A synthetic route to fused heterocycle 5 (R-1 = Et) was developed that avoids the use of troublesome azido functionality. In this approach, 3-bromofuran aldehyde 7 was synthesized from 3-bromofuran 6 using highly regioselective formylation conditions. The crude solution of 7 was treated with hippuric acid under Erlenmeyer-Plochl conditions to give enamide product 16, which was isolated by crystallization. Intramolecular amination/cyclization to the fused pyrrole was achieved under ligand-free Cu(I) catalysis in toluene, followed by diamine workup to remove the benzoyl protecting group and residual copper. The final product 5 (R-1 = Et) was crystallized directly from the reaction mixture, providing up to 60% overall yield over five chemical steps and two isolations.

An efficient one-pot cascade to indoles and related fused heterocycles has been demonstrated in renewable solvents, thereby eliminating the previously required dipolar aprotic solvent. The copper-catalyzed reaction proceeds with a range of bromobenzaldehydes to give products in good yields. In addition, the external ligand-free cross-coupling methodology provides convenient access to an investigational treatment for central nervous system disorders.

AbstractIt is demonstrated, that the reaction of o‐halobenzaldehydes and amidoacetates offers a ready access to the title compounds without the need of an external ligand.

A mild and regioselective functionalization protocol for 3-bromofuran and analogs has been developed. Selective metalation and functionalization of C2 can be achieved as a result of the directing effect of the adjacent electron-withdrawing bromo group. In addition, the C5 position can also be selectively functionalized by blocking the C2 position via silylation or by simply controlling the reaction temperature. These functionalized compounds bearing a C3 bromo substituent may be further elaborated by utilizing a Suzuki–Miyaura cross-coupling procedure.

A variety of indole-2-carboxylic esters are accessible in yields up to 61% through a ligand-free, copper-catalyzed reaction of a series of commercially available 2-halo aryl aldehydes with benign glycine amidoesters, including the common reagent ethyl acetamidoacetate. This one-pot, three-reaction format allows ready entry to the desired heterocycles from starting substrates in the reactivity order of iodo>bromo⩾chloro substituents. An assortment of functional groups is tolerated, adding to the generality of this methodology.

Biaryl compounds are prevalent in both nature and in active pharmaceutical ingredients. The palladium and nickel catalyzed cross-coupling of aryl Grignard reagents with aryl fluorides reported herein affords moderate to excellent yields of the corresponding unsymmetrical biaryls. In addition, the first example of a biaryl cross-coupling utilizing unactivated aryl fluorides under phosphine free palladium conditions is reported. Microwave technology allowed rapid optimization of catalyst systems, which identified several ligands for this cross-coupling reaction.

ChemInformVolume 35, Issue 35 Isocyclic Compounds Nickel-Catalyzed Cross-Coupling of Aryl Grignard Reagents with Aromatic Alkyl Ethers: An Efficient Synthesis of Unsymmetrical Biaryls. John W. Dankwardt, John W. Dankwardt DSM Pharm. Chem., Inc., Greenville, NC 27834, USASearch for more papers by this author John W. Dankwardt, John W. Dankwardt DSM Pharm. Chem., Inc., Greenville, NC 27834, USASearch for more papers by this author First published: 06 August 2004 https://doi.org/10.1002/chin.200435078Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume35, Issue35August 31, 2004 RelatedInformation

AbstractFor Abstract see ChemInform Abstract in Full Text.

Transition-metal-mediated cyclization of aromatic enynes provides high yields of substituted naphthalene compounds. The reaction can tolerate a wide range of substituents on both the olefin and the alkyne. The most useful catalysts were found to be [Rh(CO)(2)Cl](2), PdCl2 and PtCl2. In addition, a facile silyl migration occurs when the acetylene is substituted with a triorganosilyl group affording 4-silyl-naplithalenes. (C) 2001 Elsevier Science Ltd. All rights reserved.

Monocyte chemoattracant-1 (MCP-1) stimulates leukocyte chemotaxis to inflammatory sites, such as rheumatoid arthritis, atherosclerosis, and asthma, by use of the MCP-1 receptor, CCR2, a member of the G-protein-coupled seven-transmembrane receptor superfamily. These studies identified a family of antagonists, spiropiperidines. One of the more potent compounds blocks MCP-1 binding to CCR2 with a K(d) of 60 nm, but it is unable to block binding to CXCR1, CCR1, or CCR3. These compounds were effective inhibitors of chemotaxis toward MCP-1 but were very poor inhibitors of CCR1-mediated chemotaxis. The compounds are effective blockers of MCP-1-driven inhibition of adenylate cyclase and MCP-1- and MCP-3-driven cytosolic calcium influx; the compounds are not agonists for these pathways. We showed that glutamate 291 (Glu(291)) of CCR2 is a critical residue for high affinity binding and that this residue contributes little to MCP-1 binding to CCR2. The basic nitrogen present in the spiropiperidine compounds may be the interaction partner for Glu(291), because the basicity of this nitrogen was essential for affinity; furthermore, a different class of antagonists, a class that does not have a basic nitrogen (2-carboxypyrroles), were not affected by mutations of Glu(291). In addition to the CCR2 receptor, spiropiperidine compounds have affinity for several biogenic amine receptors. Receptor models indicate that the acidic residue, Glu(291), from transmembrane-7 of CCR2 is in a position similar to the acidic residue contributed from transmembrane-3 of biogenic amine receptors, which may account for the shared affinity of spiropiperidines for these two receptor classes. The models suggest that the acid-base pair, Glu(291) to piperidine nitrogen, anchors the spiropiperidine compound within the transmembrane ovoid bundle. This binding site may overlap with the space required by MCP-1 during binding and signaling; thus the small molecule ligands act as antagonists. An acidic residue in transmembrane region 7 is found in most chemokine receptors and is rare in other serpentine receptors. The model of the binding site may suggest ways to make new small molecule chemokine receptor antagonists, and it may rationalize the design of more potent and selective antagonists.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCombinational O-aryl carbamate and benzamide directed ortho metalation reactions. Synthesis of ochratoxin A and ochratoxin BMukund P. Sibi, S. Chattopadhyay, John W. Dankwardt, and V. SnieckusCite this: J. Am. Chem. Soc. 1985, 107, 22, 6312–6315Publication Date (Print):October 1, 1985Publication History Published online1 May 2002Published inissue 1 October 1985https://pubs.acs.org/doi/10.1021/ja00308a025https://doi.org/10.1021/ja00308a025research-articleACS PublicationsRequest reuse permissionsArticle Views791Altmetric-Citations43LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts