Chemistry Reference
In-Depth Information
In the context of the aforementioned applications of intermolecular C- H insertion
α
to nitrogen, it is clear that this rhodium(II) carbenoid-mediated methodology consti-
tutes a powerful strategic organic reaction. It can be considered a surrogate for the
asymmetric Mannich reaction (Scheme 4.27 ) [14,66,221] .
Mannich
reaction
O
NHR'''
O
O
NR
2
'''
NHR'''
Rh
R
R
R''
R
R''
R''
R'
R'
R'
Scheme 4.27.
C -H insertion
α
to nitrogen as a surrogate to the Mannich reaction.
to oxygen in ethers
[210,211,222,223]. Insertion of various aryldiazoacetates
95
into tetrahydrofuran (THF)
(Scheme 4.28) catalyzed by Rh
2
(
S
- DOSP)
4
proceeds in 56-74% yield with excellent
enantioselectivity (95-98% ee) [210,211]. However, the diastereoselectivity is low to
moderate (23-60% de). The remarkable chemoselectivity displayed by the donor/accep-
tor carbenoids was also exemplifi ed here since good yields were obtained with only two
equivalents of THF present in the reaction mixture [210,211]. The reaction between
methyl phenyldiazoacetate and THF was reported by Fraile, Mayoral, and others to be
effectively catalyzed by immobilized Cu-Box complexes, which gave up to 88% ee and
50% de for the insertion product [224].
Another favorable process is the intermolecular C-H insertion
α
Ar
Ar = Ph
2-Nap
4-(Cl)Ph
4-(Me)Ph
4-(MeO)Ph
CO
2
Me
Ar
O
Rh
2
(
S
-DOSP)
4
O
CO
2
Me
N
2
Hexanes, -50°C
H
9
5
121
56-74% yield
23-60% de
95-98% ee
1
2
2
Scheme 4.28.
C -H insertion
α
to oxygen in THF.
Silyl ethers proved to be excellent acyclic substrates for this chemistry, particularly
as the diastereoselectivity was effectively controlled [222,223]. For example, tetraalk-
oxysilane
123
(Scheme 4.29) underwent insertion with methylphenyldiazoacetate
104
in
70% yield, >90% de, and with excellent enantioselectivity (95% ee) [223]. Another
example is allyl silyl ethers
125
(Scheme 4.30), which are effective substrates amenable
to insertion in 70-71% yield, 96-98% de, and 74-85% ee [222]. This chemistry can be
effectively controlled, as when the silyl protecting group is substituted for an acetoxy
group, the adjacent position is electronically deactivated for insertion due to the elec-
tron-withdrawing nature of the carbonyl group [222,223,225]. Oxygen in the β - position
to a methylene site deactivates it for insertion, presumably because of the inductive
electron-withdrawing effect [225]. These types of products can readily be converted into
the corresponding
syn
- β-hydroxy esters, which are typically obtained via the asymmetric
aldol reaction [14,66,226] .
