Oximes radical reactions

The (TMS)3Si radical addition to terminal alkenes or alkynes, followed by radical cyclization to oxime ethers, were also studied (Reaction 50). The radical reactions proceeded effectively by the use of triethylborane as a radical initiator to provide the functionalized pyrrolidines via a carbon-carbon bond-forming process. Yields of 79 and 63% are obtained for oxime ethers connected with an olefin or propargyl group, respectively. 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

Finally, a rather early (but from a mechanistic viewpoint a very interesting) sequence of radical reactions has been described by Pattenden and coworkers, in which an acetylenic oxime ether 3-312 was converted into the bicyclic oxime 3-319 in 70% yield (Scheme 3.78) [126]. Hydrolysis of 3-319 led to the bicyclic enone 3-320, which in fact can also more easily be synthesized by a Robinson annulation. 

Photoreduction of aromatic and aliphatic nitro compounds gives hydroxylamines or amines, which is well reviewed.125 The radical reaction of primary nitro compounds with tin hydride does not give the denitrated product (see Chapter 7), but give the corresponding oximes (Eq. 

Recently, it was reported that a nitromethyl group was reduced to the corresponding oxime by reaction with Bu3SnH in the presence of radical initiator (Eq. 7.61).68 Interestingly, primary nitro groups are selectively reduced to oximes in the reaction of the compounds containing both primary and secondary nitro groups (Eq. 7.62).69 The product of Eq. 7.60 may not be correct, but may be the oxime. 

Radical reaction of oxime ethers. A report1 that an oxime ether, unlike the... 

A primary nitromethyl group can be reduced to the corresponding oxime by a radical reaction with tin.93 The reaction is remarkably selective for primary nitro groups over secondary groups (Scheme 43).94... 

Tin-based reagents are not always snitable owing to the toxicity of organotin derivatives and the difficulties often encountered in removing tin residues from the final product. Therefore, the same authors have carried out additional experiments with 17d and several different alkyl halides under tin-free conditions. The treatment of 16d with tert-butyldiphenylsilyl chloride (TBDPSCl) and triethylamine in the presence of silver triflate in CH2CI2 affords the bis(silyloxy)enamine 17d in 92% yield (Scheme 17). When the radical reaction was carried out with ethyl iodoacetate in the presence of 2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as the initiator in CH2CI2, the oxime ether 19 was obtained in 83% yield (Scheme 17). 

Recent advances in radical reactions have greatly benefited from the efficiency of organotin reagents as mediators. Radical reaction of alkyl iodides with trifluoromethyl phenylsulfonyl oxime ether 69 and hexamethylditin at 300 nm in benzene afforded the corresponding trifluoromethyl oxime ethers 70 in high yields (Scheme 37) . 

Pattenden and coworkers have designed and performed a cascade of radical reactions towards the synthesis of angular triquinanes72. Irradiation of the refluxed benzene solution containing a 1 1 mixture of diastereomers of bromide 7 and (TMS SiH gave the corresponding triquinane oxime 8 as a 1 1 mixture of a- and /J-methyl diastereomers in 38% yield. 

Functionalization of the carbon radical resulting from cyclization of an aminium radical is an important step for synthetic chemists in order to obtain the desired product directly or to provide a handle for further transformations. Radical reactions of A-chloroalkenylamines (Section III,B) lead to /3-chloro pyrrolidines, which are prone to rearrangement to give piperidines. Reactions of N-nitroso alkenylamines lead to 8-nitroso pyrrolidines and, if an a-hydrogen is present, ultimately to oximes of aldehydes or ketones. Advantages of the latter transformation are the formation of stable substituted pyrrolidines and the utility of the oxime moiety in regard to further transformations. 

A 6-exo-trig cyclization of a pyran derived radical onto an oxime has been employed as the key step in the synthesis of Amaryllidace alkaloid (+)-7-deoxypancratistatin [95JA7289], Treatment of 202 under reductive cyclization conditions gave 203 as a single stereoisomer in good yield. The compatibility of the radical reaction conditions with the dense functionality present in 202 is noteworthy. 

In radical reactions, conversion of alkyl halides to oximes is easy. Thus, irradiation of a mixture of alkyl halide (47) with amyl nitrite in the presence of (Bu3Sn)2 gives the oxime... 

Oximation of hydrocarbons, Naylor and Anderson irradiated a mixture of cyclohexane and nitrosyl chloride and obtained cyclohexanone oxime in 71% yield. The reaction is interpreted as a radical reaction represented in part as follows ... 

