Ramesh Giri

University of California, Berkeley, Berkeley, California, United States

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Publications (28)161.63 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: While the syntheses of novel and diverse peptides mainly rely on traditional coupling using unnatural amino acids, postsynthetic modification of peptides could provide a complementary method for the preparation of non-proteinogenic peptides. Site selectivity of postsynthetic modification of peptides is usually achieved by targeting reactive moieties such as the thiol group of cysteine or C-2 position of tryptophan. Herein, we report the development of site-selective functionalizations of inert C(sp3)-H bonds of N-terminal amino acids in di-, tri- and tetrapeptides without installing a directing group. The native amino acid moiety within the peptide is used as a ligand to accelerate the C-H activation reaction. In the long run, this newly uncovered reactivity could provide guidance for developing site-selective C(sp3)-H activation towards postsynthetic modification of a broader range of peptides.
    Journal of the American Chemical Society 11/2014; · 10.68 Impact Factor
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    ABSTRACT: Concurrent asymmetric tandem reactions, so called “multicast promoted tandem reactions,” still remain a synthetic challenge in terms of matching catalysts’ reaction rates, fine-tuning substrate and product selectivities, and reaction condition compatibility. Nonetheless, many wonderful examples of multicast promoted one-pot syntheses using chemical catalysts from various disciplines have found success. In contrast, multienzymatic systems in nature provide ample evidence of tandem catalysis in an aqueous environment. In addition, protein engineering towards industrial biocatalysis has emerged as a powerful tool for the biosynthesis of fine chemicals with high regio- and enantioselectivity. The combination of catalysts from these two very different disciplines (chemical catalysts and enzymes) for the synthesis of high-value compounds is an attractive target and has recently seen increased interest. In the Zhao and Hartwig labs, we are focused on developing novel catalytic asymmetric tandem reactions using organometallic catalysts and metalloenzymes. We have developed a tandem process to achieve successive olefin isomerization-enantioselective epoxidation, a reaction difficult to achieve occurring with a single catalytic system. This process can potentially provide a practical and efficient strategy for the enantioselective preparation of linear terminal epoxides in high ee from a mixture of simple substrates. By combining an isomerization catalyst with a purified P450 BM3 mutant in a biphasic reaction, we report for the first time that the two reactions work in tandem. Using our tandem reaction, we have achieved the successive terminal to internal olefin isomerization followed by epoxidation to yield the internal epoxides, as well as the thermodynamically challenging internal to terminal olefin isomerization followed by the terminal olefin epoxidation. We have further expanded the substrate scope of the reaction system to straight and branched aliphatic olefins, unsaturated methyl esters, acids and ketones. Overall yields of 35% can be obtained, as well as interesting substrate-dependent reaction regioselectivities. In parallel, using the robust and established chemistry of ruthenium carbene metathesis catalysts, we are investigating ways to couple them with metalloenzymes to develop novel tandem reaction systems. Several ruthenium metathesis catalysts were found to be active, stable in the presence of air and water, at room temperature and in several solvent: buffer systems to afford cross metatheses with moderate to high selectivities. We obtained preliminary data of a novel biphasic tandem cross metathesis-epoxidation/hydroxylation approach involving a Hoveyda-Grubbs 2nd generation complex and the versatile cytochrome P450 from Bacillus megaterium, for the selective hydroxylation and epoxidation of 5-dodecenoic acids in high yields. We are extending this platform to other challenging transformations, such as the epoxidation of 1-butenylbenzene generated by cross metathesis of cis-stilbene and trans-3-hexene as well as the enantioselective epoxidation of long chain alkenes generated by alkene chain elongation through cross- or self- metathesis of short chain alkenes.
    12 AIChE Annual Meeting; 10/2012
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    ABSTRACT: The origin of the high levels of reactivity and diastereoselectivity (>99:1 dr) observed in the oxazoline-directed, Pd(II)-catalyzed sp(3) C-H bond iodination and acetoxylation reactions as reported in previous publications has been studied and explained on the basis of experimental and computational investigations. The characterization of a trinuclear chiral C-H insertion intermediate by X-ray paved the way for further investigations into C-H insertion step through the lens of stereochemistry. Computational investigations on reactivities and diastereoselectivities of C-H activation of t-Bu- and i-Pr-substituted oxazolines provided good agreement with the experimental results. Theoretical predictions with DFT calculations revealed that C-H activation occurs at the monomeric Pd center and that the most preferred transition state for C-H activation contains two sterically bulky t-Bu substituents in anti-positions due to steric repulsion and that this transition state leads to the major diastereomer, which is consistent with the structure of the newly characterized C-H insertion intermediate. The structural information about the transition state also suggests that a minimum dihedral angle between C-H bonds and Pd-OAc bonds is crucial for C-H bond cleavage. We have also utilized density functional theory (DFT) to calculate the energies of various potential intermediates and transition states with t-Bu- and i-Pr-substituted oxazolines and suggested a possible explanation for the substantial difference in reactivity between the t-Bu- and i-Pr-substituted oxazolines.
