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Search for "Henry reaction" in Full Text gives 31 result(s) in Beilstein Journal of Organic Chemistry.
Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions
- Kyle F. Biegasiewicz,
- Michelle L. Ingalsbe,
- Jeffrey D. St. Denis,
- James L. Gleason,
- Junming Ho,
- Michelle L. Coote,
- G. Paul Savage and
- Ronny Priefer
Beilstein J. Org. Chem. 2012, 8, 1814–1818, doi:10.3762/bjoc.8.207
- , MA 01119, USA 10.3762/bjoc.8.207 Abstract Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction. To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity in
- /fragmentation to afford benzaldehyde, which further reacts to give benzyl benzoate [18]. Recently, we synthesized the first cubane-based Schiff base ligand (Figure 1) and screened it in the Henry reaction in the synthesis of β-nitroalcohols [19]. The cubyl moiety can be considered a cross between a tert-butyl
- 3). As previously reported, CuCl gave the best results with the Henry reaction [19]; hence, we decided to evaluate this copper source. This, however, did not yield any encouraging results with only a maximum ee value of 4% when performed in Et2O (Table 2, entry 4). We next evaluated a Cu(OTf
Graphical Abstract
Figure 1: Structure of (1R,2R)-N,N’-bis[(4-iodocuban-1-yl)methylene]-trans-1,2-diamino cyclohexane (1).
Figure 2: M06L DFT global minima for (a) (1R,2R)-N,N’-bis[(4-iodocuban-1-yl)methylene]-trans-1,2-diaminocyclo...
Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines
- Chittaranjan Bhanja,
- Satyaban Jena,
- Sabita Nayak and
- Seetaram Mohapatra
Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191
- salicylaldehydes and α,β-unsaturated nitro compounds are well documented in literature [54][55][56][57][58][59], but there are very few reports on the organocatalyzed synthesis of chiral nitrochromenes. Xu et al. [60] in 2008 first reported a novel organocatalytic tandem oxa-Michael–Henry reaction between
- 15:1 dr). In the same year Zhao et al. [70] reported an efficient synthesis of highly functionalized thiochromans having three chiral centers, using a tandem thio-Michael–Henry reaction of 2-mercaptobenzaldehydes 34 with β-nitrostyrenes 46 and using cupreine XXXIXa as catalyst in anhydrous diethyl
- organocatalytic enantioselective domino aza-Michael–Henry reaction of 2-aminobenzaldehydes 54 and aromatic/aliphatic nitro olefins 27, catalyzed by bifunctional thiourea catalyst XXXVIa in benzoic acid, to generate synthetically versatile 3-nitro-1,2-dihydroquinolines 61. Synergistic activation of both reactants
Graphical Abstract
Figure 1: Some representative molecules having chromene, thiochromene or 1,2-dihydroquinolin structural motif...
Figure 2: Screened chiral proline and its derivatives as organocatalysts. Rb = rubidium.
Figure 3: Screened chiral bifunctional thiourea, its derivatives, cinchona alkaloids and other organocatalyst...
Scheme 1: Diarylprolinolether-catalyzed tandem oxa-Michael–aldol reaction reported by Arvidsson.
Scheme 2: Tandem oxa-Michael–aldol reaction developed by Córdova.
Scheme 3: Domino oxa-Michael-aldol reaction developed by Wei and Wang.
Scheme 4: Chiral amine/chiral acid catalyzed tandem oxa-Michael–aldol reaction developed by Xu et al.
Scheme 5: Modified diarylproline ether as amino catalyst in oxa-Michael–aldol reaction as reported by Xu and ...
Scheme 6: Chiral secondary amine promoted oxa-Michael–aldol cascade reactions as reported by Wang and co-work...
Scheme 7: Reaction of salicyl-N-tosylimine with aldehydes by domino oxa-Michael/aza-Baylis–Hillman reaction, ...
Scheme 8: Silyl prolinol ether-catalyzed oxa-Michael–aldol tandem reaction of alkynals with salicylaldehydes ...
Scheme 9: Oxa-Michael–aldol sequence for the synthesis of tetrahydroxanthones developed by Córdova.
