Baran Group Meeting
3/27-2010
Organoaluminium in Synthesis
IUPAC:
Aluminium (or Aluminum)
Atom number: 13
AlCl3 + RLi/RMgX
AlR3 + LiCl/MgXCl
DIBAL
R
Al-O bond ∼138 kcal/mol
AliBu2
R
R
Me
"Zr"
R
AlMe2
R
Reduction potential: -1.66 V
AlMe3
R
R3Al + RLi
R
CH2
AlMe2
Cl
Tebbe's reagent: Cp2Ti
Aluminium is the most abundant (8.3% by weight) metallic element, in the
Earth's crust, and the third most abundant of all elements (after oxygen and
silicon). It is produced in over 30 mill. tons a year and is easy to recycle.
Feldspars, the most common group of minerals in the Earth's crust, are
aluminosilicates. It occurs in the minerals beryl, cryolite, garnet, spinel and
turquoise. Impurities in Al2O3, such as chromium or cobalt yield the
gemstones ruby and sapphire, respectively. Pure Al2O3, known as corundum,
is one of the hardest materials known.
H
R
Oxidation states: (+I, +II) +III
First isolated in impure form by Ørsted in 1825
Mikkel Jessing
R3AlR Li
Four-membered/Six-membered/β-hydride transfer
R R
R
O Al R
O
R
Al
R
R R
O
R
Al
Al
R
R
H
Stoichiometry
The Washington Monument was completed,
with the 100 ounce (2.8 kg) aluminium capstone
being put in place on December 6, 1884, in an
elaborate dedication ceremony. It was the
largest single piece of aluminium cast at the
time, when aluminium was as expensive as
silver. Aluminium has been produced in
commercial quantities for just over 100 years.
Organoaluminums posses a rather low intrinsic nucleophilicity,
conversion to (filled-octet) aluminates markedly increases the carbanion
character
Solvent dependable
Different reactivity for different alkyl-/arylgroups
Me3Al
N
N
AlMe3
airstable AlMe3 reagent
Reviews:
Zweifel and Miller; Org. React. 1984, 375
Maruoka and Yamamoto; Tetrahedron, 1988, 5001
Negishi and Kondakov; Chem. Soc. Rev. 1996, 417
Negishi: Bull. Chem. Soc. Jpn., 2007, 233
von Zezschwitz; Synthesis, 2008, 1809
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
Bu
CH2Br
Me
O
HO
C
2) CH2(OMe)2
Sonic.
MeI + Al
O
CH2OMe
1) Al, Et2O
Mikkel Jessing
70% Bu
J. Organometal. Chem., 1986, 83
Me3Al2I3
2 h, I2
AlEt3
tBu
tBu
tBu
AlMe3
Me2AlCl
Me2AlBr
Me2AlI
AlMe3
Me2AlI
Me3Al
Sonic.
tBu
C 6H 6
C6H6
C 6H 6
C 6H 6
THF
THF
+
tBu
0:100
7:93
20:80
99:1
0:100
98:2
Ph
Ph
Ph
Ph
Ph
Ph3Al
Et2O
rt.
Al
Ph
Ph
O
Ph
Ph
Ph
Al
Ph
O
HO
Ph
Ph
Ph2Be
Ph2Zn
Ph3Al
PhMnI
PhCaI
PhK
PhNa
PhLi
Ph
O
Ph
+
Ph
tBu
97%
70%
57%
47%
75%
42%
J. Organometal. Chem., 1986, 273
O
Me
JOC, 1979, 4792
Ph
Ph
90%
91%
94%
77%
45%
52%
4%
39%
13% 69%
O
OH
Al(iBu)3
Al
iBu
+
R R
O
HO
R R
Al(iBu)3
JACS, 1941, 875
O
iPr
Al
Al
H
R
R
iPr
O
Et
O
.
Ph
Et3Al X
C6H6
HO
+
Ph
X: 8%
OEt2 16%
OPr2 24%
OAmyl2 27%
Et
Ph
69%
48%
61%
53%
Bull. Chem. Soc. Jpn., 1968, 928
eq.