    Journal of the American Chemical Society 07/2012; 134(34):14118-26. · 10.68 Impact Factor
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    ABSTRACT: AICHE abstract Directed Evolution of Metalloenzymes for Organic Synthesis Carl Denard, Lars Martin Jarenmark, Ramesh Giri, John F. Hartwig and Huimin Zhao, UIUC Catalytic asymmetric tandem reactions have been reported extensively in synthetic chemistry literature. The use in tandem of catalysts from different disciplines has been reported. However, there are no reports on combining two metal catalysts from completely different fields, i.e., an organometallic catalyst and a metalloenzyme. In the Zhao and Hartwig labs, we have developed a novel catalytic asymmetric tandem reaction to achieve a successive olefin isomerization-enantioselective epoxidation, a reaction that is difficult to envision occurring with a single catalytic system. This process can potentially provide a practical and efficient strategy for the enantioselective preparation of linear terminal epoxides in high ee from a mixture of simple substrates. To address the issue of catalyst activity in the biocompatible solvent hexadecane, ruthenium hydride complexes were synthesized that can isomerize several olefins of interest with high activity and interesting selectivities, at room temperature and at enzymatic conditions. Sulfur activation further enhances the isomerization reaction rates. By combining the isomerization catalyst with cell lysates or purified P450 BM3 mutants coupled with a cofactor regeneration system, we report for the first time that the two reactions work in tandem. Starting with a terminal olefin, we were able to detect the corresponding internal epoxide at a ratio of 1.5:1 to 2:1 compared to the terminal epoxide concentration. In addition, we tackled the thermodynamically challenging internal to terminal isomerization in tandem with the epoxidation reaction and were able to detect the terminal epoxide. In the case of 4-methyl-cis- and 4-methyl-trans-2-pentene, we obtained the most promising result of detecting the terminal epoxide in an equimolar amount to the internal epoxides. This represents the first report that shows that two metal catalysts from very different fields, namely a metalloenzyme and an organometallic catalyst, are capable of working in tandem to tackle an important synthetic challenge. We have further expanded the substrate scope of the reaction system to a number of straight and branched C5-C7 aliphatic olefins. This tandem process should be generally applicable to other high-impact and challenging transformations that require excellent selectivities.
    2011 AIChE Annual Meeting; 10/2011
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    Ramesh Giri, John F Hartwig
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    ABSTRACT: A series of Cu(I)-amido complexes both lacking ancillary ligands and containing 1,10-phenanthroline (phen) as ancillary ligand have been prepared. These complexes react with iodoarenes to form arylamine products, and this reactivity is consistent with the intermediacy of such complexes in catalytic Ullmann amination reactions. The stoichiometric reactions of the Cu(I)-amido complexes with iodoarenes are autocatalytic, with the free CuI generated during the reaction serving as the catalyst. Such autocatalytic behavior was not observed for reactions of iodoarenes with copper(I) amidates, imidates, or phenoxides. The selectivity of these complexes for two sterically distinct aryl halides under various conditions imply that the autocatalytic reaction proceeds by forming highly reactive [CuNPh(2)](n) lacking phen. Reactions with radical probes imply that the reactions of phen-ligated Cu(I)-amido complexes with iodoarenes occur without the intermediacy of aryl radicals. Density functional theory calculations on the oxidative addition of iodoarenes to Cu(I) species are consistent with faster reactions of iodoarenes with CuNPh(2) species lacking phen in DMSO than reactions of iodoarenes with LCuNPh(2) in which L = phen. The free-energy barrier computed for the reaction of PhI with (DMSO)CuNPh(2) was 21.8 kcal/mol, while that for the reaction of PhI with (phen)CuNPh(2) was 33.4 kcal/mol.
    Journal of the American Chemical Society 10/2010; 132(45):15860-3. · 10.68 Impact Factor
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    Angewandte Chemie International Edition 03/2010; 49(12):2185-9. · 11.34 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 41(28).
  • [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 41(7).
  • Ramesh Giri, Jonathan K Lam, Jin-Quan Yu
