Azodicarboxylic esters reduction

Formal two-electron reduction of a-diketones, a-imminoketones, a-sulfoxyketones, and 2-butene-diones has been achieved by addition to dicarbonyl complexes, ( -CsRslzTilCO (R=H, Me), forming the corresponding titana-cycles (72 and 73, Scheme 13).49 Analogous reactivity is observed with azodicarboxylic esters 74. 

A wide variety of N-alkyl hydrazinedicarboxylic esters may be obtained in excellent yields by the hydrohydrazination reaction depicted in Eq. 49.215 Use of cobalt complexes results in more highly regioselective reactions at the cost of lower reaction rates as compared to additions where manganese complexes are employed. Di(fert-butyl) azodicarboxylate is the preferred azo ester reduction of the N=N double bond becomes more prominent when less hindered azo esters are used. Alcoholic solvents are essential the reaction fails when methylene chloride or THF is used. 

A considerable amount of work has been carried out on the animation with azodicarboxylic esters of p-hydroxy esters, a class of compounds where both enantiomers are readily available by asymmetric reduction of 3-keto esters. Yields are in the range of 50-70% for lithium115,415-417 (Eq. 115),417 magnesium,416 zinc,416,418-424 and titanium enolates,416 but diastereoselectivities are highest with zinc enolates (Eq. 116)416 Attack from the less hindered side of zinc enolate 57 accounts for the observed anti selectivity. Similar results are obtained with the other enantiomer 416 The lithium enolate of the rigidized derivative of ester 56 gives higher yields with a somewhat reduced anti selectivity (Eq. 117). 416... 

The synthesis of BENZYL ISOCYANIDE from benzaldehyde via reductive amination with 5-aminotetrazole followed by oxidation of the resultant amine with sodium hypobromite provides a general method for the synthesis of isocyanides. The preparation of BIS(2,2,2-TRICHLOROETHYL) AZODICARBOXYLATE makes available an alternative to dimethyl azodicarboxylate that is not only more reactive in Diels-Alder reactions but whose ester groups can be removed under neutral conditions. 

Direct Asymmetric a-Amination Reaction of 2-Keto Esters. The cir-DiPh-Box copper complex catalyzes highly enantioselective direct a-amination reaction of 2-keto esters with dialkyl azodicarboxylates and thus provides convenient access to optically active jyn-3-amino-a-hydroxy esters (eq 2). This enantioselective, direct a-amination is applicable to a range of 2-keto esters when dibenzyl azodicarboxylate is used as the nitrogen source. The immediate product of the amination reaction is prone to racemization. Stereoselective reduction of the keto functionality by L-selectride enables further synthetic operations to be carried out without loss of enantiopurity. 

Phthalic acid, 259 Phthalic anhydride, 104 a-Picoline, 161 a-Picoline N-oxide, 161 Picolinic acid, 16 Picramic acid, 271 Picric acid, 271 Pinacol reduction, 7 Pinosylvin, 31 Piperazines, 322 Piperidine, 33, 291 2-Piperidone, 194 Pivaldehyde, 105 Podophyllotoxin, 337 Podophyllotoxone, 337 Polonovski reaction, 308 Polyisoprenoids, 300-301 Polymethoxybenzophenones, 30—31 Polymethylhydrosiloxane, 294 Polyphosphate ester (PPE), 229-230 Polyphosphoric acid, 227, 231—232 Potassium, 232, 233 Potassium acetate, 96 Potassium amide, 232—233, 310 Potassium azodicarboxylate, 100 Potassium r-butoxide, 26, 45, 47, 77-78, 85, 133, 188, 212, 222, 225, 233-234, 236, 246... 

Theil et al. developed a method for chemoenzymatic synthesis of both enantiomers of cispentacin [89]. frans-2-Hydroxymethylcyclopentanol, obtained by the sodium borohydride reduction of ethyl 2-oxocyclopentanecarboxylate, was monosilylated with tert-butyldimethylsilyl (TBDMS) chloride to afford 55. Lipase PS-catalysed transesterification with vinyl acetate in /erf-butyl methyl ether furnished the ester 56 and the alcohol 57. The deacetylated 58 was obtained by the Mitsunobu reaction with phthalimide, triphenylphosphine and diethyl azodicarboxylate (DEAD) to furnish the cis oriented 59 with inversion of configuration (not retention as mentioned in the original article) (Scheme 9). Desilylation, Jones oxidation and subsequent deprotection with aqueous methylamine gave the ( R,2S) enantiomer 5 [89]. The (15, 2/f) enantiomer was prepared by the same route from the silyl alcohol 57. 

Kauhaluoma and Samanta used miinchnone as the key intermediate to obtain a triazole core (Scheme 9.41). Starting with Ameba resin 351, 3.84 equiv of amino acid ester 352 and 25 equiv of NaBHaCN were employed for the reductive alkylation in 1% acetic acid in DMF at room temperature for 12 h. Resin 353 was treated with 10 equiv of carboxylic acid chloride 354 in the presence of 12 equiv of A,A-diisopropylethylamine in DCM at room temperature for 12h to form amide 355, which was treated with 5% KOH in dioxane H20 (3 1) for 4h to give the corresponding carboxylic acid. Resin 356 was treated with 23.5 equiv of acetic acid anhydride, 3 equiv of DEAD (diethyl azodicarboxylate) 357, and 3 equiv of 4-phenyl-4/f-l,2,4-triazoline-3,5-dione 358 in DCM at room temperature for 5-10 h, giving the miinchnone intermediate 359, which reacted with compound 357 or 358 to form resin 360. Treatment of this with 30% TFA in DCM at room temperature for 1.5 h resulted in cleavage from the resin, producing 361. 

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