Volume 82, Issue 9

The 22nd International Congress on Heterocyclic Chemistry (ICHC-22) was held 2-7 August 2009 in St. John's, Newfoundland and Labrador, Canada. St. John's, the capital of Canada's youngest Province, Newfoundland and Labrador, is also Canada’s oldest and North America’s most easterly city. The Conference was chaired by Prof. Mohsen Daneshtalab (School of Pharmacy, Memorial University of Newfoundland) and was organized by the School of Pharmacy and the Chemistry Department at Memorial University of Newfoundland. Approximately 260 participants from over 30 different countries attended. The scientific program consisted of 10 plenary lectures, 19 invited lectures, 52 short communications, and 115 posters. Prof. Samuel Danishefsky (Sloan-Kettering Institute for Cancer Research, Columbia University) was honored with the 2009 ISHC Senior Award in Heterocyclic Chemistry, and Prof. John Wood (Colorado State University) was the 2009 Katritzky Junior Award winner. A special symposium entitled "Focus on heterocycles in organic synthesis today and tomorrow" was held during the Congress as a tribute to Prof. Victor Snieckus (Queen's University, Kingston) for his research accomplishments and long-time contribution to the International Society of Heterocyclic Chemistry (ISHC). The five Congress themes were: - New Methods in Heterocyclic Chemistry - Biologically Active Heterocycles (Pharmaceuticals/Agrochemicals) - Heterocyclic Natural Products and their Analogues - Applications of Heterocycles in Organic Synthesis - Heterocycles in Materials Science Besides the collection of 9 papers that are based on the plenary and invited lectures included in this issue of Pure and Applied Chemistry , the ICHC-22 Book of Abstracts is available online and can be downloaded for free from http://www.ichc2009.ca/abstract_book.pdf in pdf format. ICHC-23 will be held in Glasgow, Scotland, 31 July to 5 August 2011 with the following five main themes of heterocyclic chemistry: synthetic methodology, natural products and complex molecule synthesis, materials, medicinal chemistry, and nanochemistry. The conference will be chaired by Prof. Colin Suckling (University of Strathclyde). The organizers are grateful to all who contributed to a successful scientific program, especially to the speakers and to our public and private sponsors: City of St. John's, Memorial University of Newfoundland, IUPAC, Thieme, Wiley-Blackwell, Elsevier, Taiho Pharmaceutical Co., ChemRoutres Corporation, and American Diagnostica, Inc. Paris E. Georghiou Conference Editor

The furanobisindole alkaloid, phalarine, possesses a unique structural framework within the alkaloid family of natural products. Our laboratory recently disclosed the racemic total synthesis of phalarine, featuring an efficient azaspiroindolenine rearrangement; this achievement is revisited in detail. Upon completion of the first-generation total synthesis, we explored some interesting mechanism-level issues with regard to the key azaspiroindolenine rearrangement. These investigations provided valuable insights into the mechanism of racemization during the azaspiroindolenine rearrangement en route to synthetic phalarine. In addition, in the course of these studies, we demonstrated the Pictet–Spengler capture reaction for C 2 -aryl indoles, and successfully isolated the elusive azaspiroindolenine intermediate of the Pictet–Spengler reaction. Key insights into the remarkably subtle stereoelectronics that govern this rearrangement for C 2 -arylated indoles are discussed.

β-Lactams represent flexible building blocks suitable for the preparation of a large variety of nitrogen-containing target compounds. In the present study, the formerly neglected synthetic potential of 4-haloalkyl-β-lactams has been elaborated in detail with a focus on the preparation of different mono- and bicyclic heterocycles. A first approach involved ring transformations of these halogenated building blocks toward stereodefined aziridines, azetidines, pyrrolidines, and piperidines via intermediate aziridinium or azetidinium ions. In a second part, novel and stereoselective entries into 1,4- and 3,4-fused bicyclic β-lactams were developed through either a radical or an ionic cyclization protocol. Furthermore, the ring enlargement of halogenated β-lactams into functionalized mono- and bicyclic pyrrolidin-2-ones was established as the aza-analog of the cyclobutylmethylcarbenium ion to cyclopentylcarbenium ion rearrangement. Finally, chiral versions toward azetidin-2-ones and ring transformation products were elaborated, involving the synthesis of 3( S )-alkoxy-4( S )-[1( S )-chloroethyl]azetidin-2-ones and the preparation of bicyclic β-lactams annelated to piperazines, morpholines, and diazepanes.

