Herein, we report an efficient strategy for the remote C–H pyridylation of hydroxamates with excellent ortho-selectivity by designing a new class of photon-absorbing O-aryl oxime pyridinium salts generated in situ from the corresponding pyridines and hydroxamates. When irradiated by visible light, the photoexcitation of oxime pyridinium intermediates generates iminyl radicals via the photolytic N–O bond cleavage, which does not require an external photocatalyst. The efficiency of light absorption and N−O bond cleavage of the oxime pyridinium salts can be modulated through the electronic effect of substitution on the O-aryl ring. The resultant iminyl radicals enable the installation of pyridyl rings at γ-CN position, which yields synthetically valuable C2-substituted pyridyl derivatives. This novel synthetic approach provides significant advantages in terms of both efficiency and simplicity and exhibits broad functional group tolerance in complex settings under mild and metal-free conditions.
https://ift.tt/2YJKel2
Half-sandwich iridium(III) complexes are found to be efficient catalysts for homogeneous oxime hydrogenation to hydroxylamine products. Only if equipped with an aryl-imine ligand and operating under strong acidic conditions. Remarkably they do not hydrogenolyse the fragile N−O bond. Experimental evidence suggests an unusual acid-assisted ionic hydrogenation mechanism which may be applicable to the reduction of other challenging substrates.
Abstract
We found that cyclometalated cyclopentadienyl iridium(III) complexes are uniquely efficient catalysts in homogeneous hydrogenation of oximes to hydroxylamine products. A stable iridium C,N-chelation is crucial, with alkoxy-substituted aryl ketimine ligands providing the best catalytic performance. Several Ir-complexes were mapped by X-ray crystal analysis in order to collect steric parameters that might guide a rational design of even more active catalysts. A broad range of oximes and oxime ethers were activated with stoichiometric amounts of methanesulfonic acid and reduced at room temperature, remarkably without cleavage of the fragile N−O bond. The exquisite functional group compatibility of our hydrogenation system was further demonstrated by additive tests. Experimental mechanistic investigations support an ionic hydrogenation platform, and suggest a role for the Brønsted acid beyond a proton source. Our studies provide deep understanding of this novel acidic hydrogenation and may facilitate its improvement and application to other challenging substrates.
https://ift.tt/3dL3kMt
The iridium‐catalyzed intramolecular chemo‐ and enantioselective N‐allylation of oximes is reported. The method employs E/Z mixtures of oximes and furnishes cyclic nitrones with high enantioselectivity. Tandem N‐allylation/dipolar cycloaddition sequences provide access to enantioenriched tricyclic isoxazolidines and enable the formal synthesis of the marine natural product Halichlorine.
Abstract
The enantio‐ and chemoselective iridium‐catalyzed N‐allylation of oximes is described for the first time. Intramolecular kinetic resolution provides access to cyclic nitrones and enantioenriched aliphatic allylic alcohols. Salient features of this transformation are its ability to employ E/Z‐isomeric mixtures of oxime starting materials convergently and high functional group tolerance. The implementation of N‐allylation/1,3‐dipolar cycloaddition reaction sequences furnishes tricyclic isoxazolidines in highly enantio‐ and diastereoselective fashion. The synthetic utility of the approach is demonstrated by the efficient, formal synthesis of the marine natural product (+)‐halichlorine.
https://ift.tt/3cPVTCc
Hi all,
This week on Synthesis Workshop we are joined by Dr. Josep Mas-Roselló, who takes us through his work in the Cramer group at EPFL on the asymmetric Hydrogenation of oximes, which was recently published in Science!
https://youtu.be/BDZibkCTevw
An efficient iron‐catalyzed radical relay protocol enabled the rapid assembly of a wide array of structurally interesting fused pyridines from alkyne‐tethered oximes and alkenes (see scheme). Preliminary biological investigations suggest that some of the fused pyridines exhibit good anti‐inflammatory activity by restoring the imbalance of inflammatory homeostasis of macrophages in a lipopolysaccharide‐induced model.
