Oxazoline Ring Research Articles

Hydrogenation condition for sequential processes to (+)-trifluoromethyl monomorine

(+)-Trifluoromethyl monomorine has been synthesized under mild hydrogenation condition by initiating reductive cleavage of the oxazoline ring followed by deprotection and intramolecular reductive amination reaction. The precursors could be prepared concisely by condensation and palladium-catalyzed coupling reaction.

Turn-over of an oxazoline ring induced by chiral change of a folded ascidiacyclamide analogue: cyclo(Ile-D–aThr–D-Val–Thz–Ile–D-Oxz–D-Val–Thz)N,N-dimethylformamide disolvate

Ascidiacycl­amide (ASC) has two oxazoline (Oxz) residues with 2S,3R configurations. In the title compound, C36H54N8O7S2·2C3H7NO, these Oxz residues were replaced with d-aThr and (2R,3S)–Oxz (d-Oxz). The overall structure is similar to the folded from of ASC analogues previously reported, but a difference was found at the d-Oxz residue. The d-Oxz ring was turned over in relation to the disposition of the Oxz rings in natural ASC. This result suggested that the modification of Oxz could induce a new type of molecular folding in ASC.

Development of a novel chiral spiro ligand bearing oxazoline

The synthesis of bis(oxazoline) ligand 1 bearing a spiro skeleton is achieved via double ring-closing metathesis (RCM) of tetraene 2 and subsequent oxazoline ring formation using N-bromosuccinimide (NBS). The Cu-spiro bis(oxazoline) complexes prepared from 1 and Cu(OTf) 2 or Cu(OAc) 2 act efficiently as chiral catalysts for promoting carbonyl-ene reactions or Henry reactions with good enantiocontrol.

Decomposition of oroidin in DMSO/TFA

Oxidative cyclization of the pyrrole–imidazole alkaloids oroidin and sventrin in DMSO/TFA (1:1) yields oxazolines via nucleophilic attack of the carbonyl oxygen at the alkenyl double bond. Oxidation takes place in the benzylic position of the imidazole ring. On prolonged reaction times, the oxazoline ring is hydrolyzed yielding the corresponding ester of pyrrole-2-carboxylic acid containing a free amino group. Overall, the double bond of oroidin is dioxygenated.

Preparation of Pyrrolidine—Oxazoline Containing Ligands and Their Application in Asymmetric Transfer Hydrogenation.

Abstract Nine members of a new ligand class incorporating both an oxazoline ring and a pyrrolidine unit were prepared in an efficient four-step synthesis starting from readily available chiral amino alcohols and proline. A study of these ligands in the asymmetric transfer hydrogenation of acetophenone showed that the catalysts formed from [Ir(cod)Cl]2 were the most active while those derived from [Ru(p-cymene)Cl2]2 gave the highest enantioselectivities (up to 61% ee).

Rhodium and iridium complexes bearing an alkyloxazoline-substituted indenyl ligand (Indox ligand) and their stereoselective construction of metal-centered chirality

