Handbook of Functionalized Organometallics Applications in S

12.3 Functionalized Organotitanium Derivatives
Obviously, as carbonyl derivatives react with titanium derivatives the presence
of functional groups is therefore limited.
However, a very useful adaptation of the original protocol for the conversion of
esters to cyclopropanols with titanacyclopropane towards a highly versatile preparation
of cyclopropylamines has been developed [68]. N,N-dialkylaminocyclopropanes
with up to three additional substituents are readily obtained from carboxylic
acid N,N-dialkylamides and ethyl- as well as substituted ethylmagnesium bromide
in the presence of titanium tetraisopropoxide. These transformations were also
possible with substoichiometric amounts of Ti(OPr-i) 4, but the yields were significantly
better with stoichiometric amounts.
If titanacyclopropane reacts faster with one of the reagents, namely the ester or
the dialkylamide, the functionalized cyclopropyl derivative can be selectively
obtained. In the hydroxycyclopropanation of alkenes, esters may be more reactive
than N,N-dialkylamide when succinic acid mono ester monoamide 74 was used
(Scheme 12.49) [69]. However, the reactivities of both ester, as well as amide-carbonyl
groups can be significantly influenced by the steric bulk around them.
Thus, in an intermolecular competition for reaction between N,N-dibenzylformamide
75 and tert-butyl acetate 76 as well as between N,N-dibenzylacetamide 77
and tert-butyl acetate 76, the amide won both times to yield only the corresponding
cyclopropylamine (Scheme 12.49).
H
Me
N
O
75
O
77
O
74
NBn 2
NBn 2
Scheme 12.49
+
+
O
OMe
O
76
O
76
+ OTiPS
OBu-t
OBu-t
EtMgBr
MeTi(OPr-i) 3
20 ºC, 14 h
BuMgBr
MeTi(OPr-i) 3
20 ºC, 60 h
c-C 5H 9MgCl
ClTi(OPr-i) 3
40%
Et
NBn 2
87%
+
E/Z = 2.1/1
TIPSO
Me
NBn 2
O
OBu-t
Organozinc reagents are less nucleophilic than organomagnesium compounds
and can be easily prepared with a variety of functional groups (see Chapter 7), several
of them were tested for the reductive cyclopropanation of amides. Therefore,
a new protocol was devised for the efficient preparation of various tert-butoxycarbonyl
and chloroalkylsubstituted cyclopropylamine derivatives (Scheme 12.50)
[70].
OH
58%
O
527
N