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Synthesis of 2-oxazolines

Recent Literature

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.

A Mo(VI) dioxide complex stabilized by substituted picolinic acid ligands catalyzes an effective and practical oxazoline and thiazoline formation, which can facilitate the synthesis of natural products, chiral ligands, and pharmaceutical intermediates. This method tolerates a broad range of functional groups.
G. E. Evenson, W. C. Powell, A. B. Hinds, M. A. Walczak, J. Org. Chem., 2023, 88, 6192-6202.

Low loadings of a 1,3,5,2,4,6-triazatriphosphorine (TAP)-derived organocatalyst promote a metal-free, biomimetic cyclization of N-(2-hydroxyethyl)amides to the corresponding 2-oxazolines in very good yields. This dehydrative cyclization exhibits a broad substrate scope and high functional-group tolerance can can be conducted on a gram scale.
F. S. Movahed, S. W. Foo, S. Mori, S. Ogawa, S. Saito, J. Org. Chem., 2022, 87, 243-257.

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.

Methods for the regiodivergent aminooxygenation of aryl olefins under electrophotocatalytic conditions employ a trisaminocyclopropenium ion catalyst with visible light irradiation under a controlled electrochemical potential to provide oxazolines with high chemo- and diastereoselectivity. With the choice between water and urethane, either 2-amino-1-ol or 1-amino-2-ol derivatives can be prepared.
H. Huang, T. H. Lambert, J. Am. Chem. Soc., 2022, 144, 18803-18809.

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 chiral triazole-substituted iodoarene catalyzes an enantioselective oxidative cyclization of N-allyl carboxamides to provide highly enantioenriched oxazolines and oxazines. Quaternary stereocenters can be constructed and, besides N-allyl amides, the corresponding thioamides and imideamides are well tolerated as substrates.
A. H. Abazid, T.-N. Hollwedel, B. J. Nachtsheim, Org. Lett., 2021, 23, 5076-5080.

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.

Using a simple catalytic electrosynthetic protocol, an in situ generated hypervalent iodine species eliminates chemical oxidants and the inevitable chemical waste associated with their mode of action. The developed method has been used for syntheses of dihydrooxazole and dihydro-1,3-oxazine derivatives, and the α-tosyloxylation of ketones.
M. Elsherbini, W. J. Moran, J. Org. Chem., 2023, 88, 1424-1433.