Mitsunobu reagent

Amino acid synthesis.1 Optically pure amino acids can be prepared in two steps from serine, readily available as either the d- or L-enantiomer. Reaction of N-benzylserine (or of N-benzyl-N-Boc-serine) with the preformed Mitsunobu reagent in CH3CN at -55° provides the protected serine (J-lactone (2) in almost quantitative yield. The lactone reacts with lithium organocuprates (R2CuLi) to... 

Furthermore, the apphcabihty in a Mitsunobu esterification reaction and a Diels-Alder reaction was proven (Scheme 10.13). The polymer-bound benzyl alcohol (70) was reacted with 4-acetamidophenol in the presence of the Mitsunobu reagent to give phenyl ether (71) in quantitative yield. It was released from the polymeric support in high yield. 

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]. 

The reaction of -protected aminomalonate with the Mitsunobu reagent (TPP and DIAD) gave a mixture of a triazoline as the main product and 53 (31%). This compound was formed by the attack of the azodicarboxylate oxygen rather than nitrogen during the cyclization step (88TL4661). 

Bifunctionally tagged Mitsunobu reagents 21 and 22, quaternary ammonium carbonate resin 65, tetrafluorophthalic anhydride (as a solution-phase linking reagent), and amine-functionalized resin 2 were used in a three-step solution-phase synthesis of a series of substituted hydroxypiperidines.39 No further purification (e.g., liquid-phase extraction or chromatography) was required, and products were isolated in good yields and purities. 

Starkey, G. W. Parlow, J. J. Flynn, D. L. Chemically-Tagged Mitsunobu Reagents for Use in Solution-Phase Chemical Library Synthesis, Bioorg. Med. Chem Lett. 1998, 8, 2385. 

Oxazolines.1 Hydroxy amides, prepared from p-hydroxy amines and acid chlorides, are converted into 2-oxazolines with the Mitsunobu reagent at 0 — 25° (equation I). 

Aziridines.2 2-Aminoethanols can be converted into aziridines by the Mitsunobu reagent if the two carbon atoms between oxygen and nitrogen bear at least one substituent. 

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... 

Tsunoda T, Ozaki F, Ito S, Novel Reactivity of Stabilized Methylenetributyl-phosphorane A new Mitsunobu Reagent, Tetrahedron Letters, 35(81) 5081-82, 1994, TMAD. 

Oxidation of esters of a-amino acids. These substrates are oxidized by the Mitsunobu reagent (1) at the a-position to give either a-keto esters or adducts. For example, the N-benzyloxyphenylglycine methyl ester 2 is oxidized to methyl phenylglyoxalate 3 in 93% yield. In contrast, reaction of N-formylphenylglycine methyl ester (4) results in a triazoline (5) in 80% yield. ... 

Allylic chlorides. The last steps in a synthesis of cis-maneonene-A (4), a natural product isolated from a Hawaiian alga, require conversion of the allylic alcohol 2 into the chloro compound 3. Ghosez s chloroenamine (1) proved more effective than the Mitsunobu reagent, PfQHjlj-NCS, or CHjSOjCl-LiCl. The reaction with 1 occurs with inversion. ... 

Azetidines. Reaction of the salt (1) of a p amino alcohol with the Mitsunobu reagent produces the azetidine 2 (50% yield). 

Several fluorous counterparts of common reagents have been reported and many of these are also commercially available. Of some interest is the development of fluorous Mitsunobu reagents. A first generation fluorous DEAD reagent was found to have poor reactivity when difficult Mitsunobu reactions were encountered it has since been replaced with two enhanced, second-generation reagents, (1) and (2), for use in parallel or sequential fluorous chromatography and rapid F-SPE isolation, respectively. 

Studies on 1-0-activation with the Mitsunobu reagent have not attained general importance. ... 

A combination of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobu reagent) is useful for the rapid conversion of aromatic hydroxamic acids (211) to 0-(yV-arylcarbamyl)hydroxamates (212), products of the Lossen rearrangement. In some cases, a spontaneous second Lossen rearrangement occurs to give diarylureas (213), as shown in Scheme 33. The yields of (212) and (213) are 70-85%. The intermediacy of the phosphonium salts (214) has been suggested. 

Mitsunobu reagent. Pairing bis[3-(nonatrifluoro-t-butoxypropyl)] azodicarboxylate with PhyP constitutes a fluorous version of the Mitsunobu reagent ... 

Dehydration. The Mitsunobu reagent (PhyP-DEAD) successfully achieves selective dehydration of a secondary alcohol (apparently an equatorial cyclohexanol) in the presence of an angular OH group is achieved at room temperature. 

One of two diastereoisomers of 101 did not react w ith the Mitsunobu reagent, which might indicate steric congestion by the bulky TBDMS group, although this was unclear. 

Triphenylphosphine-diisopropyl azudic Guanidines. An exceptionally mild 1 of a modified Mitsunobu reagent combia... 

Intramolecular cyslisation of the phosphine oxide (64) with the Mitsunobu reagent gave the l,2,X -azaphosphetidine (65) which was characterised by... 

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