Factors influencing the reverse-Cope approach to 1,2,5-oxadiazinanes from allylamines and nitrones: Optimization of a new vicinal diamine synthesis

The reverse Cope cyclisation: a classical reaction goes backwards

“…These and a number of related examples showed that the overall sequence was retarded by both electron-donating and, especially, electron-withdrawing substituents. 40 In line with many of the foregoing results, the allylamines 216 -218 failed to form oxadiazinanes, probably due, respectively, to too much terminal substitution, an inability to adopt a planar transition state and a lack of amine nucleophilicity. The lengthy reaction times, together with some poor yields, then led us to use other nitrones, when we discovered that the phenyl group of the nitrone 184 engendered a significant overall rate retardation.…”

“…40 All of the foregoing trends were seen again in reactions between allylthiol and aldehyde-derived nitrones (Scheme 61). 41 These results also provided excellent evidence in support of the overall mechanism (Scheme 50), as the initial reverse Cope products, in this case the 1,3-thiazoline-N-oxides 228, were isolated as the sole products.…”

“…For example, the C-cyclopropylnitrone 219 reacted smoothly with N-methylallylamine 204 (R 1 ¼Me; R 2 ¼H) at ambient temperature, to give a quantitative yield of the oxadiazinane 220 (Scheme 58). 36, 40 The reaction even occurred during 3 days at 220 8C. Unfortunately, this enhanced reactivity was insufficient to overcome the rate retardation present in N-benzylcinnamylamine 206 (Scheme 56) at ambient temperature, while heating resulted in extensive decomposition.…”

“…This proved to be a useful idea: the formaldehyde nitrone 221 reacted very rapidly (,0.25 h) at ambient temperature with N-methylallylamine 204 to give only the oxadiazinane 222, despite the slight inhibiting effect of the N-benzyl group (Scheme 58). 40 The instability of the nitrone 221 led us to generate it in situ; after 18 h at ambient temperature, reaction with amine 204 gave the oxadiazinane 222 along with the amino-hydroxylamine 223 in 95% combined yield and in a ratio of 1 was presumably formed by interception of the Meisenheimer iminium salt intermediate (cf. Schemes 50 and 55) by water.…”

Theoretical study on the mechanism of the reaction for alkene hydroaminations catalyzed by chiral aldehyde

“…As the catalyst, IM0(IM0 0 ) undergoes an attack of allylamine 2 from different faces forming a chiral mixed aminal IM1. In this aspect, the work of Knight et al [30,31] on the reaction of nitrones with allylic amines provided strong support for the formation of the transient hydroxylamine. Then, the addition of the hydroxylamine portion to the highly electron-deficient olefin part produces to a tertiary amine oxide IM2, which is named as the "reverse Cope elimination."…”