14 research outputs found
Continuous proline catalysis via leaching of solid proline
Herein, we demonstrate that a homogeneous catalyst can be prepared continuously via reaction with a packed-bed of a catalyst precursor. Specifically, we perform continuous proline catalyzed α-aminoxylations using a packed-bed of L-proline. The system relies on a multistep sequence in which an aldehyde and thiourea additive are passed through a column of solid proline, presumably forming a soluble oxazolidinone intermediate. This transports a catalytic amount of proline from the packed-bed into the reactor coil for subsequent combination with a solution of nitrosobenzene, affording the desired optically active α-aminooxy alcohol after reduction. To our knowledge, this is the first example in which a homogeneous catalyst is produced continuously using a packed-bed. We predict that the method will not only be useful for other L-proline catalyzed reactions, but we also foresee that it could be used to produce other catalytic species in flow
Bench-Stable Nickel Precatalysts with Heck-type Activation
Herein, we report the synthesis and characterization of a new class of air- and moisture-stable phosphine-containing nickel(II) precatalysts, which activate through a Heck-type mechanism. The activities of the precatalysts are demonstrated with a carbonyl-ene coupling reaction.NIGMS (Ruth L. Kirschstein National Research Service Award, no. F32GM120852)National Science Foundation (grant no. CHE-0946721
Bench-stable N -heterocyclic carbene nickel precatalysts for CâC and CâN bond-forming reactions
Herein, we introduce a new class of bench-stable N-heterocyclic carbene (NHC) nickel-precatalysts for homogeneous nickel-catalysis. The nickel(II) complexes are readily activated to Ni0 in situ under mild conditions, via a proposed Heck-type mechanism. The precatalysts are shown to facilitate carbonyl-ene, hydroalkenylation, and amination reactions.NIH Ruth L. Kirschstein National Research Service Award (no. F32GM120852
Synthesis and Reactivity Profile of Ylidenemalononitrile Enamines and Their Ester Analogs Towards Electrophiles and Nucleophiles
Herein,
we describe the synthesis and reactivity of enamines derived
from ylidenemalononitriles and ylidenecyanoacetates. The enamine scope
was expanded by (1) increasing yields of aldehyde-derived ylidenemalononitriles,
(2) incorporating silyl functionalities, and (3) using other amide
acetals to expand the substitution patterns of pyridines resulting
from enamine cyclization. In addition, methods to produce α-pyrones
and polysubstituted pyridines from both ylidenemalononitriles and
ylidenecyanoacetates are described
Bench-Stable Nickel Precatalysts with Heck-type Activation
Herein, we report
the synthesis and characterization of a new class
of air- and moisture-stable phosphine-containing nickelÂ(II) precatalysts,
which activate through a Heck-type mechanism. The activities of the
precatalysts are demonstrated with a carbonylâene coupling
reaction
Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine
2-Chloro-3-amino-4-picoline (CAPIC) is a strategic building block for the preparation of nevirapine, a widely-prescribed non-nucleosidic reverse transcriptase inhibitor for the treatment of HIV-infected patients. A continuous synthesis to the bromo derivative of a CAPIC intermediate, 2-bromo-4-methylnicotinonitrile, that terminates in a dead-end crystallization is described. The route uses inexpensive, acyclic commodity-based raw materials and has the potential to enable lower cost production of nevirapine as well as other value added structures that contain complex pyridines. The route terminates in a batch crystallization yielding high purity CAPIC. This outcome is expected to facilitate regulatory implementation of the overall process
Improved Synthesis of Mono- and Disubstituted 2âHalonicotinonitriles from Alkylidene Malononitriles
Pyridines with 2,3,4 and/or 5 substitution remain challenging to prepare. Existing strategies to form multisubstituted 2-halonicotinonitriles via enamines suffer from dimerization of the starting alkylidene malononitriles resulting in low yields. Through alteration of reaction conditions, a new high yielding method into enamines was realized by condensing DMFâDMA and alkylidene malononitriles in the presence of substoichiometric acetic anhydride. Cyclization of the resulting enamines under Pinner conditions provided 2-halonicotinonitriles in high overall yields
Continuous Synthesis and Use of <i>N</i>âHeterocyclic Carbene Copper(I) Complexes from Insoluble Cu<sub>2</sub>O
It is demonstrated that homogeneous <i>N</i>-heterocyclic carbeneâcopper(I)-chloride complexes can be prepared continuously by flowing NHC precursors through a packed bed of solid Cu<sub>2</sub>O suspended in molecular sieves. The method enables the synthesis of a wide range of complexes including those that are challenging to prepare using standard approaches. Our strategy enables both sustained output of complex production for long-term catalytic reactions (greater than 5 h) and for generation of gram quantities for storage (greater than 1 g of complex in âŒ16 min)
Assessing Carbazole Derivatives as Single-Electron Photoreductants
The
electron-donating capabilities of carbazoles have stimulated
interest in their use as photoinduced single-electron reductants.
Due to the modularity of the carbazole, a further broadening and understanding
of their reactivity could be achieved by manipulating the structure.
Herein, eight carbazole derivatives were synthesized, characterized,
and assessed as single-electron photoreductants in the hydrodehalogenation
of aryl halides and the arylation of N-methylpyrrole
Ylidenemalononitrile Enamines as Fluorescent âTurn-Onâ Indicators for Primary Amines
Ylidenemalononitrile enamines undergo
rapid amine exchange followed
by a cyclization with primary amines to yield fluorescent products
with emission intensities as high as 900 times greater than the starting
materials. After identifying the fluorescent species by X-ray crystallography,
we demonstrate that the rate of amine exchange is substrate dependent
and that by simple structural variation the fluorescence can be tuned
over the entire visible spectrum. We further demonstrate their potential
application in biomolecule labeling