Chemistry Reference
In-Depth Information
in the area of rhodium carbenoid chemistry has been the development of donor/accep-
tor-substituted carbenoid precursors, which give carbenoid complexes that are much
more stable and hence more chemoselective [11,42,43,85,130,203,204]. This has been
developed to the extent that many transformations via this route can be considered
strategic synthetic transformations equivalent to many classical organic reactions [66].
4.2.4.1. Asymmetric C-H Insertion into Alkanes
Early attempts to develop intermo-
lecular C-H insertion processes focused on the traditional carbenoid sources that formed
acceptor and acceptor/acceptor carbenoid complexes [10,44,139,205]. Chemoselectivity
was poor however, and carbene dimerization was a prominent problem. For example,
reaction of ethyldiazoacetate with common dirhodium(II) catalysts in 2-methylbutane
afforded a complex mixture of all possible insertion products [44,205]. Although it was
observed that the product ratio was dependent on catalyst and the C-H bond strength,
no methods were developed that effectively controlled the reaction outcome. Recently,
the C-H insertions of acceptor carbenoids have been improved by using bulky copper
and silver catalysts, but asymmetric examples have yet to be reported [103,198-202].
The only carbenoid system that has been applied extensively in chemo- and stereose-
lective intermolecular transformations is the donor/acceptor carbenoid class, particularly
based on aryl- and vinyldiazoacetates [3,11,14,16,42,43,66,206]. The extra stabilization
of the carbenoid, imparted by the donor group, renders these species signifi cantly more
selective and effectively suppresses carbene dimerization [3,49]. The substrate can even
be used as a limiting reagent in many cases, which is quite unusual in the area of metal
carbenoid chemistry, since excess trapping agent is commonly used to suppress side
reactions of the highly reactive intermediate [207-209]. The fi rst practical, highly enan-
tioselective intermolecular C-H insertions were carried out with cycloalkanes as sub-
strates [206,210]. A variety of aryldiazoacetates (
95
) were decomposed in cyclopentane
and cyclohexane with Rh
2
(
S
- DOSP)
4
as catalyst and underwent intermolecular C- H
insertion in 23-81% yield with 88-96% ee under optimal conditions (Scheme 4.19) [211].
Electron-donating aryl groups tend to decrease the yield of the insertion product, pre-
sumably because the carbenoid is less electrophilic. Furthermore, the enantioselectivity
drops with increasing ester group size, which is characteristic for this catalyst system
[210,211]. A range of other alkanes can be effectively functionalized (Fig. 4.9) with
remarkable chemoselectivity by this method [206]. In general, the insertion occurs into
the weakest C-H bond, but due to steric requirements, methylene sites are approxi-
mately as reactive as methine sites. Primary sites are the least reactive [211]. Insertion
into adamantane gave only the tertiary insertion product
98
in 67% yield and 90% ee.
Further studies on acyclic alkanes (products
99 - 101
) led to the use of 2,2-dimethylbutane
(2,2-DMB) as a suitable, inert nonpolar solvent for this chemistry [11,43,206,210,211].
For Rh
2
(
S
- DOSP)
4
catalyzed C-H insertion, the major product enantiomer can be
rationalized based on a simple model in which the catalyst is considered to exist in a
Ar
CO
2
Me
Ar
Ar = Ph
4-(Br)Ph
4-(Cl)Ph
4-(Me)Ph
4-(CF
3
)Ph
Rh
2
(
S
-DOSP)
4
Solvent, 10°C
N
2
CO
2
Me
n
n
n
= 1,2
23-81% yield
88-96% ee
9
96
9
7
Scheme 4.19.
C -H activation of cycloalkanes.
