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

352 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
Tol
O
S
+
−
H
O
O
OEt
R
N
O
1
+
−
Kinetic control conditions:
Thermodynamic control conditions:
R 1
N
O
R 2
+
−
:
R 2
N
O
− +
551
R 1
;
R 2
O
H
Tol
O
S
N
O
H
H
endo
OEt
major (98%–80%)
minor (2%–13%)
Me
N
−
O Ph
+
585
Scheme 2.274
+
R 1
reflux or longer times
R 2
O
H
Tol
+ O
S
N
O
−
exo
H
H
OEt
minor (2%–20%)
major (98%–87%)
stereoselectivity of these reactions suggests that the sulÞnyl group plays a
signiÞcant role by facilitating the cyclo-reversion (787).
Cyclo-reversions proceed readily in reactions of enantiopure D7i and D7i ent
with cyclic (551) and acyclic (585) nitrones. The sulÞnyl group in lactones D7i
and D7i ent controls the π-facial selectivity and is also controller of the endo/exo
selectivity (Scheme 2.274) (788).
Dipolarophiles D8 . 1,3-Dipolar cycloadditions of acrylamide with cyclic
nitrones (626) and (627) have been employed in the synthesis of new dipeptide
isosteres with a pyrrolizidinone skeleton (789). Treatment of nitrones (626)
and (627) with acrylamide (2 equiv) in water at 60 ◦ for 14 h afforded a mixture
of adducts with similar regioselectivity, favoring the 2-substituted adducts (628,
630). The trans-(632a, 633a) andcis-(632b, 633b) pyrrolizidinones were readily
obtained from the exo-(628a, 630a) andendo-(628b, 630b) adducts by hydrogenation
in the presence of a catalytic amount of Pd(OH)2 and 10 mol equiv. of
AcOH (Scheme 2.275).
1,3-Dipolar cycloadditions of 2-tert-butoxycarbonyl-1-pyrroline N -oxide
(627) with several chiral acrylamides (634a–f) (Scheme 2.276) followed by
hydrogenolysis of cycloadducts (635) and (636) has been used in the synthesis of
enantiopure tert-butyl (2R,7aR)- and (2S ,7aS )-2-hydroxy-3-oxo-tetrahydro-1H -
pyrrolizine-7a(5H )-carboxylates, useful intermediates for the synthesis of Gly-
(s-cis)Pro dipeptide mimetic (790).
The regioselectivity and diastereoselectivity of these reactions were strongly
dependent on the chosen chiral auxiliary X. Regioisomeric ratio (635)/(636)
changed depending on the acrylamide structure: (a) 77:23, (b) 86:14, (c) 67:33,
(d) 69:31, (e) and (f) 100:0. In all cases a substantial endo selectivity in