Synthesis of N-Heterocycles
A high-yielding, asymmetric synthesis of novel 4-formyl-1-(2- and 3-haloalkyl)azetidin-2-ones was developed as valuable starting materials for the synthesis of different enantiomerically enriched bicyclic azetidin-2-ones, such as piperazine, morpholine, and 1,4-diazepane annulated β-lactam derivatives.
W. Van Brabandt, M. Vanwalleghem, M. D'hooghe, N. De Kimpe, J. Org. Chem., 2006, 71, 7083-7086.
Bisphosphine-catalyzed mixed double-Michael reactions between amino-acid-derived pronucleophiles as Michael donors and electron-deficient acetylenes as acceptors afford β-amino carbonyl derivatives of oxazolidines, thiozolidines, and pyrrolidines in excellent yields and with high diastereoselectivities under operationally simple and mild conditions.
V. Sriramurthy, G. A. Barcan, O. Kwon, J. Am. Chem. Soc., 2007, 129, 12928-12929.
A simple, commercially available iridium catalyst allows the use of sulfoxonium ylides as a carbene source for various intra- and intermolecular X-H bond insertions, including a practical ring-expansion strategy for lactams. The safety and stability of sulfoxonium ylides recommend them as preferable surrogates to traditional diazo ketones and esters.
I. K. Mangion, I. K. Nwamba, M. Shevlin, M. A. Huffman, Org. Lett., 2009, 11, 3566-3569.
[RuCl2(CO)3]2/dppp is a highly effective catalyst system for the intramolecular oxidative amination of various aminoalkenes in presence of K2CO3 and allyl acetate in N-methylpiperidine to give the corresponding cyclic imines and indoles in excellent yields.
T. Kondo, T. Okada, T.-A. Mitsudo, J. Am. Chem. Soc., 2002, 124, 186-187.
An efficient chiral Lewis acid-catalyzed inverse-electron-demand Diels-Alder reaction of N-sulfonyl 1-aza-1,3-dienes is based on the combination of Ni(II)-DBFOX complex as catalyst and the use of a metal-coordinating (8-quinolyl)sulfonyl moiety. The reaction provides highly functionalized piperidine derivatives in good yields with excellent endo-selectivity, and good enantioselectivities.
J. Esquivias, R. G. Arrays, J. C. Carretero, J. Am. Chem. Soc., 2007, 129, 1480-1481.
A wide screening of substrates in ring-closing metathesis reactions reveals the great efficiency of phosphabicyclononane (phoban)-containing ruthenium-based pre-catalysts. Comparison of the catalytic activities with Grubbs' first-generation pre-catalyst illustrates the key role of the Phoban ligand.
F. Boeda, H. Clavier, M. Jordaan, W. H. Meyer, S. P. Nolan, J. Org. Chem., 2008, 73, 259-263.
Aminocarbonyl Group Containing Hoveyda-Grubbs-Type Complexes: Synthesis and Activity in Olefin Metathesis Transformations
D. Rix, F. Caijo, I. Laurent, F. Boeda, H. Clavier, S. P. Nolan, M. Mauduit, J. Org. Chem., 2008, 73, 4225-4228.
Δ3-Aryl/heteroaryl substituted heterocycles via sequential Pd-catalysed termolecular cascade/ring closing metathesis (RCM)
H. A. Dondas, B. Clique, B. Cetinkaya, R. Grigg, C. Kilner, J. Morris, V. Sridharan, Tetrahedron, 2005, 61, 10652-10666.
Organic phosphine-catalyzed [4 + 2] annulation of ethyl 2-(substituted-methyl)-2,3-butadienoates as 1,4-dipole synthons with N-tosylimines gave ethyl 2,6-cis-disubstituted-1-(4-tosyl)-1,2,5,6-tetrahydro-pyridine-3-carboxylates in excellent yields with complete regioselectivity and high diastereoselectivity.
X.-F. Zhu, J. Lan, O. Kwon, J. Am. Chem. Soc., 2003, 125, 4716-4717.
Fully substituted 4-aminopyrrolones are easily accessed starting from imines, ketones, or α-bromophenyl acetonitriles. Imines are reacted with KCN/NH4Cl, whereas ketones are transformed to the desired α-amino nitriles using a modified Strecker reaction. Reaction with a suitable acyl halide produces the corresponding amides. Ttreatment of these amides with ethanolic KOH gives 4-amino-1H-pyrrol-2(5H)-one derivatives in good yields.
H. Zali-Boeini, M. Mobin, K. Hajibabaei, M. Ghani, J. Org. Chem., 2012, 77, 5808-5812.
Pentafluorophenyl anion and trifluoromethyl anion as leaving groups enable a new synthesis of 1,2,4-oxadiazol-5-ones from amidoximes using pentafluorobenzoyl chloride or trifluoroacetic anhydride (TFAA) as a double acylating agent.
T. Gerfaud, H.-L. Wei, L. Neuville, J. Zhu, Org. Lett., 2011, 13, 6172-6175.
A reaction between N-benzylideneanilines and Danishefsky's diene proceeds smoothly in acidic aqueous medium in the presence of a catalytic amount of copper(II) triflate and sodium dodecyl sulfate to afford the corresponding 1,2-diphenyl-2,3-dihydro-4-pyridones in excellent yields. The aqueous solution containing the catalyst can be recovered and reused without any loss in efficiency.
