Nitrones, addition with Grignard reagents

The diastereoselectivity of the nucleophilic addition to nitrone 2 may be rationalized by assuming that magnesium bromide preferentially coordinates with the nitrone oxygen. The Grignard reagent is therefore forced to interact with the acetal oxygen in position 3. 

On the other hand, following the same sequences from the differently protected serine-derived nitrone 168, through the formation of hydroxylamines 169, C2 epimers of carboxylic acid and aldehydes are obtained, i.e., (2S,3R)-170 and (2S,3R)-171. Moreover, the syn adducts 164 were exclusively obtained in the addition of Grignard reagents to the nitrone 163, whereas the same reactions on nitrone 168 occurred with a partial loss of diastereoselectivity [80]. Q, j6-Diamino acids (2R,3S)- and (2R,3R)-167 can also be prepared from the a-amino hydroxylamines 164 and 169 by reduction, deprotection and oxidation steps. The diastereoselective addition of acetylide anion to N,N-dibenzyl L-serine phenyhmine has been also described [81]. 

O - P h e n y 1 - /V - e r y t h r o s y 1 nitrone (336), as a Ci,C i-bis-electrophile, when subjected to the double addition of Grignard reagents (in a domino style), leads to acyclic hydroxylamine (338) via the formation of open-chain nitrone (337 ). The reaction proceeds at 0°C with variable diastereoselectivity ranging from medium to good, depending on the organometalic reagent used (Scheme 2.140) (564). 

Double addition of Grignard reagents to A-glycosyl nitrones (336), in a domino fashion, affords hydroxylamines. Their usefulness has been shown with the synthesis of pyrroloazepine (418) via a ring closing metathesis key step (Scheme 2.187) (564). 

A sHghdy earher synthesis of (+)-steviamine (eni-352) by Yu and coworkers began with the diastereoselective (de >95%) addition of Grignard reagent 362 to cycHc nitrone 363, derived from D-ribose, to give the adduct... 

The conjugate addition of Grignard reagents to nitroalkenes like 162 leads to magnesium nitronates of type 163, which can be readily converted into nitroalkanes, hydroxymoyl halides, or carlwxylic acids (Scheme 2-64). The reaction of RMgX with nitroalkenes in the presence of CeCls, followed by treatment with 100% acetic acid, has been developed as efficient synthesis of complex nitroalkanes. ... 

Interaction of 3-imidazoline-3-oxide nitroxides with Grignard reagent proceeds with the involvement of the radical center and leads to reduction products 6a,c and methoxy derivatives 35a,c. Meanwhile, in the interaction of methylmagnesium iodide with the methoxy derivatives 1,3-addition to the nitrone group occurs, and 1-methoxy-3-hydroxy-4-alkyl (aryl)-... 

Recently, semiempirical PM3 computational analysis (568) and first ab initio study (569) of the nucleophilic addition to chiral nitrones of Grignard reagents have been carried out. The data revealed that all reactions are exothermic and proceed through /w-complexation of nitrones with the organometalic reagent. 

Organomagnesium compounds add to polycyclic aromatic hydrocarbons under forcing conditions, bnt with electron-withdrawing substituents the addition occurs more easily. Alkyl Grignard reagents add 1,4 and/or 1,6 to nitroaromatics, and the nitronate intermediate may be converted to a number of useful products (equation 45). Aryl Grignards yield hydroxylamines (by means of a 1,2 process), which can be reduced to diarylamines. ... 

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