0.5
1.0
2.0
1.0
solvent
pentane
pentane
pentane
Et2O
86%
64%
24%
96%
15% (based on 53% conversion)
36%
76%
JOC, 1982, 4640
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
O
O
Ph
O
Tet. Lett., 1972, 2627
CO2Me
O
6 CO2Me
Et2O-ligroin
6 CO2Me
O
94%
HO
85%
R1 = OH
R2 = (CH2)6CO2Me
CH2OTBS
Ph
Mikkel Jessing
R1 = H
R2 = CO2Me
AlEt2
OH
Et2Al
Ph
OH
n
Pr
n
Hex
3
i
dr 2:1
toluene
THF-ligroin
R1 = OH 35%
R2 = (CH2)6CO2Me
Hex
Al
Et2O
CH2OTBS
HO
n
OTES
n
Pr
Bu2Al
-60 oC (1,2-addition at rt)
2) AcOH, THF, H2O
Tet. Lett., 1986, 2885
O
JACS, 1971, 7320
Tet. Lett., 1975, 4217
R2
R1
O
O
n
AlnPr3
i
O
-78 oC
Bu2Al
Hex
toluene
n
6 CO2H
Pr
75%
solvent independant
free radical mechanism
MeLi, Et2O
2) AcOH, THF, H2O
n
HO
40%
i
n
Hex
SO2Ph
MeLi, Et2O
R1 = OTHP
R2 = (CH2)6CO2THP
JACS, 1973, 4428
Bu2Al
TBSO
O
JOC, 1979, 1438
6 CO2Et
O
O
H
OH
1) Me2AlSePh
O
H
OH
AIBN
2) CH2=CHC(Me)2CHO
Bu3SnH
SePh
63%
H
80%
Tet. Lett., 1985, 6431
O
Hex
H
76%
R1 = H
R2 = (CH2)6CO2Et
Tet. Lett., 1972, 4083
R
R1 = OTBS
R2 = SO2Ph
AlMe3
cis
86%
AlEt3
cis
65%
AliBu3
cis
32%
Et2AlCCTMS 31 cis:51 trans 100%
n
Hex
Synlett, 1999, 1313
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
R
PhO2S
O
O
R
R
CO2H OMOM PhO2S
DCM
HO
HO
(R)-SO(4-Tol)
>95:5
71%
Bu
>95:5
56%
n
>95:5
n
O
(R)-SO(4-Tol)
R = Me
O
R DCM
O
R
N
Ph
O
R
hν 254 nm
hexane
O
Pr
19:81
Ph
88:12
O Ph
92:8
4-ClPh 90:10
N
Ph
O
Ph
2) O2
3)Ac2O, DMAP
n
OAlMe2
Ni(acac)2
Ac2O
Et2O
91%
OH
MeCHO
toluene
61%
63%
56%
46%
O
O
R
J. Organomet. Chem.,
1974, 365
O
83% tBu
J. Organomet. Chem.,
1974, 373
O
MeLi
MeMgX
O
N
R
O
AlMe3
Me2AlCl
R
PhO2S
53%
O
O
O
OAc
JOC, 1996, 6758
O
O
Tet. Lett. 1992, 7407
Bu
O
OMOM
AlMe3
HO
(R)-SO(4-Tol)
MeO2C
R
PhO2S
Me2AlR
R
AlMe3 PhO2S
OMOM DCM
MeO2C
O
Mikkel Jessing
O
O
cat. Cu
cat. Cu
O
OAc
50%
Ph
77:23
ACIEE, 1991, 694
O
O
O
Me3Al
Me3Al
O LiAlMe
4
LiAlMe3OAr
cat. Cu 70% 100:0
cat. Ni 92% 64:36
cat. Ni 90% 38:62
cat. Ni 90% 15:85
ACIEE, 1993, 1368
Chem. Ber., 1996, 963
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
Mikkel Jessing
O
CHO
R
CHO
OH
O
AlMe3
AlMe3 (TMSCl)
AlEt3
AliBu3
R
AlR3
THF
CuBr2
95%
89%
74%
69%
90:10
89:11
36:64
25:75
HO
R
O
CONMe2
85% (0:1) 88% ee
O3
MeOH
CHO
R
O
CHO
R
R
t
KMnO4
NaIO4
i
BuOK
PrOH
OH
CO2H
57%
JACS, 1984, 5004
Synthesis, 1986, 130
CuCN.2LiCl
THF-Et2O
R
R = (CH2)4OTIPS
(CH2)4OTBS
76%
7%
O
10%
87%
O
R
AlMe2
Me:
AlEt3 (>95%) 97% ee
Et:
AlEt3 (84%) 96% ee
95% ee
(CH2)2CH=CH2: AlMe3 80%
cat. Cu
R
R
CONMe2
AlMe3
CONMe2
O
97% (6.5:1) 88% ee
AlMe2
O
HO
(ClCH2)2 CHCl3
Ac2O-Py.
