- Tandem oxidation-dehydrogenation of (hetero)arylated primary alcohols via perruthenate catalysis
-
Tandem oxidative-dehydrogenation of primary alcohols to give a,b-unsaturated aldehydes in one pot are rare transformations in organic synthesis, with only two methods currently available. Reported herein is a novel method using the bench-stable salt methyltriphenylphosphonium perruthenate (MTP3), and a new co-oxidant NEMO&middoPF6 (NEMO = N-ethyl-N-hydroxymorpholinium) which provides unsaturated aldehydes in low to moderate yields. The Ley-Griffith oxidation of (hetero)arylated primary alcohols with N-oxide co-oxidants NMO (NMO = N-methylmorpholine N-oxide)/NEMO, is expanded by addition of the N-oxide salt NEMO&middoPF6 to convert the intermediate saturated aldehyde into its unsaturated counterpart. The discovery, method development, reaction scope, and associated challenges of this method are highlighted. The conceptual value of late-stage dehydrogenation in natural product synthesis is demonstrated via the synthesis of a polyene scaffold related to auxarconjugatin B.
- Bettencourt, Christian J.,Chow, Sharon,Moore, Peter W.,Read, Christopher D.G.,Jiao, Yanxiao,Bakker, Jan Peter,Zhao, Sheng,Bernhardt, Paul V.,Williams, Craig M.
-
p. 652 - 659
(2021/09/08)
-
- Enantiodivergent One-Pot Synthesis of Axially Chiral Biaryls Using Organocatalyst-Mediated Enantioselective Domino Reaction and Central-to-Axial Chirality Conversion
-
Enantiodivergent one-pot synthesis of biaryls was developed using a catalytic amount of a single chiral source. A domino organocatalyst-mediated enantioselective Michael reaction and aldol condensation provided centrally chiral dihydronaphthalenes with excellent enantioselectivity, from which an enantiodivergent chirality conversion from central-to-axial chirality was achieved. Both enantiomers of biaryls were obtained with excellent enantioselectivity. All transformations can be conducted in a single reaction vessel. A plausible reaction mechanism for the enantiodivergence is proposed.
- Hayashi, Yujiro,Koshino, Seitaro,Kwon, Eunsang,Monde, Kenji,Taniguchi, Tohru
-
p. 15786 - 15794
(2021/10/14)
-
- Substrate-Controlled Chemo-/Enantioselective Synthesis of α-Benzylated Enals and Chiral Cyclopropane-Fused 2-Chromanone Derivatives
-
Substrate-controlled cascade reactions between α,β-unsaturated aldehydes or their analogues and 2,4-dinitrobenzyl chloride in the presence of a chiral secondary amine as the catalyst and base were developed, to obtain a broad spectrum of α-benzylated enals and enantioenriched cyclopropane-fused chroman-2-one derivatives. The cyclopropane-tethered iminium ion clearly served as a key intermediate in these reactions to trigger stereochemical outcomes, one of which was supported by a control experiment. (Figure presented.).
- Byeon, Huimyoung,Ryu, Sunghyeon,Yoo, Eun Jeong,Yang, Jung Woon
-
supporting information
p. 5085 - 5091
(2021/09/20)
-
- Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics
-
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.
- Buijs, Ned,Campagna, Roberto,Emanuelli, Monica,Gao, Yongzhi,Innocenti, Paolo,Jespers, Willem,Martin, Nathaniel I.,Parsons, Richard B.,Sartini, Davide,Van Haren, Matthijs J.,Van Westen, Gerard J. P.,Zhang, Yurui,Gutiérrez-De-Terán, Hugo
-
p. 12938 - 12963
(2021/09/11)
-
- Method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and diphosphine ligand used in method
-
The invention discloses a method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and a diphosphine ligand used in the method. According to the invention, indole-substituted phosphoramidite diphosphine ligand which is stable in air and insensitive to light is synthesized by utilizing a continuous one-pot method, and the indole-substituted phosphoramidite diphosphine ligand and a rhodium catalyst are used for jointly catalyzing to successfully achieve a hydroformylation reaction of aromatic terminal alkyne and terminal conjugated eneyne under the condition of synthesis gas for the first time, so that an olefine aldehyde structure compound can be rapidly and massively prepared, and particularly, a polyolefine aldehyde structure compound which is more difficult to synthesize in the prior art can be easily prepared and synthesized, and a novel method is provided for synthesis and modification of drug molecules, intermediates and chemical products.