Scheme 10: Synthesis of tetrahydroxanthones developed by Xu.
Scheme 11: Diphenylpyrrolinol trimethylsilyl ether catalyzed oxa-Michael–Michael–Michael–aldol reaction for th...
Scheme 12: Enantioselective cascade oxa-Michael–Michael reaction of alkynals with 2-(E)-(2-nitrovinyl)-phenols...
Scheme 13: Domino oxa-Michael–Michael–Michael–aldol reaction of 2-(2-nitrovinyl)-benzene-1,4-diol with α,β-uns...
Scheme 14: Tandem oxa-Michael–Henry reaction catalyzed by organocatalyst and salicylic acid, as reported by Xu....
Scheme 15: Asymmetric synthesis of nitrochromenes from salicylaldehydes and β-nitrostyrene, as reported by San...
Scheme 16: Domino Michael–aldol reaction between salicyaldehydes with β-nitrostyrene, as reported by Das and c...
Scheme 17: Enantioselective synthesis of 2-aryl-3-nitro-2H-chromenes, as reported by Schreiner.
Scheme 18: (S)-diphenylpyrrolinol silyl ether-promoted cascade thio-Michael–aldol reactions, as reported by Wa...
Scheme 19: Organocatalytic asymmetric domino Michael–aldol condensation of mercaptobenzaldehyde and α,β-unsatu...
Scheme 20: Organocatalytic asymmetric domino Michael–aldol condensation between mercaptobenzaldehyde and α,β-u...
Scheme 21: Hydrogen-bond-mediated Michael–aldol reaction of 2-mercaptobenzaldehyde with α,β-unsaturated oxazol...
Scheme 22: Domino Michael–aldol reaction of 2-mercaptobenzaldehydes with maleimides catalyzed by cinchona alka...
Scheme 23: Domino thio-Michael–aldol reaction between 2-mercaptoacetophenone and enals developed by Córdova an...
Scheme 24: Enantioselective tandem Michael–Henry reaction of 2-mercaptobenzaldehyde with β-nitrostyrenes repor...
Scheme 25: Enantioselective tandem Michael–Knoevenagel reaction between 2-mercaptobenzaldehydes and benzyliden...
Scheme 26: Cinchona alkaloid thiourea catalyzed Michael–Michael cascade reaction, as reported by Wang and co-w...
Scheme 27: Domino aza-Michael–aldol reaction between 2-aminobenzaldehydes and α,β-unsaturated aldehydes, as re...
Scheme 28: (S)-Diphenylprolinol TES ether-promoted aza-Michael–aldol cascade reaction, as developed by Wang’s ...
Scheme 29: Domino aza-Michael–aldol reaction reported by Hamada.
Scheme 30: Organocatalytic asymmetric synthesis of 3-nitro-1,2-dihydroquinolines by a dual activation protocol...
Scheme 31: Asymmetric synthesis of 3-nitro-1,2-dihydroquinolines by cascade aza-Michael–Henry–dehydration reac...
Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity
- Tatyana E. Shubina,
- Matthias Freund,
- Sebastian Schenker,
- Timothy Clark and
- Svetlana B. Tsogoeva
Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168
- for its ability to mediate the enantioselective C–C bond-formation reactions. As an initial model transformation we studied the Henry reaction of 3-phenylpropionaldehyde (8) with nitromethane (9) in the presence of 10 mol % of 7, with the reaction proceeding for 48 h at room temperature in toluene
- (m, 1H), 3.44–3.58 (m, 1H), 3.71–3.98 (m, 1H), 4.60 (br s, 4H), 7.22–7.50 (m, 5H) ppm; MS–FAB (m/z): 107, 120, 136, 154, 176, 199, 286, 307, 320 [M + H]+, 376, 391. Henry reaction of 3-phenylpropionaldehyde (8) and nitromethane (9), mediated by 7: 4-Phenyl-1-nitro-2-butanol (10): A solution of 7 (0.1
- ). Bond lengths are in Å. Synthesis of guanidine-thiourea organocatalyst 7. Henry reaction of 3-phenylpropionaldehyde (8) with nitromethane (9). Michael addition of (12) and (14) to trans-β-nitrostyrene (11). Energy profile for the first step of the reaction between catalyst 7 and malonate 14. Energies
Graphical Abstract
Scheme 1: Synthesis of guanidine-thiourea organocatalyst 7.
