Mitsunobu dehydration

Oxidation of oxazolines using Mn02 was also employed in the synthesis of a beminamycin A fragment by Shin and co-workers ° and in the preparation of the naturally occiuring 2,4-disubstituted oxazole, phenoxan 28, by Yamamura s group" (Scheme 1.5). For beminamycin, the oxazoline 25 was synthesized in 61% yield by Mitsunobu dehydration of the serine-derived amide 24. 

Another interesting class of five-membered aromatic heterocycles has recently been published by Tron et al. [54]. These compounds have biological activity in the nM range. An example of the formation of these furazan (1,2,5-oxadiazole) derivatives is shown in Scheme 9. The diol 50 was oxidized to the diketone 51 using TEMPO and sodium hypochlorite. Transformation to the bisoxime 52 was performed in an excess of hydroxylamine hydrochloride and pyridine at high temperature for several days. Basic dehydration of 52 formed two products (53a and b). A Mitsunobu reaction was then employed using toluene as solvent to form compound 53b in 24% yield. 

A remarkable stereospecific dehydrative alkylation of (3-disulfones was reported by Falck et al. [406] under Mitsunobu conditions (triethyl phosphine, diethyl azodicarboxylate). The synthesis of a pheromone component of the lesser tea tortrix emphasizes some of the possibilities offered by coupling this reaction with further uses of the sulfone functionality. In the present case, monodesulfonylation with lithium naphthalenide (-78°C, 5 min), in situ alkylation (-78 to 23°C, 1 h), and Li-naphthalene cleavage of the second sulfonyl group (—78°C, 5 min) yielded in a one-pot procedure a THP ether which was converted into the sought after pheromone through direct acetylation. 

MITSUNOBU REACTION. Intcrnioleculur dehydration reaction occurring between alcohols and acidic components on treatment with diethyl azodtearboxylate and triphcnyl phosphine under mild neutral conditions. The reaction exhibits stereospecilicity and regional and functional selectivity. 

The Mitsunobu reaction of perhydropyrido[l,2-a]pyrazine-l,4-dione 230 at ambient temperature gave dehydrated product 231 in 15% yield. When the reaction was carried out with excess PBu3 and diethyl azodicar-boxylate at 40 °C the incipient 231 spontaneously underwent enolization and tautomerization, [4+2] aza-Diels-Alder reaction to provide a 2.4 1 mixture of diastereomers 232 and 233 (07T6124). No reaction occurred when isolated 231 was treated under similar conditions. 

Rather surprisingly this strategy works.5 It was better to use the diketone 36 (rather than 33), made by acylation of the morpholine enamine 35 of 34 and reductive amination of with 3-aminopropanol to give 37 that is dehydrated in acid to the amine 38. A Mitsunobu-like treatment with Ph3P-Br2 converts the OH to Br whereupon cyclisation of 32 X = Br gives 31. 

The use of standard Mitsunobu conditions for the cyclization of (Z)-l,5-jy -diol 220 leads to a considerable decrease in the enantiomeric excess of the resulting 3,6-dihydropyran. Cyclization of (Z)-l,5-jy -diol 221, using the phospho-nium salt 222 as a dehydrating agent, provides an asymmetric synthesis of 2,6-tf //-5,6-dihydropyran 223 (Equation 103) <2005MIBJ07>. 

One of the most widely used procedures for dehydrative coupling and cyclization reactions is the Mitsunobu reaction in which the components are treated with triphenylphosphine and diethyl azodicarboxylate (DEAD, EtOaC—N=N—COiEt). The overall equation for reaction of an alcohol 67 with an acid 68 to form the ester 69 is as shown and the active species is the zwitterionic... 

In the total syntheses of squamocin A and squamocin D, acetogenins from Annonaceae, a double cyciization has been demonstrated to be feasible for the assembly of bis-tetrahydrofuran motifs (Equation 71) <2000EJ01889>. Intramolecular dehydration to afford tetrahydrofurans can efficiently be carried out by the Mitsunobu reaction <2003JOC4422> and a cationic platinum-catalyzed dehydration <2005SL152>. 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

Grochowski, E., Hilton, B. D., Kupper, R. J., Michejda, C. J. Mechanism of the triphenylphosphine and diethyl azodicarboxylate induced dehydration reactions (Mitsunobu reaction). The central role of pentavalent phosphorus intermediates. J. Am. Chem. Soc. 1982,104, 6876-6877. 

There are two good ways to do this. Dehydration of alkyl nitrocompounds 68, either with PhNCO or with Ph3P and DEAD (Et02C-N=N-C02Et) in a Mitsunobu elimination gives nitrile oxides 69, as does the 1,3-elimination of HC1 from chloro-oximes 70. In the next section we shall show only the nitrile oxide but you should recall that it is generated in the reaction mixture by one of these reactions. 

There are efficient ways in which to use starting materials that have the carboxylic acid component already installed on both heteroatoms conversion to bis(silyloxy) derivatives, or simply heating with p-toluenesulfonic acid. An excellent route to mono-acylated precursors utilises mixed anhydrides. A very mild method for the dehydrative ring closure of ortfto-hydroxyarylamino-amides utilises typical Mitsunobu conditions - triphenylphosphine and diethyl azodicarboxylate. ... 

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. 

The enantioselective synthesis of monoprotected fra 5-2,5-pyrrolidine dialcohol 1119, a potentially useful intermediate for the construction of pyrrolizidine alkaloids, uses ( S)-malic acid as the chiral source and radical cyclization to fabricate the heterocycle (Scheme 164) [236]. The crucial intermediate 1112 is prepared from acetonide 454b by a Mitsunobu reaction of 1110 with oxazolidine-2,4-dione, resulting in inversion of configuration at the hydroxyl-bearing carbon. Reduction of the 4-carbonyl group of heterocycle 1111 with sodium borohydride followed by dehydration of the resulting alcohol furnishes 1112. 

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