Michael A. Tarselli

Bio: Michael A. Tarselli is an academic researcher from Novartis. The author has contributed to research in topics: Allylic rearrangement & Nucleophile. The author has an hindex of 10, co-authored 19 publications receiving 875 citations. Previous affiliations of Michael A. Tarselli include University of North Carolina at Chapel Hill & Scripps Research Institute.

Big Data from Pharmaceutical Patents: A Computational Analysis of Medicinal Chemists’ Bread and Butter

Abstract: Multiple recent studies have focused on unraveling the content of the medicinal chemist’s toolbox. Here, we present an investigation of chemical reactions and molecules retrieved from U.S. patents over the past 40 years (1976–2015). We used a sophisticated text-mining pipeline to extract 1.15 million unique whole reaction schemes, including reaction roles and yields, from pharmaceutical patents. The reactions were assigned to well-known reaction types such as Wittig olefination or Buchwald–Hartwig amination using an expert system. Analyzing the evolution of reaction types over time, we observe the previously reported bias toward reaction classes like amide bond formations or Suzuki couplings. Our study also shows a steady increase in the number of different reaction types used in pharmaceutical patents but a trend toward lower median yield for some of the reaction classes. Finally, we found that today’s typical product molecule is larger, more hydrophobic, and more rigid than 40 years ago.

Mechanistic Surprises in the Gold(I)‐Catalyzed Intramolecular Hydroarylation of Allenes

Abstract: Gold(I)-catalyzed carbon-carbon bond forming reactions continue to fascinate the synthetic community but are less well investigated than many conventional metal catalysts.[1] In many cases a cationic gold(I)-species activates an unsaturated C-C bond and isomerizes or functionalizes it to build molecular complexity through reactive intermediates that include gold-π-complexes, gold-vinyls, and gold-carbenes. Support for these intermediates is mainly based on gold(I) organometallic chemistry, though computational studies and the isolation of proposed catalytic intermediates have been reported.[2–5]

Gold(I)-catalyzed intramolecular hydroarylation of allenes.

Abstract: Gold(I) complexes react with 4-allenyl arenes in an exo fashion to furnish vinyl-substituted benzocycles. Phosphite gold(I) monocations were found to be optimal, and the catalyst was tolerant of ethers, esters, and pyrroles. Reactions proceeded in unpurified solvent at room temperature.

Ligand effects in homogeneous Au catalysis.

Abstract: 1.1. Context and Meta-Review Despite the ubiquity of metallic gold (Au) in popular culture, its deployment in homogeneous catalysis has only recently undergone widespread investigation. In the past decade, and especially since 2004, great progress has been made in developing efficient and selective Au-catalyzed transformations, as evidenced by the prodigious number of reviews available on various aspects of this growing field. Hashmi has written a series of comprehensive reviews outlining the progression of Au-catalyzed reaction development,1 and a number of more focused reviews provide further insight into particular aspects of Au catalysis. A brief meta-review of the available range of perspectives published on Au catalysis helps to put this Chemical Reviews article in context. The vast majority of reactions developed with homogeneous Au catalysts have exploited the propensity of Au to activate carbon-carbon π-bonds as electrophiles. Gold has come to be regarded as an exceedingly mild, relatively carbophilic Lewis acid, and the broad array of newly developed reactions proceeding by activation of unsaturated carbon-carbon bonds has been expertly reviewed.2 Further reviews and highlights on Au catalysis focus on particular classes of synthetic reactions. An excellent comprehensive review of Au-catalyzed enyne cycloisomerizations is available.3 Even more focused highlights on hydroarylation of alkynes,4 hydroamination of C-C multiple bonds,5 and reactions of oxo-alkynes6 and propargylic esters7 provide valuable perspectives on progress and future directions in the development of homogeneous Au catalysis. Most of the reviews on Au catalysis emphasize broad or specific advances in synthetic utility. Recently, we have invoked relativistic effects to provide a framework for understanding the observed reactivity of Au catalysts, in order to complement empirical advancements.8 In this Chemical Reviews article, we attempt to enumerate the ways in which selectivity can be controlled in homogeneous Au catalysis. It is our hope that lessons to guide catalyst selection and the design of new catalysts may be distilled from a thorough evaluation of ligand, counterion, and oxidation state effects as they influence chemo-, regio-, and stereoselectivity in homogeneous Au catalysis.

Gold-catalyzed organic transformations.

Abstract: Thanks to its unusual stability, metallic gold has been used for thousands of years in jewelry, currency, chinaware, and so forth. However, gold had not become the chemists’ “precious metal” until very recently. In the past few years, reports on gold-catalyzed organic transformations have increased substantially. Thanks to gold-based catalysts, various organic transformations have been accessible under facile conditions with both high yields and chemoselectivity.

Gold-catalyzed carbon-heteroatom bond-forming reactions.

Abstract: A.L.-P. thanks CSIC for a contract under the JAE-doctor program. Financial support by PLE2009 project from MCIINN and Consolider-Ingenio 2010 (proyecto MULTICAT) are also acknowledged.

Gold-catalyzed nucleophilic cyclization of functionalized allenes: a powerful access to carbo- and heterocycles.

Abstract: Allenes are highly valuable synthetic precursors in preparative organic chemistry because of their ability to undergo a variety of transformations. Among many different reaction modes, activation of the cumulated double bonds by treatment with a Brønsted or Lewis acid is particularly useful because it allows a nucleophilic attack, which leads to the formation of a new C-C or Cheteroatom bond in an interor intramolecular fashion. Because of their axial chirality, allenes can undergo this bond formation with chirality transfer, which renders the method attractive for stereoselective target-oriented synthesis. Because of their soft and carbophilic character, gold catalysts are particularly well suited for the selective activation of allenes in the presence of other reactive functionalities. Compared to intermolecular additions, gold-catalyzed cyclization reactions of allenes by intramolecular nucleophilic attack have received much more attention. Here, the gold catalyst can coordinate to either allenic double bond, and the regioselectivity of the subsequent nucleophilic attack depends on the structure of the substrate, in particular the length of the tether connecting allene and nucleophile (Scheme 1). Hence, four different endoor exo-cyclization products can be obtained, but the formation of fiveor sixmembered rings via σ-gold species A or D, i.e., by nucleophilic attack at a terminal allenic carbon atom, is favored in most cases, whereas products arising from nucleophilic attack at the central allenic carbon atom (via intermediates B and C) are rare. Normally, these cyclization products are chiral and can be accessed in a stereoselective manner either from chiral allenes by axis-to-center chirality transfer or from achiral allenes utilizing chiral gold catalysts. This account comprises gold-catalyzed cyclization reactions of allenes by attack of carbon or heteroatom nucleophiles. Intermolecular addition reactions to allenes, as well as gold-catalyzed transformation of nonallenic substrates in which an allene is generated in situ (e.g., by sigmatropic rearrangement) and converted without isolation, will not be covered.