H3O+
O
CONMe2
CONMe2
Tetrahedron, 1995, 743
O
CONMe2
O
Et2O
O
R
Me/Et
O
O
i
CuCN.2LiCl
THF-Et2O
79%
R = (CH2)4OH
(CH2)4OTBDPS -
Ar
10%
100%
O
JOC, 1991, 5761
O
P
N
Ar
Bu:
Ph:
: AlMe3 81%
AlMe3 85%
AlMe3 (70%)
95% ee
98% ee
72% ee
ACIEE, 2005, 1376
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
Mikkel Jessing
OAc
O
HO
O
1) [Rh(cod)OMe]2
(S)-BINAP, THF
2) ketone,
AlMe3
84%, 98% ee
AlR3
chiral cat. Ni
Me2Al
Ph
TMS
DCM
O
Ph
O
t
BuOMe
86%, 88% ee
ACIEE, 2007, 7122
R
Ph
O
Me3 96%, 96:4
Bu3 74%, 94:6
Bu 85%, 100:0
TMS
i
Et2Al
Org. Lett., 2004, 3385
OBn
(S)-BINOL
Ti(OiPr)4
O
HO
Br
O
Br
BnO
HO
O
O
85%
3
Ph
Br
R
Et2Al
91%, 87% ee
JACS, 2006, 14808
O
2) CH3CO(CH2)4CHO
BnO
O
Ph
Ph
OH
ClCH2CH2Cl
88% Bull. Chem. Soc. Jpn., 1986, 446
O
OH
1) Et3Al
O
2) Al
O
OH
Org. Lett. 2000, 2707
Ar3Al.THF
toluene
O
BnO
1) DMDO
90%, 82% ee
(S)-BINOL
Ti(OiPr)4
Li
H
R
Ar3Al.THF
toluene
Chem. Lett., 1987, 2215
OBn
BnO
Ph
R
OH
82%, 89:11
OH
OH
OMOM
OH
1) HCl, MeOH 90%
2) HN=NH 65%
OH
toluene
HO
O
O
exo-brevicomin
OH
R
R
O
JOC, 1984, 1096
OH
Me2Al
CH(OtBu)(CH2)4CH3
LiMe2Al
CH(OtBu)(CH2)4CH3
3.3:1
2
1:5
JOC, 1985, 3923
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
Me3Al
cat. Cp2ZrCl2
R
R
H(R)
R
H(R)
H(R)
AlMe2
H
Me
AlMe2
Me
R
Cl
Me2Al
R
ZrCp2Me
THF
E
R
Me
Al
Cl ZrCp2Me
Pent
Cl
Me
Pd(PPh3)4
Pent
CHO
CH2=CHCH(OMe)2
2)H3O+
Pd(PPh3)4
CH2=CHCH(OEt)3
2)H3O+
R
Cl
R
AlMe3
Cp2ZrCl2 Pent
Pent
Mikkel Jessing
CO2Et
69%
JOC, 1985, 3406
50%
R
ClCp2Zr
R
Me
Cl AlMe2
Cp2ZrCl2
R
Me3Al
Cp2ZrCl2
Cl
AlMe2
Me
Me
OH
ZrCp2Me
Al
Me
R
Me2Al
R
+
Me
R
R
OH
2) I2
Cl
I
enroute to bipinnatn J
Org. Lett., 2006, 345
R
Cl ZrCp2
Explain double bond geometry:
R
JOC, 1997, 784
R
R
R
Cp2Zr
AlEt2
R
Cl
Al
Et
Cp2ZrCl2
DIBAL
2 Et3Al
Et
Cp2Zr
H
AlEt2
Cp2Zr
Cl
P2CZr
Bu
Bu
1) 3 AlEt3
Bu
0.1 Cp2ZrCl2
Bu
