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One aryl or two? The title reaction predominantly gives monoarylation products with various amounts of diarylation product being observed in almost all cases (see scheme). Aryl iodides as well as aryl bromides were reactive under the optimized reaction conditions. The multiple nitrogen atoms in the purine, and oxygen atoms in the saccharide posed no problems in these transformations.

In the typical introductory organic chemistry course, students work questions out of a textbook for which a solutions manual is available. They struggle with a question for a few minutes, look up the answer, and then believe they know how to answer the question. It isn't until exam time that they realize that knowing an answer to a question and knowing how to answer a question are two entirely different propositions.Computer programs that tell a student that a response is incorrect without supplying the correct answer are likely to be more effective teaching tools. Many Web-based chemistry homework programs exist (1-5), but most require text-based, numeric, or multiple-choice answers. In organic chemistry, however, answers are usually structural drawings. The only program we are aware of that allows a student to draw a chemical structure in response to a question is OWL 1 (1), as implemented at the Web site for McMurry's Organic Chemistry ( 6).The electronic program for organic chemistry homework (EPOCH) is a Web-based application designed specifically for instructors and students of introductory organic chemistry. EPOCH prompts students to construct a structural response to a posed question with a graphical structure-drawing interface. EPOCH offers feedback that explains why a response is correct or incorrect, guiding students to the correct answer. The author of a question decides what characteristics of a student's response should elicit what feedback from EPOCH: for example, the presence of a particular atom or functional group ("Br is a leaving group; it should not be present in your product."), the absence of a certain skeleton ("No C-C bonds should be formed or broken in this reaction."), or the configuration of a stereocenter ("What is the stereochemical result of an S N 2 reaction?"). EPOCH never reveals the correct answer; students must attack the question repeatedly until they answer it correctly. EPOCH's designers understand that students learn far more from struggling to answer a question correctly than from being told the correct answer. By contrast, most Web-based homework programs do not provide feedback for wrong answers, and most allow the student to give up before answering the question correctly (1,3,4). To our knowledge, the only program that provides feedback to students that is based on their free responses (not multiple-choice responses) is the Quantum Tutor (2).

Palladium-catalyzed C–H bond activation and oxidation of C6 arylpurines as well as C6 arylpurine nucleosides can be accomplished using Pd(OAc)2/PhI(OAc)2 in CH3CN. Despite the presence of four nitrogen atoms in the purine moiety as well as the polyoxygenated saccharide and a labile glycosidic bond in the nucleosides, these reactions can be effectively conducted. Notably, the generally more labile 2′-deoxyribonucleosides also undergo reaction. The reaction conditions can be tuned to yield either monoacetoxylated or diacetoxylated products predominantly. In the course of these investigations, a dimeric PdII-containing cyclopalladated C6 naphthylpurine derivative has been obtained and crystallographically characterized. This compound is competent in catalyzing the oxidization with PhI(OAc)2, indicating its plausible intermediacy in the chemistry. The X-ray structure of a monoacetoxylated product from this reaction has also been obtained.

Summary(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From 31P{1H}, [18O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO− and AtO− produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO− is a nucleofuge, several Bt-OCH2Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO− has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.

C À H bond activation represents an efficient approach to molecular functionalization. [1,2] In directed CÀH bond activation, Lewis basic sites are exploited to draw the catalyst proximal to the reactive center. We have been interested in the C À H bond activation and arylation of nucleobases and nucleosides using the nitrogen atoms of the purine itself as the Lewis basic sites. In this context, 6-arylpurine has embedded 2-phenylpyridine and 4-phenylpyrimidine motifs. 2-Arylpyridines, and benzo[h]quinoline, which can be considered as containing a rigidified 2-phenylpyridine structure, have been the subject of CÀH bond activation/arylation strategies using Pd, Ru, Rh, and Fe. [3][4][5][6] However, any metal-catalyzed conversion of purines and purine nucleosides is a challenging proposition owing to the presence of four nitrogen atoms in the nucleobases, plus additional oxygen atoms in the sugar unit; all of these heteroatoms could participate in metal sequestration and deactivation of catalytic processes.As shown in Scheme 1, the N1 nitrogen atom of purine is well positioned to direct C À H bond activation. Alternatively, N7 can also function in a similar capacity. To gain preliminary insight, energy minimization was performed, using DFT at the B3LYP/6-311 ++ G(2d,2p) level of theory, on 2-phenylpyr-idine as well as 9-benzyl-6-phenyl-9H-purine. The distances between the metal-directing nitrogen atom and the orthohydrogen atom on the phenyl ring were calculated from the energy-minimized structures, and are shown in Figure 1.Consistent with known X-ray structures of 2-phenylpyridine derivatives, [7] the aryl rings in 2-phenylpyridine are not coplanar. The distance between the pyridyl nitrogen atom and the ortho-hydrogen atom of the aryl ring in this case is 2.49 . By comparison, in the energy-minimized structure of 9benzyl-6-phenyl-9H-purine, the C6-aryl group is coplanar with the purine ring. We next compared the computed structure of 9-benzyl-6-phenyl-9H-purine to the crystallographic structures of 9-benzyl-6-phenyl-8-(p-tolyl)-9H-purine and 8,8'-bis(9-benzyl-6-phenyl)-9H-purine. [8] In both compounds, the C6-phenyl group is coplanar with the purinyl system. We also evaluated the distance between N1 and the ortho-hydrogen atom of the C6-aryl group for these cases. In 9-benzyl-6-phenyl-8-(p-tolyl)-9H-purine, this distance is 2.43 whereas the distance to N7 is 2.34 . Similar distances of 2.43 and 2.36 , respectively, were obtained for 8,8'bis(9-benzyl-6-phenyl)-9H-purine. These data closely match the DFT-derived distances for 9-benzyl-6-phenyl-9H-purine shown in Figure 1. Given the similar distances between the nitrogen atom and the aryl hydrogen atom in 9-benzyl-6phenyl-9H-purine and 2-phenylpyridine, we reasoned that C À H bond activation in purines and nucleosides should be feasible. In support of this hypothesis, serendipitously, undesired arylation of the C6-phenyl group has been observed in the Pd/Cu-mediated C8 arylation of 9-benzyl-6-Scheme 1. N-directed CÀH bond activation in 2-phenylpyridine, and two plau...

Ein Katalysezyklus, bei dem ein Rutheniumkatalysator genutzt wird, ermöglicht die Arylierung von Nucleosiden. In der Zuschrift auf beschreiben M. K. Lakshman et al. die C‐H‐Bindungsaktivierung/‐arylierung von C6‐Arylpurin‐2′‐desoxyribonucleosiden, bei der vermutlich ein Purin‐Stickstoffatom die Ruthenierung steuert. Aryliodide und ‐bromide können eingesetzt werden, und das Hauptprodukt wird durch Monoarylierung gebildet. Das Titelbild wurde von Satish Lakshman gestaltet.

A catalytic cycle involving a ruthenium catalyst leads to the arylation of nucleosides. In their Communication on page 11 400 ff., M. K. Lakshman and co-workers describe CÀH bond activation/arylation of C6 aryl purine 2'-deoxyribonucleosides, wherein a purine nitrogen atom presumably directs the ruthenation. Both aryl iodides and aryl bromides can be used, and the major product results from monoarylation. The cover picture was designed by Satish Lakshman.