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

364 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
C 6H 5CH 2 N
668
+
O
H R
R = Et, Bu t , Ph, 2-Furyl
−
+
O2
S
O
669
toluene
reflux
24 h
Scheme 2.290
O
C6H 5CH 2N
670
H
R
H
H
O
S
O2
or dominant heterocycle substituted at position four by an electron-withdrawing
group (810–812). A remarkably high degree of regioselectivity and stereoselectivity
was also observed in reactions of 1-propene-1,3-sultone (669) with nitrones
(668) (Scheme 2.290) (813).
Cycloaddition reactions of vinyl trimethylsilane with C -glycosyl nitrones gave
moderate to good yields (67%–74%). Estimation of diastereoselectivities from
isolated yields showed total endo preference for the reaction of the D-galacto
nitrone. High endo preference was observed for the D-ribo analog, but exo preference
for the D-xylo one (814).
Recently, dipolarophile D13 (fumaronitrile) (777) has been used in the synthesis
of indolizine lactone (677). Both, intermolecular and intramolecular cycloadditions
were studied. Intermolecular 1,3-cycloaddition of nitrone (671)toD13 led
to the formation of isoxazolidine (672). Subsequent deprotection and esteriÞcation
of the obtained alcohol (673) with (674) gave isoxazolidine (675) in 65% yield.
Ester (675), when reßuxed in xylene for 10 min, after elimination of fumaronitrile
by cyclo-reversion, underwent spontaneously intramolecular cycloaddition
to give the tricyclic cycloadduct (676) in 84% yield (Scheme 2.291).
Dipolarophiles D14 . The 1,3-dipolar cycloaddition of nitrones to dimethyl
maleate and dimethyl fumarate is widely used in the synthesis of polyhydroxy
alkaloid derivatives of dihydroindolizidinone (81), pyrrolizidine (119), (−)codonopsinine,
and ( + )-hyacinthacines A1 and A2 (312). In cases of unstable
nitrones, syntheses of cycloadducts are performed in situ (81).
The highly stereoselective 1,3-dipolar cycloaddition of C -phenyl-N -
glycosylnitrones (336) and (679) to dimethyl maleate D14, with the sugar moiety
acting as a chiral auxiliary, has been used in enantioselective syntheses of
isoxazolidines (678) and (678 ent) (Scheme 2.292) (118).
Cycloaddition reaction of nitrone (−)-(394) with dimethyl maleate D14 has
been used for the synthesis of two new polyhydroxyl pyrrolizidines (687) and
(688) (Schemes 2.293, 2.294). These compounds are analogs of alkaloids rosmarinecine
and crotanecine, which were assayed for their inhibitory activities
toward 22 commercially available glycosidase enzymes. One of them ((−)-7a-epicrotanecine)
(−)-(688) is a potent and selective inhibitor of α-mannosidases
(310). The reaction of (−)-(394) with dimethyl maleate gave a 9.6:6:1 mixture
of cycloadducts (−)-(680), ( + )-(680), and (−)-(681), which arise from anti-exo,