- -
-
Paragraph 0155-0157
(2021/05/29)
-
- Palladium-catalyzed ring-closing reaction via C-N bond metathesis for rapid construction of saturated N-heterocycles
-
The ring-closing reactions based on chemical bond metathesis enable the efficient construction of a wide variety of cyclic systems which receive broad interest from medicinal and organic communities. However, the analogous reaction with C-N bond metathesis as a strategic fundamental step remains an unanswered challenge. Herein, we report the design of a new fundamental metallic C-N bond metathesis reaction that enables the palladium-catalyzed ring-closing reaction of aminodienes with aminals. The reactions proceed efficiently under mild conditions and exhibit broad substrate generality and functional group compatibility, leading to a wide variety of 5- to 16-membered N-heterocycles bearing diverse frameworks and functional groups.
- Yu, Bangkui,Zou, Suchen,Liu, Hongchi,Huang, Hanmin
-
supporting information
p. 18341 - 18345
(2020/11/17)
-
- Enantioselective Aldol Addition of Acetaldehyde to Aromatic Aldehydes Catalyzed by Proline-Based Carboligases
-
Aromatic β-hydroxyaldehydes, 1,3-diols, and α,β-unsaturated aldehydes are valuable precursors to biologically active natural products and drug molecules. Herein we report the biocatalytic aldol condensation of acetaldehyde with various aromatic aldehydes to give a number of aromatic α,β-unsaturated aldehydes using a previously engineered variant of 4-oxalocrotonate tautomerase [4-OT(M45T/F50A)] as carboligase. Moreover, an efficient one-pot two-step chemoenzymatic route toward chiral aromatic 1,3-diols has been developed. This one-pot chemoenzymatic strategy successfully combined a highly enantioselective aldol addition step catalyzed by a proline-based carboligase [4-OT(M45T/F50A) or TAUT015] with a chemical reduction step to convert enzymatically prepared aromatic β-hydroxyaldehydes into the corresponding 1,3-diols with high optical purity (e.r. up to >99:1) and in good isolated yield (51-92%). These developed (chemo)enzymatic methodologies offer alternative synthetic choices to prepare a variety of important drug precursors.
- Biewenga, Lieuwe,Charnock, Simon J.,Guo, Chao,Poelarends, Gerrit J.,Saifuddin, Mohammad,Saravanan, Thangavelu
-
p. 2522 - 2527
(2020/03/11)
-
- Bioinspired Radical Stetter Reaction: Radical Umpolung Enabled by Ion-Pair Photocatalysis
-
A bioinspired, intermolecular radical Stetter reaction of α-keto acids and aldehydes is disclosed that is contingent on a formal “radical umpolung” concept. Enabled by secondary amine activation, electrostatic recognition ensures that the α-ketocarboxylic acids, which function as latent acyl radicals, are proximal to the in situ generated iminium salts. This photoactive contact ion pair is an electron donor–acceptor (EDA) complex, and undergoes facile single electron transfer (SET) and rapid decarboxylation prior to radical–radical recombination. Importantly, decarbonylation is mitigated by this strategy. The initial computational validation on which the process is predicated matches closely with experiment. Synergising organo- and photocatalysis activation principles finally expands the mechanistic and synthetic scope of the classic Stetter reaction to include α,β-unsaturated aldehydes as acceptors.
