Diols Mitsunobu reactions

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. 

Scheme 21 shows the synthesis of a dihydrofuran derivative 86. Synthesis of this compound was described by Nam et al. [68] utilizing a furanone compound 87 synthesized by Kim et al. [61] via a similar synthetic approach as described in Scheme 17. The lactone was reduced using lithium aluminum hydride to give the diol 88 and intramolecular etherification using the Mitsunobu reaction afforded the dihydrofuran 86 in moderate yield (47%).

Iodination reagents combined with aryl phosphines and imidazole can also effect reductive conversion of diols to alkenes. One such combination is 2,4,5-triiodoimidazole, imidazole, and triphenylphosphine.215 These reagent combinations are believed to give oxyphosphonium intermediates which then serve as leaving groups, forming triphenylphosphine oxide as in the Mitsunobu reaction (see Section 3.2.4). The iodide serves as both a... 

Diols are directly converted into oxiranes with Ph3P in the presence of diisopropyl azodicarboxylate (Mitsunobu reaction) (8isi). 

Treatment of L-biopterin with DMFDMA (or DMFDEA), then acetic anhydride in pyridine, gives l 2 -di-0-acety]-/V -(/V,ALdimethylaminoethylene)-L-biopterin (87). This can be converted by the Mitsunobu reaction into 3-methyl and 3-p-nitrophenethyl derivatives. The protective groups on the side chain diols and N1 of these compounds can be selectively cleaved to give biopterin. These reactions indicate their potential for biopterin modification [95MI31. 

The Mitsunobu reaction has been successfully applied to the synthesis of carbohydrate epoxides directly from diols (Scheme 3.15c).84 The more accessible and nucleophilic hydroxyl is converted into an alkoxyphos-phonium ion, which in turn is intramolecularly displaced by a hydroxyl to give an epoxide. Again it is of critical importance that a coplanar SN2 transition state be attained. 

Diols are directly converted into oxiranes with Ph3P or other phosphines in the presence of diisopropyl azodicarboxylate (Mitsunobu reaction). Simple alkenes can be converted into nonracemic epoxides in high yields and with excellent ee values via a two-step sequence of asymmetric dihydroxylation and Mitsunobu cyclodehydration of the intermediate diol (Scheme 18) <20010L2513>. These reactions give best results using electron-poor alkenes . 

The elegant formal total synthesis of morphine, accomplished by Parker, shows some similarities to that of Fuchs through analogous disconnections. In both syntheses, the core of the molecule was formed as a result of a tandem process in this case as a result of a radical cascade.79 80 The immediate cyclization precursor 191 was prepared via a Mitsunobu reaction between monoprotected cw-diol 189 (prepared in 8 steps from 2-((3-methoxyphenyl)ethylamine) in 47% overall yield) and phenol 188, followed by cleavage of the silyl ether, Scheme 21. The key step, homolytic cleavage of the Ci2-Br... 

Scheme 9 Santonin (41) was converted to the derivative (99), whose conversion to alcohol (100) by metal hydride reduction and Mitsunobu reaction. Diol (102), prepared from (100), on acid catalysed cyclization and followed by subjection to Mitsunobu reaction, gave (104), which was converted to ketone (106), whose transformation to homoallylic alcohol (108), was achieved by standard organic reactions. Phenylselenylation afforded (110), which was finally converted to phytuberin.

In 2007, Hudlicky and co-workers reported the preparation of enf-codeine (ent-2) with the enzymatically derived cyclohexadiene diol 49 as the starting material (Scheme 8) [50]. Key steps in this synthesis involve the introduction of the aryl moiety via a Mitsunobu reaction, a Heck reaction to establish the carbon bond between the aromatic ring and C13 followed by a second Heck reaction to close... 

D-Xylose has been converted to (25)-3-(indol-3-yl)propane-l,2-diol 237 by two different routes, one involving direct Fischer indolization of 238. The dibenzyl-dithioacetal 239 was elaborated to the fused triazoline 240 following reaction with MCPBA. Initial oxidation was followed by elimination of acetic acid allowing intramolecular 1,3-dipolar cycloaddition reaction to construct the triazole ring. The bicyclic iV,S -acetals 242 and 241 were prepared by reaction of the 2,3-0-isopropylidene-D-ribofuranose with 2-aminoethane thiol followed by Mitsunobu reaction. These products are considered analogues of castanosper-mine and australine. ... 

Conformationally-locked C-nucleosides such as 147 have been reported from Imanishi s laboratory. These were prepared by formation of the C-T-O bond in Mitsunobu reactions, the necessary diols being formed by stereoselective addition of Grignard derivatives of the heterocycles to an aldehyde. Use of lithiated heterocycles gave substantially more of the other epimers of the diols, thus permitting access to the a-anomers after Mitsunobu reaction. The oxazole 147 and the compound without the phenyl group were incorporated into oUgonuc-leotides, and the triplex-forming ability of the these towards a purine sequence of duplex DNA was studied. ... 

The same group [126] and that of Reynolds [127] have recently developed a new methodology based on a Mitsunobu reaction between 3,4-dihydroxy-2,5-dicarboethoxythiophene and various diols. 

The total synthesis of ditryptophenaline (651) used stereoisomer 637, which was oxidized (—> 645) and reduced to give diol 646 (Scheme 10.5). Analogous to the previously described synthesis, 646 was subjected to a Mitsunobu reaction and reduction to furnish cyclization product 647. Benzyl deprotection and coupling with a Fmoc-protected W-methyl-(5)-phenylalanine derivative yielded tetrapeptide 648. TMSE-deprotection, two oxidations (—> 650), Fmoc-deprotection, and DCC-mediated cyclization finally led to the natural product ditryptophenaline (651). 

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