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

REACTIONS OF DIPOLAR 1,3-CYCLOADDITION ([3 + 2] CYCLOADDITION) 307
X
•
O
+
N
O
−
•
X =
S
O2
toluene, heat
0.01 M
N
Scheme 2.220
exclusively cis-fused isoxazolidines (cyclohexanols) (452a,b) (Scheme 2.221).
Nitrones (451a,b) with 2,3-O-trans-diacetyl blocking groups give a mixture
of cis-(457a,b), trans-(458a,b) and bridged bicyclo[4.2.1]isoxazolidines (cycloheptanols)
(459a,b) and (460a,b) (Scheme 2.222). The bridged isoxazolidines
(cycloheptanols) (459a,b) and (460a,b) were synthesized for the Þrst time from
unbranched sugar derivatives (451a,b). These INAC reactions showed insigniÞcant
temperature dependence, but important solvent dependence. In the case of
nitrones (451a,b), the INAC in 2-propanol gave the highest yield of fused isoxazolidines
(cyclohexanols) (457) and (458), whereas the INAC in dichloromethane
afforded the highest yield of bridged isoxazolidines (cycloheptanols) (459) and
(460) (719).
According to general (or principal) Scheme 2.211b, intramolecular 1,3-cycloadditions
of nitrones derived from 3-oxa-6-heptenals (461) and (462) proceed
stereoselectively, leading to cycloadducts (463–465) (Scheme 2.223) and
(466–468) (Scheme 2.224) in good yields (720).
In agreement with Schemes 2.211b and 2.211c, intramolecular cycloadditions
of nitrones to 5-allyl- (Scheme 2.225) or 5-homoallylproline (Scheme 2.226),
are fully regio- and stereoselective. These reactions are the key steps in the
synthesis of functionalized azaoxobicyclo[X .3.0] alkane amino acids, mimics of
a homoSer-Pro dipeptide (721).
As shown in Scheme 2.211d, starting with N -allyl carbohydrate-nitrones (469),
a series of chiral six- (470) and seven-membered(471) N -heterocycles were
synthesized (Scheme 2.227). A very interesting and useful aspect of this cycloaddition
is the control of regioselectivity by the substitution at the nitrogen atom.
Therefore, it is possible to direct reactions towards the syntheses of preferred
six- or seven-membered heterocycles from carbohydrate derivatives (722).
Similarly, according to Scheme 2.211 d, the INAC reaction of N -allylcarbohydrate
nitrone (472) gave the pyrrolo[1,2-a]azepine derivative (473)
(Scheme 2.228) (723).
X
•
X
•
O
O
N
O
41%
+
N
O
49%
H
H