Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

REACTIONS OF DIPOLAR 1,3-CYCLOADDITION ([3 + 2] CYCLOADDITION) 321
Isoxazolidine cycloadducts (491) undergo easy transformation into α-aminoγ-lactones
(494), which can be readily converted into γ- hydroxy-α-amino acids
(495) (Scheme 2.240) (Table 2.19).
Cycloaddition of N -substituted C -phosphorylated nitrones (496) to terminal
alkenes leads to C-5 substituted isoxazolidines (497) and (498) with moderate
(20%) to high (up to 90%) trans to cis diastereoselectivities (Scheme 2.241)
(Table 2.20). In ZnCl2-catalyzed cycloadditions, mixtures enriched in cis diastereomers
were produced (263).
Improvements in 1,3-dipolar cycloaddition were achieved at high pressures
(15 kbar) (74), and by solvent-free microwave activation (739).
Brandi et al. performed 1,3-dipolar cycloadditions of nitrones (499) to methylenecyclopropane
(500). The resulting isoxazolidines (501), on subsequent heating,
were transformed to piperidones (502). Addition of nitrone (499) tobicyclopropylidene
(503) yielded isoxazolidines (504), which upon heating, gave
piperidones (505) with annulated spirocyclopropane groups (Scheme 2.242) (740,
741). Compounds arising from 1,3-dipolar cycloadditions of appropriately substituted
cyclic nitrones, for instance DMPO, lead to aza analogs (507), having
the structure and major functionalities of the cytotoxic illudines and ptaquilosides
(741).
Dipolarophiles D3 . 1,3-Dipolar cycloadditions of suitably functionalized
cyclic nitrones with terminal alkenes, which have potential leaving groups X
at the end of the alkane chain -(CH2)n- (D3), were successfully used for the
synthesis of pyrrolozidine, indolizidine and quinolizidine alkaloids, such as ( + )and
(−)-lentiginosine, a potent amyloglucosidase inhibitor (Scheme 2.243) (742).
Reductive cleavage of the N–O bond in the cycloadduct is important for the
subsequent cyclization to pyrrolozidines, indolizidines, and quinolizidines.
MeN
Bu t
−
O
O H
O
N
O
491 a-c
+
NH 3 OH
495 a-c
R
R
1. Zn/HOAc/Ac2O 2. K2CO3/MeOH, reflux
68%
Scheme 2.240
MeN
Bu t
R
O H
NR
OR
492 a-c (R = Ac)
493 a-c (R = H)
99%
O
R
6N HCl/THF, reflux, 22h
O NH 3Cl
494 a-c