- Morack, Tobias,Mück-Lichtenfeld, Christian,Gilmour, Ryan
-
p. 1208 - 1212
(2019/01/04)
-
- Highly Enantioselective Synthesis of Functionalized Glutarimide Using Oxidative N-Heterocyclic Carbene Catalysis: A Formal Synthesis of (?)-Paroxetine
-
A simple yet highly effective approach toward enantioselective synthesis of trans-3,4-disubstituted glutarimides from readily available starting materials is developed using oxidative N-heterocyclic carbene catalysis. The catalytic reaction involves a formal [3 + 3] annulation between enals and substituted malonamides enabling the production of glutarimide derivatives in a single chemical operation via concomitant formation of C-C and C-N bonds. The reaction offers easy access to a broad range of functionalized glutarimides with excellent enantioselectivity and good yield. Synthetic application of the method is demonstrated via formal synthesis of (?)-paroxetine and other bioactive molecules.
- Porey, Arka,Santra, Surojit,Guin, Joyram
-
p. 5313 - 5327
(2019/04/16)
-
- Iron(III)/O2-Mediated Regioselective Oxidative Cleavage of 1-Arylbutadienes to Cinnamaldehydes
-
A simple, efficient, and environmentally benevolent regioselective oxidative cleavage of 1-arylbutadienes to cinnamaldehydes mediated by iron(III) sulfate/O2 has been developed. The reaction offered good yields and excellent regioselectivity and showed good functional group tolerance (31 examples). The method is important, as few reports with limited substrate scope are available for such excellent oxidative cleavage of conjugated dienes.
- Bhowmik, Amit,Fernandes, Rodney A.
-
supporting information
p. 9203 - 9207
(2019/11/14)
-
- Silylative Reductive Amination of α,β-Unsaturated Aldehydes: A Convenient Synthetic Route to β-Silylated Secondary Amines
-
Described here is a reductive amination/hydrosilylation cascade of α,β-unsaturated aldehydes mediated by a Lewis acidic borane catalyst. The present reaction system provides an one-pot synthetic route towards β-silylated secondary amines that have not been accessible by other previous catalysis. Comparative 1H NMR studies on the silylative reduction of enimines revealed that steric bulkiness of primary amine reactants strongly affects both catalytic efficiency and regioselectivity. This strategy was applicable to a broad range of substrates and amenable to one-pot gram-scale synthesis. Moreover, a diastereoselective introduction of the β-silyl group was also found to be feasible (d.r. up to 71:29).
- Kim, Eunae,Park, Sehoon,Chang, Sukbok
-
supporting information
p. 5765 - 5769
(2018/03/28)
-
- Modular synthesis of (E)-cinnamaldehydes directly from allylarenes via a metal-free DDQ-mediated oxidative process
-
An efficient synthesis of (E)-cinnamaldehydes by a metal-free DDQ-mediated oxidative transformation of allylarenes was developed. The protocol provides a practical method to prepare diverse (E)-cinnamaldehydes with broad functional group tolerance in good to excellent yields, including easy access to natural products randainal and geranyloxy sinapyl aldehyde from plant extracts. Finally, the mechanism of a single-electron transfer process was proposed.
- Xu, Ting-Ting,Jiang, Tao-Shan,Han, Xiao-Lan,Xu, Yuan-Hong,Qiao, Jin-Ping
-
p. 5350 - 5358
(2018/08/03)
-
- Oxygenative and Dehydrogenative [3 + 3] Benzannulation Reactions of α,β-Unsaturated Aldehydes and γ-Phosphonyl Crotonates Mediated by Air: Regioselective Synthesis of 4-Hydroxybiaryl-2-carboxylates
-
Regioselective synthesis of 4-hydroxybiphenyl-2-carboxylates via the base-mediated oxygenative [3 + 3] benzannulation reaction of α,β-unsaturated aldehydes and γ-phosphonyl crotonates is reported. A hydroxyl group is installed in the final product on the originally phosphorus-bound carbon via a novel oxygenative and dehydrogenative transformation. The reaction proceeds rapidly in an open flask, uses atmospheric oxygen as an oxidant, and affords good yields of substituted biaryl phenols. (Chemical Equation Presented).
