Oxazoline thioureas

Electron-deficient oxazoline thiourea 222 turned out to be the most effective catalyst concerning activity (93% yield/48h/THF) and asymmetric induction (88% ee/rt) in contrast to 218-221, which gave poor results (Figure 6.62). The solvent screening revealed aprotic THF to be the solvent of choice, while polar prohc... 

Figure 6.62 Oxazoline-thioureas screened in the aza-Henry reaction of N-Boc-protected benzaldimine with nitromethane.

Scheme 6.183 Proposed bifunctional activation mode of oxazoline-thiourea catalyst 222.

In contrast to the above additions A-allyl- and substituted A-allyl-amides, -urethanes, -ureas and -thioureas undergo intramolecular cyclization only in 6(3-96% sulfuric acid to give the corresponding oxazolinium and thiazolinium salts. Treatment of these cations with base yields 2-oxazolines and 2-thiazolines in moderate to good yields. The reaction is illustrated by the conversion of A-2-phenylallylacetamide (342) into 2,5-dimethyl-5-phenyl-2-oxazoline (343) in 70% yield 70JOC3768) (see also Chapter 4.19). 

Whereas the use of 1,3-dicyclohexylcarbodiimide affords 1,3-oxazolines from the 7V-(2-hydroxyethyl)thioureas (Scheme 62).146 148... 

Since 1980 the interest in this reaction increased because enantiospecificity was introduced and much more valuable products could be made. A wide variety of ligands was tested, such as chiral dipyridines, phenanthrolines, diphosphines, aminoalcohols, bis-oxazolines, bis-oxazolines with a third donor atom in the centre, bis-thioureas, diamines, etc [33], In 1981 the highest e.e. reported was still only 20%. For many years the best results were obtained with chiral diimines and phenanthrolines but e.e. s were below 70% [34], Pfaltz introduced bis-oxazolines for this reaction and obtained e.e. s as high as 91% [35] in 1991. 

One Nitrogen Atom and One Oxygen Atom Substituted 2-amino-2-oxazolines (88) have been prepared by a number of workers from l-(2-hydroxyethyl)-2-thioureas (87). These... 

Toward a complete synthesis of trehazolin (2), 2,3,4,6-tetra-O-benzyl-1 -deoxy-z-D-glucopyranosyl isothiocyanate (7)52 was brought into reaction with the amines 5 and 374 in the presence of triethylamine to afford the x-D-glucopyranosyl thiourea derivatives 375 or 376, respectively (Scheme 46).38 Subsequent treatment with 2-chloro-3-ethylbenzoxazolium tetrafluoroborate and triethylamine afforded the corresponding amino oxazoline derivatives 377 and 378. Finally, hydrogenation over Pd(OH)2 on carbon afforded trehazolin (2). 

Hydrolysis of the oxazolidinone 236 gave the corresponding amino alcohol, which without isolation was coupled with the sugar 4-isothiocyanate 2653 to provide the thiourea 452 (Scheme 67).105 Cyclization of 452 to the isourea 453 was carried out with yellow mercuric oxide, and the resulting oxazoline 453 was debenzylated to give... 

N-(/3-hydroxy)amides are cyclized with DIPCD in the presence of a catalytic amount of Cu(OTf)2 to give 2-oxazolines. Similarly, N-(2-hydroxyethyl)thioamides and N-(2-hydroxyethyl)thioureas are converted with DCC in refluxing acetonitrile to give 2-oxazolines in 88-94% yield." Benzo-fused heterocycles 465 ( = 0,1,2) are obtained from the thiourea derivatives 464 and DCC (Yields 81-92%)... 

The chiral catalysts that have been used in nitroaUcene conjugate additions include bw-oxazolines with Cu(OTF)2 [281] or Zn(OTf)2 [282], tridentate bw-oxazolines with Zn(OTf)2 [283], mixed thiazoline-oxazolines with Zn(OTf)2 [284], imidazoUne-aminophenols with CuOTf [285], bis-trifluoromethylsulfonamides [286], binaphthyl sulfonamides [287], binaphthyl imines [288], thioureas [289], and quinoUnyl thioureas [290]. A BINOL-phosphoric acid with 3A molecular sieves gave ee values consistently at 90% and above with both p-alkyl and p-aryl nitroalkenes [291]. 

The reaction of thioureas with nucleophiles has been only sparsely studied in the past. Guanidines have been prepared by treatment of corresponding thioureas with propylamine in the presence of lead oxide, and thioureas with a hydroxy-group at the / -position of the N-substituent have been cyclized to oxazolines by refluxing in ethanol in the presence of cupric acetate. The latter reaction was shown to proceed via an intermediate copper complex. ... 

Synthesis from Thioamides and Related Compounds. Type B, CgHs—N-—C—S.) The action of a large excess of thionyl chloride on substituted thioureas of type (22) (incorporating a jS-hydroxy-group in their Aralkyl group) produces 2-aminobenzothiazole derivatives (23) preferentially, rather than thiazolines (24) or oxazolines. Thionyl chloride, like sulphuryl... 

On the other hand, another cooperative catalysis approach was developed by Oh and Kim with a highly diastereo- and enantioselective domino aldol-cyclisation reaction occurring between aldehydes and methyl a-isocyanoacetate. The process employed a combination of a chiral cobalt complex derived from brucine amino diol and an achiral thiourea. The reaction was applicable to a range of aliphatic, aromatic and heteroaromatic aldehydes, providing the corresponding chiral oxazolines in good yields and diastereoselectivities of up to >90% de combined with good to excellent enantioselectivities of up to 98% ee, as shown in Scheme 7.12. 

The synthesis and reactions of l,2-dideoxy-hexopyrano[2,l-d]oxazolines and oxazolinium salts have been reviewed. Acid-catalysed cyclisations of N-(glycos-2-yl)-urea and -thiourea derivatives have provided imidazolin-2-one and 2-thiazoline derivatives, e g. (76)-(78). 

Imidazolidines are quite common species, and may be prepared in numerous ways, for example by treatment of a guanidine amidine-thiourea with a 1,2-di-iminium species, or reaction of metallated isocyanides with nitrones, or even by thermolysis of 3-oxazolin-5-ones. The most novel preparation of imidazolidines in 1980 has surely been the work of Coyle et on the... 

Heck Reactions. The Heck reaction is a Pd-catalyzed olefi-nation usually performed between an aryl halide or triflate and an acrylate ester. While phosphines are traditionally used as ancillary ligands, new Pd(dba)2-mediated reactions have been performed with a variety of other ligand types. These include chelating Wheterocyclic carbene/phosphine ligands, benzimidazoles, and quinolinyl oxazolines. Air stable catalysts have been prepared from Pd(dba)2 and sterically hindered thiourea ligands (eq 24). An effective immobilized catalyst has been prepared from Pd(dba)2 and a dendritic phosphine-containing polymer. ... 

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