Synthesis of 2-oxazolines
Various aromatic and aliphatic aldehydes were converted into the corresponding 2-aryl and 2-alkyl-2-oxazolines, respectively, in good yields by reaction with 2-aminoethanol and 1,3-diiodo-5,5-dimethylhydantoin.
S. Takahashi, H. Togo, Synthesis, 2009, 2329-2332.
Various 2-oxazolines were prepared from aromatic aldehydes and 2-aminoethanol with pyridinium hydrobromide perbromide in water at room temperature. The reaction of aromatic aldehydes with ethylenediamine gave 2-imidazolines in good yields under the same reaction conditions.
S. Sayama, Synlett, 2006, 1479-1484.
The synthesis of various 2-(hetero)aryloxazolines from nitriles and aminoalcohols has been achieved without metals and catalysts in good to excellent yields. The reaction tolerates many functional groups and allows the introduction of many important biologically active motifs such as azoles, ring-fused azoles, saturated heterocyclics, and amines.
P. Garg, S. Chaudhary, M. D. Milton, J. Org. Chem., 2014, 79, 8668-8677.
Using copper-NHC complexes, the reaction of nitriles with aminoalcohols provided 2-substituted oxazolines under milder and less wasteful conditions than those of previously reported methods.
M. Trose, F. Lazreg, M. Lesieur, C. S. J. Cazin, J. Org. Chem., 2015, 80, 9910-9914.
Transamidation of thioamides with 2-aminoethanol, followed by cyclodehydrosulfurisation of the resultant N-(β-hydroxyethyl)thioamides, enables a mild and efficient synthesis of 2-oxazolines.
D. R. Goud, U. Pathak, Synthesis, 2012, 44, 3678-3682.
Efficient and convenient three-component couplings of aryl halides, amino alcohols and tert-butyl isocyanide under palladium catalysis provide a range of oxazolines in excellent yield. The use of 1,2-amino phenols instead of amino alcohols enables the synthesis of benzoxazoles.
P. J. Boissarie, Z. E. Hamilton, S. Lang, J. A. Murphy, C. J. Suckling, Org. Lett., 2011, 13, 6184-6187.
A mild reaction of α,α-difluoroalkyl amines with β-amino alcohols, β-amino thiols, and β-diamines affords the corresponding oxazoline, thiazoline, and imidazoline derivatives, respectively. The conditions are applicable for the synthesis of optically active heterocyclic compounds.
T. Fukuhara, C. Hasegawa, S. Hara, Synthesis, 2007, 1528-1534.
DAST and Deoxo-Fluor reagents enable a mild and highly efficient cyclization of β-hydroxy amides to oxazolines. A one-pot protocol for the synthesis of oxazoles from β-hydroxy amides is also presented.
A. J. Philipps, Y. Uto, P. Wipf, M. J. Reno, D. R. Williams, Org. Lett., 2000, 2, 1165-1168.
Re2O7 in hexafluoroisopropyl alcohol provides access to cationic intermediates from alcohols through the intermediacy of perrhenate esters. This system can be applied to the formation of a number of weakly basic heterocyclic systems through dehydration reactions and intramolecular nucleophilic addition.
F. O. R. del Rey, P. E. Floreancig, Org. Lett., 2021, 23, 150-154.
Polyphosphoric acid (PPA) esters promote a microwave-assisted procedure for the synthesis of 5- to 7-membered cyclic iminoethers from amido alcohols. 2-Aryl-2-oxazolines and 5,6-dihydro-4H-1,3-oxazines were efficiently prepared using ethyl polyphosphate/CHCl3 in very good yields and short reaction time. Trimethylsilyl polyphosphate under solvent-free conditions enables the synthesis of 4,5,6,7-tetrahydro-1,3-oxazepines.
M. C. Mollo, L. R. Orelli, Org. Lett., 2016, 18, 6116-6119.
ZnI2 and FeCl3 mediate a direct approach to the selective and regiocontrolled synthesis of 2-oxazolines and 2-oxazoles in very good yields under mild reaction conditions by cyclization of acetylenic amides. Various functionalities were well tolerated.
G. C. Senadi, W.-P. Hu, J.-S. Hsiao, J. K. Vandavasi, C.-Y. Chen, J.-J. Wang, Org. Lett., 2012, 14, 4478-4481.
A series of propargylic amides were transformed to the corresponding alkylideneoxazolines by a gold(I) catalyst. A subsequent autoxidation to hydroperoxides bearing the heteroaromatic oxazoles followed by reduction to the corresponding alcohols with sodium borohydride enables a highly efficient, and atom-economic access to a series of functionalized 2,5-disubstituted oxazoles.
A. S. K. Hashmi, M. C. B. Jaimes, A. M. Schuster, F. Rominger, J. Org. Chem., 2012, 77, 6394-6408.
I2-catalyzed C-O bond formation and dehydrogenation with TBHP enables a general method for the synthesis of oxazolines and oxazoles from β-acylamino ketones. Depending on the base, either oxazolines or oxazoles were selectively produced.
W.-C. Gao, F. Hu, Y.-M. Huo, H.-H. Chang, X. Li, W.-L. Wei, Org. Lett., 2015, 17, 3914-3917.
An electrochemically intramolecular functionalization of C(sp3)-H bonds with masked oxygen nucleophiles provides diverse trisubstituted 2-oxazolines in good to excellent yields. This electrochemical dehydrogenative approach in the presence of KI as the catalyst and electrolyte features external oxidant-free conditions.
H. Wang, J. Zhang, J. Tan, L. Xin, Y. Li, S. Zhang, K. Xu, Org. Lett., 2018, 20, 2505-2508.
Substituted 2-oxazolines, that are found in several families of bioactive natural products, can be prepared in an efficient and general one-pot, four-component condensation.
L. Fan, E. Lobkovsky, B. Ganem, Org. Lett., 2007, 9, 2015-2017.
New methodology for the synthesis of variously substituted 2-oxazolines and one dihydrooxazine using aldehydes, amino alcohols, and N-bromosuccinimide as an oxidizing agent is described. This one-pot synthesis is characterized by mild reaction conditions, broad scope, high yields, and its preparative simplicity.
K. Schwekendiek, F. Glorius, Synthesis, 2006, 2996-3002.
Intramolecular halooxygenation and halothionation of N-allylcarboxamides/N-allylcarbothioamides proceeded readily in the presence of (diacetoxyiodo)benzene (PIDA) as the reaction promoter and halotrimethylsilane as the halogen source, providing the corresponding 5-halomethyloxazolines/5-halomethylthiazolines in very good yields. The 5-halomethyl products could be converted to different derivatives via nucleophilic substitution.
G.-Q. Liu, C.-H. Yang, Y.-M. Li, J. Org. Chem., 2015, 80, 11339-113550.
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.
A cyclization of N-alkenylamides catalyzed by iodoarenes under oxidative conditions enables the preparation of five-, six-, and seven-membered rings with a range of substitutions. Preliminary data from the use of chiral iodoarenes as precatalysts show that enantiocontrol is feasible.
A. Alhalib, S. Kamouka, W. J. Moran, Org. Lett., 2015, 17, 1453-1456.