Chemistry Reference
In-Depth Information
O
MgBr
HO
(
i
-PrO)
3
TiCl
OMe
5.305
5.306
Scheme 5.80
(
i
-PrO)
4
Ti or (
i
-OPr)
3
TiCl
2
n
-BuMgBr
+
CO
2
Me
(
i
-PrO)
2
Ti
5.308
5.307
alkene exchange
OH
intramolecular
Kulinkovich
reaction
(
i
-PrO)
2
Ti
+
CO
2
Me
5.309
5.310
Scheme 5.81
The reaction may be extended to higher Grignard reagents by the use of the more reactive chlorotitanium
tri-
iso
-propoxide, allowing the synthesis of more highly substituted cyclopropanols
5.306
with the two
alkyl groups
cis
(Scheme 5.80).
93
It has also been found that the primary Kulinkovich intermediate, the
titanacyclopropane
5.300
, can exchange with added alkenes. This allows the use of alkenes that are not
compatible with Grignard chemistry, including ester-containing alkenes
5.308
that permit an intramolecular
Kulinkovich reaction giving bicyclic cyclopropanols
5.310
(Scheme 5.81).
94
Amides can also be employed as substrates.
95
The mechanism in this case is subtly different to the
mechanism involving the ester (Schemes 5.82-5.84). If the mechanism were the same, the amino group
would be eliminated and the same product would be obtained. Instead, as with the LiAlH
4
reduction
of amides, the oxo group is eliminated, and the amino group is retained in the product, which is an
amino cyclopropane
5.313
. As with the esters, intramolecular Kulinkovich reactions are also possible
(Schemes 5.85 and 5.86).
96
One application of these highly electron rich cyclopropanols is in their ring opening.
97
This property was
exploited in an approach to benzospiroketals (Scheme 5.87).
98
Kulinkovich reaction of the styrene
5.325
R
(
i
-PrO)
2
Ti
NR'
2
O
R
NR'
2
5
.
3
1
2
5
.
3
1
3
(
i
-PrO)
2
Ti
O
NR'
2
R
5.311
R
(
i
-PrO)
2
Ti
ester-like pathway
- not followed
O
R
HO
NR'
2
5.315
5.314
Scheme 5.82
