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

306 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
ring-fused polycyclic compounds (445) and (446). Thermal rearrangement of
(445) and (446), at acidic conditions (trißuoroacetic acid [TFA]), leads to the
tricyclic β-lactams (447) and (448). At the reaction conditions shown, (447)
undergoes lactam-amide bond cleavage to yield the bicyclic N -trißuoroacetylated
β-amino acid derivative (449) (Scheme 2.219) (717).
Stereochemical control of intramolecular 1,3-dipolar cycloadditions by route
b (Scheme 2.211) was realized in the asymmetric synthesis of 1-azaspiro[4.5]
decanes by using the chiral (2 R)-bornane-10,2-sultam (X*) auxiliary in the dipolarophilic
fragment (Scheme 2.220) (718).
Stereoselectivity and regioselectivity have been experimentally and theoretically
studied in the reactions of intramolecular nitrone-alkene cycloadditions
(INAC) of 6-heptenoses derived from carbohydrates such as D-ribose (450a,b)
(Scheme 2.221) and D-arabinose derivatives (451a,b) (Scheme 2.222) (719).
It has been found that the stereoselective outcome in these INAC reactions
is strongly affected by the 2,3-O-isopropylidene blocking group in D-ribose
derivatives (450a,b) (Scheme 2.221) and by the 2,3-O-trans-diacetyl blocking
group in D-arabinose derivatives (451a,b) (Scheme 2.222). It is also affected
by the stereochemistry of the substituents. Stereochemical directions in these
reactions have been explained by calculating transition state energies. Nitrones
(450a,b) with a 2,3-O-isopropylidene cycle undergo INAC reactions to give
1. PCC, CH2Cl2
25°C, 3 h
( ) n
2. MeNHOH HCl
Et3N, 3 Å MS
( )n Me
+
N
OH
−
O
n = 1 (78%)
443 n = 1
n = 2 (70%)
444 n = 2
HO 2C
N
H
O CF3 449 (71%)
O
N
H
448 (66%)
O
N
H
447
Scheme 2.219
O
N
Me
H
( )n
445 n = 1 (58%)
446 n = 2 (58%)
TFA, MeCN
reflux, 15 min