hexanes
2) I2, THF
I
I
Cl
AlEt2
R
SeTIPP
SeTIPP
hexane/
toluene H
AliBu2
I2
THF
R
SeTIPP
H
I
82%- 95%
enroute to tetrahydropyran subunit
of polycavernoside
Cl
Et
Et-H
R
AlEt3
R
Tetrahedron, 2006, 2331
H
TIPP:
54%
Chem. Soc. Rev., 1996, 417
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
Mikkel Jessing
Et2Al
TMS
Cp2ZrCl2
AlMe3
Cp2ZrCl2
AlMe3
TMS
Br
TMS
SO2Ph 2) CH3(CH2)5Br
Br
(CH2)4CH3
(CH2)5CH3
1) BuLi
AlCl3
SO2Ph Et2O/ClCH2CH2Cl
Mechanism:
(CH2)5CH3
JACS, 1984, 6105
(CH2)4CH3
DIBAL Bu
Bu
PhCOCl
Pd(PPh3)4
TMS
TMS
THF
AliBu2
H
71%
Bu
JACS, 1986, 1098
TMS
H
Ph
Ph
51% O
O
Bull. Chem. Soc. Jpn., 1985, 2425
OPO(OPh)2
1) LDA
Ph
H
2) ClPO(OPh)2
cat. CuCN
Et2AlSnBu3 Ph
H
Et2O
SnBu3
Ph
Et2Al
H
Pd(PPh3)4
Ph
H
Bu3Sn
H
Et2Al
Ph
70%
Bull. Chem. Soc. Jpn., 1984, 108
88%, 79:21
H
SnBu3
H
HO
Tet. Lett., 1984, 2151
OTIPS
HO
MeSSMe2 BF4
ClCH2CH2Cl
SMe
LiEt2Al
R
SMe
2
TIPSO
THF/toluene
SMe2
BF3
OTIPS
88%
OTIPS
TIPSO
KHMDS
NaAlH(OCH2CH2N(CH3)2)3
D/H
THF, -78oC
OTIPS
50%
enroute to the Kedarcidin core
(CH2)4CH3
JACS, 1984, 4623
Tett. Lett., 1998, 9633
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
N
O
Mikkel Jessing
OH
AlMe3
N
Cl
84%
Tetrahedron, 1988, 5001
Mechanism:
AlMe3
Cl2ZrCp2*
R
CH3(CH2)5 88% 72% ee
Bu
92% 74%ee
c-Hex
80% 65% ee
Bn
77% 70% ee
HO(CH2)4 79% 75% ee
Et2N(CH2)3 68% 71% ee
JACS, 1995, 10771
i
R
OH
DCM
2)O2
Cp* =
CH3(CH2)5 64% 92% ee
i
Bu
77% 90%ee
Bn
69% 93% ee
Et2N(CH2)3 56% 95% ee
JACS, 1996, 1577
For AlEt3:
DIBAL
O
Ni(acac)2
OBn
O2
O
i
Bu2Al
77%
O
R
HO
OBn
OBn
42%
JACS, 1997, 6478
cat, R3B
Cl2AlH
AlMe3
Cl2ZrCp2*
E+
Et2O
OH
Et
Si
AlCl2
60-80%
OH
DCM
2)O2
E
JACS, 1983, 6036
CH3(CH2)9
cat. Et3B
Cl2AlH
CH3(CH2)9
Et2O
AlEt3
Cl2ZrCp2*
CH3COCl
AlCl2
Cl
CO2Me
n
82%
O
O
CH3(CH2)9
OMe
71%
OMe
JACS, 1995, 10771
For AlEt3: 66% 96% ee