Scheme 2: Henry reaction of 3-phenylpropionaldehyde (8) with nitromethane (9).
Scheme 3: Michael addition of (12) and (14) to trans-β-nitrostyrene (11).
Figure 1: Optimized geometries of four conformers of catalyst 7. Energies are in kcal·mol−1, B3PW91/6–31G(d) ...
Scheme 4: Energy profile for the first step of the reaction between catalyst 7 and malonate 14. Energies are ...
Figure 2: Complexes (CatN1–CatN5) between catalyst 7 and nitrostyrene 11. Energies are in kcal·mol−1, B3PW91/...
Scheme 5: Two possible routes for ternary complex formation. Energies are in kcal·mol−1, B3PW91/6–31G(d) (fir...
Figure 3: Geometries of transition states for R and S products. Relative energies (with respect to Init10) ar...
Figure 4: Geometries of transition states for R and S products. Relative energies (with respect to Init10) ar...
Figure 5: B3PW91/6–31G(d) (first entry), DFT-PCM (second entry), MP2/6–31G(d)//B3PW91/6–31G(d) (third entry) ...
Figure 6: Geometries of transition states for R and S products with 7-TABD catalyst. Relative energies (to In...
Control over molecular motion using the cis–trans photoisomerization of the azo group
- Estíbaliz Merino and
- María Ribagorda
Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119
- inaccessible. The trans–cis photoisomerization process changes the disposition of the aromatic rings, unlocking access to the basic center of the piperidine. This switch, of Brønsted base type, has been tested in the Henry reaction between p-nitrobenzaldehyde and nitroethane ensuring that only the cis isomer
Graphical Abstract
Figure 1: Photoisomerization process of azobenzene.
Figure 2: Representative example of an UV spectrum of an azocompound of the azobenzene type (blue line: trans...
Figure 3: Mechanistic proposals for the isomerization of azobenzenes.
Figure 4: Representation of the photocontrol of a K+ channel in the cellular membrane based on the isomerizat...
Figure 5: (a) MAG interaction with iGluR; (b) photocontrol of the opening of the ion channel by trans–cis iso...
Figure 6: Photocontrol of the structure of the α-helix in the polypeptide azoderivative 2. Reprinted (adapted...
Figure 7: Recognition of a guanidinium ion by a cis,cis-bis-azo derivative 3.
Figure 8: Recognition of cesium ions by cis-azo derivative 4.
Figure 9: Photocontrolled formation of an inclusion complex of cyclodextrin trans-azo 5+6.
Figure 10: Pseudorotaxane-based molecular machine.
Figure 11: Molecular hinge. Reprinted (adapted) with permission from Org. Lett. 2004, 6, 2595–2598. Copyright ...
Figure 12: Molecular threader. Reprinted (adapted) with permission from Acc. Chem. Res. 2001, 34, 445–455. Cop...
Figure 13: Molecular scissors based on azobenzene 12. Reprinted (adapted) with permission from J. Am. Chem. So...
Figure 14: Molecular pedals. Reprinted by permission from Macmillan Publishers Ltd: Nature, 2006, 440, 512–515...
Figure 15: Design of nanovehicles based on azo structures. Reprinted (adapted) with permission from Org. Lett. ...
Figure 16: Light-activated mesostructured silica nanoparticles (LAMs).
Figure 17: Molecular lift.
Figure 18: Conformational considerations in mono-ortho-substituted azobenzenes.
Scheme 1: Synthesis and photoisomerization of sulfinyl azobenzenes. Reprinted (adapted) with permission from ...
Figure 19: Photoisomerization of azocompound 22 and its application as a photobase catalyst.
Figure 20: Effect of irradiation with linearly polarized light on azo-LCEs. Reprinted by permission from Macmi...