Abstract
We have rationally designed a new class of alkyne‐tethered oximes and applied them in an unprecedented iron‐catalyzed radical relay protocol for the rapid assembly of a wide array of structurally new and interesting fused pyridines. This method shows broad substrate scope and good functional‐group tolerance and enabled the synthesis of several biologically active molecules. Furthermore, the fused pyridines could be diversely functionalized through various simple transformations, such as cyclization, C−H alkylation, and a click reaction. DFT calculation studies indicate that the reactions involve cascade 1,5‐hydrogen atom transfer, 5‐exo‐dig radical addition, and cyclization processes. Moreover, preliminary biological investigations suggest that some of the fused pyridines exhibit good anti‐inflammatory activity by restoring the imbalance of inflammatory homeostasis of macrophages in a lipopolysaccharide‐induced model.
https://ift.tt/2GOanpR
With readily available oximes as five‐atom units, a variety of azepine and spiro‐tetrahydropyridine derivatives have been synthesized through the iminyl‐radical triggered 1,5‐hydrogen atom transfer/(5+2) or (5+1) annulation cascade protocol. This method exhibits broad substrate scope and good functional group compatibility.
Abstract
By integration of iminyl radical‐triggered 1,5‐hydrogen atom transfer and (5+2) or (5+1) annulation processes, a series of structurally novel and interesting azepine and spiro‐tetrahydropyridine derivatives have been successfully prepared in moderate to good yields. This method utilizes FeCl2 as the catalyst and readily available oximes as five‐atom units, while showcasing broad substrate scope and good functional group compatibility. The annulation products can be easily converted into many valuable compounds. Moreover, DFT calculation studies are performed to provide some insights into the possible reaction mechanisms for the (5+2) and (5+1) annulations.
https://ift.tt/2Zttlsw
An Ir‐catalyzed C(sp3)−H alkynylation of aliphatic ketones, aldehydes, and alcohols was achieved by using the corresponding oxime derivatives and a IrIII catalyst. This general reaction is selective towards primary C(sp3)−H bonds and can be used for the late‐stage C−H alkynylation of complex molecules.
Abstract
An Ir‐catalyzed C(sp3)−H alkynylation of aliphatic ketones, aldehydes, and alcohols was achieved by using the corresponding oxime derivatives and a IrIII catalyst. This general reaction is selective towards primary C(sp3)−H bonds and can be used for the late‐stage C−H alkynylation of complex molecules.
https://ift.tt/2U98Kam
Cyanines comprising either a benzo[e]‐ or benzo[c,d]indolium pattern facilitate initiation of radical photopolymerization combined with high power NIR‐LED prototypes emitting at 805 nm, 860 nm or 870nm while different oxime esters functioned as radical coinitiator. The conversion was studied FTIR. Sensitizers used depict different structural patterns. Radical photopolymerization followed an initiation mechanism based in the participation of excited states requesting addiitonal thermal energy to overcome an existing intrinsic activation barrier. Heat released by nonradiative deactivation of the sensitizer favored the system to work even under conditions where a thermal activated photoinduced electron transfer controls the reaction protocol. The heat generated internally by the NIR sensitizer applying intense NIR irradiation promotes generation of initiating reactive radicals based on the participation of excited states. This gives the photoinitiating system a certain threshold useful to handle systems under ambient room light. Sensitizers with barbiturate group at the meso ‐position preferred to bleach directly while sensitizers carrying a cyclopentene moiety in the middle unexpectedly generated in the photosensitized mechanism a cyclopentadiene moiety exhibiting one additional bond more in the unsaturated pattern resulting in a hypsochromic shift of absorption by about 100 nm.
https://ift.tt/2SmqFZP
A new robust Pd/Xiang‐Phos catalytic system for the asymmetric carboetherification of β,γ‐unsaturated ketoximes with either aryl or alkenyl halides is reported. The ligand (S,Rs)‐NMe‐X2 is responsible for the excellent reactivities and enantioselectivities. The salient features of this transformation include mild reaction conditions, general substrate scope, good functional group tolerance, easy scale‐up, and application in the late‐stage modification of bioactive compounds.
