Phosphites with nitrones

Attack on Oxygen. Nitrones have been deoxygenated to the parent imine with trimethyl phosphite under vigorous conditions.45 Virtually quantitative yields of the enol-phosphates (54) and (55) were obtained from the reaction of tris(trimethylsilyl) phosphite with a-diketones and /j-benzoquinone. 4 6... 

Treatment of the conanine (372) with bromine-aqueous sodium carbonate yields192 (100%) the conenium salt (375) which is readily converted into (376) (80%). Compound (376) is also formed starting from (373). When C-20 is substituted by two methyl groups as in (374) the product is (377). The conanine (373) is photo-oxygenated,193 in the presence of methylene blue, to (376). The nitrone (378) is quantitatively deoxygenated by triphenyl phosphite with trimethyl phosphite the reaction is more complex.194... 

Pheny 1-3-pheny 1 imino-3-// -indole N -oxide (an indolic nitrone) reacts with triethyl and triisopropyl phosphite in refluxing xylene and fert-butylbenzene to give 2-phenylimino-3// -indole (indolenine) in very good yield (505). 

Nitrone reactions with lithiated dialkyl phosphite results in the formation of a-(hydroxyamino)phosphonate, which, depending on the character of the R substituent at a-C lead to a-phosphorylated nitrones (429) or fS-phosphorylated nitroxyl radicals (430) after successive oxidations (Scheme 2.200) (686—689). 

The main procedure for deoxygenation of similar nitronates is based on their reaction with trialkyl phosphites (Scheme 3.114). These reactions readily proceed with live- (45, 55, 320, 321) and six- membered (143) cyclic nitronates. 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

Di(octadecyl)hydroxylamine (18) (Seltzer et al., 1989 PospiSil and Nespurek, 1997) was recently introduced commercially for the stabilization of PO, PP in particular. 18 is a hydrolysis-resistant processing stabilizer used in combination with aromatic phosphites, and a long-term heat stabilizer used in combination with suitable HAS. Di-alkylhydroxylamine is considered as scavenger of radicals POO" and P. The latter are trapped by nitroxide or nitrone, arising from the parent hydroxylamine (Eq. 3-7). 

Deoxygenation of a nitrone. Some years ago Todd and co-workers noted that 1-pyrroline-1-oxides can be obtained by reductive cyclization of a y-nitro ketone. This reaction was used recently in a synthesis of chlonns related to vitamin B,. Thus the nitro ketone 1 on reduction with zinc and acetic acid gives the pyrroline N-oxide 2 in high yield. The N-oxide is stable to triphenylphosphiue or trimethyl phosphite, but is reduced to the imine 3 in high yield by TiCl,. 

Other sugar aldonitrones also give phosphonates on treatment with dialkyl phosphites. For example, a-deoxysugar derivatives give the (5A)-epimer of the phosphonate as the major product (the epimers could be separated by column chromatography). Flowever, in the case of nitrones with an unsubstituted 3-hydroxy group (R1 = H), the (5R)-epimcric phosphonates 12 and 13 (R1 = H) are the sole products44. 

The reaction of the nitrone (23) with alkyl phosphites has been studied. With trimethyl phosphite in refluxing MeOH (23) afforded a mixture of the epimers (32), whereas in AcOH (33) was obtained. It was shown that (33) was not formed from (32) by loss of MeOH. With triethyl phosphite analogous products were formed, but in this case a large amount of the deoxygenated compound (34) was also obtained. With trimethyl phosphite the formation of an immonium structure, reducible to conanine (35), was suggested by the presence in the n.m.r. spectrum of the reaction mixture of a N—Me group. The structures of these compounds were deduced from their spectral data. 

In the presence of DBU and MejSiCl in CH2CI2, the addition of diethyl phosphite to the readily available nitroalkenes gives transient a-phosphonyl nitronates, which are smoothly converted into P-ketophosphonates on treatment with MCPBA. The procedure is useful to prepare a variety of diethyl l-aryl-2-oxoaIkyIphosphonates (Scheme 7.53). ... 

Tervalent phosphorus compounds (phosphorous derivatives) are weil-established reagents for the deoxygenation of amine oxides and nitrones, and they provide a clean and convenient method for the preparation of furazans from furoxans. Mukaiyama et al.425 and Grundmann426 used trialkylphosphites, and they have been widely employed since that time, both with and without solvents.80,85,93,95,97,352 The simple dialkyl- and diarylfuroxans usually require more vigorous conditions (e.g., refluxing triethyl phosphite) than do strained derivatives or the benzofuroxans.85,97... 

No reactions occur between dialkyl phosphite salts and the A -glycosyl-C-arylnitrones 366 (R = Ph or substituted phenyl) On the other hand, reactions with tris(trimethylsi-lyl) phosphite do take place in the presence of a Lewis acid (ZnCl2, HCIO4) and proceed smoothly. Some unusual results are to be observed, particularly in relation to the nature of the catalyst otherwise, the general course of the present reaction is similar to that found for reactions of the nitrones 366 with dialkyl phosphite anions. Thus, the reaction between... 

The hydroxy-nitrone (8a) gave the isomeric hydroxy-nitrone (9) on treatment with acid. The latter hydroxy-nitrone underwent base-catalysed deuteriation at C-21, presumably via the dihydroxy-enamine tautomer. Treatment of either hydroxy-nitrone with methanolic sulphuric acid gave the unstable methoxy-nitrone (10), which yielded the dimeric compound (11) on attempted crystallization. The reaction of nitrone (8b) with dialkyl phosphite derivatives was reported earlier details of this study have now been published. ... 

Silicon Lewis acids are useful for the C-heteroatom bond-forming reaction of nitrones. For instance, the t-BuMe2SiOTf-promoted reaction of nitrones with diethyl phosphite realizes an efficient synthesis of a-amino phosphonates [146]. 

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