Figure 21: Chemically and photochemically triggered memory switching cycle of the [2]rotaxane 25.
Figure 22: Unidirectional photoisomerization process of the azobenzene 26.
An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals
- Marcus Baumann,
- Ian R. Baxendale,
- Steven V. Ley and
- Nikzad Nikbin
Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57
Graphical Abstract
Figure 1: Structures of atorvastatin and other commercial statins.
Figure 2: Structure of compactin.
Scheme 1: Synthesis of pentasubstituted pyrroles.
Scheme 2: [3 + 2] Cycloaddition to prepare 5-isopropylpyrroles.
Scheme 3: Regiospecific [3 + 2] cycloaddition to prepare the pyrrole scaffold.
Scheme 4: Formation of the pyrrole core of atorvastatin via [3 + 2] cycloaddition.
Scheme 5: Formation of pyrrole 33 via the Paal–Knorr reaction.
Scheme 6: Convergent synthesis towards atorvastatin.
Figure 3: Binding pocket of sunitinib in the TRK KIT.
Scheme 7: Synthesis of sunitinib.
Scheme 8: Alternative synthesis of sunitinib.
Scheme 9: Key steps in the syntheses of sumatriptan and zolmitriptan.
Scheme 10: Introduction of the N,N-dimethylaminoethyl side chain.
Scheme 11: Japp–Klingemann reaction in the synthesis of sumatriptan.
Scheme 12: Synthesis of the intermediate sulfonyl chlorides 62 and 63.
Scheme 13: Alternative introduction of the sulfonamide.
Scheme 14: Negishi-type coupling to benzylic sulfonamides.
Scheme 15: Heck reaction used to introduce the sulfonamide side chain of naratriptan.
Scheme 16: Synthesis of the oxazolinone appendage of zolmitriptan.
Scheme 17: Grandberg indole synthesis used in the preparation of rizatriptan.
Scheme 18: Improved synthesis of rizatriptan.
Scheme 19: Larock-type synthesis of rizatriptan.
Scheme 20: Synthesis of eletriptan.
Scheme 21: Heck coupling for the indole system in eletriptan.
Scheme 22: Attempted Fischer indole synthesis of elatriptan.
Scheme 23: Successful Fischer indole synthesis for eletriptan.
Scheme 24: Mechanistic rationale for the Bischler–Möhlau reaction.
Scheme 25: Bischler-type indole synthesis used in the fluvastatin sodium synthesis.
Scheme 26: Palladium-mediated synthesis of ondansetron.
Scheme 27: Fischer indole synthesis of ondansetron.
Scheme 28: Optimised Pictet–Spengler reaction towards tadalafil.
Figure 4: Structures of carvedilol 136 and propranolol 137.
Scheme 29: Synthesis of the carbazole core of carvedilol.
Scheme 30: Alternative syntheses of 4-hydroxy-9H-carbazole.
Scheme 31: Convergent synthesis of etodolac.
Scheme 32: Alternative synthesis of etodolac.
Figure 5: Structures of imidazole-containing drugs.
Scheme 33: Synthesis of functionalised imidazoles towards losartan.
Scheme 34: Direct synthesis of the chlorinated imidazole in losartan.
Scheme 35: Synthesis of trisubstituted imidazoles.
Scheme 36: Preparation of the imidazole ring in olmesartan.
Scheme 37: Synthesis of ondansetron.
Scheme 38: Alternative route to ondansetron and its analogues.
Scheme 39: Proton pump inhibitors and synthesis of esomeprazole.
Scheme 40: Synthesis of benzimidazole core pantoprazole.
Figure 6: Structure of rabeprazole 194.
Scheme 41: Synthesis of candesartan.
Scheme 42: Alternative access to the candesartan key intermediate 216.
Scheme 43: .Medicinal chemistry route to telmisartan.
Scheme 44: Improved synthesis of telmisartan.
Scheme 45: Synthesis of zolpidem.
Scheme 46: Copper-catalysed 3-component coupling towards zolpidem.
Figure 7: Structure of celecoxib.
Scheme 47: Preparation of celecoxib.
