Mitsunobu method

Alkyl aryl ethers and enol ethers are also accessible by the Mitsunobu method. Cyclic ethers can be obtained by an intramolecular variant, which is especially suitable for the synthesis of three- to seven-membered rings ... 

The synthesis of chiral liquid-crystalline allenes was reported by Tschierske and co-workers (Scheme 4.10) [14]. An asymmetric reduction of 41 with Alpine borane was a key step to an enantioenriched allene 44. After removal of the silyl group, the allenic alcohol was etherified by the Mitsunobu method to give 45, the first liquid-crystalline allene derivatives. 

Weinreb and co-workers 79 were the first to use the Mitsunobu reaction, which offered an efficient route for the synthesis of A-alkyl amino adds. One of the great advantages of the Mitsunobu method is that it uses mild conditions thus allowing its application to SPPS. jV°-Boc-and 7V -Z-protected amino acids are not N -alkylated under these mild reaction conditions. 

The application of Mitsunobu method in solid phase has required the use of other solvents and redox systems due to the properties of resin support [46]. After the examinations of several Mitsunobu reagents and conditions, the... 

It is interesting to note that the inventors of (/ )-K-13675, in the first reported synthetic approach, targeted the racemic compound 1, and contracted separation of the enantiomers by preparative chiral chromatography to the expert company in this field, Diacel Chemical Indistries Ltd. [37]. Continuing scale-up investigations, the authors succeeded in replacing the Mitsunobu method, in the ether bond-forming reaction, by the technically much more simple use of triflate 21, prepared on a kg scale from (5)-n-butyl-2-hydroxybutanoate 20 (Scheme 3.8) [38]. 

Methyl jS-D-glucopyranuronate glycosides of palmityl alcohol and p-bromophenol have been prepared by Koenigs-Knorr and Mitsunobu methods,... 

In the olivanic acid series of carbapenems the ( )-acetamidoethenyl grouping can be isomerised to the (Z)-isomer (19) (22) and reaction with hypobromous acid provides a bromohydrin that fragments to give a thiol of type (20) when R = H, SO H, or COCH. The thiol is not isolated but can react to provide new alkyl or alkenyl C-2 substituents (28). In the case of the nonsulfated olivanic acids, inversion of the stereochemistry at the 8(3)-hydroxyl group by way of a Mitsunobu reaction affords an entry to the 8(R)-thienamycin series (29). An alternative method for introducing new sulfur substituents makes use of a displacement reaction of a carbapenem (3)-oxide with a thiol (30). Microbial deacylation of the acylamino group in PS-5 (5) has... 

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... 

The Wenker aziridine synthesis entails the treatment of a P-amino alcohol 1 with sulfuric acid to give P-aminoethyl sulfate ester 2 which is subsequently treated with base to afford aziridine 3. Before the discovery of the Mitsunobu reaction, wbicb transforms an amino alcohol into an aziridine in one step under very mild conditions, the Wenker reaction was one of the most convenient methods for aziridine synthesis. However, due to the involvement of strong acid and then strong base, its utility has been limited to substrates without labile functionalities. 

The role of the DEAD is to activate the triphenylphosphine toward nucleophilic attack by the alcohol. In the course of the reaction the N=N double bond is reduced. As is discussed later, this method is applicable for activation of alcohols to substitution by other nucleophiles in addition to halide ions. The activation of alcohols to nucleophilic attack by the triphenylphosphine-DEAD combination is called the Mitsunobu reaction.76... 

The sequence detailed here provides 3-(S)-((tert-butyldiphenylsilyl)oxy)-2-butanone in high purity and on a preparative scale from inexpensive (S)-ethyl lactate. This optically active ketone should be a useful intermediate for the preparation of a variety of enantiomerically pure materials. It has been used in our laboratory for an asymmetric synthesis of (+)-muscarine3 and in the preparation of various other optically active tetrahydrofurans.4 Mitsunobu inversion of (S)-ethyl lactate followed by protection to provide 2-(R)-((tert-butyldiphenylsilyl)oxy)propanoate5 affords, by this method, ready access to the enantiomer of the title compound. 

Cyclodehydration of p-hydroxythioamides under Mitsunobu conditions (Method a) has provided peptide thiazoline in 80% yield with 78 22 ratio of A B and 56% de. Treatment of p-hydroxythioamides with Me02CNS02NEt3,... 

The corresponding syn-compound can also be synthesized by simply inverting the stereochemistry of the hydroxyl group of the epoxy alcohol by the Mitsunobu reaction [54], Therefore, this method provides a simple and reliable method for the synthesis of any enantiomers and diastereomers of straight-chain 1,2-polyols. 

Asymmetric introduction of azide to the a-position of a carbonyl has been achieved by several methods. These include amine to azide conversion by diazo transfer,2 chiral enolate azidation,3 and displacement of optically active trifluoromethanesulfonates,4 p-nitrobenzenesulfonates,5 or halides.6 Alkyl 2-azidopropionates have been prepared in optically active form by diazo transfer,2 p-nitrobenzenesulfonate displacement,5 and the Mitsunobu displacement using zinc azide.7 The method presented here is the simplest of the displacement methods since alcohol activation and displacement steps occur in the same operation. In cases where the a-hydroxy esters are available, this would be the simplest method to introduce azide. 

Epimerization of carbohydrate stractures to the corresponding epi-hydroxy stereoisomers is an efficient means to generate compounds with inverse coirfiguration that may otherwise be cumbersome to prepare. Several different synthetic methods have been developed, including protocols based on the Mitsunobu reaction,sequential oxidation/reduction... 

A new method for the preparation of pyrrolo[2,l-c][l,4]benzothiazepine 292 starting from aldehyde 291 with an intramolecular Mitsunobu cyclization in the last step has been reported (Scheme 63 (1999T1479)). A disadvantage of this procedure is the redox nature of the Mitsunobu reaction, which is responsible for a side oxidation of the thiol group and poor isolated yields of the product. 

---