Abstract
Reported here is a highly efficient Pd/Xiang‐Phos catalyzed enantioselective carboetherification of alkenyl oximes with either aryl or alkenyl halides, delivering various chiral 3,5‐disubstituted and 3,5,5‐trisubstituted isoxazolines in good yields with up to 97 % ee. The sterically bulky and electron‐rich (S,Rs)‐NMe‐X2 ligand is responsible for the excellent reactivities and enantioselectivities. The salient features of this transformation include mild reaction conditions, general substrate scope, good functional‐group tolerance, good yields, high enantioselectivities, easy scale‐up, and application in the late‐stage modification of bioactive compounds. The obtained products can be readily transformed into useful chiral 1,3‐aminoalcohols.
https://ift.tt/2EL1Dwa
We found that cyclometalated cyclopentadienyl iridium(III) complexes are uniquely efficient catalysts in homogeneous hydrogenation of oximes to hydroxylamine products. A stable iridium C,N‐chelation is crucial, with alkoxy‐substituted aryl ketimine ligands providing the best catalytic performance. Several Ir‐complexes were mapped by X‐ray crystal analysis in order to collect steric parameters that might guide a rational design of even more active catalysts. A broad range of oximes and oxime ethers were activated with stoichiometric amounts of methanesulfonic acid and reduced at room temperature, remarkably without cleavage of the fragile N‐O bond. The exquisite functional group compatibility of our hydrogenation system was further demonstrated by additive tests. Experimental mechanistic investigations support an ionic hydrogenation platform, and suggest a role for the Brønsted acid beyond a proton source. Our studies provide deep understanding of this novel acidic hydrogenation and may facilitate its improvement and application to other challenging substrates.
https://ift.tt/3dL3kMt
Hi all,
This week on Synthesis Workshop we are joined by Dr. Josep Mas-Roselló, who takes us through his work in the Cramer group at EPFL on the asymmetric Hydrogenation of oximes, which was recently published in Science!
Hi all,
This week on Synthesis Workshop we are joined by Dr. Josep Mas-Roselló, who takes us through his work in the Cramer group at EPFL on the asymmetric Hydrogenation of oximes, which was recently published in Science!
We have rationally designed a new class of alkyne‐tethered oximes, and applied them into an unprecedented iron‐catalyzed radical relay protocol for the rapid assembly of a wide array of structurally new and interesting fused pyridines. This method showcases broad substrate scope and good functional group tolerance, and can be applied for a few biologically active molecules. In addition, the fused pyridines can be diversely functionalized through various simple transformations, such as cyclization, C‐H alkylation, and click reaction. DFT calculation studies indicate that the reactions involve cascade 1,5‐hydrogen atom transfer, 5‐exo‐dig radical addition, and cyclization processes. Moreover, preliminary biological investigations suggest that some of the fused pyridines exhibit good anti‐inflammatory activity by restoring the imbalance of inflammatory homeostasis of macrophages in a lipopolysaccharide‐induced model.
https://ift.tt/2GOanpR
By integration of iminyl radical‐triggered 1,5‐hydrogen atom transfer and (5+2) or (5+1) annulation processes, a series of structurally novel and interesting azepine and spiro‐tetrahydropyridine derivatives have been successfully prepared in moderate to good yields. This method utilizes FeCl 2 as the catalyst and readily available oximes as five‐atom units, and showcases broad substrate scope and good functional group compatibility. The annulation products can be easily converted into many valuable compounds. Moreover, DFT calculation studies are performed to provide some insights into the possible reaction mechanisms for the (5+2) and (5+1) annulations.
https://ift.tt/2Zttlsw