- Joshi, Prabhakar Ramchandra,Nanubolu, Jagadeesh Babu,Menon, Rajeev S.
-
supporting information
p. 752 - 755
(2016/03/01)
-
- Expanding the scope of the Babler–Dauben oxidation: 1,3-oxidative transposition of secondary allylic alcohols
-
We report the catalytic chromium-mediated oxidation of secondary allylic alcohols to give α,β-unsaturated aldehydes with exclusive (E)-stereoselectivity. This facile procedure employs catalytic PCC (5?mol?%) and periodic acid (H5IO6) as a co-oxidant. This transformation occurs specifically with aromatic substituted allyl alcohols containing both electron withdrawing and electron donating substituents as well as a range of functional groups.
- Killoran, Patrick M.,Rossington, Steven B.,Wilkinson, James A.,Hadfield, John A.
-
supporting information
p. 3954 - 3957
(2016/08/09)
-
- Organocatalytic Kinetic Resolution of Sulfoximines
-
An efficient kinetic resolution of sulfoximines with enals was realized using chiral N-heterocyclic carbene (NHC) catalysts. The stereoselective amidation proceeds without additional acyl transfer agent. Both enantiomers of the sulfoximines can be obtaine
- Dong, Shunxi,Frings, Marcus,Cheng, Hanchao,Wen, Jian,Zhang, Duo,Raabe, Gerhard,Bolm, Carsten
-
supporting information
p. 2166 - 2169
(2016/03/05)
-
- One-Pot Synthesis of (S)-Baclofen via Aldol Condensation of Acetaldehyde with Diphenylprolinol Silyl Ether Mediated Asymmetric Michael Reaction as a Key Step
-
An efficient asymmetric total synthesis of (S)-baclofen was accomplished via a one-pot operation from commercially available materials using sequential reactions, such as aldol condensation of acetaldehyde, diphenylprolinol silyl ether mediated asymmetric Michael reaction of nitromethane, Kraus-Pinnick oxidation, and Raney Ni reduction. Highly enantioenriched baclofen was obtained in one pot with a good yield over four reactions.
- Hayashi, Yujiro,Sakamoto, Daisuke,Okamura, Daichi
-
supporting information
p. 4 - 7
(2016/01/15)
-
- A metal-free one-pot cascade synthesis of highly functionalized biaryl-2-carbaldehydes
-
A metal-free one-pot cascade annulation of acyclic substrates dienaminodioate, cinnamaldehydes and allyl amine was achieved for the synthesis of polyfunctional biaryl-2-carbaldehydes. The reaction proceeds at room temperature by a trifluoroacetic acid mediated Diels-Alder pathway. Synthetic applications of the resulting biaryl-2-carbaldehyde have been demonstrated by conversion into an array of diverse molecules with biological and materials chemistry relevance. The present work offers a complementary route to the existing metal mediated cross-coupling methods for the preparation of biaryls.
- Challa, Chandrasekhar,Vellekkatt, Jamsheena,Ravindran, Jaice,Lankalapalli, Ravi S.
-
supporting information
p. 8588 - 8592
(2014/12/11)
-
- Synergistic catalysis: Enantioselective addition of Alkylbenzoxazoles to Enals
-
A novel catalytic enantioselective methodology based on synergistic catalysis is reported. The strategy involves: 1) the metal-Lewis-acid activation of alkylazaarenes, and 2) the secondary-amine activation of enals. Consequently, highly functionalized chiral alkylazaarenes were obtained in good yields and with reasonable stereoselectivity.
- Meazza, Marta,Ceban, Victor,Pitak, Mateusz B.,Coles, Simon J.,Rios, Ramon
-
supporting information
p. 16853 - 16857
(2015/01/09)
-
- Br?nsted acid-catalyzed meyer-schuster rearrangement for the synthesis of α, β -unsaturated carbonyl compounds
-
An efficient and simple protocol for the Meyer-Schuster rearrangement of propargyl alcohols into α,β-unsaturated carbonyl compounds has been developed using catalytic amounts of p-toluenesulfonic acid in 1,2-dichloroethane.
