Pyrrolinones, synthesis

The general form of metal-assisted cycloaddition as shown in Scheme 31 can be readily elaborated using monohaptopropargyl complexes (Scheme 32)61 specific examples illustrating the synthesis of A3-pyrrolinone derivatives are shown in Scheme 33.59... 

The action of phosphorus halides on pyrrolinones and related compounds offers an alternative route to chloropyrroles. Yields of around 60% of 2,5-dichloropyrroles were obtained in this way from N-substituted succinimides (82ZC126). Vilsmeier reaction of N-alkylsuccinimidals formed chlorinated pyrrole aldehydes in modest yields (90CJC791), and there are other examples [66YZ158 81H(15)547]. A useful synthesis of chloropyrrole-2-carboxylates employed the action of phosphorus pentachloride on pyrrolidin-2-one-5-carboxylates (40) (87CB45) (Scheme 15), and in a Pummerer-type reaction pyrrol-3-yl sulfoxides were transformed by thionyl chloride into chloropyrroles. Yields were increased to >80% by the use of oxalyl chloride (88JOC2634) (Scheme 15). 

A new /3-lactam synthesis has been devised which relies on the formal ring contraction of the A3-pyrrolinone (271), readily prepared from commercially available mucochloric... 

The reaction of DMAD with the pyrrolinone 332 has been used202 for the synthesis of vinylpyrrolinones (333), which are useful for the preparation of bile pigments the isoindole 324 was also obtained. 

The main interest in the reaction with unsaturated carbonyl compounds lies in the synthesis of heterocycles, mainly pyridines. Simple pyridines can be obtained starting with an alkyl aminocrotonate and acrolein73, an acetal-substituted enol ether74 or benzoylacrylonitriles75 (equation 52). Pyrrolinones are obtained by SnCl4-catalysed action of 3-ethoxycarbonylacrylonitriles on enaminoester75 (equation 53). 

Koch and coworkers reported an efficient synthesis of alkoxy aminocyclopropane derivatives by the photolysis of alkoxypyrrolinones (320) . The primarily formed isocyanates (321/322) were converted into urea or urethane derivatives (323/324) (equation 76). Pyrrolinone photoreaction was shown to be a very convenient basis for the... 

The synthesis of pyrrolinones 120 from diimines 117 and diphenylcyclopropenone 118 was reported as proceeding via rearrangement of the ketene intermediates 119198 (equation 48). 

HeterocycUziotion a -Aminoalkynones undergo a 5-endo-dig cyclization that results in pyrrolinones. This process has been applied to a synthesis of (+)-preussin. 

Smith, A. B., Ill, Keenan, T. R, Holcomb, R. C., Sprengeler, R. A., Guzman, M. C., Wood, J. L., Caroll, R J., Hirschmann, R. Design synthesis and crystal structure of a pyrrolinone-based peptidomimetic possessing the conformation of a (3-strand potential application to the design of novel inhibitors of proteolytic enzymes. J. Am. Chem. Soc. 1992,114, 10672-10674. 

Scheme 7.7. Synthesis of a tetrapeptide mimetic pyrrolinone oligomer containing three heterocyclic rings...

Asymmetric synthesis of pyrrolidines and pyrrolinones. This chiral -hydroxy-amine (1) reacts with a y-keto acid in refluxing toluene to form a chiral bicyclic lactam 2 in 75-98% yield. Treatment of 2 with excess alane, generated from AlCly and LiAlH4,... 

A.B. Smith, W.Y. Wang, P.A. Sprengeler, R. Hirschmann, Design, synthesis, and solution structure of a pyrrolinone-based beta-turn peptidomimetic, J. Am. Chem. Soc. 2000, 122,11037-11038 A.B. 

A. Pasternak, W.Q. Yao, P.A. Sprengeler, M.K. Holloway, L.C. Kuo, Z.G. Chen, P.L. Darke, W.A. Schleif, An orally bioavailable pyrrolinone inhibitor of Hiv-1 protease computational analysis and X-ray crystal structure of the enzyme complex, J. Med. Chem. 1997, 40, 2440-2444 P.V. Murphy, J.L. O Brien, L.J. Gorey-Feret, A.B. Smith, Synthesis of novel Hiv-1 protease inhibitors based on carbohydrate scaffolds, Tetrahedron 2003, 59, 2259-2271 P.V. Murphy, J.L. O Brien, L.J. Gorey-Feret, A.B. Smith, Structure-based design and synthesis of Hiv-1 protease inhibitors employing beta-D-mannopyranoside scaffolds, Bioorg. Med. Chem. Lett. 2002, 12, 1763-1766. 

Notable new general syntheses of butenolides include the addition of the three-carbon synthon Li(PhS)C=CMeC02Me to aldehydes R CHO (R = alkyl or aryl) to yield the thioethers (19), the related reaction of lithio-j8-lithio-acrylates R CLi=CR C02Li with benzaldehyde to give compounds (20 R = H or Me), and the formation of (21) from the iodinated allyl alcohol ICMe=CHCH20H and carbon monoxide in the presence of bis(triphenylphos-phine)palladium(ii) chloride. Chloral reacts with dimethyl (benzylamino)fu-marate to yield the butenolide (22), whereas aromatic aldehydes give hydroxy-pyrrolinones (23). The total synthesis of piperolide (24) has been reported. 

A. B. Smith III, T. P. Keenan, R. C. Holcomb, P. A. Sprengeler, M. C. Guzman, J. L. Wood, P. J. Carroll, and R. Hirschmann,/. Am. Chem. Soc., 114,10672 (1992). Design, Synthesis, and Crystal Structure of a Pyrrolinone-Based Peptidomimetic Possessing the Conformation of a p-Strand Potential Application to the Design of Novel Inhibitors of Proteolytic Enzymes. 

Hydroxy-2(5H)-furanones were successfully involved in DKRs using lipase PS, offering an attractive route to the enantioselective synthesis of a series of 5-acyloxy-2(5H)-furanones with optimal chiral economy. In the same way, the corresponding 5-(acyloxy)pyrrolinones were submitted to esterification using Candida antarctica lipase B via DKR (Scheme 3.18). ... 

In 1988, new investigations on the Reformatsky route were published. Synthesis of cTudal intermediates and crossing experiments using two different benzo-nitriles strongly indicated that the reaction did not proceed via an oxidative dimerization mechanism and the intermediate 4. Instead, it could be shown, that the lactam S is formed during the reaction, and a new mechanism was postulated involving a sequential build up of the DPP via the pyrrolinone ester 6A as the crucial intermediate (Scheme 11-3). 

Oxidation of C-H bonds to C=0 bonds by O2 only or N-oxides and DMSO Synthesis of A -bipyrrolinones and pyrrolino[3,2-h]pyrrolinones from 2,6-diazasemibullvalenes. 

There are some unique transformations of alkynes with adjacent reactive functional groups that take place under hydroformylation conditions. Such reactions were used in the synthesis of the thiazepinone [31] and the pyrrolinone [32] framework of pharmacologically active compounds. In the first case, the reaction of acetylenic thiazole 25 with carbon monoxide and hydrogen afforded thiazepinone 26 via a cyclohydrocarbonylative ring expansion (Equation 12.2), whereas pyrrolinones (e.g., 28) were obtained by a tandem cyclohydrocarbonylation - CO insertion sequence (Equation 12.3). 

Use of the retro-Diels—Alder reaction in the synthesis of chiral pyrrolidine and pyrrolinone products has been described by several groups. The... 

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