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

REACTIONS OF DIPOLAR 1,3-CYCLOADDITION ([3 + 2] CYCLOADDITION) 319
Table 2.17 1,3-Dipolar cycloaddition of C-α-alkoxyalkyl-substituted nitrones to
styrene
Yield erythro- threo- erythro- threo- erythro:
Entry Nitrone (%) cis cis trans trans threo cis:trans
1 479 a 94 82 9 5 4 87:13 91:9
2 479 b 82 81 12 7 — 88:12 93:7
3 479 c 85 69 17 10 4 79:21 86:14
4 480 84 90 5 3 2 93:7 95:5
The stereoselectivity of these cycloaddition reactions is inßuenced by the steric
hindrance of both, the N -andC -substituent of the nitrone, that is, the selectivity
increases as the nitrogen substituent of the nitrone becomes bulkier. As shown in
Table 2.17, the highest diastereoselectivity in these reactions was observed with
N -benzyl nitrones (479b) and (480).
The major products (481) and (485) were found to have the erythro-conÞguration
at C-3/C-4 ′ and cis-substitution at C-3/C-5. The high diastereoselectivity
found in reactions of (479b) with styrene can be ascribed to the more favored
approach of the dipole (479b) to styrene, to give erythro-cis (481b) andthreo-cis
(482b), as depicted in Fig. 2.34. It is likely reasonable that attack of Z -(479b)
proceeds via the less hindered endo transition state, in an antiperiplanar manner
in regard to the largest group of the heterocyclic acetal to give the major
product, (481b), with C-3/C-4 ′ erythro and C-3/C-5 cis-conÞguration. The more
pronounced steric hindrance, present in the approach to the threo-cis-diastereomer
(482b), might explain the observed ratio erythro/threo 88:12 (Table 2.17).
Chiral oxazinone-derived nitrone (16), being of particular interest as a prototype
for the synthesis of γ-oxygenated α-amino acids, reacts with alkenes (D2)
efÞciently and with high stereoselectivity, to give cycloadducts (489) (Scheme
2.239) (73).
Cycloaddition of homochiral imidazolone-derived nitrone (490) to various
alkenes (D1,D2) (Scheme 2.239) (Table 2.18) affords good yields of cycloadducts
(491 a–c) with high stereoselectivity (738).
Ph
O
H
H O
N
−
O
+
Bn
OH
Major
product
HO
O
+
H N
H O
481b 482b
Fig. 2.34
O −
Bn
Ph