- Park, Jungmin,Yun, Jihee,Kim, Jaehyun,Jang, Dong-Jin,Park, Cheol Ho,Lee, Kooyeon
-
p. 1924 - 1929
(2014/07/07)
-
- Emission wavelength prediction of a full-color-tunable fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one
-
In this paper we report on a novel fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one, which we named Seoul-Fluor, having tunable and predictable photophysical properties. Using a concise and practical one-pot synthetic procedure, a 68-member library of new fluorescent compounds was synthesized with diverse substituents. In Seoul-Fluor, the electronic characteristics of the substituents, as well as their positional changes, have a close correlation with their photophysical properties. The systematic perturbation of electronic densities on the specific positions of Seoul-Fluor, guided with the Hammett constant, allows emission wavelength tunability covering the full color range. On the basis of these observations and a computational analysis, we extracted a simple first-order correlation of photophysical properties with the theoretical calculation and accurately predicted the emission wavelength of Seoul-Fluors through the rational design. In this study, we clearly demonstrate that Seoul-Fluor can provide a powerful gateway for the generation of desired fluorescent probes without the need for a tiresome synthesis and trial-and-error process.
- Kim, Eunha,Koh, Minseob,Lim, Byung Joon,Park, Seung Bum
-
p. 6642 - 6649
(2011/06/19)
-
- A simple route to 9-fluorenylidenes by domino Suzuki/Heck coupling reactions
-
A palladium catalyzed domino intermolecular Suzuki followed by intramolecular Heck coupling is described. This strategy afforded a novel and convenient synthesis of various 9-fluorenylidene derivatives in one-pot under relatively mild reaction condition.
- Paul, Sunanda,Gorai, Tumpa,Koley, Arijit,Ray, Jayanta K.
-
supporting information; experimental part
p. 4051 - 4055
(2011/08/09)
-
- Design, synthesis, and X-ray crystallographic studies of α-aryl substituted fosmidomycin analogues as inhibitors of mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate reductoisomerase
-
The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR
- Andaloussi, Mounir,Henriksson, Lena M.,Wi?ckowska, Anna,Lindh, Martin,Bj?rkelid, Christofer,Larsson, Anna M.,Suresh, Surisetti,Iyer, Harini,Srinivasa, Bachally R.,Bergfors, Terese,Unge, Torsten,Mowbray, Sherry L.,Larhed, Mats,Jones, T. Alwyn,Karlén, Anders
-
supporting information; experimental part
p. 4964 - 4976
(2011/10/01)
-
- Palladium-catalyzed oxidative tandem reaction of allylamines with aryl halides leading to α,β-unsaturated aldehydes
-
A novel tandem protocol involving a Heck reaction process for the synthesis of α,β-unsaturated aldehydes has been developed. In the presence of Pd(OAc), PPh3, NaOAc, TBAB and air, N-allylbenzenamines underwent the reaction with various aryl hal
- Jiang, Tao-Shan,Li, Jin-Heng
-
supporting information; experimental part
p. 7236 - 7238
(2010/03/25)
-
- A RhCl(PPh3)3/BF3·OEt2 co-promoted direct C-C cross-coupling of alcohols at β-position with aldehydes
-
A novel RhCl(PPh3)3/BF3·OEt2 co-promoted direct C-C cross-coupling of primary and secondary alcohols at β-position with aldehyde was developed. This reaction could provide an efficient synthesis of a series of α
- Zhang, Shu-Yu,Tu, Yong-Qiang,Fan, Chun-An,Yang, Ming,Zhang, Fu-Min
-
body text
p. 4178 - 4181
(2009/12/01)
-
- ANALGESIC 5, 9 - METHANOCYCLOOCTA (b) PYRIDIN - 2 (1H) - ONE DERIVATIVES, THEIR PREPARATION METHOD AND USE
-
Compounds represented by the Formula I or salts, hydrates thereof, wherein R1, R8, R11 and R12 are H or C1-4 hydrocarbonyl respectively; R2, R3, R6 and R7 are H, halogen or C1-4 hydrocarbonyl respectively; R4 is C1-6 hydrocarbonyl or Ar; or =CR4R3 is cyclopentylidene, cyclohexylidene, 1-methylpiperidyl-4-idene or indenyl-1-idene; R5 is H, 1-4 same or different F, Cl, Br, CF3, R9, OR9, NR9R10, NO2, CN, COOR9, O2CR9, CONR9R10, NR9C(O)R10, heterocyclic, aryl or groups represented by the Formula II respectively; R9 and R10 are H or C1-6 hydrocarbonyl; Ar is aromatic ring; m is 0, 1 or 2; n is 0, 1, 2, 3 or 4, for treating mammal pain, functional painful syndrome, organic painful syndrome or tissue painful syndrome, and their preparation method.
