Biomedical Engineering Reference
In-Depth Information
been extensively employed for the synthesis of a variety of important alkaloid skeletons.
Methods for both [1,2]- and [2,3]-shifts of ammonium ylides have been developed to
allow concise and stereoselective syntheses of indolizidine and related structures, as
well as more complex molecules, such as derivatives of isopavine alkaloids.
In this chapter, we describe the use of rearrangements of ammonium 1,2-ylides
and cycloadditions of 1,3-ammonium ylides with
-systems as methods for the
formation of natural products. While we have mainly restricted our discussion to
examples that actually report the synthesis (or formal synthesis) of a specific natural
product, we have also included some method development to provide context for the
regio- and stereoselectivity of reactions.
p
13.2. AMMONIUM 1,3-YLIDES
13.2.1. Isomunchnones as Dipoles
The 1,3-oxazolium-4-oxide class of 1,3-dipoles (isom
unchnones) can be readily
obtained through the transitionmetal-catalyzed cyclization of a suitable
€
-diazoimide
precursor [1]. Mesoionic oxazolium ylides correspond to the cyclic equivalent of a
carbonyl ylide and these reactive intermediates readily undergo 1,3-dipolar cyclo-
addition with suitable dipolarophiles. The first successful preparation and isolation of
an isomunchnone induced by a transition metal process was described in 1974 [2].
Heating a sample of diazoimide
1
in the presence of a catalytic amount of Cu(acac)
2
afforded a red crystalline material that precipitated from the reaction mixture
(Scheme 13.1). The red solid was assigned as isom
a
unchnone
4
on the basis of its
spectral data and elemental analysis. Mesoionic ylide
4
was found to be air stable for
several weeks and its overall stability was attributed to its dipolar aromatic resonance
structure. Formation of the isom
€
unchnone ring can be rationalized by initial gener-
ation of a metallocarbenoid species, which is then followed by intramolecular
cyclization onto the neighboring carbonyl oxygen to form the dipole [3].
The Padwa [4-6] and Maier [7,8] research groups have further utilized the
Rh(II)-catalyzed reaction of diazoimides as a method for generating isom
€
unchnones.
The starting diazoimides are readily constructed by acetoacylation [9] or malonyl-
acylation [10] of the corresponding amides, followed by standard diazo transfer
techniques [11]. Intramolecular trapping of the rhodium carbenoid by the lone pair of
electrons of the neighboring carbonyl group leads to the desired mesoionic system
6
€
NO
2
PhNO
2
PhNO
2
−
Cu(acac)
2
O
O
-
O
O
O
N
N
N
2
Ar
Ar
CH
3
N
O
CH
3
CH
3
Ar
1
Ar = Ph
2
Ar = p-MeOPh
3
Ar =
p
-BrPh
4a
4b
SCHEME 13.1
Search WWH ::
Custom Search