Synthesis of N-Heterocycles
| Synthesis of | ||||||
 Cyclic amines |
 Lactams |
 Imidazolidones |
 Oxazolidinones and Derivatives |
 Hydantoins |
 Urazoles |
 Sultams |
 3-Pyrrolines |
 2-Isoxazolines |
 2-Oxazolines |
 2-Imidazolines |
|||
 Pyrroles |
 Imidazoles Benzimidazoles |
 Pyrazoles |
 1,2,3-Triazoles |
 1,2,4-Triazoles |
 Tetrazoles |
|
 Oxazoles Benzoxazoles |
 Isoxazoles |
 Thiazoles Benzothiazoles |
 1,3,4- Oxadiazoles |
 1,2,4- Oxadiazoles |
 1,3,4- Thiadiazoles |
Related: |
 Indoles |
 Carbazoles |
 Oxindoles |
 Indolines |
|||
 Azaindoles |
 Indolizines |
|||||
 Dihydro- pyridines |
 Pyridines, and rel. comp. |
 Quinolines and rel. comp. |
 1,8- Naphthyridines |
 Pyrimidines and rel. comp. |
 1,3,5-Triazines |
|
Name Reactions
Recent Literature
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.
A chiral Ti(IV) catalyst can be successfully utilized in the asymmetric
1,3-dipolar cycloaddition reactions between various nitrones and acrolein to
give the corresponding endo cycloadducts (isoxazolidines) with high to
excellent enantioselectivities.
T. Kano, T. Hashimoto, K. Maruoka, J. Am. Chem. Soc., 2005, 70, 11926-11927.
[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.
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.
Upon treatment with aqueous sodium hydroxide in DMF, a range of chalcones
underwent Michael addition reactions with nitroalkanes. The resulting
adducts were reduced in situ with Zn/HCl (aq) to afford substituted Δ1-pyrrolines
in high yields after a cyclization.
Y. Liang, D. Dong, Y. Lu, Y. Wang, W. Pan, Y. Chai, Q. Liu, Synthesis, 2006, 3301-3304.
The dehydration of primary nitro compounds can be performed by bases in the
presence of dipolarophiles. Among the organic bases examined, DABCO gave the
best results. The reaction is applicable to activated nitro compounds and to
phenylnitromethane and affords isoxazoline derivatives in higher yields
compared with those of other methods. The reaction, however, is not
compatible with nitroalkanes.
L. Cecchi, F. De Sarlo, F. Machetti, Eur. J. Org. Chem., 2006,
4852-4860.
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.
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.
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.
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 one-pot synthesis of nitrogen-containing heterocycles from alkyl dihalides
and primary amines and hydrazines occurs under microwave irradiation via a
simple and efficient cyclocondensation in an alkaline aqueous medium.
Y. Ju, R. S. Varma, J. Org. Chem., 2006, 71, 135-141.
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.
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 aza Diels-Alder reaction of an in situ generated novel iododiene works
well with aryl- and benzyl-N-substituted imines. Moderate
diastereoselectivities can be obtained using simple α-methylbenzyl chiral
imines.
C. Timmons, A. Kattuboina, L. McPherson, J. Mills, G. Li, Tetrahedron, 2005,
61, 11837-11842.
Imidazolinium salts are
capable of catalysing an aza-Diels-Alder reaction with a range of imines and
Danishefsky's diene, leading to the desired products in good to excellent yields.
V. Jurcik, R. Wilhelm, Org. Biomol. Chem., 2005, 3, 239-244.
The use of cationic silver (AgSbF4) as a catalyst for intra- and
intermolecular alkyne-carbonyl coupling is described.
J. U. Rhee, M. J. Krische, Org. Lett., 2005, 7, 2493-2495.
Intermolecular [2 + 2 + 1] ruthenium-catalyzed cocyclization of isocyanates,
alkynes, and CO proceeded smoothly mesitylene at 130°C to give a variety of
polysubstituted maleimides in excellent yields with high selectivity.
T. Kondo, M. Nomura, Y. Ura, K. Wada, T. Mitsudo, J. Am. Chem. Soc., 2006, 128, 14816-14817.
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.
A mild ICl-induced cyclization of heteroatom-substituted alkynones provides
a simple, highly efficient approach to various 3-iodochromones,
iodothiochromenones, iodoquinolinones and analogues in good to excellent
yields. Subsequent palladium-catalyzed transformations afford a rapid
increase in molecular complexity.
C. Zhou, A. V. Dubrovsky, R. C. Larock, J. Org. Chem., 2006, 71, 1728-1731.
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.
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 chiral BINOL-derived phosphoric acid diester catalyzed an inverse
electron-demand aza Diels-Alder reaction of aldimine with enol ethers to give
tetrahydroquinoline derivatives with excellent enantioselectivity.
T. Akiyama, H. Morita, K. Fuchibe, J. Am. Chem. Soc., 2006, 128, 13070-13071.
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.
A three-component condensation gave
2-amino-4H-1,3-oxazines or 2-amino-4H-1,3-thiazines from alkynes, urea or
thiourea, and aldehydes.
S. Huang, Y. Pan, Y. Zhu, A. Wu, Org. Lett., 2005, 7, 3797-3799.
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.
S. Huang, Y. Pan, Y. Zhu, A. Wu, Org. Lett., 2005, 7, 3797-3799.