JACS, 1996, 1577
n
Oct
AlEt
O2
Oct
OH
OH
hexane
CH3(CH2)9
JACS, 1983, 6036
OMe
n
81% 74% ee
Si
Syn. Commun., 1988, 1029
Oct
AlEt3
Cl2ZrCp2*
CH3CHCl2
n
Oct
H
Al
Et
Et
Et
O2
n
Oct
H
OH
65% 33%ee
63% 92% ee
Et
JACS, 1996, 1577
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
AlMe3, CH2I2
CH3(CH2)9
CH3(CH2)9
DCM
with CH3CHI2: CH3(CH2)9
OH
Al, PbBr2
X
98%
Mikkel Jessing
DMF or
THF or
MeOH/H2O
94%
R2
O
R1
Other electrophiles:
CHO
CO2Me (2 allyls)
CN (2 allyls)
RN=R1R2
CH(OMe)2 (1 or 2)
R1
71-99%
R2
JOC, 1985, 4412
OH
O
R1
OH
i
Bu3Al/CH2I2
Et2Zn/CH2I2
OH
76
2
1
74
H
Al, PbBr2
R1
CX4, DMF
H
OH
OH
time or acid
CX3
X
R1
75-97%
X
4
3
OH
Br
JOC, 1985, 4412
R
R2
CHO
Al, CrCl2, NiBr2
R
R2
TMSCl, DMF
R1
R1
25-83%
NHK catalytic in Cr
AlMe3
CCl4
DCM
Cl
86%
I
R
Al, PbBr2
N
CCl3
R
AlMe3
CF3I
R
Br
AlMe3
BrCCl3
R
CCl3
R
R1
95%
R2
CF3
76%
OMe
Chem. Lett., 1985, 1689
Ar
OMe
R
NH HN
TFA or AlBr3
R1
THF
2) hydrolysis
R2 R 2
Al, PbBr2
OMe
AlBr3, THF
Ar
R
R1
63-90%
Ar
OMe 37-90%
Curr. Org. Chem., 2004, 1027
Organoaluminium in Synthesis
Baran Group Meeting
3/27-2010
H
H
H
AlPr3
H
N
N
I
Mikkel Jessing
Br
TMS
Br
DIBAL
H
OTs
N
60%
AlMe3
Cp2ZrCl2
ZnCl2
Pd2(dba)3
TFP
N
H H H
pumillotoxin C
JACS, 1983, 2831
Me
OMs
H
N
Et2AlCl, hexane
-78 oC
Me
(CH2)4CH3
Me
48%
O
Me
2) rt OTMS
Me
Me
β-carotene
90%
(CH2)4CH3
Mechanism:
multiple steps
3different reaction
sequences
53%
Me
Me
Me
γ-carotene
Me
Me
OH
48%
R
N
OTMS
R
AlMe3
Cl2ZrR*2
H2O
R3Al
NH
DCM
Ph
NH
Ph
Bu
71% (3:2)
77% (1:1)
TMS
55% (1:1)
n
1) CuI/DMF
73%
NH
2) Na/NH3
80%
Me
Ph
TMS
TIPS
Ph
DCM
2)O2
Me
TIPS
68% (3.7:1)
N
H
OH
Org. Lett. 2001, 719
Vitamin A
Me
OH
TIPS
1) TBAF
2) AlMe3
Cp2ZrCl2
then I2
DCM
3)TBSOTf
crude 85%, 73% ee
pure 63%, 97% ee
Me
I
Me
84%
OTBS
Chem. Eur. J., 2008, 311
Ph
Pure & Appl. Chem., 1983, 1853