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    ABSTRACT: A Pd(II)-catalyzed reaction protocol for the carboxylation of ortho-C-H bonds in anilides to form N-acyl anthranilic acids has been developed. This reaction procedure provides a novel and efficient strategy for the rapid assembly of biologically and pharmaceutically significant molecules, such as benzoxazinones and quinazolinones, from simple anilides without installing and removing an external directing group. The reaction conditions are also amenable to the carboxylation of N-phenyl pyrrolidinones. A monomeric palladacycle containing p-toluenesulfonate as an anionic ligand has been characterized by X-ray crystallography, and the crucial role of p-toluenesulfonic acid in the activation of C-H bonds in the presence of carbon monoxide is discussed. Identification of two key intermediates, a mixed anhydride and benzoxazinone formed by reductive elimination from organometallic Ar(CO)Pd(II)-OTs species, provides mechanistic evidence for a dual-reaction pathway.
    Journal of the American Chemical Society 12/2009; 132(2):686-93. · 10.68 Impact Factor
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    ABSTRACT: This critical review discusses historical and contemporary research in the field of transition metal-catalyzed carbon-hydrogen (C-H) bond activation through the lens of stereoselectivity. Research concerning both diastereoselectivity and enantioselectivity in C-H activation processes is examined, and the application of concepts in this area for the development of novel carbon-carbon and carbon-heteroatom bond-forming reactions is described. Throughout this review, an emphasis is placed on reactions that are (or may soon become) relevant in the realm of organic synthesis (221 references).
    Chemical Society Reviews 11/2009; 38(11):3242-72. · 24.89 Impact Factor
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    ABSTRACT: A Cu(II)/I2-mediated C–H bond activation is described. A variety of 2-phenylpyridine derivatives are oxidatively dimerized at the ortho-position of the phenyl ring in which a net loss of two hydrogen atoms results in the formation of a biaryl compound via a double C–H activation/C–C bond-forming process. Moderate functional group tolerance was observed on both the aryl and the pyridyl rings. A single electron transfer (SET) or electrophilic metalation process for iodination followed by Ullmann coupling of the intermediate iodinated product is proposed as the operating mechanism for the dimerization process.Graphical abstract
    Tetrahedron 04/2009; 65(16):3085-3089. · 2.80 Impact Factor
  • Ramesh Giri, Jin-Quan Yu
    ChemInform 01/2009; 40(10).
  • ChemInform 01/2009; 40(33).
  • Ramesh Giri, Jin-Quan Yu
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    ABSTRACT: A Pd(II)-catalyzed reaction protocol for the direct carboxylation of benzoic and phenylacetic acid derivatives to form dicarboxylic acids has been developed. The reaction conditions are also applicable for the carboxylation of vinyl C-H bonds. The first C-H insertion Pd-aryl complex from carboxylic acids has been characterized by X-ray crystallography.
    Journal of the American Chemical Society 11/2008; 130(43):14082-3. · 10.68 Impact Factor
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    ABSTRACT: O-Methyl hydroxamic acids, readily available from carboxylic acids, are found to be extremely reactive for beta-C-H activation by Pd(OAc)2. This reactivity is exploited to develop the first example of cross-coupling sp3 C-H bonds with sp3 boronic acids. Air was shown to be a suitable stoichiometric oxidant for the catalytic oxidative coupling reaction. A biologically active natural product is readily converted to its novel analogues through this coupling reaction.
    Journal of the American Chemical Society 07/2008; 130(23):7190-1. · 10.68 Impact Factor
  • Angewandte Chemie International Edition 06/2008; 47(28):5215-9. · 11.34 Impact Factor
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    ABSTRACT: Pd(OAc)2-mediated dehydrogenation of an alkyl group to a double bond or a η3-allylic complex via sp3 C−H bond activation and allylic oxidation is reported. A novel redox is proposed for this double oxidation under oxidant-free conditions. A catalytic protocol using benzoquinone as the stoichiometric oxidant has also been developed for the dehydrogenation of cyclopentylcarboxamides.
    Organometallics 03/2008; 27(8). · 4.15 Impact Factor
  • Angewandte Chemie International Edition 06/2008; 47(28):5215-9. · 11.34 Impact Factor
  • ChemInform 01/2008; 39(43).
  • Source
    Jiao-Jie Li, Ramesh Giri, Jin-Quan Yu
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    ABSTRACT: Iodination of remote aryl C–H bonds has been achieved using palladium acetate as the catalyst and iodoacetate (IOAc) as the oxidant. Systematic kinetic isotope studies imply a mechanistic regime shift as the number of bonds separating the directing heteroatom and the target C–H bond increases. Both isotope and electronic effects observed in remote C–H bond activation are consistent with an electrophilic palladation pathway in which the initial palladation is slower than the C–H bond cleavage.
    Tetrahedron. 01/2008; 64(29):6979-6987.

Publication Stats

707 Citations
161.63 Total Impact Points

Institutions

  • 2012
    • University of California, Berkeley
      Berkeley, California, United States
  • 2008–2012
    • The Scripps Research Institute
      • Department of Chemistry
      La Jolla, CA, United States
  • 2009–2011
    • University of Illinois, Urbana-Champaign
      • • Department of Chemical and Biomolecular Engineering
      • • Department of Chemistry
      Urbana, Illinois, United States
  • 2005–2007
    • Brandeis University
      • Department of Chemistry
      Waltham, MA, United States