Artis Klapars

Bio: Artis Klapars is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: Aryl & Amination. The author has an hindex of 13, co-authored 27 publications receiving 4986 citations.

A general and efficient copper catalyst for the amidation of aryl halides.

Abstract: An experimentally simple and inexpensive catalyst system was developed for the amidation of aryl halides by using 0.2−10 mol % of CuI, 5−20 mol % of a 1,2-diamine ligand, and K3PO4, K2CO3, or Cs2CO3 as base. Catalyst systems based on N,N‘-dimethylethylenediamine or trans-N,N‘-dimethyl-1,2-cyclohexanediamine were found to be the most active even though several other 1,2-diamine ligands could be used in the easiest cases. Aryl iodides, bromides, and in some cases even aryl chlorides can be efficiently amidated. A variety of functional groups are tolerated in the reaction, including many that are not compatible with Pd-catalyzed amidation or amination methodology.

Expanding Pd-catalyzed C-N bond-forming processes: the first amidation of aryl sulfonates, aqueous amination, and complementarity with Cu-catalyzed reactions.

Abstract: The first general method for the Pd-catalyzed amination of aryl tosylates and benzenesulfonates was developed utilizing ligand 1, which belongs to a new generation of biaryl monophosphine ligands. In addition, the new catalyst system for the first time enables amidation of aryl arenesulfonates and aqueous amination protocols that do not necessitate the use of cosolvents. The substrate scope has been significantly expanded to include aryl halides containing primary amides and free carboxylic acid groups. In the case of multifunctional substrates, the Pd-catalyzed amination can provide selectivity that is complementary to the Cu-catalyzed C−N bond-forming processes.

The Copper-Catalyzed N-Arylation of Indoles

Abstract: A general method for the N-arylation of indoles using catalysts derived from CuI and trans-1,2-cyclohexanediamine (1a), trans-N,N'-dimethyl-1,2-cyclohexanediamine (2a), or N,N'-dimethyl-ethylenediamine (3) is reported. N-Arylindoles can be produced in high yield from the coupling of an aryl iodide or aryl bromide with a variety of indoles.

Escape from flatland: increasing saturation as an approach to improving clinical success.

Abstract: The medicinal chemistry community has become increasingly aware of the value of tracking calculated physical properties such as molecular weight, topological polar surface area, rotatable bonds, and hydrogen bond donors and acceptors. We hypothesized that the shift to high-throughput synthetic practices over the past decade may be another factor that may predispose molecules to fail by steering discovery efforts toward achiral, aromatic compounds. We have proposed two simple and interpretable measures of the complexity of molecules prepared as potential drug candidates. The first is carbon bond saturation as defined by fraction sp3 (Fsp3) where Fsp3 = (number of sp3 hybridized carbons/total carbon count). The second is simply whether a chiral carbon exists in the molecule. We demonstrate that both complexity (as measured by Fsp3) and the presence of chiral centers correlate with success as compounds transition from discovery, through clinical testing, to drugs. In an attempt to explain these observations,...

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

Abstract: The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C−H Activation for the Construction of C−B Bonds

Abstract: A number of studies were conducted to demonstrate C-H activation for the construction of C-B bonds. Investigations revealed that the conversion of C-H bonds to C-B bonds was both thermodynamically and kinetically favorable. The reaction at a primary C-H bond of methane or a higher alkene B 2(OR)4 formed an alkylboronate ester R' -B(OR)2 and the accompanying borane H-B(OR2. The ester and the borane were formed on the basis of calculated bond energies for methylboronates and dioaborolanes. The rates of key steps along the reaction pathway for the conversion of a C-H bond in an alkane or arene to the C-B bond in an alkyl or arylboronate ester were favorable. These studies also highlighted the accessible barriers for C-H bond cleavage and B-C bond formation during the borylation of alkanes and arenes.

Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis.

Abstract: 6.4. Polyynes 3123 6.5. Using R-Hydroxy Stannanes 3124 6.6. Using the Hurtley Reaction 3124 6.7. Using a Methylenation Reaction 3125 7. Conclusions and Future Prospects 3125 8. Uncommon Abbreviations 3125 9. Acknowledgments 3125 10. Note Added in Proof 3125 11. References 3126 * Authorstowhomcorrespondenceshouldbeaddressed(evano@chimie.uvsq.fr, nicolas.blanchard@uha.fr). † Université de Versailles Saint Quentin en Yvelines. ‡ Université de Haute-Alsace. Chem. Rev. 2008, 108, 3054–3131 3054