A new iron(III) halide-promoted aza-Prins cyclization between γ,δ-unsaturated tosylamines and aldehydes provides six-membered azacycles in good to excellent yields. The process is based on the consecutive generation of γ-unsaturated-iminium ion and further nucleophilic attack by the unsaturated carbon−carbon bond. Homoallyl tosylamine leads to trans-2-alkyl-4-halo-1-tosylpiperidine as the major isomer. In addition, the alkyne aza-Prins cyclization between homopropargyl tosylamine and aldehydes gives 2-alkyl-4-halo-1-tosyl-1,2,5,6-tetrahydropyridines as the only cyclic products. The piperidine ring is widely distributed throughout Nature, e.g., in alkaloids,1 and is an important scaffold for drug discovery, being the core of many pharmaceutically significant compounds.2,3 The syntheses of these type of compounds have been extensively studied in the development of new drugs containing six-membered-ring heterocycles.4 Reactions between N-acyliminium ions and nucleophiles, also described as amidoalkylation or Mannich-type condensations, have been frequently used to introduce substituents at the R-carbon of an amine.5 There are several examples that involve an intramolecular attack of a nucleophilic olefin into an iminium cation for the construction of a heterocyclic ring system.6 Traditionally, the use of hemiaminals or their derivatives as precursors of N-acyliminium intermediates has been a common two-step strategy in these reactions.6a Among this type of cyclization is the aza-Prins cyclization,7 which uses alkenes as intramolecular nucleophile. However, cy† X-ray analysis. E-mail address: malopez@ull.es. (1) (a) Fodor, G. B.; Colasanti, B. Alkaloids: Chemical and Biological PerspectiVes; Pelletier, S. W., Ed.; Wiley: New York, 1985; Vol. 23, pp 1-90. (b) Baliah, V.; Jeyarama, R.; Chandrasekaran, L. Chem. ReV. 1983, 83, 379-423. (2) Watson, P. S.; Jiang, B.; Scott, B. Org. Lett. 2000, 2, 3679-3681. (3) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. ReV. 2003, 103, 893-930. (4) Buffat, M. G. P. Tetrahedron 2004, 60, 1701-1729 and references therein. (5) Speckamp, W. N.; Moolenaar, M. J. Tetrahedron 2000, 56, 3187- 3856 and references therein. (6) (a) Hiemstra, H.; Speckamp, W. N. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, O., Heathcock, C. H., Eds.; Pergamon: New York, 1991; Vol. 2, pp 1047-1081. (b) Speckamp, W. N.; Hiemstra, H. Tetrahedron 1985, 41, 4367-4416. (7) (a) Dobbs, A. P.; Guesne, S. J. J.; Hursthouse, M. B.; Coles, S. J. Synlett 2003, 11, 1740-1742. (b) Dobbs, A. P.; Guesne, S. J. J.; Martinove, S.; Coles, S. J.; Hursthouse, M. B. J. Org. Chem. 2003, 68, 7880-7883. (c) Hanessian, S.; Tremblay, M.; Petersen, F. W. J. Am. Chem. Soc. 2004, 126, 6064-6071 and references therein. (d) Dobbs, A. P.; Guesne, S. J. Synlett 2005, 13, 2101-2103. ORGANIC

Iron-Catalyzed Reactions in Organic Synthesis

Introduction Cationic domino reactions Anionic domino reactions Radical domino reactions Pericyclic domino reactions Photochemically induced domino processes Transition metal catalysis Domino reactions initiated by oxidation or reduction Enzymes in domino reactions Multicomponent reactions Special techniques in domino reactions

Domino Reactions in Organic Synthesis

10. Patented Literature 2616 10.1. Esterification 2616 10.2. Ether Formation 2619 10.2.1. Etherification without Cyclization 2619 10.2.2. Etherification with Cyclization 2624 10.3. N-Alkylation 2625 10.4. Other Reactions 2627 11. Summary and Outlook 2628 12. Note Added in Proof 2628 13. Abbreviations Used in This Review 2629 14. Acknowledgments 2629 15. Supporting Information Available 2630 16. References 2630

