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

(a)
REACTIONS OF DIPOLAR 1,3-CYCLOADDITION ([3 + 2] CYCLOADDITION) 331
(b)
Ph 2P
O
Ph2P O O O N
R
R
+ −
N O
PhMe
85 ° C
C(O)Ph
Ph N +
−
O
CH2Cl2
r.t.
Ph 2P
535 a–c 536 a–c
O
Ph2P 535 a–c 537 a–c
Scheme 2.251
5'
R
R
5
1
4
O
2
3
N
Ph
O
a R = H
b R = Me
c R = Et
Ph
a R = H
b R = Me
c R = Et
product: (536a), in reactions (a) and (537a) inthoseof(b) (Scheme 2.251). With
α-chiral alkenes (535 b,c), the reactions are still believed to involve exo transition
states. Two diastereoisomeric products are formed, of which the major exerts anti
stereochemistry across the 5,5’chiral centers.
Cycloaddition of nitrone (26) to allylamine (538) leads to the synthesis of
chiral tetracyclic isoxazolidine (539) which is used in the preparation of compound
R107500. This compound has been found to be active as an antiolytic
and antidepressant. It also has the potential to inhibit drug abuse (Scheme 2.252)
(80).
Dipolarophiles D4 . 1,3-Dipolar cycloaddition between acrylonitrile (D4) and
chiral nonracemic nitrones is a key step in an efÞcient synthetic route to isoxazolidinyl
analogs of thiazofurin (540) (Scheme 2.253). Opposite diastereofacial
induction was observed when the chiral group was placed at either the carbon or
the nitrogen atom of the nitrone function (753).
The 2-isoxazolidine nitriles (540b) and (540a) obtained, were further converted
into the enantiomeric target compounds (541) and (542) by producing
the thiazole ring via condensation with L-cysteine (Scheme 2.254) and (Scheme
2.255) (753).
Dipolarophiles D5 . Electron-deÞcient alkenes based on acrolein and its
analogs are widely used as dipolarophiles. To carry out asymmetrical 1,3-dipolar
cycloadditions between various nitrones and acrolein, the bis-titanium catalyst
(543) (Fig. 2.37) was used as the chiral Lewis acid (Table 2.22) (754a).
In enantioselective, 1,3-dipolar cycloadditions of nitrones to methacrolein the
catalysts used were (η 5 -C5Me5)MR-Prophoscontaining complexes (M = Rh, Ir
and (R)-Prophos = 1,2-bis(diphenylphosphino)propane) (754b).
Cationic 3-oxobutylidenaminatocobalt complexes (544a), with hexaßuoroantimonate
as a counter anion, activate α,β-unsaturated aldehydes in 1,3-dipolar