Chemistry Reference
In-Depth Information
O
Tandem
Claisen/Cope
rearrangement
OR
O
R'
RO
R'
R'
O
RO
Rh
R''
R''
R'''
R''
R'''
R''
Tandem
aldol reaction/
siloxy-Cope
rearrangement
O
OR
O
R'
R'
RO
O
R'
RO
Rh
TMSO
R''
R''
O
TMSO
R''
Scheme 4.52.
The
combined
C -H activation/Cope rearrangement as a strategic synthetic
reaction.
siloxy-Cope rearrangement, and can therefore act as a surrogate for this reaction
(Scheme 4.52 ) [66,241] .
4.3. METAL NITRENOID - MEDIATED C
-
H INSERTION
4.3.1. Generation of Metal Nitrenoids and Their Reactions
The amine functional group is commonly encountered in organic synthesis and is an
important component of many biologically active compounds [12,21,218]. Classically,
amine groups have been introduced by nucleophilic substitution, nitration, or additions
to imines [21,242]. The direct introduction of a C-N bond from a C-H bond would
greatly increase the synthetic potential of such transformations [19]. Consequently,
effi cient generation of nitrenes for insertion into C-H bonds has been the subject of
many studies in recent years [12,23,51,77,243-250]. Metal-catalyzed reactions of tosyl-
imidophenyliodinane (
184
, Fig. 4.12), and other
N
- arenesulfonyl imidoiodinanes
183 -
185
, that form metal nitrenoids capable of inserting into C-H bonds, were demonstrated
by Breslow and Gellman [251,252] and Mansuy [9]. This class of compounds was dis-
covered to be relatively effective as nitrene precursors. Mn(III)-, Fe(III)-, or Rh(II)-
catalyzed intra- and intermolecular C-H insertions has been achieved with
tosylimidophenyliodinane
184
[251] . Effective intermolecular C -H amination was later
demonstrated by Muller and others using
p
- nitrophenylsulfonyl imidoiodinane
185
[71,75,77]. This class remains the most widely used among nitrene precursors. They are
typically prepared from an appropriate sulfonamide (ArSO
2
NH
2
), a base and iodoben-
zene diacetate PhI(OAc)
2
or PhI= O as oxidants [253 - 256] .
The mechanism of metal nitrenoid formation is still under debate, but is believed to
occur via an
in situ
-formed iodonium ylide, which generates the reactive metal nitrenoid
intermediate in the presence of an appropriate metal M (Fig. 4.13) [204-214]. If a suit-
able C-H bond is present, the nitrene will insert to form the corresponding sulfonamide.
The major intrinsic factors controlling the selectivity of the nitrene intermediate are (i)
the catalyst and (ii) the electron - withdrawing group [24] .