Scheme 48: Alternative synthesis of celecoxib.
Scheme 49: Regioselective access to celecoxib.
Scheme 50: Synthesis of pazopanib.
Scheme 51: Syntheses of anastrozole, rizatriptan and letrozole.
Scheme 52: Regioselective synthesis of anastrozole.
Scheme 53: Triazine-mediated triazole formation towards anastrozole.
Scheme 54: Alternative routes to 1,2,4-triazoles.
Scheme 55: Initial synthetic route to sitagliptin.
Figure 8: Binding of sitagliptin within DPP-IV.
Scheme 56: The process route to sitagliptin key intermediate 280.
Scheme 57: Synthesis of maraviroc.
Scheme 58: Synthesis of alprazolam.
Scheme 59: The use of N-nitrosoamidine derivatives in the preparation of fused benzodiazepines.
Figure 9: Structures of itraconazole, ravuconazole and voriconazole.
Scheme 60: Synthesis of itraconazole.
Scheme 61: Synthesis of rufinamide.
Scheme 62: Representative tetrazole formation in valsartan.
Figure 10: Structure of tetrazole containing olmesartan, candesartan and irbesartan.
Scheme 63: Early stage introduction of the tetrazole in losartan.
Scheme 64: Synthesis of cilostazol.
Figure 11: Structure of cefdinir.
Scheme 65: Semi-synthesis of cefdinir.
Scheme 66: Thiazole syntheses towards ritonavir.
Scheme 67: Synthesis towards pramipexole.
Scheme 68: Alternative route to pramipexole.
Scheme 69: Synthesis of famotidine.
Scheme 70: Efficient synthesis of the hyperuricemic febuxostat.
Scheme 71: Synthesis of ziprasidone.
Figure 12: Structure of mometasone.
Scheme 72: Industrial access to 2-furoic acid present in mometasone.
Scheme 73: Synthesis of ranitidine from furfuryl alcohol.
Scheme 74: Synthesis of nitrofurantoin.
Scheme 75: Synthesis of benzofuran.
Scheme 76: Synthesis of amiodarone.
Scheme 77: Synthesis of raloxifene.
Scheme 78: Alternative access to the benzo[b]thiophene core of raloxifene.
Scheme 79: Gewald reaction in the synthesis of olanzapine.
Scheme 80: Alternative synthesis of olanzapine.
Figure 13: Access to simple thiophene-containing drugs.
Scheme 81: Synthesis of clopidogrel.
Scheme 82: Pictet–Spengler reaction in the preparation of tetrahydrothieno[3,2-c]pyridine (422).
Scheme 83: Alternative synthesis of key intermediate 422.
Figure 14: Co-crystal structures of timolol (left) and carazolol (right) in the β-adrenergic receptor.
Scheme 84: Synthesis of timolol.
Scheme 85: Synthesis of tizanidine 440.
Scheme 86: Synthesis of leflunomide.
Scheme 87: Synthesis of sulfamethoxazole.
Scheme 88: Synthesis of risperidone.
Figure 15: Relative abundance of selected transformations.
Figure 16: The abundance of heterocycles within top 200 drugs (5-membered rings).
Continuous flow based catch and release protocol for the synthesis of α-ketoesters
- Alessandro Palmieri,
- Steven V. Ley,
- Anastasios Polyzos,
- Mark Ladlow and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2009, 5, No. 23, doi:10.3762/bjoc.5.23
- first reported example of Henry reaction conducted in flow and we intend to elaborate on this important transformation in future studies. Figure 2 illustrates the examples and yields of α-ketoester products afforded by this new approach. While the list is not extensive, we have established that the
Graphical Abstract
Figure 1: The Uniqsis FlowSyn™ continuous flow reactor comprising of a column holder and heating unit (A) and...
Scheme 1: General procedure for the flow synthesis of α-ketoester products 4a–j.
Scheme 2: General procedure for the batch synthesis of nitroolefinic esters 1a–j.
Scheme 3: General procedure for the flow synthesis of nitroolefinic esters 1a,c.
Figure 2: α-Ketoesters prepared and isolated yields.
