Mitsunobu procedure

An asymmetric synthesis of phosphonylated thiazolines has been described. The phosphonodithioacetate 46 was aminated with a chiral amino alcohol 47 to give the phosphonylated thioamide 48 in good yield. This was then cyclised using a Mitsunobu procedure to give the chiral thiazoline phosphonate 49 in good yields under mild conditions. Homer-Wadsworth-Emmons reaction of these phosphonylated thiazolines gave chiral vinylic thiazolines 50 <00S1143>. 

When discussing the specific features of various leaving groups in the synthesis of nitronates presented in Scheme 3.12, the possibility of the use of the OH group as the leaving group should be separately discussed. As in the synthesis of acyclic nitronates, the Mitsunobu procedure (10) is apparently suitable for intramolecular cyclization of acyclic y-nitro alcohols (Scheme 3.17). 

Transformation of a primary amine to a secondary amine using 2,4-dinitro-benzenesulfonyl chloride and an alcohol. Also known as Fukuyama-Mitsunobu procedure. 

The first one (Scheme 55) uses the p-oxyphenylsulfonyl linker attached to the Wang resin by the Mitsunobu procedure [216, 217] whereas the second one (Scheme 56) utilizes alkylation of the lithium salt of a mesylate [218] with the terminal of the Merrifield resin [216, 219]. 

The successful synthesis of optically active 7 then led to the first synthesis of verrucarin A (8), a macrotrilactone with significant cytostatic activity. The synthesis involved esterification of the primary alcohol of verrucarol (the tricyclic fragment) with the acetate of 7 (DCC, 4-pyrrolinopyridine) and then with a protected derivative of (E, Z)-muconic acid. After deprotection (Bu4NF), lactonization was effected by the Mitsunobu procedure (7,405-406). 

Another approach to the preparation of iV-alkyl derivatives 26 is the Mitsunobu reaction. The Mitsunobu procedure is now a well-known method for preparing amines from alcohols using acidic imide derivatives as a nitrogen nucleophile < 198IS 1, 19960PP127>. The remarkably high acidity of l,2,4-dithiazolidine-3,5-dione 12 (pA), 2.8) <2000SL1622>... 

It has been found that the results of this new variant of the Mitsunobu procedure are generally comparable with the results of the traditional Mitsunobu reaction both with respect to the yields and enantiomeric excess (ee) of chiral compounds 26. Thus, products prepared from alcohol 86e using both methods had ee 70% and 72%, and from (Tl-methyl lactate 86i 92% and 99%, respectively. However the new variant of the Mitsunobu procedure has a significant synthetic advantage over the traditional procedure imides 26 can be transformed into primary amines under milder conditions in comparison with the deprotection of /V-alkylphthalimides (see Section 6.03.6.1.3). 

The Mitsunobu procedure for the incorporation of carbohydrate moiety into combinatorial peptide libraries has been executed on solution phase, by using gluco-tyrosine as glycoamino acid model (prepared as shown in Figure 3.15) and improved on a solid support for model peptide GlyGly-Tyr (jS-tetra acetyl glucose)-GlyGly. 

Vertaline (61) was synthesized through two routes that involve an W-acylimin-ium ion cyclization (20) and an intermolecular [3 + 2] cycloaddition (21,22) as the key steps, respectively. Model studies (20, 24) for assembling the quinolizi-dine moiety by the W-acyliminium ion cyclization are shown in Scheme 7. The benzyl alcohol 65 was converted to glutarimide 66 by the Mitsunobu procedure in 55% yield. Reduction of imide 66 with diisobutylaluminum hydride afforded 67, which was subjected to V-acyliminium cyclization to give the lactam 68 in 40% overall yield from 66. Lactam 68 possesses the correct stereochemistry at all chiral centers required for vertaline (61). 

Venugopalan et al. also prepared some ethers and thioethers of dihydroartemisinin.Haynes et al. synthesized many new C-12 esters and ethers of dihydro- artemisinin. Compared with similar work performed 20 years ago, they successfully prepared some (3-aromatic esters of dihydroartemisinin by means of Schmit and Mitsunobu procedures. 

Once again, the drive for improved performance in transition metal ion-catalysed processes has continued to stimulate the synthesis of new types of organophosphine and tervalent phosphorus-ester and -amide ligands. Activity in the chemistry of heteroaromatic phosphorus ring systems and low-coordination number p -bonded systems has also remained at a high level. New mechanistic insights into the Mitsunobu reaction have been reported, and interest in synthetic applications of Staudinger/Mitsunobu procedures has continued to develop. 

The Mitsunobu procedure, which uses diethyl azodicarboxylate (DEAD) or diisopropyl azodi-carboxylate (DIAD) to react with PPh3 and alcohols providing configuration-inversed substitution products via alkoxytriphenylphosphonium ion intermediates (O Scheme 28), presents another route for introducing halogen atoms into carbohydrates [48]. 

Alkyl alcohols or enolizable aldehydes are converted in a steieospeciHc manner to alkyl chlorides or vinyl chlorides in good yields on treatment with a Mukaiyama-type chlorobenzoxazolium salt (Scheme 7). The very good activation of hydroxy groups by the Mitsunobu procedure may be useful in some difficult cases (Scheme 8). ... 

A preformed complex of diethyl azodicarboxylate/PhsP activates primary and secondary alcohols sufficiently for SN2-type reactions with LiF (Scheme 33). This Mitsunobu procedure is a rare example of a reaction useful with all four halogens. 

The Mitsunobu procedure has found considerable application, so it has been used for diolide formation in pyrenophorin (equation 138) °° and colletodioF° syntheses. Yamaguchi s method is much infe-rior. As expected, the ring closure in equation (138) proceeds with inversion of configuration. In a... 

The Keck macroiactonization was used by R.J.K. Taylor et al. to close the 10-membered ring of (+)-apicularen A. The lactonization was attempted using both the Yamaguchi and Mitsunobu procedures and neither gave even a trace of the cyclic product. However, when the Keck conditions were applied, the desired lactone was isolated in moderate yield. 

The Mitsunobu procedure was reported to be efficient in the case of fluoroalkyl alcohols [42], Unlike nonfluorinated alcohols, the acidic fluoro-alcohols [43] are efficiently deprotonated by the PPh3-DEAD adduct. This facilitates the displacement of the oxyphosphonium leaving group by an alkoxide. With the use of this reaction, a range of ethers 9 were prepared from fluoro-alcohols in good (from primary alcohols) to moderate yields (secondary alcohols) with high P-stereoselectivity (see Scheme 6.3 and Table 6.1). 

The allyl silane 126 is coupled with the imide 127 by a Mitsunobu procedure and one of the carbonyl groups is reduced to give the alcohol 129. Treatment with CF3C02H now cyclises the allyl silane to give a new heterocyclic ring 130. 

The corresponding 3a-hydroxy lactone 42 was synthesized from 68 using the Mitsunobu procedure (diethyl azodicarboxylate/triphenylphosphine/formic acid) for inversion of the hydroxy function in position 3.73 The resulting 3oc-formyloxy ester 73, upon hydrolysis afforded the 3a-alcohol 74. Asymmetric dihydroxylation of 74 yielded 24-epityphasterol (75) as the main product. Baeyer-Villiger oxidation of 75 led to 2-deoxy-24-epibrassinolide (42) and its isomeric lactone 76 in a 1 0.6 ratio.74... 

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