Mitsunobu condensation

Indolizidines quinolizidines.1 Mitsunobu condensation of 1 with succinimide provides the imide 2, which can be converted as shown into the indolizidine (4). A similar sequence but starting with glutarimide provides the quinolizidine (5). 

Campbell, D. A., and Bermak, J. C. (1994) Phosphonate ester synthesis using a modified Mitsunobu condensation. J. Org. Chem. 59, 658-660. 

Many examples of the synthesis of tetrahydropyrans are based on the cyclization of 1,5-diols and related compounds which can provide an electrophilic site for ring closure . Thus, pentane-1,5-diols can be quantitatively cyclized to the pyran in the presence of BuSnCl3 <1988G483> or via an intramolecular Mitsunobu condensation with cyanomethylenetributylphosphorane <1996TL2463>. Tetrahydrothiopyrans are prepared similarly by cyclizations of suitably substituted thiols . 

Bisai and Singh elucidated an efficient approach to 2-substituted A-tosylpipcridincs with the key cyclizahon step consisting of a Mitsunobu condensation that occurred in excellent yields of 90-96% <07TL1907>. 

The Ugi reaction followed by Mitsunobu condensation was applied to the synthesis of the pyrrolidine-fused 1,4-oxazocane 230 (Scheme 30) <2007JOC2151>. It was expected that the pyrrolidine ring in the precursor 229 could furnish a steric bias favoring the cyclization. Indeed, the compound 230 was formed in 70% yield (cf. Scheme 29). 

The most general methods of C-N bond formation used for heteronine formation are alkylation or Mitsunobu condensation. Azonine 213 was synthesized starting from 2-nitrobenzenesulfonamides and using conventional alkylation procedures or Mitsunobu conditions (Scheme 44) <2002SL697, 2002T6267>. 

Facile formation of nine-membered N,N -protected cyclic sulfamide 214 was carried out in two steps by an intermolecular Mitsunobu condensation and subsequent intramolecular N-alkylation (Scheme 45) <2003T6051>. 

In contrast, our Mitsunobu condensation chemistry proceeded nearly quantitatively after 4 hr at rt (by 31P-NMR isolated yield >80%) when conducted in dry dioxane using 1.5 equiv of AZT, TPP and DIAD. 

Other examples include reactions, such as the Mitsunobu condensation, where polystyrene-diphenylphos-phine can be used instead of triphenylphosphine, avoiding production of the difficult-to-remove by-product, triphenylphosphine oxide. 

Fuchs elegant approach to the morphinan skeleton utilized an intramolecular conjugate addition/alkylation sequence, in which connections C12-C13 and C9-C14 were formed as a result of one tandem process.73-74 Mitsunobu condensation between alcohol 164 (from 2-allylcyclohexene-l,3-dione in five steps and 43% overall yield) and phenol 163 (from isovanilline in 6 steps and overall yield of 40%)73c gave the ether 165, Scheme 19. TBDMS deprotection followed by an oxidation/reduction sequence set the aryl ether... 

The Mitsunobu condensation of 2,3,4,6-tetra-(9-acetyl-D-glucose with amino acid-derived 2-nitrobenzenesulfonamides led to formation of the protected... 

In an interesting study on antibody-catalysed prodrug activation, the phosphonate 205 was prepared by Mitsunobu condensation of the phosphonic acid with the 3 -t2-Tbdms derivative of FdU. This hapten was linked to keyhole limpet hemocyanin and bovine serum albumin via the carboxylate group. The monoclonal antibodies specific for 205 were found to catalyse the hydrolysis of 5 -C -(/V-acetyl-D-valyl)-FdU, an FdU prodrug that was not hydrolysed by endogenous esterases, and a combination of 205 and antibody was as effective as FdU itself in preventing the growth of E.coli in vitro. ... 

An other approach to the synthesis of type I side-chain NLO polymers is the post-fiinctionalization of a preformed polymer chain with a NLO chromophore (Fig. 2.16). Examples include post-functionalization by azo coupling, Knoevenagel condensation, Mitsunobu condensation between imide or carboxy functions of the polymer chain and alcohol functions of the chromophore [66-68]. This approach to NLO polymers has several advantages as the possibility of easy modulation of the chromophore content in the functionalized polymer and, in some cases, the possibility of using commercially available polymers as substrates for the post-functionalization. 

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