Mitsunobu imidazoles

Entry 10 illustrates the application of the Mitsunobu reaction to synthesis of a steroidal iodide and demonstrates that inversion occurs. Entry 11 shows the use of the isolated Ph3P-Br2 complex. The reaction in Entry 12 involves the preparation of a primary iodide using the Ph3P-I2-imidazole reagent combination. 

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... 

A variety of phosphorus-coutaining reagents have been employed in sugar chemistry in the direct SN2 replacement of hydroxy groups mainly by halide ions [35], Most of these reagents used a combination of triphenylphosphine with an electrophilic halogen source such as /V-halosuccinimide [36,37], carbon tetrahalides [38-41], and more recently, tri-haloimidazole or iodine and imidazole [42-45] or related reagents [46J. The Mitsunobu... 

Cyclization of alcohols 334 under Mitsunobu condition was very sluggish, but it happened easily when alcohol was treated with Ph3P, imidazol and I2 to give perhydropyrido[l,2-a]pyrazine-3-carboxylates 335 (08SL702). C3 Epimer of 335 was prepared similarly. 

Several stereoselective syntheses of 4-(ribofuranosyl)imidazole nucleosides were reported. Imidazole 53 was obtained from 50 by a Mitsunobu cyclization [95TL3165]. Treatment of a suitably protected ribofuranosyl chloride with two equivalents of a lithioimidazole afforded the 1-(5-imidazolyl)ribofuranoid glycal (54) directly which undergoes elimination to the furylimidazole (55) [95CPB152]. 

N-Arylation of various azoles (or their anions) was readily accomplished with p-tolyllead triacetate in the presence of copper(II)acetate [95JOC5678] however, die applicability of this procedure to other aryllead triacetates was not discussed. Solvent-dependent palladium-mediated allylations [95JHC1325] and Mitsunobu-based asymmetric alkylations [95JOC2008] of imidazoles and benzimidazoles have also been reported. 

Under Mitsunobu conditions, see Scheme 2.6, it is possible to prepare imidazoles with chiral side chains that can subsequently be converted into ionic liquids.11051 One of the features of many of the chiral ionic liquids reported to date, that could limit their application in catalysis, is their high viscosity. However, by combining chiral imidazolium cations with anions described above that help to reduce viscosity, this problem could potentially be overcome. 

Scheme 2.6 Preparation of chiral imidazoles under Mitsunobu conditions...

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. ... 

Thioethers. Alkylation of thiols with alcohols under the Mitsunobu reaction conditions is catalyzed by imidazole. 

Thirdly, total synthesis of antipodal koumine was achieved by Magnus et al. In the final stage for coupling the C-7 and C-20 position, they utilized the Mitsunobu condition (diethyl azodicarboxylate, PhsP, a catalytic amount of imidazole, and NaH) and obtained koumine in moderate yield (73). 

In an imusual application of the Mitsunobu reaction, the chiral pyridinium compoimd 243 was selectively cyclised to 244, an advanced intermediate in the synthesis of l-e/7i-L-entiginosine. A similar approach has been used for the alkylation of pyridines and imidazoles to prepare the corresponding salts. ... 

An improved route to 3-(p-D-ribofuranosyl)pyrazole has been described, starting from 2,3-O-isopropylidene-D-ribofuranose and involving acetylenic intermediates. A stereocontrolled route to 4(5)-(P-D-ribofuranosyl)imidazole (115) has also been developed the epimeric mixture 114 was obtained via addition of a lithiated imidazole to 2,3,5-tri-O-benzyl-D-ribofuranose, and cyclization of this under modified Mitsunobu conditions gave selectively the P-product. A mechanistic rationale was presented, and the 2 -deoxycompound was similarly made. Various other 2 -deoxy-C-nucleosides of type 116 have been prepared in a non-stereoselective way by reaction of lithiated heterocycles with 3,5-(9-Tips-2-deoxyribose, followed by acid-catalysed cyclization compoimds made included the 2-furyl, 2-indolyl, 2-pyridyl and benzothiophen-2-yl analogues. ... 

Oba and coworkers observed racemization when eliminating a mesylate derived from a 4,5-cis-substituted pyrrolidin-2-one en route to a chiral 3-pyrrolin-2-one (2009TL5053). In order to combat this problem, they inverted the stereochemistry of the hydroxy group using a Mitsunobu-like reaction (Scheme 122). Treatment of alcohol 451 with iodine, polymer-supported triphenylphosphine (PS-PPh3), and imidazole gives the 3-pyrrolin-2-one 453 via intermediate iodide 452. 

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