Furthermore, the isopropylated product has been converted into a-amino acid (Scheme 7.19) through cleavage of the N-N bond of the diaster-eochemically pure product by hydrogenolysis in the presence of Pearlman s catalyst. In earlier work on triethylborane-induced radical reactions in organic solvents, oxime ether showed excellent reactivity. Thus we expect that the direct comparison of indium-mediated reactions with triethylborane-induced reactions would lead to informative and instructive suggestions regarding the reactivity and stereochemical course of the transformation in question. 

Unlike the classical nitroxides such as porphyrexide and other derivatives of quadrivalent nitrogen, the new radicals, called nitroxyls (or iminoxyls) could undergo reactions without involvement of the radical site. In 1961, E. G. Rozantsev and Yu. G. Mamedova were the first to realize the "non-radical reactions of free radicals" (3,4) e.g., the formation of 2,2,6,6-tetramethyl-4-oxopiperidine-l-oxyl oxime without chemical involvement of the free... 

Et2Zn instead of 136 as a radical initiator was also effective for the radical reaction. In these tin-free reactions, the mechanism of propagation is proposed to be a process in which boron or zinc Lewis acids complex to the oxime, promoting addition. Once addition of a radical to the complexed oxime occurs, fragmentation of the EtsB or Et2Zn complex generates an ethyl radical that propagates the chain. 

This free-radical acylation approach is extended for the synthesis of a-keto esters and ketones using phenylsulfonyl methoxycarbonyl oxime ether 5 [23] and bis-methanesulfonyl oxime ether 6, respectively (Scheme 6) [24], 5 is more reactive and effective than 2b. For instance, radical reaction of tert-butyl iodide with 5 gave tert-butyl oxime ester in 65% yield, whereas the use of 2b gave the corresponding tert-butyl oxime ether in 15% yield. In free-radical-mediated ketone synthesis via a sequential radical acylation approach, 6 is used as a carbonyl equivalent geminal radical acceptor. This method works well with primary alkyl iodides but somewhat less efficiently with secondary iodides and can be applied to prepare unsymmetrical acyclic ketones as well as cyclic ketones. It is noteworthy that stable allylic and benzylic radicals react smoothly with 6. 

The radical carbonylation of an alkyl iodide in the presence of Kim s sulfonyl oxime ethers [58, 59, 60] provides a new type of multicomponent coupling reaction where plural radical Cl synthons are consecutively combined [61]. In the transformation, allyltin was used to serve as a trap of benzenesulfonyl radical which converts sulfonyl radical to a tin radical, thus creating a chain. Scheme 14 illustrates such an example, where the product was easily dehydroxylated to give the corresponding tricarbonyl compound on treatment with zinc/AcOH. The radical acylation reaction by Kim s sulfonyl oxime ethers can be conducted under irradiation with the addition of hexamethylditin. This is an alternative path for achieving a similar transformation without the use of photolysis equipment. Scheme 15 illustrates several examples where carbon monoxide and Kim s sulfonyl oxime ethers are successfully combined to create new tandem radical reaction sequences [61],... 

Recent syntheses of indol-2-ones (oxindoles) include Chuang s p-toluenesulfo-nyl radical induced cyclization of allylsulfones and the oxidative free-radical reactions of a,a-dimethylsulfonyl substituted anilides [62], the tin-free synthesis of 3-aminoindolinones from O-benzyl oxime substituted amidocyclohexadienes [63], and Pudlo s 5-exo-trigl5-exo-trig tandem radical cyclization of acrylamides to give 3-pyrrolidinone substituted oxindoles, shown below [64]. 

Radical reactions are not restricted to cyclizations onto alkenes or alkynes. Increasingly popular is the use of an imine or imine derivative, such as an oxime or hydrazone. ° Most examples involve 5- or 6-exo-trig cyclization to give cyclopentane or cyclohexane ring systems. Thus, treatment of the bromide 77 withtributyltin hydride gave the cyclopentane 78 (4.66). The stereoselectivity of the cyclization is in line with that expected on the basis of a chair-like transition state (compare with Scheme 4.53). 

Pattenden, G. and Schulz, D.J. (1993) Cascade Radical Reactions in Synthesis. A New Radical Mediated Double Ring Expansion-Cyclization Process with Oxime Ethers, Tetrahedron Lett. 34, 6787-6790. 

---