Methyl azodicarboxylate reagent

A further development of the method by immobilization of DEAD effects an easily separable (insoluble) and non-explosive reagent in Mitsunobu reactions. The methyl azodicarboxylate reagent immobilized on polystyrene 1742 functions well in Mitsunobu reactions and gives yields comparable to those obtained with soluble DEAD [1279]. Diphenylcarbodiimide was obtained in 41% yield. 

Tests show that either methyl or ethyl azodicarboxylate can be detonated by shock or heat (C. S. Sheppard, H. N. Schack, and O. L. Mageli, U.S. Patent 3, 347, 845 [1967]), Methyl azodicarboxylate is far more easily detonated than the ethyl ester. Hence, since the chemical properties of the two esters are similar, ethyl azodicarboxylate is almost always the preferred reagent. 

Cydization of P-hydroxy-a-amino esters under Mitsunobu reaction conditions is an alternative approach to aziridine-2-carboxylic esters [6b, 13-16], In this case the P-hydroxy group is activated by a phosphorus reagent. Treatment of Boc-a-Me-D-Ser-OMe 13 (Scheme 3.5) with triphenylphosphine and diethyl azodicarboxylate (DEAD), for example, gave a-methyl aziridinecarboxylic acid methyl ester 14 in 85% yield [15]. In addition to PPh3/DEAD [13b, 15], several other reagent combi-... 

The hydroxymethyl and carboxyl group of Ser can participate in pyrazole-ring formation, as shown in the transformation of A -protected L-Ser with the Mitsunobu reagent into a /3-lactone which afforded the N-protected serine hydrazide upon treatment with methyl hydrazine. Cyclization to 25 was achieved by diisopropyl azodicarboxylate (DIAD) and TPP [90H(31)79]. 

Much work has been done on configuration and conformation, e.g. of 2-methoxy-2-oxo-4,5-diphenyl-l,3,2-dioxaphospholanes with 170 and lsO labelled reagents (81CC245). A large number of 2-dimethylamino-l,3,2-dioxaphospholanes or 3-methoxy-2-methyl-l,3,2,-oxazaphospholanes are mentioned in a recent publication, in which spiro compounds of the general structure (108) were prepared by addition to diethyl azodicarboxylate (equation (69)) (80PS(8)147>. 

AD-mix-P 9-BBN Bn Boc Bz BOM CDI m-CPBA CSA Cy DBU DDQ DEAD DIAD DIBAL-H DIPT DME DMF DMAP DMSO EDC HMPA HOBT KHMDS LDA MEM MOM MoOPH NaHMDS NBS NMM NMO Piv PMB Reagent for Sharpless asymmetric dihydroxylation 9-Borabicyclo[3.3.1 ]nonyl Benzyl t-Butoxy carbonyl Benzoyl B enzyloxy methyl Carbonyldiimidazole m-Chloroperoxybenzoic acid Camphorsulfonic acid Cyclohexyl 1,8 -Diazabicy clo[5.4.0] undec-7-ene 2,3 -Dichloro-5,6-dicyano-p-benzoquinone Diethyl azodicarboxylate Diisopropyl azodicarboxylate Diisobutylaluminum hydride Diisopropyl tartrate Dimethoxyethane A,N-Dimethylformamide 4-Dimethylaminopyridine Dimethyl sulfoxide N-(3-Dimethylaminopropyl)-A -ethylcarbodiimide Hexamethylphosphoramide 1 -Hydroxybenzotriazole Potassium hexamethyldisilazane Lithium diisopropylamide Methoxyethoxymethyl Methoxymethyl Oxidodiperoxymolybdenum(pyridine)(hexamethylphophoramide) Sodium hexamethyldisilazane N - Bromosuccinimide A-Methylmorpholine A-Methylmorpholine A-oxide Pivaloyl /j-Methoxybenzyl... 

Iodides can also be prepared from alcohols by a procedure which has been shown to result in clean inversion of stereochemistry in cyclic systems. The reagents used are triphenylphosphine, diethyl azodicarboxylate, and methyl iodide. Again an alkoxyphosphonium ion is the key intermediate. 

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