Nitrones organometallic reagents

Table 6. Addition of Organometallic Reagents to Racemic Nitrones S8-9...

Michael addition of alkyl organometallic reagents to a,/ -disubstituted nitroalkenes followed by protonation of the intermediate nitronate anion generally gives mixtures of syn- and anti-diastereomers with poor diastereoselectivity19. 

Nitrones have a more reactive C=N bond toward nucleophilic addition compared to imines. In spite of this fact, there have been only a limited number of studies on the nucleophilic addition reactions of nitrones, particularly organometallic reagents.352-355 During the last decade, research related to reactions of nitrones with zinc-containing reagents was essentially focused on (i) dialkylzinc-assisted alkynylations356-358 and vinylations359 of nitrones, (ii) catalytic asymmetric nucleophilic additions to the C=N bond,360-364 and (iii) nitrone allylations by allylzinc halides.365,366... 

Nucleophilic addition of organometalic reagents occurs when the nitrone form is in equilibrium with the hydroxylamine form, for instance, in the case of N -benzyl-/V-glycosyl hydroxylamines (Scheme 2.130) (213). 

Addition of various organometalic reagents to chiral nitrones, derived from L-erythrulose, proceeds with variable diastereoselectivity, depending on Lewis acids as additives. ZnBr2 facilitates the attack at the Si face of the C=N bond, whereas Et2AlCl makes the attack at the Re face more preferable. The obtained adducts can be transformed into derivatives of /V - h y d r o x y - u. u - d i s u b s t i t u t e d -a-amino acids, with their further conversion into a,a-disubstituted a-amino acids (193, 202). 

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). 

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. 

Reactions of Vmylation and Ethynylation Vinylation and ethynyla-tion of nitrones using vinyl (137, 202, 563, 564) and ethynyl (199, 213, 219) organometalic reagents is a convenient method for synthesizing various nitrogen-containing compounds such as a-amino aldehydes, a-amino acids, amino... 

Table 17 Additions of Organometallic Reagents to Cyclic Nitrones...

In 1993,Ukaji,Inomata and co-workers documented the enantioselective alkylation of a nitrone as the acceptor [39a]. It was anticipated that the oxygen atom of the nitrone would strongly coordinate a metal incorporated in a chiral environment to activate the nucleophihc addition of an organometallic reagent. Using the in situ generated metal alkoxide of (2S,31 )-4-dimethylamino-l,2-diphenyl-... 

A major synthetic effort, however, has been focused on asymmetric induction resulting from the addition of organometallic reagents to aldimines/aldimine derivatives derived h om chiral amines/hydrazines. A variety of chiral aldimines (8), nitrones (9) and hydrazones (all of which contain as part of... 

The reaction of various organometallic reagents with the ketone (21) leading to the branched-chain sugars (22) has been described (Scheme 6)." The products were used to prepare cyclopentane fused isoxazolidines (23) by a nitrone-alkene cycloaddition process (see Clhapter 18). 

Cyclopentylidene -1,4- dideoxy-1,4 -N- hydroxyimino- d, l- erythritol (a mejo-pyrrolidine described in Vol. 25, p. 206, ref. 44) can be readily converted into a nitrone with mercury(II) oxide and trapped in a selective manner with organometallic reagents (Grignards, alkyllithiums, etc.) to give the racemic N-hydroxypyrrolidines 32 (R = Me, Ph, PhCsC etc.). The compounds readily oxidize to aminoxyl free radicals. ... 

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