
0oC, DMF, 0.2M, 48h MS 5A
N
H
OO
R'
R
NPh2P Boc
O
O
HOligand
Shu Kobayashi, Chem. Commun., 2007, 1236
Mannich reaction
50
NPPh2
R H
OO
OBn
Ba(OAr)2(0.5-10 mol%)
THF, 0oCAr= 4-MeO-C6H4
or chiral ligand
O
OBn
NH
R
Ph2P
O
53-88% yieldup to 80% ee
Masakatsu Shibasaki, O. L. 2007, Vol. 9, No. 17, 3387
OH
OH
O
O
chiral ligand
51
HN
R R1
O
R2
Ba(HMDS)2 (10mol%) ligand(10mol%)
tBuOMe/THF=9/1 rt, 24h 0.05M, MS 4A
HN
R
R1R2
O
SiPh3
SiPh3
OH
OH
Kobayashi, Chem.sAsian J. 2010, 5, 1974
Friedel-Crafts-type Reaction
52
conclusion
1. The Alkaline earth metals can be used in Many important reactions. But some of the mechanisms are unclear, still.
Their positive use as catalysts in asymmetric synthesis is limited, also.
2. Their strong Bronsted basicity and mild Lewis acidity can influence their catalytic activity, as well as chiral modification of a complex in a positive manner. So synthesis of new ligands need to be considered.
53
Thank you for your attention!
54