The Indox ligands, [{( S)-( i Pr)Indox} n ]H ( 1) [ n=2 ( a), 3 ( b)] and [{(H)Indox} n=3 ]H ( 2), in which an indenyl group and an oxazoline ring are connected by an ethylene or propylene spacer, have been prepared. Reaction of [Ir(coe) 2Cl] 2 or [RhCl(C 2H 4) 2] 2 with the potassium salt of 1 afforded η 5-[{( S)-( i Pr)Indox} n ]Ir(coe) 2 ( 3) or η 5-[{( S)-( i Pr)Indox} n ]Rh(C 2H 4) 2 ( 6) as a 1:1 mixture of two diastereomers. The oxazoline ring in 3 and 6 did not coordinate to the metal center. When the complexes 3 or 6 reacted with iodine in diethyl ether, oxidative addition proceeded and the oxazoline ring coordinated to the metal center to give diiodoiridium(III) or rhodium(III) complexes, η 5:η 1-[{( S)-( i Pr)Indox} n ]M(I) 2 [M=Ir ( 4), Rh ( 7)]. The corresponding diiodoiridium(III) complex bearing the Indox ligand 2, η 5:η 1-[{(H)Indox} n=2 ]Ir(I) 2 ( 5), was also prepared by a similar method. Reaction of 4 or 7 with PPh 3 in THF afforded diiodo-phosphine complexes, η 5-[{( S)-( i Pr)Indox} n ]M(PPh 3)(I) 2 [M=Ir ( 8), Rh ( 9)] as a 1:1 mixture of two diastereomers in which the oxazoline ring dissociated from the metal center. The related reaction of 8 or 9 with more than 2 equiv. of AgOTf afforded the cationic complexes, [η 5:η 1-[{( S)-( i Pr)Indox} n ]M(PPh 3)(OTf)]OTf [M=Ir ( 10), Rh ( 11)], having a stereogenic center at the metal center as a mixture of only two diastereomers. From 1H and 31P NMR analyses, each diastereomer of 8 or 9 afforded only a single isomer of 10 or 11. The corresponding iridium(III) complex bearing the Indox ligand 2, [η 5:η 1-[{(H)Indox} n=3 ]Ir(PPh 3)(OTf)]OTf ( 12) was also prepared. The coordinated triflate ligand of 12 was slowly replaced by water in CDCl 3 to afford the dicationic aquo complex, ( S * pl, R * Ir)-[η 5:η 1-[{(H)Indox} n=3 ]Ir(PPh 3)(H 2O)](OTf) 2 ( 13). The monocationic complex, [η 5:η 1-[{( S)-( i Pr)Indox} n=2 ]Ir(PPh 3)(I)]OTf ( 14a), having metal-centered chirality, was observed as a mixture of only two diastereomers in the reaction of 10a (a mixture of two diastereomers) with 1 equiv. of AgOTf. These observations indicated that the ligand exchange reaction of 8 or 9 with AgOTf contained the following three steps: (i) abstraction of one of the two prochiral iododes by AgOTf, (ii) recoordination of the oxazoline ring, and (iii) exchange of the remaining iodide for the triflate by AgOTf. The stereochemistry around the metal center was determined at the second step. All complexes have been characterized by usual spectroscopic methods as well as elemental analyses, and 4 and 13 have been characterized by X-ray analyses.

Novel Cyclic 1,2‐Diacetals Derived from (2R,3R)‐(+)‐Tartaric Acid: Synthesis and Application as N,O Ligands for the Enantioselective Alkylation of Benzaldehyde by Diethylzinc

AbstractA chiral cyclic 1,2‐diacetal derived from tartaric acid was used as the basic structural unit for novel ligands. Monooxazoline carbinols in which the degree of substitution of the alcohol and the nature of the stereocentre in the oxazoline ring were varied were synthesized in moderate to good yields. The influence of these structural factors on asymmetric induction was examined in the enantioselective addition of diethylzinc to benzaldehyde. Up to 60% ee was observed with a secondary or a tertiary alcohol as the metal‐chelating group. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Preparation of pyrrolidine–oxazoline containing ligands and their application in asymmetric transfer hydrogenation

Nine members of a new ligand class incorporating both an oxazoline ring and a pyrrolidine unit were prepared in an efficient four-step synthesis starting from readily available chiral amino alcohols and proline. A study of these ligands in the asymmetric transfer hydrogenation of acetophenone showed that the catalysts formed from [Ir(cod)Cl] 2 were the most active while those derived from [Ru( p-cymene)Cl 2] 2 gave the highest enantioselectivities (up to 61% ee).

Synthesis of new central and planar chiral enantiomerically pure 5-ferrocenyl-oxazolines and a 5-ferrocenyl-thiazoline

Enantiomerically pure central and planar chiral ferrocenyl cyanohydrins have been used for the synthesis of previously unreported 5-ferrocenyl-oxazolines and a 5-ferrocenyl-thiazoline where the central chirality lies on the carbon bearing the oxygen or the sulfur atom. The epimerization at C 5 of the oxazoline ring has also been investigated.

A Ruthenium(II) Complex with a Tetradentate C2‐Symmetric Bis(phosphino)‐bis(oxazoline) Ligand for Asymmetric Transfer Hydrogenation of Aromatic Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Aerobic Oxidation of 1‐Phenylethanol Catalyzed by Palladaheterocycles

AbstractCyclometallated palladium compounds with pyridine were shown to serve as more efficient catalysts for the aerobic oxidation of 1‐phenylethanol than a previously investigated analogue with an oxazoline ring. Substituents with different electronic properties in the phenyl ring were shown to exhibit an only minor influence on the reactivity of the catalytic system. The first step in the reaction consists of the splitting of the acetate bridge in the dimeric starting complex and coordination of a ligand to palladium. By ab initio calculations it was shown that, in the presence of solvent, a complex with pyridine was more stable than that with the alcohol, whereas the opposite situation was found in the gas phase. The complex with coordinated alcohol was stabilized by hydrogen bonding. Good agreement was found between the computed structure and the X‐ray structure of the initial palladaheterocycle 1.

