3-Pyrazolidinones synthesis

Intramolecular phosphonate-based olefination has been used to construct five-membered rings in a number of syntheses for example in a novel approach to [3.3.0] fused pyrazolidinones (244) (Scheme 35), a totally synthetic class of antibacterial agents. 44 new, convergent synthesis of the fungal metabolite and useful synthetic intermediate (+)-terrein (248) has been reported. 45 The method is based on two phosphonate olefination steps. The diphosphonate (245), obtained from L-tartaric acid, gives, on treatment with base, a mixture of the required phosphonate (24 6) and the diphosphonate (247). However, under appropriate conditions (246) is the major product and can be converted into (+)-terrein by reaction with acetaldehyde (Scheme 36). Olefination of the ketone (249) with dimethyl diazomethylphosphonate (250) provides, via carbene insertion, the cyclopentene (251) and hence a new route to (-)-frontalin (252) (Scheme 37).146... 

The synthesis of pyrazolidinones is readily achieved by condensation of an a,/ -unsaturated acid,1550 ester1209,1569 or amide758 with a hydrazine. In eq. 4 is shown the reaction for an amide. 

The 5-oxo-3-pyrazolincarboxylic acids react normally. A number of their reactions have already been discussed in connection with the synthesis of analogous aldehydes and ketones. The Curtius rearrangement of the azide will be discussed in more detail in the section concerning 5-imino-3-pyrazolidinones. Both the 3- and 4-carboxylic acids decarboxylate at elevated temperatures.107,108,370 Hydrolysis of 4-carboxanilides with hydrochloric acid first forms the acid which then loses carbon dioxide.826... 

As was mentioned previously (eq. 4, p. 10), the principal method used for synthesis of 3-pyrazolidinones is the reaction of hydrazines with a,j8-unsaturated acids,446, sie.911.1342.1550 oc, -unsaturated esters581,762,911,1209,1569 and a,j8-unsaturated amides.758 In many cases these reactions do not give l-substituted-3-pyrazolidinones, as shown in eq. 4, but the isomeric 2-substituted-3-pyrazolidinones, as shown for one particular case in eq. 244. Most frequently aryl hydrazines have... 

Modification of this synthesis can be achieved by treating the hydrazide with diethyl carbonate or diethyl thiocarbonate. In the latter case the products are 5-thiono-3-pyrazolidinones. 

One of the most widely used methods for the preparation of 5-imino-3-pyrazolidinones is from 5-oxo-3-pyrazolin-3-carboxylic acids or their derivatives by use of the Hofmann167,697 or Curtius167,1387,1395 rearrangements (eq. 264). A similar synthesis is from the analogous... 

An imine-enamine annulation has been used in the synthesis of the indoloquinolizidine alkaloid ( )-deplancheine.52 The annulation of dialkyl (1-alkoxycarbonyl)vinylphosphonates via a Horner-Wadsworth-Emmons reaction has been developed in the synthesis of [3.3.0] fused pyrazolid-inones from monocyclic pyrazolidinones. - Treannent of diethyl l-(ethoxycarbonyl)vinylphos-phonate in excess (2 eq) with imide anions such as phthalimide, maleimide, and succinimide successfully produces the corresponding six-membered fused heterocycles. Similarly, synthesis of functionalized cyclohexenylphosphonates is achieved by condensation of diethyl l-(ethoxycar-bonyl)vinylphosphonate (2 eq) with cyclopentanone enolates (Scheme 8.29). - ... 

Temansky, R.J., and Draheim, S.E., The chemistry of substituted pyrazolidinones. Apphcations to the synthesis of bicychc derivatives. Tetrahedron, 48, 111, 1992. 

An efficient and regioselective method for the synthesis of pharmaceutically important intermediates (323) has been developed. It is based on the intramolecular Wadsworth-Horner-Emmons condensation of monocyclic compound (322), which is available by a selective stepwise functionalization of pyrazolidinone (321) (Scheme 64). The overall yield is about 25% <90TL2805>. 

Similar methodology as used for the 5-5 fused pyrazolidinones (see Section 8.31.12.1.2) based on an acid-induced cyclization of exocyclic hydrazonium intermediates is also useful for the synthesis of similar 5-6 bicycles as is shown in Scheme 87 <94RTC145>. 

In principle, binding a copper catalyst to a surface requires that during the catalytic cycle the copper ions will not be released into the solvent. Recently, it was shown that this is even the case for Cu(0H)a Al203 which contains ca. 10% water as a catalyst for the catalytic synthesis of A7, A -bicyclic pyrazolidinone in organic solvents, a process which involves Cu(I) as the reactive intermediate 171). 

Dipolar cycloaddition reactions with stable and easily prepared azomethine imines, for the synthesis of a diverse array of heterocycles, have attracted considerable attention [125]. The complex RhjldS-MPPlM) (47) catalyzes the highly diastereoselective [3-l-2-l-l]-cycloaddition reaction between a diazo ketone and azomethine imines [126]. The final products are multi-functionalized bicyclic pyrazolidinone derivatives isolated in moderate to high yields (Scheme 9.12). 

Fernandez, M., Reyes, E., Vicario, J. L., Badfa, D., Carrillo, L. (2012). Organocatalytic enantioselective synthesis of pyrazolidines, pyrazolines and pyrazolidinones. Advanced Synthesis Catalysis, 354, 371—376. 

Asymmetric 1,3-dipolar cycloadditions of azomethine imines with terminal alkynes have been catalysed by 11 chiral ligand (8) coordinated metal amides to form N,N-bicyclic pyrazolidinone derivatives. Mechanistic studies have established the factors that determine the regioselectivity of the stepwise reaction. Novel phosphoramidite ligands (9) coordinated with palladium have been used to effect enantioselective synthesis of pyrrolidines by 3-P 2-cycloaddition of trimethylenemethane (from 2-trimethylsilylmethyl allyl acetate) to a wide range of imine acceptors (Scheme 11). ... 

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