Mitsunobu reaction, improved

The Mitsunobu reaction is usually used to introduce an ester with inversion of configuration. The use of this methodology on an anomeric hydroxyl was found to give only the /3-benzoate, whereas other methods gave mixtures of anomers. Improved yields are obtained in the Mitsunobu esterification when p-nitrobenzoic acid is used as the nucleophile/ Bis(dimethylamino) azodicarboxylate as an activating agent was... 

Develop alternatives to the Mitsunobu reaction to improve yield and to reduce... 

I. D. Jenkins and M. B. Goren, Improved synthesis of cord factor analogues via the Mitsunobu reaction, Chem. Phys. Lipids, 41 (1986) 225-235. 

Xeptagen S.p.A. has improved a computer assisted combinatorial chemistry approach, based on an innovative application of Mitsunobu reaction, that could be used to design and synthesize new peptido-mimetic libraries, in order to find novel leads efficient in different biological targets (Figure 3.10). 

The Mitsunobu reaction leads to the alkylation of alcohols with various nucleophiles or acids (HA) via a redox system, composed by diethylazadi-carboxylate (DEAD) and triphenylphosphine (TPP) (Figure 3.14). A limit in the application of Mitsunobu process is the pKa value of the acid counterpart, that must be usually smaller than 11 therefore, many improved redox systems have been developed in order to solve this problem. 

Once again, the drive for improved performance in transition metal ion-catalysed processes has continued to stimulate the synthesis of new types of organophosphine and tervalent phosphorus-ester and -amide ligands. Activity in the chemistry of heteroaromatic phosphorus ring systems and low-coordination number p -bonded systems has also remained at a high level. New mechanistic insights into the Mitsunobu reaction have been reported, and interest in synthetic applications of Staudinger/Mitsunobu procedures has continued to develop. 

Townsend, C. A., Nguyen, L. T. Improved asymmetric synthesis of (-)-3-aminonocardicinic acid and further observations of the Mitsunobu reaction for -lactam formation in seryl peptides. Tetrahedron Lett. 1982, 23,4859-4862. 

By the Mitsunobu reaction l,l -(azodicarbonyl)dipiperidine, MesP, 61-85% yield. This reaction was used for the alkylation of thioglycosides. The addition of imidazole improves the process. ... 

Mitsunobu reactions. An improved reagent pair consists of diphenyl(2-pyridyl)-phosphine and di-/-butyl azodicarboxylate. 

Treatment of MBH addcut 1 with carboxylic adds under Mitsunobu conditions gave almost exclusively the S 2 products 4, rather than S 2 product 5. Weak and bulky carboxylic acids and low temperatiues favor S 2 addition. Although the reaction conditions were effective for alkyl substituted derivatives, the addition of EtsN to the Mitsunobu conditions was necessary to improve the 5n2 S 2 ratios for the vinyl and phenyl derivatives (Scheme 3.3). " More recently, it was found that the nucleophilic substitution reaction mediated by triphenylphosphine linked to non-crosslinked polystyrene 6 led to a significantly more regioselective transformation. Tri-substituted alkenes 4 were obtained almost quantitatively via a highly regioselective 5n2 Mitsunobu reaction (Scheme 3.3). ... 

In a related application of a phenol-like ether formation via Mitsunobu reaction, Deleris et al. prepared a series of Z-ascorbic acid derivatives using the unprotected acid. The reaction was selective for the 3 position of ascorbic acid 90, the most acidic of the four alcohol substituents of the acid. Use of the A iiV.iV .iV -tetramethylaza-dicarboxylate/tributylphos-phine reagent combination did not improve the yield of the reaction. 

---