ADDP dipiperidine

Another well-known process that utilizes a nucleophilic phosphane is the Mit-sunobu reaction, that is, the reaction between an acidic partner and an alcohol, typically facilitated by an azodicarboxylate and a phosphane. Two options are possible, anchoring of the electrophilic part to the solid support, dealt with in the next section, or anchoring of the nucleophilic phosphane. Georg et al. used polystyrene-bound triphenylphosphane and DEAD (diethyl azodicarboxylate) in their synthesis of aryl ethers [31]. Alcohols were reacted successfully with electron-rich and electron-deficient phenols, giving the desired products in good yield and purity. More recently, Wilhite and coworkers disclosed an efficient protocol for the synthesis of pyridine ethers using ADDP [l,l -(azodicarbonyl)dipiperidine] and polymer-supported triphenylphosphane (Scheme 6.9) [32], Both methods eliminate purification problems caused by triphenylphosphane oxide, but chromatography is still needed. 

This reaction has been extensively modified, including the fixation of phosphine and dialkyl azodicarboxylate onto a polymer or fluorous reagent and the introduction of a basic moiety to a phenylphosphine. In addition, bis(2-(l-adamantyl)ethyl) azodicarboxylate (BadEAD), bis(l-adamantylmethyl) azodicarboxylate (BadMAD), bis(5-norbornen-2-ylmethyl) azodicarboxylate (DNAD), di-t rt-butyl azodicarboxylate (DBAD), fluorous azodicarboxylate (FDEAD), A,A,A, A -tetramethylazodicarboxamide (TMAD), and l,T-(azodicarbonyl)dipiperidine (ADDP), have also been developed for the Mitsunobu reaction. 

The commercially available diethyl azadicarboxylate like reagents are listed below. DEAD (4) and DIAD (5) are by far the most frequently used. The methyl (6), benzyl (7) and terr-butyl (8) analogs of the most commonly used reagents are also known, but used much less frequently. Bis-(2,2,2-trichloroethyl)azadicarboxylate, another commercially available compound, has also been reported, but applications thereof appear to be very limited. ADDP, l,r-(azodicarbonyl)-dipiperidine (10), was first reported by Tsunoda. This reagent appears be useful for more difficult Mitsunobu reactions related reagents in which the piperidine moiety has been replaced by morpholine or A-methyl piperazine are also known. These reagents and the reduced hydrazine products thereof can often be precipitated out by the addition of hexanes to Ae reaction mixture additionally, treatment with mild acid can be useful in the removal of the A-methyl piperidine reagent. 

In the alkylation of imidodicarbonates and tosylcarba-mates, the yield of alkylated product increases as the acidity of the NH acids increases. Thus imidodicarbonates and tosylcarbamates with p/sTa<13 give the corresponding N-alkylated products in 83-93% yields, while lower yields are obtained with less acidic substrates.The combination of l,l -(Azodicarbonyl)dipiperidine (ADDP) with Tri-n-butylphosphine appears to be superior to that of DEAD with TPP in the alkylation of amides. In the presence of DEAD and TPP, dibenzyl imidodicarbonate does not react with alcohols, but it does react with a-hydroxy stannanes to give the corresponding A -alkylated products (eq 27). ... 

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