Mitsunobu and Related Reactions: Advances and Applications

Die organisch-chemische Synthese hat stets eine grose Faszination auf den Chemiker ausgeubt, und sie wird auch in Zukunft nichts von ihrer Bedeutung verlieren. Es ist eine Binsenweisheit, das alle Chemiker - und nicht nur die - auf die Synthese chemischer Verbindungen, mit denen sie arbeiten wollen, angewiesen sind. So ist die organisch-chemische Synthese heute mehr denn je die Schnittstelle von Organischer Chemie, Biologie. Biochemie, Medizin, Physik und Materialwissenschaft. Man sollte auch nicht vergessen, das die Grundlage der chemischen Industrie die Synthese ist. Fur den Synthetiker aus Leidenschaft aber ist die Synthese weit mehr als nur Mittel zu dem Zweck, Verbindungen in die Hand zu bekommen; sie ist Ausdruck seiner Kreativitat. Intelligenz und seines handwerklichen Konnens, aber auch seiner Ausdauer.

Sequentielle Transformationen in der Organischen Chemie eine Synthesestrategie mit Zukunft

Innovation has frequently been described as the key to drug discovery. However, in the daily routine, medicinal chemists often tend to stick to the functional groups and structural elements they know and love. Blockbuster cancer drug Velcade (bortezomib), for example, was rejected by more than 50 companies, supposedly because of its unusual boronic acid function (as often repeated: "only a moron would put boron in a drug!"). Similarly, in the discovery process of the pan-CDK inhibitor BAY 1000394, the unconventional proposal to introduce a sulfoximine group into the lead series also led to sneers and raised eyebrows, since sulfoximines have seldom been used in medicinal chemistry. However, it was the introduction of the sulfoximine group that finally allowed the fundamental issues of the project to be overcome, culminating in the identification of the clinical sulfoximine pan-CDK inhibitor BAY 1000394. This Minireview provides an overview of a widely neglected opportunity in medicinal chemistry--the sulfoximine group.

Sulfoximines: A Neglected Opportunity in Medicinal Chemistry

Synthesis via sigmatropic rearrangement. 12. Total synthesis of (+)-dihydrocostunolide via tandem Cope-Claisen rearrangement

On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine (apio-ddA), novel apio-neplanocin A analogues 5a−d, combining the properties of two nucleosides, were stereoselectively synthesized. The apio moiety of the target nucleosides 5a−d was stereoselectively introduced by treating lactol 10 with 37% formaldehyde in the presence of potassium carbonate. The carbasugar moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs catalyst in methylene chloride. The final nucleosides 5a−d were synthesized from the condensation of the glycosyl donor 14 with nucleic bases under the standard Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio-methanocarbaadenosine 7 were derived from the common intermediate 13 using catalytic hydrogenation and Simmons−Smith cyclopropanation as key steps. All of the final nucleosides 5a−d, 6, and 7 did not show significant inhibitory activity against S-adenosylhomocysteine hydrolase (SAH) up to 100 μM, maybe due to the abse...

Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Selective A3 Adenosine Receptor Agonists

Diastereoselective 1,2-addition of lithiated N-(trialkylsilyl)methylphenylsulfoximines to aldehydes: preparation of 1,4,3-oxathiazin-2(6H)-one 4-oxides as novel cyclic sulfoximines

Practical routes to two functionalized decalones for the synthesis of quassinoids

Synthese de benzenesulfonimidoyl-acetone, -acetate de methyle, -propanol-1 et du dimethylacetal du propanal

Ki Jun Hwang

Papers

Synthesis via sigmatropic rearrangement. 12. Total synthesis of (+)-dihydrocostunolide via tandem Cope-Claisen rearrangement

Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Selective A3 Adenosine Receptor Agonists

Diastereoselective 1,2-addition of lithiated N-(trialkylsilyl)methylphenylsulfoximines to aldehydes: preparation of 1,4,3-oxathiazin-2(6H)-one 4-oxides as novel cyclic sulfoximines

Practical routes to two functionalized decalones for the synthesis of quassinoids

N-(trimethylsilyl)methylphenylsulfoximine: a convenient intermediate for the preparation of functionalized sulfoximines