An Efficient and Versatile Method for the Synthesis of Optically Active 2-Oxazolines: An Acid-catalyzed Condensation of Ortho Esters with Amino Alcohols

Kamata, Kazuyuki; Agata, Isao; Meyers, A. I.

doi:10.1021/jo971161x

Cited by 80 publications

(24 citation statements)

References 23 publications

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“…(S)-4,5-Dihydro-4-phenyloxazole (1) was prepared by reaction of (S)-2-amino-2-phenylethanol with ethyl orthoformate in the presence of trifluoroacetic acid in dichloromethane (55 % yield). [18] (27) and (S)-2-(methylamino)-2-phenylethanol (36) are commercially available. Ethyl (S)-1-methylpyrrolidine-2-carboxylate (10) was obtained in three steps from -proline by N-methylation using formaldehyde, followed by catalytic hydrogenation (99 % yield) [19] and esterification (EtOH, cat.…”

Section: Resultsmentioning

confidence: 99%

An Approach to Enantioselective 5‐endo Halo‐Lactonization Reactions

2007

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Enantioselective lactonization of 4‐substituted but‐3‐enoic acids using iodobis(N‐methylephedrine) hexafluoroantimonate in dichloromethane at low temperatures is reported. The presence of bis(N‐methylephedrine)silver(I) hexafluoroantimonate, derived from the excess amounts of N‐methylephedrine and silver hexafluoroantimonate that were necessary for the generation of the iodo complex in the reaction mixture, is crucial for the success of this reaction. The different parameters of these cyclization reactions have been examined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Section: Resultsmentioning

confidence: 99%

An Approach to Enantioselective 5‐endo Halo‐Lactonization Reactions

2007

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“…However, cyclization of the i-Pr-substituted amide 5d to the (2-fluorophenyl)benzoxazine 7d (Scheme 3) with triflic anhydride and Et 3 N gave low yields ( 25%). This could be overcome by extending a recently reported protocol for dihydrooxazole synthesis to the oxazines [17]. Refluxing 2-fluorobenzoic acid triethyl orthoester 8 and the (aminoalkyl)phenol ()-( S )-4b in 1,2-dichloroethane in the presence of AcOH afforded the benzoxazine (À)-( S )-7d in 84% yield ( Scheme 6).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of New Chiral Bidentate (Phosphinophenyl)benzoxazine P,N-Ligands

Kündig

Meier

1999

HCA

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Two new chiral bidentate (phosphinophenyl)benzoxazine P,N‐ligands 2a and 2b were synthesized from highly enantiomer‐enriched 2‐(1‐aminoalkyl)phenols 4. Ligand rac‐2a was obtained on refluxing the t‐Bu‐substituted (aminomethyl)phenol 4a with 2‐(diphenylphosphino)benzonitrile in chlorobenzene in the presence of anhydrous ZnCl2 followed by decomplexation (Scheme 2). This reaction, when carried out with (+)‐(S)‐4a, was accompanied by racemization at the stereogenic center of the alkyl side chain. The enantiomerically pure ligands (+)‐(R)‐2a and (−)‐(S)‐2a were obtained using a stepwise procedure via the amides (−)‐(R)‐ and (+)‐(S)‐5b, respectively, followed by cyclization to benzoxazines (+)‐(R)‐ and (−)‐(S)‐7b, respectively, with triflic anhydride and by F‐atom substitution by diphenylphosphide (Schemes 3 and 5). In the case of the i‐Pr analogue 2b, this last step resulted in racemization (Scheme 6). This was overcome by preparing the bromo derivative and introducing the diphenylphosphine group via Br/Li exchange and reaction with chlorodiphenylphosphine (Scheme 7). The first application of (+)‐(R)‐2a in an asymmetric Heck reaction showed high enantioselectivity (91%) (Scheme 8).

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“…The reaction of carboxylic acids [12][13][14][15][16][17] or acid derivatives like ester [18][19][20][21][22] with 2-aminoethanol is the most common method for the synthesis of oxazolines. In addition, other substrates such as imidate hydrochlorides [23], N-(2-hydroxyethyl) amides [24][25][26][27][28][29], ortho esters [30], imino ether hydrochlorides [31], aldehydes [32][33][34][35][36][37] and nitriles [38][39][40][41][42][43][44][45][46] have been used to prepare the oxazolines. Despite the potential applications of the reported procedures in the synthesis of 2-oxazoline derivatives, some of them suffered from one or more shortcomings such as prolonged reaction times, expensive catalysts, hazardous reaction conditions, tedious work-up procedures and lack of general applicability.…”

Section: Introductionmentioning

confidence: 99%