Oxime ethers alkyl radical addition

Furthermore, we also performed kinetic studies for alkyl radical additions onto different types of C=N bonds such as imines and oxime ethers. The kinetic data are summarized in Figure S. Kinetic analysis of the intramolecular addition of alkyl radicals to C=N bonds provides several experimentally important results. First, alkyl radical additions to C=N bonds are much faster than the corresponding additions to C=C bonds, indicating that C=N bonds are much better radical acceptors than C=C bonds. Furthermore, 5-exo cyclization is faster than 6-exo cyclization. Second, the intramolecular additions of alkyl radicals to C=N bonds are essentially irreversible. Third, alkyl radical additions to oxime ethers and hydrazones are faster than alkyl radical additions to imines, suggesting the possibility of a dependence of the cyclization rate on the electron density at the carbon atom of the radical acceptor. 

Scheme 22 Alkyl radical additions to phenylsulfonyl oxime ethers by Kim and Kim [ 14]...

Scheme 24 Alkyl radical addition to oxime ethers by Naito [15,16]...

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... 

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). 

An alkyl group (primary, secondary, or tertiary) can be added to the oxime ether CHr=NOCH2Ph by treatment with the appropriate alkyl halide and an equimolar amount of bis(trimethylstannyl)benzopicolinate.483 This reaction, which is a free radical addition, is another way to extend a chain by one carbon. 

Tandem radical addition-aldol-type reaction of a,/3-unsaturated oxime ethers bearing an Oppolzer sultam auxiliary leads to stereoselective incorporation of alkyl groups in the 5- and 3-positions in tetrahydrofurans (Scheme 77) <2005AGE6190>. The observed /ra r,/ra r-stereoselectivity was explained by invoking a cyclic six-membered ring transition state. 

Miyabe et al. developed a tandem addition/cycUzation reaction featuring an unprecedented addition of alkoxycarbonyl-stabihzed radicals on oxime ethers [117], and leading to the diastereoselective formation of /1-amino-y-lactone derivatives [118,119]. The reaction proceeds smoothly in the absence of toxic tin hydride and heavy metals via a route involving a triethylborane-mediated iodine atom-transfer process (Scheme 37). Decisive points for the success of this reaction are (1) the differentiation of the two electrophilic radical acceptors (the acrylate and the aldoxime ether moieties) towards the nucleophilic alkyl radical and (2) the high reactivity of triethylborane as a trapping reagent toward a key intermediate aminyl radical 125. The presence of the bulky substituent R proved to be important not only for the... 

Kim and Kim [14] have reported the addition of alkyl radicals derived from alkyl iodides to phenylsulfonyl oxime ether 107 attached to Wang resin (Scheme 22). Treatment of 107 with a range of alkyl iodides and hexam-ethylditin with irradiation at 300 nm gave the expected adducts such as 109, in moderate to good yield after cleavage from the solid support. 

It is noteworthy that this Cl reagent can be applied to a wide range of organic radicals involving rather stable radicals such as a-keto radical, a-alkoxyalkyl radical, and the benzyl radical for which the aforementioned radical formylation system with CO cannot be applied. The high reactivity of phenyl sulfonyl oxime ether is supported by kinetic studies [29]. The approximate rate constants for the addition of a primary alkyl radical to this phenyloxime ether was determined to be k=9.6xl0 M s at 25 °C, which is 1.8 times faster than the addition to aery-... 

Naito and co-workers investigated aqueous medium radical addition to glyoxylic oxime ether due to its good reactivity in organic solvents.9 Its noteworthy that triethylborane acts as a radical initiator and terminator to trap the intermediate alkyl radical (Scheme 7.6). 

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],... 

The Naito group has also prepared pyrrolidines [23] on solid phase by a combination of intermolecular radical addition to alkene 43 (Scheme 10) followed by intramolecular oxime ether cyclization to yield 44. These reactions proceeded sluggishly with triethylborane at room temperature, while the analogous solution-phase process was kinetically much faster. Radical additions to the phenylsulfonyl oxime ether 45 were reported by Jeon et al. [24]. Yields were better with primary and secondary alkyl iodides, and the tandem cyclization sequence with iodide 46 to afford bicyclic 47 was also accomplished, albeit in modest yield. 

A related application is the sysnthesis of a-substituted a-amino esters by addition of the intermediate alkyl radicals to glyoxylic oxime ethers. ... 

The addition of alkyl radicals to vinyl sulfones to give functionalized alkenes via an addition-elimination sequence has been investigated by Russell and coworkers in some details [132, 147]. This reaction has recently been extended to unsaturated sulfimides, allowing the synthesis of styryl tetrahydrofurans and tetrahydropyrans [148]. The extension of this approach to phenylsulfonyl oxime ethers and heteroaromatic aryl sulfones (/p o-substitution) has recently been obtained with success [149, 150]. An example which comes from the work of Kim et al. is reported in equation (76) [149]. In this radical sequence, the alkyl radical generated photochemically from an alkyl iodide, in the presence of 1.2 equivalent of hexabutylditin, adds readily to the C=N bond of the oxime ether to... 

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