Browsing by Author "Ess, Daniel H."

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Dirhodium-catalyzed C-H arene amination using hydroxylamines
    (AAAS, 2016) Paudyal, Mahesh P.; Adebesin, Adeniyi Michael; Burt, Scott R.; Ess, Daniel H.; Ma, Zhiwei; Kürti, László; Falck, John R.
    Primary and N-alkyl arylamine motifs are key functional groups in pharmaceuticals, agrochemicals, and functional materials, as well as in bioactive natural products. However, there is a dearth of generally applicable methods for the direct replacement of aryl hydrogens with NH2/NH(alkyl) moieties. Here, we present a mild dirhodium-catalyzed C-H amination for conversion of structurally diverse monocyclic and fused aromatics to the corresponding primary and N-alkyl arylamines using NH2/NH(alkyl)-O-(sulfonyl)hydroxylamines as aminating agents; the relatively weak RSO2O-N bond functions as an internal oxidant. The methodology is operationally simple, scalable, and fast at or below ambient temperature, furnishing arylamines in moderate-to-good yields and with good regioselectivity. It can be readily extended to the synthesis of fused N-heterocycles.
  • Thumbnail Image
    Item
    Practical Organocatalytic Synthesis of Functionalized Non-C2-Symmetrical Atropisomeric Biaryls
    (Wiley, 2016) Gao, Hongyin; Xu, Qing-Long; Keene, Craig; Yousufuddin, Muhammed; Ess, Daniel H.; Kürti, László
    An organic acid catalyzed direct arylation of aromatic C(sp2)H bonds in phenols and naphthols for the preparation of 1,1′-linked functionalized biaryls was developed. The products are non-C2-symmetrical, atropoisomeric, and represent previously untapped chemical space. Overall this transformation is operationally simple, does not require an external oxidant, is readily scaled up (up to 98 mmol), and the structurally diverse 2,2′-dihydroxy biaryl (i.e., BINOL-type), as well as 2-amino-2′-hydroxy products (i.e., NOBIN-type) are formed with complete regioselectivity. Density-functional calculations suggest that the quinone and imino-quinone monoacetal coupling partners are exclusively arylated at their α-position by an asynchronous [3,3]-sigmatropic rearrangement of a mixed acetal species which is formed in situ under the reaction conditions.
  • Thumbnail Image
    Item
    Practical Singly and Doubly Electrophilic Aminating Agents: A New, More Sustainable Platform for Carbon–Nitrogen Bond Formation
    (American Chemical Society, 2017) Kattamuri, Padmanabha V.; Yin, Jun; Siriwongsup, Surached; Kwon, Doo-Hyun; Ess, Daniel H.; Li, Qun; Li, Guigen; Yousufuddin, Muhammed; Richardson, Paul F.; Sutton, Scott C.; Kürti, László
    Given the importance of amines in a large number of biologically active natural products, active pharmaceutical ingredients, agrochemicals, and functional materials, the development of efficient C–N bond-forming methods with wide substrate scope continues to be at the frontier of research in synthetic organic chemistry. Here, we present a general and fundamentally new synthetic approach for the direct, transition-metal-free preparation of symmetrical and unsymmetrical diaryl-, arylalkyl-, and dialkylamines that relies on the facile single or double addition of readily available C-nucleophiles to the nitrogen atom of bench-stable electrophilic aminating agents. Practical single and double polarity reversal (i.e., umpolung) of the nitrogen atom is achieved using sterically and electronically tunable ketomalonate-derived imines and oximes. Overall, this novel approach represents an operationally simple, scalable, and environmentally friendly alternative to transition-metal-catalyzed C–N cross-coupling methods that are currently used to access structurally diverse secondary amines.
  • Thumbnail Image
    Item
    Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds
    (Springer Nature, 2016) Gao, Hongyin; Zhou, Zhe; Kwon, Doo-Hyun; Coombs, James; Jones, Steven; Behnke, Nicole Erin; Ess, Daniel H.; Kürti, László; BioScience Research Collaborative
    Arylmetals are highly valuable carbon nucleophiles that are readily and inexpensively prepared from aryl halides or arenes and widely used on both laboratory and industrial scales to react directly with a wide range of electrophiles. Although C−C bond formation has been a staple of organic synthesis, the direct transfer of primary amino (−NH2) and hydroxyl (−OH) groups to arylmetals in a scalable and environmentally friendly fashion remains a formidable synthetic challenge because of the absence of suitable heteroatom-transfer reagents. Here, we demonstrate the use of bench-stable N−H and N−alkyl oxaziridines derived from readily available terpenoid scaffolds as efficient multifunctional reagents for the direct primary amination and hydroxylation of structurally diverse aryl- and heteroarylmetals. This practical and scalable method provides one-step synthetic access to primary anilines and phenols at low temperature and avoids the use of transition-metal catalysts, ligands and additives, nitrogen-protecting groups, excess reagents and harsh workup conditions.
  • Thumbnail Image
    Item
    Transition metal-free direct dehydrogenative arylation of activated C(sp3)–H bonds: synthetic ambit and DFT reactivity predictions
    (Royal Society of Chemistry, 2018) Lovato, Kaitlyn; Guo, Lirong; Xu, Qing-Long; Liu, Fengting; Yousufuddin, Muhammed; Ess, Daniel H.; Kürti, László; Gao, Hongyin
    A transition metal-free dehydrogenative method for the direct mono-arylation of a wide range of activated C(sp3)-H bonds has been developed. This operationally simple and environmentally friendly aerobic arylation uses tert-BuOK as the base and nitroarenes as electrophiles to prepare up to gram quantities of structurally diverse sets (>60 examples) of α-arylated esters, amides, nitriles, sulfones and triaryl methanes. DFT calculations provided a predictive model, which states that substrates containing a C(sp3)-H bond with a sufficiently low pK a value should readily undergo arylation. The DFT prediction was confirmed through experimental testing of nearly a dozen substrates containing activated C(sp3)-H bonds. This arylation method was also used in a one-pot protocol to synthesize over twenty compounds containing all-carbon quaternary centers.