Aminocyclopentadienyl Ruthenium Chloride: Catalytic Racemization and Dynamic Kinetic Resolution of Alcohols at Ambient Temperature

Abstract

Dynamic kinetic resolution (DKR) is an attractive method for the complete transformation of a racemic mixture into a single enantiomer. [1] The DKR of secondary alcohols is a prominent example, for which transition-metal-catalyzed racemization is coupled with enzymatic acylation. [2] In particular, B‰ckvall and co-workers have introduced a notable catalyst system that provides a wide range of chiral acetates in good yields and excellent optical purities. [2b±f] However, the catalyst for the racemization of secondary alcohols is activated at high temperature, and needs the corresponding ketones as hydrogen mediators. [3] Thus, the catalyst system requires a thermally stable lipase; p-chlorophenyl acetate has been selected as an acyl donor, [2c] because oxidation of the starting alcohols occurs when the conventional alkenyl acetates are used as acyl donors. [4] derivative has been determined. The decomposition of these complexes suggests rate-limiting loss of nitrous oxide leads to unusual and reactive late-transition-metal terminal oxo intermediates. Experimental Section3 a: [Ni(dppf)Cl 2 ], [27] (268 mg) dissolved in CH 2 Cl 2 (15 mL) was treated in one addition with 1 [22] (2 equivalents, 249 mg) suspended in methanol (60 mL). Rapidly a deep orange color developed and the solution volume was immediately reduced to ca 10 mL by evaporation at ambient temperatures. The resulting bright orange crystals were isolated by filtration and washed with portions of cold methanol (4 Â 10 mL) or until the filtrate was colorless. Recrystallization of this product from dichloromethane/ethanol at room temperature returns 243 mg (93 % yield) of 3 a. Elemental analysis calcd (%) C 34 H 28 FeN 2 NiO 2 P 2 ¥ 1 ³2CH 2 Cl 2 : C 59.26, H 4.05, N 3.88; found: C 59.43, H 4.28, N 3.64; IR (KBr,): n Ä 1480 m, 1449 s, 1436 s, 1307 m, 1194 w, 1182 w, 1168 m, 1096 s, 1036 m, 1028 m, 999 w, 983 m, 917 m, 827 w, 799 m, 744.3 s, 692 s, 638 w, 625 m, 556 m, 510, s, 494 s, 471 cm À1 m; 1 H NMR (400 MHz, CD 2 Cl 2 ): d 7.84 (m, 8 H), 7.52 (m, 4 H), 7.42 (t, J 7.3 Hz, 8 H), 4.42 (m, 4 H), 4.26 ppm (m, 4 H); 3 P NMR (162 MHz, CD 2 Cl 2 ): d 25.0 ppm (s) (UV/Vis: l max , (e max , m À1 cm À1 ) in CH 2 Cl 2 : 406 nm (655); differential scanning calorimetry (DSC): DH À 802 kcal mol À1 T onset 75 8C. Crystals suitable for X-ray diffraction were grown from CH 2 Cl 2 / Et 2 O at À 15 8C. Crystal data for 3 a: C 35 H 28 Cl 2 FeN 2 NiP 2 O 2 , M 755.99, 143 K, triclinic space group P1 ≈ , a 10.6210(8), b 11.3831(9), c 15.515(2) ä, a 84.021(2), b 72.745(2), g 69.790(1)8, V 1681.0(3) ä 3 , Z 2, 1 calcd 1.494 Mg m À3 , F(000) 772, 426 parameters; R 1 (wR 2 ) [I > 2s(I)] 0.064 (0.15), s(GOF) 0.98. Crystals of 3 a were mounted on glass fibers with epoxy resin and diffraction data was collected on a Bruker Smart CCD diffractometer equipped with a sealed molybdenum tube which was monochromated to give l 0.71073 ä. The structure was solved using direct methods and refined using full-matrix least-squares on F 2 with SHELXTL. With the exception of the disordered di...

Opportunities and challenges for combining chemo- and biocatalysis

“…Following the abovementioned pioneering work in this field 11,13 , tremendous extensions of the technology by various groups led to efficient, robust processes, with wide-ranging substrate suitability, in which a lipase-catalysed resolution via acylation of a racemic alcohol or amine substrate was combined with a metalcatalysed substrate racemization leading to the desired alcohol or amine product in high enantiomeric purity [20][21][22][23] . In addition to the use of chemocatalysts for simple racemization purposes, as is the case with DKR, numerous other types of chemocatalytic transformations, such as C-C bond-forming reactions, have been combined with biotransformations, with the objective of a onepot, multistep synthesis.…”

Lipases: Valuable catalysts for dynamic kinetic resolutions

“…Several complexes of Ru (II) have been combined with lipases for DKR of alcohols, some of which are depicted in Fig. 8 (Agrawal et al, 2014;Akai et al, 2004;Benaissi et al, 2009;Bogár and Bäckvall, 2007;Bogár et al, 2007aBogár et al, , 2007bChen and Yuan, 2010;Choi et al, 2002Choi et al, , 2004Csjernyik et al, 2004;Das and Nanda, 2012;Do et al, 2010;Edin et al, 2006;Ema et al, 2012;Engstrom et al, 2011;Fransson et al, 2006;Hilker et al, 2006;Johnston et al, 2010;Kim et al, 2003Kim et al, , 2004Kim et al, , 2005Kim et al, , 2008H. Kim et al, 2011;C.…”

Ordered Mesoporous Silica as Supports in the Heterogeneous Asymmetric Catalysis

“…Besides that, oxidative kinetic resolution of racemic alcohols is also another feasible approach giving optically active alcohols [87][88][89][90]. