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

APPLICATIONS OF NITRILE OXIDES 87
Intramolecular nitrile oxide—oleÞn cycloaddition of oxazolidine and thiazolidine
oximes 407 (R = H, Me; R 1 = H, Me; X = O, S; n = 1,2) proceed stereoselectively,
yielding tricyclic fused pyrrolidines and piperidines. Thus, 407 (n = 2;
R = H; R 1 = Me; X = S) has been oxidized to the nitrile oxides with sodium
hypochlorite, in the presence of triethylamine in methylene chloride, to give
the isoxazolothiazolopyridine 408 in 68% yield. Reduction of 408 with lithium
aluminum hydride affords mercaptomethylmethylpiperidine 409 in 24% yield
(448).
R
X
N OH
N
CH 2 CH CH 2
n
O
407
S
O
H
N
N
408
O
H
Me
Me
HS
Me N
NH 2
409
OH
Me
Me
Examples of one-pot 1,3-dipolar cycloaddition in water have been described,
affording novel benzopyran, quinoline, and cyclophane isoxazolines (Scheme
1.49) (38).
A variety of cyclic ethers, 410, have been obtained via both, solution-phase
and polymer-supported methods in the [3 + 2] cycloadditions of nitrile oxides to
alkenes and dienes to give isoxazolines (Scheme 1.50). Both simple and substituted
dienes have been found suitable for polymer-supported formation of cyclic
ethers of ring sizes Þve through seven (449).
Chiral 10 to 12-membered nitrogen and oxygen heterocycles, fused to isoxazoline
rings have been prepared with high regio- and stereoselectivity by INOCs of
tethered N- and O-allyl carbohydrate derivatives. The use of a -Y-Ar-CH2 tether,
containing a 1,2-disubstituted aromatic ring between the heteroatom attached to
X = O, NH
CH=NOH
X Ph
CH=NOH
O
O
NaOCl
H2O or H2O-THF
NaOCl
H2O or H2O-THF Scheme 1.49
N O
X
O
H
N O
Ph
O
O
O
O N