Sulfide-oxazolines

The synthesis of block copolymers by sequential polymerization requires a living polymer prepared from the less nucleophilic monomer (first block) and the addition of a more nucleophilic monomer to the active species located on this first block. The general order of nucleophilicities of heterocyclic monomers is as follows Siloxanes orthoesters < acetals < ethers < sulfides < oxazolines < amines. Depending on substitution and ring strain some changes may occur in these positions. 

Aromatic and vinylic sulfides take part in cross-coupling reactions with Grignard reagents in the presence of Ni catalysts.336,337 This reaction has been applied to the enantioselective synthesis of binaphthyls using a standard chiral oxazoline ligand (Equation (25)) 338... 

The readily available oxazolines (L19) are used in the cross-coupling of arylboronic acids with aryl bromides, including nonactivated ones in the system (Pd(OAc)2/L, Cs2C03, dioxane, 80 °C). It is notable that the system works well at 1 1 Pd L ratio.442 A simple sulfide complex showed similar activity (PdCl2(SEt2)2, K3P04, DMF, 130°C).18 A series of bidentate N,N-donor ligands... 

The 1-t-butylphospholane sulfide intermediate to TangPhos was also used to prepare the P,N ligands 48 by reacting the lithium complex with C02 and then oxazoline formation with a range of chiral amino alcohols [69b, 74]. The Ir complexes of these ligands have been successfully used in the reduction of / -methylcinnamic esters (80-99% ee) and methylstilbene derivatives (75-95% ee), a particularly challenging class of unfunctionalized olefins [4 c]. 

Meyers and Ford (76JOCI735), and Hirai et al. (72CPB206) have used 2-(alkylthio)-2-oxazolines or thiazolines to prepare the corresponding thi-iranes upon treatment with bases and subsequently with carbonyl compounds. The reactions of 2-pyridyl sulfides are expected to proceed similarly as shown in Scheme 22, since the oxazoline ring is a good leaving group in the intramolecular substitution reaction. When optically active oxazolines are used, asymmetric induction takes place to afford the optically active thiiranes in 19-32% enantiomeric excess (ee). The process is shown in Scheme 23. 

Uemura and co-workers discovered that prochiral sulfides react with [N-(p-toluenesulfonyl)imino]phenyliodinane 207 in the presence of bis(oxazoline) ligands to form the corresponding chiral sulfimides. ° For example, ( )-cinnamyl phenyl sulfide 220 reacted with 207 in the presence of copper(I) triflate and ent-6 to form the chiral sulfimide 221 in 80% yield (58% ee) as shown in Figure 9.63. 

Reactions of Acetoin and Aldehydes with Ammonium Sulfide. This reaction leads to the various substituted oxazolines, thiazolin-es, and Imidazolines. Additional heterocyclic systems identified in this reaction include thiophenes and pyrazines. All these products are important aroma compounds in the food industry. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

The treatment of various sulfides with Phi = NTs in the presence of cuprous triflate leads to the corresponding N-tosylsulfimides (N-tosylsulfilimines) 21 [30]. The presence of the chiral bis(oxazoline) ligand 22 in the reaction medium results in coordination of the copper(III)-nitrene intermediate, L Cu(III) = NTs, and enables the enantioselective production of 21 (Scheme 12). Similar copper-catalyzed reactions of allylic sulfides with Phi = NTs lead to formal insertion of the NTs group into the carbon-sulfur bond of the substrates, and proceed via a [2,3]-rearrangement with allylic inversion, to give sulfonamides 23 [30]. 

Aqueous mixtures containing a-hydroxyketones (3-hydroxy-2-butanone, l-hydroxy-2-propanone, l-hydroxy-2-butanone) or a-dicarbonyls (2,3-butanedione, 2,3-pentanedione) and ammonium sulfide were reacted at 25 °C for 2 hr. Among the heterocyclic flavor compounds formed were oxazoles, oxazolines, thiazoles, thiazolines and pyrazines. 2-(l-Hydroxyalkyl)-3-oxazolines and 2-( 1 -hydroxyalkyl)-3-thiazolines were major intermediate compounds identified in a-hydroxyketone systems and on the other hand, 5-hydroxy-3-oxazolines and 5-hydroxy-3-thiazolines were proposed as intermediate compounds in o-dicarbonyl systems. 

Takken (2) identified thiazoles and 3-thiazolines from the reaction of 2,3-butanedione and 2,3-pentanedione with ammonia, acetaldehyde and hydrogen sulfide at 20 °C. Study of tetramethylpyrazine (5) also showed that it can be readily formed in 3-hydroxy-2-butanone and ammonia model reaction at 22 C. Recent study of the model reaction of 3-hydroxy-2-butanone and ammonium acetate at low temperature revealed an interesting intermediate compound, 2-(l-hydroxyethyl)-2,3,4-trimethyl-3-oxazoline, along with 2,4,5-trimethyloxazole, 2,4,5-trimethyl-3-oxazoline, and tetramethylpyrazine were isolated and identified 4,5). We hypothesized that with the introducing of H2S, replacement of oxygen by sulfur could happen and sulfur-containing heterocyclic compoimds such as thiazoles and thiazolines could be formed along with oxazoles, oxazolines and pyrazines. 

In the studies of the reactions of l-hydroxy-2-propanone and l-hydroxy-2-butanone and ammonium sulfide, despite four possible intermediates were predicted, only two intermediate compounds were tentatively identified by GC/MS in our study. The mass spectral data of these compounds showed very distinctive base peak p attem (Table I). These results agreed with results from previous study of five different 2-alkyl-2,4,5-trimethyl-2,5-dihydrooxazolines (7) which showed same mass spectral fragmentation pattern (m/z = 112) of same types of intermediate con5>ounds. Further study of GC/MS-CI results suggested their molecular weights and as the results, they were tentatively identified as 2-(1 -hydroxymethyl)-2,4-dimethyl-3-oxazoline, 2-( 1 -hydroxymethyl)-2,4-... 

Proposed reaction mechanism of l-hydroxy-2-propanone or l-hydroxy-2-butanone with ammonium sulfide is shown in Figure 5. 2-Iminoalcohols, which were derived from the reaction of ammonia and a-hydroxyketones, were condensed with another molecule of a-hydroxyketone to form 2-(l-hydroxymethyl)-2,4-dialkyl-3-oxazolines. The substitution of -OH group with -SH group resulted in the formation of 2-(l-hydroxyemthyl)-2,4-dialkyl-3-thiazolines. No 2-(l-mercaptomethyl)-substituted isomers were found in either reaction. Upon heating, these intermediates were further converted to the corresponding oxazolines, oxazoles, thiazolines and thiazoles. 

---