Rational design of a bimodular model system for the investigation of heterocyclization in nonribosomal peptide biosynthesis.

Cyclization (Cy) domains in NRPS catalyze the heterocyclization of cysteine and serine/threonine to thiazoline and oxazoline rings. A model system consisting of the first two modules of bacitracin synthetase A fused to the thioesterase (Te) domain of tyrocidine synthetase was constructed (BacA1-2-Te) and shown to be active in production of the heterocyclic IleCys(thiazoline). Based on this model system, the feasibility of Cy domain module fusions was investigated by replacing the BacA2 Cy-A-PCP-module with modules of MbtB and MtaD from the biosynthesis systems of mycobactin and myxothiazol, revealing the formation of novel heterocyclic dipeptides. To dissect the reaction sequence of the Cy domain in peptide bond formation and heterocyclization, several residues of the BacA1-2-Te Cy domain were analyzed by mutagenesis. Two mutants exhibited formation of the noncyclic dipeptide, providing clear evidence for the independence of condensation and cyclization.

New Chiral Ligands Derived from Mandelic Acid: Synthesis and Application in the Asymmetric Phenyl Transfer Reaction to an Aromatic Aldehyde

Starting from inexpensive enantiopure (R)- and (S)-mandelic acid, a range of u-hydroxy-2-oxazolines has been prepared. The synthesis involves the condensation of the acid chloride with a vicinal amino alcohol, followed byintramolecular cyclization to form the oxazoline ring. The resulting compounds have been used as ligands in the asymmetric phenyl transfer reaction to 4-chlorobenzaldehyde, employing a mixture of triphenylborane and diethylzinc as the phenyl source. Good yields (up to 76%) and moderate enantioselectivities (up to 35%) have been achieved.

Novel ferrocenyl-oxazoline ligands: first preparation of non-symmetrical bis(oxazoline)

New ferrocenyl-arenylethenyl-oxazoline derivatives have been prepared ( 5– 10) from the mono- and (1,1 ′)-disubstituted (nitrile-ethenylaryl)ferrocene compounds ( 1 and 2) and the appropriated β-aminoalcohol ( 3 and 4) in one step synthesis. The X-ray crystal structure of one of the ferrocenyl-ethenylaryl-oxazoline ( 5) is described, revealing the unusual quasi-planarity of the oxazoline ring with the phenyl and cyclopentadienyl cycles. Two compounds end-capped ( 9 and 10) with both, nitrile and oxazoline groups, are the key intermediates to obtain the non-symmetrical bis(oxazoline) 11, containing two different substituted heterocycles.

C2-symmetric bis(oxazolinato)lanthanide catalysts for enantioselective intramolecular hydroamination/cyclization.

C(2)-symmetric bis(oxazolinato)lanthanide complexes of the type [(4R,5S)-Ph(2)Box]La[N(TMS)(2)](2), [(4S,5R)-Ar(2)Box]La[N(TMS)(2)](2), and [(4S)-Ph-5,5-Me(2)Box]La[N(TMS)(2)](2) (Box = 2,2'-bis(2-oxazoline)methylenyl; Ar = 4-tert-butylphenyl, 1-naphthyl; TMS = SiMe(3)) serve as precatalysts for the efficient enantioselective intramolecular hydroamination/cyclization of aminoalkenes and aminodienes. These new catalyst systems are conveniently generated in situ from the known metal precursors Ln[N(TMS)(2)](3) or Ln[CH(TMS)(2)](3) (Ln = La, Nd, Sm, Y, Lu) and 1.2 equiv of commercially available or readily prepared bis(oxazoline) ligands such as (4R,5S)-Ph(2)BoxH, (4S,5R)-Ar(2)BoxH, and (4S)-Ph-5,5-Me(2)BoxH. The X-ray crystal structure of [(4S)-(t)BuBox]Lu[CH(TMS)(2)](2) provides insight into the structure of the in situ generated precatalyst species. Lanthanides having the largest ionic radii exhibit the highest turnover frequencies as well as enantioselectivities. Reaction rates maximize near 1:1 BoxH:Ln ratio (ligand acceleration); however, increasing the ratio to 2:1 BoxH:Ln decreases the reaction rate, while affording enantiomeric excesses similar to the 1:1 BoxH:Ln case. A screening study of bis(oxazoline) ligands reveals that aryl stereodirecting groups at the oxazoline ring 4 position and additional substitution (geminal dimethyl or aryl) at the 5 position are crucial for high turnover frequencies and good enantioselectivities. The optimized precatalyst, in situ generated [(4R,5S)-Ph(2)Box]La[N(TMS)(2)](2), exhibits good rates and enantioselectivities, comparable to or greater than those achieved with chiral C(1)-symmetric organolanthanocene catalysts, even for poorly responsive substrates (up to 67% ee at 23 degrees C). Kinetic studies reveal that hydroamination rates are zero order in [amine substrate] and first order in [catalyst], implicating the same general mechanism for organolanthanide-catalyzed hydroamination/cyclizations (intramolecular turnover-limiting olefin insertion followed by the rapid protonolysis of an Ln-C bond by amine substrate) and implying that the active catalytic species is monomeric.

