Oxime ether anions

Many of the same features of imine and imine anion structure previously discussed (Section 4.1.3.2) are apparent with hydrazones and their anions and with oxime ether anions. A number of investigations of the structure of A A -dialkylhydrazone and oxime ether anions as well as oxime dianions have been carried out. Most notable are the experimental studies of Collum and Clardy, " and the theoretical treatment by Glaser and Streitwieser. As might be expected, and as was observed for lithiated imine anions iyida supra), lithiated hydrazones exist in the solid as aggregates, with two lithiums coordinated to the aza anion system (Figure 3). ... 

In qualitative terms, the rearrangement reaction is considerably more efficient for the oxime acetate 107b than for the oxime ether 107a. As a result, the photochemical reactivity of the oxime acetates 109 and 110 was probed. Irradiation of 109 for 3 hr, under the same conditions used for 107, affords the cyclopropane 111 (25%) as a 1 2 mixture of Z.E isomers. Likewise, DCA-sensitized irradiation of 110 for 1 hr yields the cyclopropane derivative 112 (16%) and the dihydroisoxazole 113 (18%). It is unclear at this point how 113 arises in the SET-sensitized reaction of 110. However, this cyclization process is similar to that observed in our studies of the DCA-sensitized reaction of the 7,8-unsaturated oximes 114, which affords the 5,6-dihydro-4//-l,2-oxazines 115 [68]. A possible mechanism to justify the formation of 113 could involve intramolecular electrophilic addition to the alkene unit in 116 of the oxygen from the oxime localized radical-cation, followed by transfer of an acyl cation to any of the radical-anions present in the reaction medium. 

On the other hand, since oxime ethers were electrochemically more inert than ketones under the electroreduction conditions, the electroreductive intra- and inter-molecular coupling of ketones with oxime ethers proceeded via anion radicals in good yields (equations 5 and 6) °4i. Moreover, cobaloxime-mediated intramolecular radical addition onto oxime functions in the electrolysis media proceeded to afford the cyclized aminoethers (equation 7). ... 

Other approaches to synthesize highly substituted cyclopentanes, including amino and hydroxy groups, from y- and lactones, has been radical and anionic Michael cyclizations of the a-iodo-y- and -<5-lactones [94]. Likewise, methods using radical cyclization to oxime ethers have been reported to give amino substituted cyclopentanes [95,103,104]. It should be noted that although only one isomer is often obtained [103], such cyclizations generating a secondary radical may not be stereospecific [95,100,101]. 

Ambident reactivity was shown by oximate anions normally, Oarylation predominated over N-arylation, with ratios of oxime ethers to nitrones ranging from 9 1 (for the benzophenone oxime anion) to 1.7 1 (for the fluorenone oxime anion) [77]. The arylation of two heterocyclic oximes was performed under mild conditions and led mainly to the corresponding oxime ethers which served as good precursors for the generation of unstable aryl fulminates, ArONC [79,80],... 

When studying the lithiation reactions it was found that from an E and Z mixture of oxime ether 61, syn and anti anions are obtained, but an equilibrium process enriches the Z lithium compound. 

In the reaction of the lithium salt of 62 with acetone after a short lithiation time of 30 min, a 10% or 25% E Z mixture of 63 was obtained together with the addition product 64 in 65% yield (equation 42)65. The formation of only one addition product, and the quick disappearance of the -isomer, are due to a fast deprotonation process the -isomer compared with the Z-isomer, and the high rate of equilibration between the lithium compounds that greatly favors the syn anion, which reacts with acetone to give 64. These results point out that the formation of the syn lithium compounds is favored in oxime ethers for kinetic as well as for thermodynamic reasons. The kinetic preference, according to Ensley and Lohr65, is due to coordination between the lithium amide and the oxime oxygen. 

Because previous investigations showed that there is no syn-anti isomerization in oxime dianions , in contrast to dimethylhydrazone anion where a syn-anti mixture gives after lithiation only one (jy/i) monoanion, Ensley and Lohr checked the ability of the oxime ether to undergo isomerization of this type. An E and Z mixture of the 2-heptanone tetrahydropyranyl oxime gave, after lithiation and reaction with acetone, a substitution product only on the methyl group (equation 41). 

Since 5,6-dihydro-3-phenyl-6-trimethylsilylmethyl-4/f-l,2-oxazine can be considered as an oxime ether of a ketone, its exclusive cis deuteration is mentioned 4. A complexed anion is thought to be responsible for this remarkable stereoselection. 

Kinetics of the synthesis and aminolysis of 2,4-dinitrophenyl and 5-nitropyridine N-hydroxy oxime derivatives have been studied spectrophotometrically in acetonitrile. The reaction of several cholesterol-related oximes with 2-chloroethylamine in the presence of methoxide ion gives the corresponding oxime ethers DFT calculations indicate an oximate anion intermediate. ... 

DCA-sensitized irradiation of oxime ethers 39e and 40c afforded the corresponding cyclopropanes 41e and 42c in low yield. However, for unknown reasons, irradiation of compound 39f under these conditions gave a complex mixture of products in which the corresponding 1-ADPM product was not present. Irradiation of oxime ether 40c also afforded the [4-1-4]-cycloadduct 60." The mechanism shown in Scheme 15 could justify the formation of 60. This involves the generation of a radical-cation/radical-anion pair 61. Intramolecular cyclization of the radical-cation within the solvent cage generates the intermediate 62, which undergoes intermolecular cycHzation, to yield the observed product (Scheme 15). 

O-Substituted oxime derivatives are synthetically useful in a wide variety of transformations. Hoffman and Butani have observed that reaction of a series of aldehydes and ketones with the potassium salt of Af,0-bis(trimethylsilyl)hydroxylamine 4a or 4b (a rapid equilibrium between 4a and its Af,N-bis(silylated) isomer 4b probably exists in solution) gave high yields of the corresponding oximate anion 5, formed via the Peterson-type reaction, together with the silyl ether 6. Anion 5 could be protonated to the oxime 7 or trapped in situ with a variety of electrophiles to give 0-substituted oxime derivatives (Scheme 6). 

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