Nitrones, addition onto

Chiral nitrones were used in [3+2] qrcloadditions for the resolution of olefinic compounds. 1,3-Dipolar addition of an enantiomericaUy pure 3,4-dihydroxypyrrolidine-derived nitrone 61 onto racemic 2,3-dihydro-l-phenyl-IH-phosphole 1-oxide 62 led to a regio- and stereoselective formation of cycloadducts 63 and 64 combined with an efficient resolution of the phosphole oxide 62 [59]. The nitroxide 61a afforded a 66% yield of a 10 1 diastereomeric ratio for 63 64, the recovered phosphole 62 (21% yield, calculated on l.Sequiv phosphole initially involved) showing 59% ee. An increased (96%) ee for unreacted 62 was obtained from the reaction of 61b at higher conversion (91% yield of 63 64, calculated on nitrone). However, under these latter conditions, the yield of recovered (S)-62 was around 20% and the diastereoselectivity for 63 64 only 2.9 1. 

The electrophile-induced cyclization of heteroatom nucleophiles onto an adjacent alkene function is a common strategy in heterocycle synthesis (319,320) and has been extended to electrophile-assisted nitrone generation (Scheme 1.62). The formation of a cyclic cationic species 296 from the reaction of an electrophile (E ), such as a halogen, with an alkene is well known and can be used to N-alkylate an oxime and so generate a nitrone (297). Thus, electrophile-promoted oxime-alkene reactions can occur at room temperature rather than under thermolysis as is common with 1,3-APT reactions. The induction of the addition of oximes to alkenes has been performed in an intramolecular sense with A-bromosuccinimide (NBS) (321-323), A-iodosuccinimide (NIS) (321), h (321,322), and ICl (321) for subsequent cycloaddition reactions of the cyclic nitrones with alkenes and alkynes. 

Addition of nityl tnol tthen to ii/f/wireiies. In the presence of 1 equiv. of TASF, silyl enol cthcis add to nitroalkcncs to form unstable ortho and/or pare nitronates, which are oxidized in situ by Brj or DDO to niuoaryl catbonyl coni pounds. Hie position of substitution depends on the substitution pattern of the atene and the size of the silicon reagent. With less hindered silyl derivatives onto addition is strongly favored. 

Being anionic carbonyl synthons, the nitroalkanes have been explored extensively for their conversion into the corresponding carbonyl compounds. For example, the embedment of a nitroalkane onto an activated basic silica gel or the blockage of the C-protonation of nitronate with a protonated concave pyridine. The reaction under the latter condition is called the soft Nef reaction. In addition, the introduction of a y-trimethylsilyl group is proved to smooth the Nef reaction. Moreover, when a primary nitroalkane is treated with nitrite/acetic acid, a carboxylic acid is resolved. Furthermore, the oxidative Nef reaction has successfully converted the nitro cyclohexadienes into the substituted phenols via a nucleophilic addition. 

A few years later, the same authors reported a second synthesis of hyacinthacine A2 starting from the same sugar-derived nitrone 31 [14]. This approach was very close to the one previously described by Martin et al. [12], the key step being based on the RCM of the same diolefin intermediate 29 (Scheme 5). The nucleophilic addition of vinylmagnesium bromide onto 31 led diastereoselectively to hydroxylamine 36, proceeding by the less... 

There has been no report so far of a synthesis of (+)-hyacinthacines Ci, C4, and C5 bearing substituents at each carlxMi of the pyrrolizidine skeleton. Therefore, their absolute configurations have yet to be determined. Yu and colleagues described recently the total synthesis of the proposed structure of ( )-hyacinthacine C5 [21] based on an original nucleophilic addition of a dithiane onto the xylose-derived nitrone 62 followed by a Cope-House cycli-zation (Scheme 13). 

Intramolecular Michael Addition of Nitronates onto Conjugated Esters... 

The bridged oxazines were afforded via a nitrone-tethered cyclopropane, which was formed in situ from a condensation reaction between an aldehyde-tethered cyclopropane and a hydroxylamine. This was followed by an intramolecular cyclization upon addition of Yb(OTf)3. It was noted that the presence of an electron-withdrawing or electron-donating group on the cyclopropane tethered aldehydes did not affect the efficiency of the reaction, producing adducts in excellent yields. The mechanism of the reaction was thought to take place via an attack of the malonate ion onto the iminium... 

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