D. Lanari, O. Piermatti, F. Pizzo, L. Vaccaro, Synthesis, 2012, 2181-2184.
Ring-closing olefin metathesis (RCM)/elimination and RCM/oxidation/deprotection of nitrogen-containing dienes are the key processes of new synthetic routes to substituted 3-hydroxypyridines. An application of RCM/oxidation/deprotection allows the synthesis of 3-aminopyridine derivatives.
K. Yoshida, F. Kawagoe, K. Hayashi, S. Horiuchi, T. Imamoto, A. Yanagisawa, Org. Lett., 2009, 11, 515-518.
Acid-catalysed intramolecular hydroamination of 2-alkenylarylethylamine derivatives gives smoothly isoindolines via benzylic carbenium ion generation.
L. Henderson, D. W. Knight, A. C. Williams, Synlett, 2012, 1667-1669.
Various N-substituted isoindolinones can be synthesized in excellent yields through the reductive C-N coupling and intramolecular amidation of 2-carboxybenzaldehyde with amines in the presence of ultrathin Pt nanowires as catalysts under 1 bar of hydrogen. These unsupported catalysts can also be used for the synthesis of phthalazinones in high yield when hydrazine or phenyl hydrazine is used instead of amines.
L. Shi, L. Hu, J. Wang, X. Cao, H. Gu, Org. Lett., 2012, 14, 1876-1879.
A one-pot strategy allows the synthesis of phthalazines and pyridazino-aromatics starting from aromatic aldehydes. A variety of substituents ranging from electron withdrawing to donating is tolerated furnishing the desired 1,2-diazine in good to excellent yields. A subsequent bidentate Lewis acid catalyzed inverse electron-demand Diels-Alder (IEDDA) reaction opens a novel two-step entry into substituted naphthalenes, such as Naproxen.
S. N. Kessler, H. A. Wegner, Org. Lett., 2012, 14, 3268-3271.
Iodine-mediated intramolecular cyclization of enamines leads to a various 3H-indole derivatives bearing multifunctional groups in good to high yields under transition metal-free reaction conditions.
Z. He, H. Li, Z. Li, J. Org. Chem., 2010, 75, 4296-4299.
Rhodium(II) perfluorobutyrate-mediated decomposition of vinyl azides allows rapid access to a variety of complex, functionalized N-heterocycles in two steps from commercially available starting materials.
B. J. Stokes, H. Dong, B. E. Leslie, A. L. Pumphrey, T. G. Driver, J. Am. Chem. Soc., 2007, 129, 7500-7501.
Sequential coupling-imination-annulation reactions of ortho-bromoarylaldehydes and terminal alkynes with ammonium acetate in the presence of a palladium catalyst under microwave irradiation gives various substituted isoquinolines, furopyridines, and thienopyridines in good yields.
D. Yang, S. Burugupalli, D. Daniel, Y. Chen, J. Org. Chem., 2012, 77, 4466-4472.
Fused bicyclic imidazole rings have been prepared in good yields by a sequence of the van Leusen three-component reaction and the ring-closing metathesis reaction.
V. Gracias, A. F. Gasiecki, S. W. Djuric, Org. Lett., 2005, 7, 3183-3186.
An efficient and convenient synthesis of [1,2,4]triazolo[4,3-a]pyridines involves a palladium-catalyzed addition of hydrazides to 2-chloropyridine, which occurs chemoselectively at the terminal nitrogen atom of the hydrazide, followed by dehydration in acetic acid under microwave irradiation.
A. Reichelt, J. R. Falsey, R. M. Rzasa, O. R. Thiel, M. M. Achmatowicz, R. D. Larsen, D. Zhang, Org. Lett., 2010, 12, 792-795.
In a regioselective and high-yielding Groebke-Blackburn-Bienaymé reaction, glyoxylic acid is used as formaldehyde equivalent leading to a regioselective, mild, convenient, and effective synthesis of 3-aminoalkyl imidazoazines.
A. Sharma, H.-y. Li, Synlett, 2011, 1407-1412.
A rhodium-catalyzed cycloisomerization converts various acyclic enynes to their cyclic diene isomers with endoselectivity. Two different catalyst systems have been developed, which are effective in promoting the C-C bond-forming cyclization of enynes to furnish carbo- and heterocycles in good to excellent yield. The mechanism is discussed.
H. Kim, C. Lee, J. Am. Chem. Soc., 2005, 127, 10180-10181.
A solvent- and metal-free regioselective cyclization affords 1,4-oxazine and 1,4-oxazepine derivatives as exo-dig products. Substrates for the cyclization step can be produced in a highly diastereomeric fashion by Grignard reaction as key synthetic step following Cram’s rule.
