Synthetic utility of epoxides for chiral functionalization of isoxazoles

Abstract

The lithio-anion of isoxazole 2 was found to ring open propylene oxide in good yields with complete regioselectivity. Vinylic and benzylic epoxides were utilized as key examples of electrophiles and found to produce a mixture of regioisomeric adducts. Additionally, the use of chiral epoxides was explored, and absolute configuration was determined by X-ray crystallography to prove that nucleophilic attack at the benzylic carbon of (R)-styrene oxide proceeds with 100% inversion at the benzylic carbon to afford the (S)-alcohol (4b).

Preparation of chiral isoxazole carbinols via catalytic asymmetric Corey-Bakshi-Shibata reduction.

“…The alcohol (S)-3j was prepared in a similar manner by the general procedure described above, in 82% yield. Spectroscopic characteristics of (S)-3j were identical to the racemate; 19 …”

“…19 The ketones 2a-j were then prepared by oxidation using the Dess-Martin Periodinane reagent. 20 The reductions illustrated in Scheme 1 were typically carried out at -45 o C in dichloromethane, monitored by TLC until consumption of the ketone, and the chemical yields were uniformly very good to excellent.…”

“…19 The remaining configurations were established by the order of elution via chiral HPLC-CSP. The stereochemical outcome appears to be consistent with the Corey transition state model.…”

Synthesis of dihydrooxazoylarylisoxazoles by conventional and under microwave conditions

“…Oxazoline complexes are useful as catalysts for the enantioselective C-C bond formation [28,29] and enantioselective terminal alkene hydrogenation [30]. Isoxazole coupled oxazolines were reported as Ca-activated K channel openers [31] and also reported as catalysts for regioselective ring opening of propylene oxides [32]. The importance of oxazolines and isoxazoles has prompted the design and synthesis of various oxazoline substituted isoxazoles and herein, we report the synthesis of a few 4-(4,5-dihydrooxazol-2-yl)-5-methyl-3-aryl isoxazole under thermal and microwave irradiation.…”