A Ruthenium(II) Complex with a Tetradentate C2-Symmetric Bis(phosphino)-bis(oxazoline) Ligand for Asymmetric Transfer Hydrogenation of Aromatic Ketones

In the past decade, oxazoline-based bidentate ligands have proven very valuable in asymmetric catalysis, mainly as heterotoditopic ligands, such as the phosphino-oxazoline III or as bis(oxazoline) ligands with or without a coordinating connecting group. In contrast to the bidentate or tridentate ligands, chiral tetradentate bis(oxazolinyl)-type ligands have been less extensively developed. A possible difficulty in using chiral tetradentate ligands is that, in comparison to their bidentate analogues, they can often offer a larger diversity of binding modes and this requires the coordination geometry of their metal complexes to be characterized with great care. An exact knowledge of the structure of a catalyst precursor is the most helpful in order to gain a better insight into the overall reaction and allow subsequent fine-tuning of the catalytic system, although it is intrinsically difficult to identify the active species in a catalytic process. We have recently developed a series of new type of C2-symmetric tetradentate chiral ligands such as (S,S)-PhosBiox 1, where the two oxazoline rings connected directly at the stereogenic center. The P,N,N,P-tetadentate ligand 1 showed excellent enantioselectivities in Rh-catalyzed hydrosilylation of ketones and Pd-catalyzed allylic substitution reactions. Ligand 1 can form a chelate in square-planar Pd(II) complexes which is an active catalyst precursor for enantioselective allylic substitution reaction. Here we report on the coordination behavior of 1 toward Ru(II) and its catalytic activity in asymmetric transfer hydrogenation of aryl alkyl ketones. Results and Discussion

Asymmetric Catalysis. Part 149 [1]. Synthesis of New Chiral Tridentate Ligands for Enantioselective Catalysis

The synthesis of new chiral tridentate ligands is reported which coordinate transition metals in a meridional way. The ligands contain a pyridine ring, an oxazoline ring, and a strongly coordinating diphenylphosphanyl group. The methionine-derived ligand forms a copper complex, which has been studied by X-ray crystallography. The new ligands were tested in models of enantioselective catalyses, such as hydrogenation of ketopantolactone, hydrosilylation of acetophenone, and transfer hydrogenation of acetophenone.

The leupyrrins: a structurally unique family of secondary metabolites from the myxobacterium Sorangium cellulosum.

The structurally unique leupyrrins A1 (1), A2 (2), B1 (3), B2 (4), C (5), and D (6) were isolated as one of three groups of secondary metabolites from Sorangium cellulosum strains So ce705 and So ce690. An unusually substituted gamma-butyrolactone ring and pyrrole and oxazoline rings are embedded in a nonsymmetric macrodiolide core structure, giving rise to compounds 1-6 as members of a novel class of secondary metabolites. Leupyrrin A1 (1) shows good biological activity against various fungi and eukaryotic cells.

Synthesis of an oxazoline analogue of apratoxin A.

[structure: see text] Michael addition of Me(2)Cu(CN)Li(2) to alpha,beta-unsaturated lactone 7 derived from beta-hydroxyl ketone 5 provides lactone 8, which is converted to alcohol 11 using Oppolzer's methodology as the key step. Connection of 11 with the l-proline moiety and subsequent installation of an oxazoline ring affords 16, which is coupled with tripeptide 21; subsequent macrocyclization then furnishes 4, an oxazoline analogue of apratoxin A.

Catalytic Asymmetric Cyclopropanation of Alkenes with Diazoesters in Protic and Biphasic Media.

AbstractFor Abstract see ChemInform Abstract in Full Text.