Silyloxy enamine

Kim and coworkers introduced silyl radical mediated addition of alkyl radical to silyloxy enamine 76. The silyloxy enamine moiety is readily accessible from a variety of functionalities. The mechanistic concept is illustrated in the Scheme 12 and involves the addition of R radical to 76 to give the radical adduct 77 and the subsequent homolytic cleavage of N-O bond to yield the desired product 78 and a silyloxy radical 79. The latter undergoes 1,2-phenyl migration to give the silyl radical 80 that abstracts halogen from the alkyl halide to regenerate the R radical. 

The radical alkylation of ketones is achieved by their conversion into the desired N-silyloxy enamines 81 (Scheme 13). The reaction of 81 with diethyl bromomalonate in the presence of EtsB (0.5 equiv) in benzene was performed in open air and stirred at room temperature for 3h. With nitro compounds it is achieved by their conversion into the desired ]V-bis(silyloxy)enamines (82) (Scheme 13). When the reaction is carried out with 82 and alkyl iodides with an electron-withdrawing substituent at the a-position, using V-70 as radical initiator (2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile)), it underwent a clean radical alkylation reaction to yield an oxime ether. Successful radical alkylation of... 

DBU-salts of nitro compounds such as 1095 react with his-lrimethylsilyloxyena-mines such as 1096 to give, via 1097 after subsequent treatment with BU4NF, nitro oximes such as 1098 in 78% yield [147]. The nucleophihdty of N,N-bis(silyloxy)enamines such as 1096 in reactions with henzyl cations has been measured and compared [149] (Scheme 7.44). 

Silylation of ethyl 2-nitropropionate 1105 to the N,N-bis(silyloxy)enamine 1106 followed by addition of triethylamine affords the triethylammonium bromide 1107 in 45% yield [135]. Migration of the trimethylsilyloxy group in 1108 gives 68% 1109 and, after transsilylation with methanol, 71% of the free 2-hydroxycyclohexa-none-oxime 1110 [135] (Scheme 7.46)... 

More recently, Kim and coworkers have developed a novel radical alkylation reaction of organic nitro derivatives 16a-d via bis(silyloxy)enamines 17a-d (Scheme 16). This method enables not only P -alkylation to the nitro gronp, bnt also the conversion of the nitro group (16a-d) into an oxime ether fnnctionahty (18a-d). The irradiation of a solntion of 16a-d with iodomethyl phenyl snlfone (or ethyl iodoacetate) and hexamethylditin in benzene at 300 nm give the oxime ethers 18a-d in good yields. 

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). 

On thermolysis, appropriately substituted A-allyl-A-silyloxy enamines 19 undergo smooth [3,3]-sigmatropic rearrangements to the corresponding A-silyloxy imino ethers laP (equation 5). Two stereogenic centers are created but no reference to chiral induction is referred. High diastereoselectivity was observed and short reaction times favoured the syn A-silyloxy imino ether diastereomers. 

Lithium aluminium hydride is also capable of reducing N-silyloxy enamines . Active methylene compounds such as open-chain and cyclic ketones can be converted into the corresponding Mannich base through the intermediacy of enaminones, which are reduced by LiAlH4 (Scheme 108). 

Silyl nitronates can also be further silylated to the interesting Ai,Af-bis(silyloxy)enamines (eq In contrast... 

Finally a general approach to synthesize A -pyrrolines must be mentioned. This is tl acid-catalyzed (NH4CI or catalytic amounts of HBr) and thermally (150°C) induced tea rangement of cyclopropyl imines. These educts may be obtained from commercial cyan> acetate, cyclopropyl cyanide, or benzyl cyanide derivatives by the routes outlined below. Tl rearrangement is reminiscent of the rearrangement of 1-silyloxy-l-vinylcyclopropancs (p. 7 83) but since it is acid-catalyzed it occurs at much lower temperatures. A -Pyrrolines constitut reactive enamines and may be used in further addition reactions such as the Robinson anei lation with methyl vinyl ketone (R.V. Stevens, 1967, 1968, 1971). 

Thiochromone reacts with 2-piperidinobuta-1,3-diene to give a single diastereoisomeric thioxanthene-3,9-dione. Reaction of 4-silyloxy-l-benzothiopyrylium triflate, derived from thiochromone, with enamines involves regioselective 1,2-addition leading to 2-substituted thiochromanones <97JCS(P1)2807>. 

A( aminopyridines are excellent precursors for further cycliza-tion reactions. Treatment of l-p-(tolylamino)-3-(p-tolylimino)-1-propene with TSH afforded 1-p-tolylpyrazole in modest yield (eq 4). Most likely TSH A( aminates the enamine nitrogen to give an enhydrazine, which subsequently adds to the imine carhon. Finally, />-toluidine is eliminated resulting in aromatization. Under similar conditions, neither silyloxy-, alkyloxy-, nor henzoyloxy amines gave AAamination. ... 

The remainder of the right-hand fragment was prepared (Scheme 5) in accord with our efforts in the theopederin D synthesis. Keto-aldehyde 21, available through the condensation of the enamine of isobutyraldehyde with acetyl chloride, was subjected to a Krische allylation to provide secondary alcohol 22 in 93% ee. Protection as a triethylsilyl ether and exposure to TMSOTf yielded enolsilane 23. The enolsilane was selected as the nucleo-phile for the fragment-coupling aldol reaction based on Evans studies on the influence of various substituents on complex aldol reactions. While the silyloxy group in aldehyde 20 was expected to direct nucleophiles toward the undesired face of the aldehyde, consistent with the extended Felkin model,the methyl group adjacent to the aldehyde was expected to direct the nucleophile to the desired face of the aldehyde, in accord with the... 

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