Chemistry Reference
In-Depth Information
10.1
INTRODUCTION
Although the existence of nitrenium ions has long been appreciated and their role as
agents of carcinogenesis studied extensively,
1
the potential of these
N-
electrophiles
as tools for target-directed synthesis has only recently begun to be realized in earnest.
That from a synthetic standpoint, nitrenium ions have hitherto been viewed as the
poor cousins of cations, carbenes and nitrenes, their isoelectronic congeners within
the electron-deficient branch of the reactive intermediate family, is keenly apparent
from the comparatively small amount of published work concerning synthetic
applications of these cations (Fig. 10.1). While this neglect undoubtedly reflects
the harsh and consequently limiting reaction conditions historically associated with
their generation, the development of milder methods to access heteroatom-stabilized,
singlet nitrenium ions has recently opened the door to the more widespread
application of these valuable intermediates.
Our goal at the outset of writing this chapter was not to compile an exhaustive
catalog of nitrenium-based transformations, but rather to place modern synthetic
nitrenium ion chemistry in a historical context and bring to the attention of the reader
those observations and applications that best illustrate the potential, and possible
pitfalls, of these versatile, yet underemployed reactive intermediates.
Notwithstanding several notable accomplishments in the field of organic synthe-
sis, to date, the majority of the published work concerning nitrenium ions has been
devoted to the study of their generation, proof of their discrete existence, their
electronic structure, and their fate in biological systems. Since this extensive body of
work has been comprehensively reviewed,
2,3
we will only briefly discuss the
electronic structure of nitrenium ions as it pertains to chemical reactivity. After
preemptively summarizing the transformations characteristic of singlet and triplet
ground-state nitrenium ions, we will initiate our review proper with a discussion of
the chemistry of the parent nitrenium and alkyl nitrenium ions. Subsequent sections
will focus on the synthetic application of more tractable
N
-electrophiles, including
aryl and mono-heteroatom-substituted nitrenium ions. While the reaction between
electrophiles and alkenes is among the most fundamentally important and well-
studied processes in organic chemistry, the involvement of nitrenium ions in this
23421
9059
5273
745
Carbene
Carbocation
Nitrene
Nitrenium ion
FIGURE 10.1.
Number of citations in a SciFinder Scholar keyword search conducted on
April 16, 2010. Duplicate citations could not be removed in the case of the carbene and
carbocation searches.