- -
-
Page/Page column 15
(2009/04/23)
-
- Inhibition of chitin synthases and antifungal activities by 2′-benzoyloxycinnamaldehyde from Pleuropterus ciliinervis and its derivatives
-
In the course of search for potent chitin synthase inhibitors from natural resources, a novel chitin synthases inhibitor, 2′-benzoyloxycinnamaldehyde (2′-BCA) (I), was isolated from the aerial parts of Pleuropterus ciliinervis NAKAI. 2′-BCA inhibited chit
- Kang, Tae Hoon,Hwang, Eui Il,Yun, Bong Sik,Park, Ki Duk,Kwon, Byoung Mog,Shin, Chul Soo,Kim, Sung Uk
-
p. 598 - 602
(2008/02/02)
-
- One-Step Synthesis of ortho-Hydroxycinnamaldehyde
-
An improved and convenient one-step procedure for the large scale synthesis of ortho-hydroxycinnamaldehyde (3a) using ortho-hydroxybenzaldehyde and vinyl acetate is described.
- Kim, Jong Han,Lee, Sangku,Kwon, Mu-Gil,Park, Yong Soo,Choi, Sung-Kyu,Kwon, Byoung-Mog
-
p. 1223 - 1228
(2007/10/03)
-
- Palladium-catalyzed tandem reactions to form 1-vinyl-1H-isochromene derivatives
-
The palladium-catalyzed reaction of pinacolone with tert-butyldimethyl(3-(2-bromophenyl)allyloxy)-silane results in direct formation of 1-vinyl-3-tert-butyl-1H-isochromene. This is the result of a ketone arylation followed by an intramolecular cyclization of the enolate with the allylic system. The use of a lithium diamide base appears to be essential for success. The tert-butyldimethylsilyl protecting group is also an essential choice as it furnishes the appropriate reactivity to promote allylic substitution after the aryl coupling process. The use of more effective leaving groups, such as acetate, results in reaction of the allylic group, and no aryl coupling is observed. Through the appropriate selection of phosphine ligand and solvent, either the cyclized isochromene product or the noncyclized intermediate may be formed selectively. A short combinatorial study of the scope and limitations of the reaction, involving 24 ketones, is described.
- Mutter,Campbell,de la Nava,Merritt,Wills
-
p. 3284 - 3290
(2007/10/03)
-
- Phase transfer Wittig reaction with 1,3-dioxolan-2-yl-methyltriphenyl phosphonium salts: An efficient method for vinylogation of aromatic aldehydes
-
Aldehydes were efficiently transformed into allylic dioxolanes by a Wittig-type reaction, using 1,3-dioxolan-2-yl-methyltriphenylphosphonium bromide under phase transfer conditions. The substituent kinetic effects were studied, and related to Hammett values and electrochemical potentials.
- Daubresse, Nicolas,Francesch, Charlette,Rolando, Christian
-
p. 10761 - 10770
(2007/10/03)
-