Preparation of highly optically pure homochiral sulfide‐containing alcohols via oxazaborolidine‐catalyzed asymmetric borane reduction of ketones

Abstract

Highly optically pure homochiral 1-(4-alkylthiophenyl) alcohols were prepared efficiently and practically via the oxazaborolidine-catalyzed asymmetric borane reduction of prochiral ketones in toluene at 25 degrees C. The coordination of the sulfur atom in the ketones to the boron atom in the catalyst and borane can be inhibited under these reduction conditions.

Influences of Electronic Effects and Anions on the Enantioselectivity in the Oxazaborolidine-Catalyzed Asymmetric Borane Reduction of Ketones

“…Many chiral 1,3,2-oxazaborolidines derived from chiral vicinal amino alcohols have been prepared and evaluated in the asymmetric borane reduction of ketones, and some of the best enantioselectivities have been achieved with them . Among them, ( S )-2-substituted 4,4-diphenyl-3,1,2-oxazaboro[3.3.0]octanes 1 , derived from ( S )-2-(diphenylhydroxymethyl)pyrrolidine, with several different substituents (such as H for 1a , Me for 1b , Ph for 1c , and MeO for 1d , as representatives, Scheme ) on the B atom, have been proven to be effective catalysts in the asymmetric reduction with excellent yields and enantioselectivities for a wide variety of ketones. ,, However, 1a and 1b are not entirely satisfactory, particularly for large-scale productions, owing to the necessity of relatively expensive reagents, such as trimethyl boroxin or methylboronic acid, for their preparation 3 and the necessity of the preparation before catalytic reactions in order to get excellent and stable enantioselectivity. Furthermore, the catalyst 1a is air and moisture sensitive .…”

“…Numerous new efficient oxazaborolidines as catalysts have been reported and a plethora of applications have appeared until now. In comparison with the numerous attempts to search for new catalysts and to improve the enantioselectivity, several papers have concentrated on the mechanistic investigation of the catalytic asymmetric reduction reaction, , and some papers have paid attention to the factors which affect the enantioselectivity in the asymmetric reduction, such as the structure, ,, stability 3a,6 (including dimerization) and the amount of the catalyst, 3a,6a, the borane source 8 and the borane amount, 3a,7c the order and rate of the addition of a ketone or borane into the reductive system, 2d,7c the reduction temperature, 7c, solvent, 6a,7c,8c additive, 9g, secondary reduction, 10a, and stabilizer in borane, etc. Although a few papers have considered the influence of the electronic effects of ketones and catalysts on the enantioselectivity, all of the results indicated that no obvious influence has been observed in the asymmetric reduction 5a,6a,13 except for the observation of Corey et al13c Very recently we investigated the temperature-dependent enantioselectivity of the asymmetric reduction and found that the noncatalytic reduction is an important factor for the enantioselectivity in asymmetric reductions 7c.…”

“…The factors governing enantioselectivity in the catalytic asymmetric reaction are usually interpreted in steric terms, affected by the temperature and solvent, etc. 6a,7c,8c, Electronic effects have been reported to control the enantioselectivity recently. In reported studies on the electronic effects on the enantioselectivity, , the underlying reasons are poorly understood in most of the cases.…”

Potassium tert-Butoxide Promoted Formation of Alkyl Aryl Thioethers at Room Temperature: Synthesis and Mechanism

“…1-(4-(Heptylthio)phenyl)ethanone (3ab): [13] Colorless liquid, 207 mg, 94% yield. 1 H NMR (500 MHz, CDCl 3 ) δ: 7.86 (d,J＝8.5 Hz,2H), 7.30 (d,J＝9.0 Hz,2H) 196.9, 144.3, 134.0, 128.6, 128.1, 48.1, 32.5, 26.3, 19.9, 18.4, 16.9;IR (neat) ν: 2966IR (neat) ν: , 2940IR (neat) ν: , 2874IR (neat) ν: , 1680IR (neat) ν: , 1589IR (neat) ν: , 1552IR (neat) ν: , 1394IR (neat) ν: , 1350IR (neat) ν: , 1262IR (neat) ν: , 1181IR (neat) ν: , 1097, 601 cm -1 ; HRMS (EI) calcd for C 13 H 18 SO: 222.1078, found 222.1080.…”

“…, 2.99 (t, J＝7.5 Hz, 2H), 2.57 (s, 3H), 1.73～1.66 (m, 2H), 1.46～ 1.43 (m, 2H), 1.34～1.26 (m, 6H), 0.89 (t, J＝7.0 Hz, 3H).1-(4-((3-Methylbutan-2-yl)thio)phenyl)ethanone (3ac): Colorless liquid, 162 mg, 84% yield. 1 H NMR (500 MHz, CDCl 3 ) δ: 7.85(d, J＝8.5 Hz, 2H), 7.35(d, J＝8.5 Hz, 2H), 3.39～3.34 (m, 1H), 2.55 (s, 3H), 1.98～1.92 (m, 1H), 1.30(d, J＝7.0 Hz, 3H), 1.04～1.00 (m, 6H);13 C NMR (125 MHz, CDCl 3 ) δ:…”