Aliphatic azidonitriles separated by three or four carbon atoms undergo facile cyclo-additions in the presence of BF 3 ·OEt 2 at room temperature or lower, to give bicyclic tetrazoles. 1-Azido-[2-aryl-1,3-dioxolanyl]-glycerols afford oxabicyclic tetrazoles with trimethylsilyl cyanide (TMSCN). Aspects of these facile proximity-induced 1,3-dipolar cycloadditions are discussed with mechanistic interpretations.

Efficient synthetic strategies for several bioactive alkaloids bearing a spirocyclic ring system have been developed. By application of an intramolecular aromatic oxidation of a phenolic intermediate, derived from l-tyrosine and glycine, with hypervalent iodine reagents, TAN1251A, isolated from Penicillium thomii RA-89, was synthesized in an optically pure form. Similarly, a novel synthetic path to TAN1251C and TAN1251D was established by employing an l-tyrosine dimer as a common starting material. Moreover, an enamide-phenol oxidative coupling reaction was applied to the synthesis of spirocyclic isoquinoline alkaloids, stepharine and annosqualine. Finally, stereoselective syntheses of securinine and viroallosecurinine in optically active forms were established by using a tandem ring-closing metathesis (RCM) of the enyne as a key reaction.

Presented here is a short summary of the recent accomplishments in total synthesis in our laboratories. In particular, recent generations of the syntheses of pancratistatin derivatives, codeine, balanol, and oseltamivir (Tamiflu) are described in relation to their common chemoenzymatic origin in toluene-dioxygenase-mediated dioxygenation of aromatic substrates. Perspectives and projections are discussed in the conclusion.

The intramolecular reaction of donor–acceptor cyclopropanes with various dipoles and dipolar equivalents allows access to a variety of bicyclic adducts with good stereocontrol. The linkers can often be cleaved to provide stereodefined products.

N -oxides possessing the pyridine framework are strong Lewis bases that can activate the C–Si bond of allylhalosilanes to such an extent that they catalyze reactions with aldehydes. N -oxides embedded in chiral scaffolds are usually capable of highly selective chirality transfer to the derived products. Our goal was to develop a general synthetic method allowing the preparation of structurally varied N , N' -dioxides suitable for enantioselective organocatalysis. The underlying synthetic strategy was based on [2 + 2 + 2]-cyclotrimerization of suitably substituted diynes with nitriles catalyzed by Co-complexes to generate the desired bipyridines, their further oxidation and resolution of which furnished the corresponding chiral N , N' -dioxides. The prepared compounds were used in catalytic allylation of aromatic aldehydes to homoallyl alcohols with high enantioselectivity (up to 96 % ee). Enantioselectivity, enantiodiscrimination, and the reaction mechanism are controlled by the choice of solvent.

Studies regarding the copper-catalyzed enantioselective aziridination of styrenes with N -tosyloxycarbamates are presented. Catalyst, ligand, and reagent optimization will be discussed. Chiral aziridines were obtained in good yields and modest-to-good levels of stereochemical induction.

Lithiated alkoxyallenes are very versatile components for the synthesis of heterocycles such as furans, pyrroles, and 1,2-oxazines, easily allowing the preparation of natural products via these heterocyclic intermediates. A surprising three-component synthesis of N-acylated enaminones allowed the synthesis of highly functionalized 4-hydroxypyridines, 5-acetyloxazoles, and pyrimidines. All these heterocyclic products are ready for further functionalizations, in particular for palladium-catalyzed reactions, leading to libraries of new interesting heterocycles.

A new class of tridentate pyridine-bis(oxazoline) ligand having gem -diphenyl groups at C5 of the oxazoline rings has been developed. Its metal complex exhibited high catalytic efficiency in asymmetric synthesis. We have shown that gem -diphenyl groups at C5 of the oxazoline rings are essential for getting high enantiomeric excess.