J. K. Vandavasi, W.-P. Hu, H.-Y. Chen, G. C. Senadi, C.-Y. Chen, J.-J. Wang, Org. Lett., 2012, 14, 3134-3137.
An Au-catalyzed synthesis of fused pyrroloheterocycles from diverse propargyl-substituted heterocycles proceeds via alkyne-vinylidene isomerization with concomitant 1,2-shift of hydrogen, silyl, and stannyl groups. This method allows for mild and efficient synthesis of diverse C-2 substituted N-heterocycles.
I. V. Seregin, V. Gevorgyan, J. Am. Chem. Soc., 2006, 128, 12050-12051.
[1,2,4]Triazolo[1,5-a]pyridines have been prepared in good yields from 2-aminopyridines by cyclization of N-(pyrid-2-yl)formamidoximes under mild reaction conditions with trifluoroacetic anhydride.
E. Huntsman, J. Balsells, Eur. J. Org. Chem., 2005, 3761-3765.
Pyridine N-oxides were converted to tetrazolo[1,5-a]pyridines in good yield in the presence of sulfonyl or phosphoryl azides and pyridine by heating in the absence of solvent. Diphenyl phosphorazidate (DPPA) was the most convenient reagent.
J. M. Keith, J. Org. Chem., 2006, 71, 9540-9543.
An efficient three-component coupling reaction of substituted picolinaldehydes, amines, and formaldehyde produces imidazo[1,5-a]pyridinium ions in high yields under mild conditions, allowing the incorporation of diverse functionality and chiral substituents. Higher order condensations are also described that provide access to multidentate NHC ligands useful for a variety of applications.
J. T. Hutt, Z. D. Aron, Org. Lett., 2011, 13, 5256-5259.
Starting from readily available o-mercaptoacylphenones, a mild S-nitrosation and a subsequent intramolecular aza-Wittig reaction lead to the construction of 3-substituted benzisothiazoles.
N. O. Devarie-Baez, M. Xian, Org. Lett., 2010, 12, 752-754.
The use of N,N′-bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene (SIPr) as a ligand and tBuONa as the base for sequential palladium-catalyzed intra- followed by intermolecular aryl amination enables the synthesis of N-arylated five-, six- and seven-membered nitrogen heterocycles.
R. Omar-Amrani, R. Schneider, Y. Fort, Synthesis, 2004, 2257-2534.
A regioselective one-pot synthesis of 2-alkyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazines under microwave heating starts from commercially available 2-aminophenols. Base-mediated regioselective O-alkylation with 2-bromoalkanoates gives acyclic intermediates. A subsequent intramolecular amidation reaction furnishes the desired products in good yields.
W.-M. Dai, X. Wang, C. Ma, Tetrahedron, 2005, 61, 6879-6885.
The use of a readily available Sc(III)-inda-pybox as the catalyst enabled an enantioselective synthesis of 2,3-dihydroquinazolinones (DHQZs) via a metal catalyzed asymmetric intramolecular amidation of an imine.
M. Prakash, V. Kesavan, Org. Lett., 2012, 14, 1896-1899.
An effective route to novel 5-hydroxy-1,5-dihydro-2H-pyrrol-2-one is described which involves the reaction of an enamine, derived from addition of a secondary amine to dibenzoylacetylene, with an arylsulfonyl isocyanate.
A. Alizadeh, F. Movahedi, H. Masrouri, L.-G. Zhu, Synthesis, 2006, 3431-3436.
Trialkylsilyl triflates effect cyclization of ester-imides and diesters. Trapping of the in situ generated, nucleophilic ketene acetal is a key aspect of the transformation. In many instances the levels of diastereoselectivity are very high. Mechanistic points are inferred from spectroscopic observations.
T. R. Hoye, V. Dvornikovs, E. Sizova, Org. Lett., 2006, 8, 5089-5091.
A tandem palladium-catalyzed arylation-ester amidation sequence allows the synthesis of various quinazolinedione products by reaction of o-halo benzoates with monoalkyl ureas. The reactions are regioselective for the formation of 3-N-alkyl isomers.
M. C. Willis, R. H. Snell, A. J. Fletcher, R. L. Woodward, Org. Lett., 2006, 8, 5089-5091.
A convenient environmentally friendly method for the cyclization of 2-aminochalcones to 2-aryl-2,3-dihydroquinolin-4(1H)-ones on the surface of silica gel impregnated with indium(III) chloride under microwave irradiation without any solvent has been reported.
K. H. Kumar, D. Muralidharan, P. T. Perumal, Synthesis, 2004, 63-68.
The reaction of o-haloaniline derivatives and carbon disulfide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene at 80-140˚C provides the corresponding 1,3-benzothiazole-2(3H)-thione derivatives in good yields.
Y. Fu, X. Hu, Y. Chen, Y. Yang, H. Hou, Y. Hu, Synthesis, 2012, 1477-1480.
tert-Butyl hypoiodite is a mild and powerful reagent for the cyclization of N-alkenylamides leading to various N-heterocycles. N-alkenylsulfonamides gave three- to six-membered saturated N-heterocycles in good yields, whereas alkenylbenzamide derivatives afforded N-, O- or N-, S-heterocycles.
S. Minakata, Y. Morino, Y. Oderaotoshi, M. Komatsu, Org. Lett., 2006, 8, 3335-3337.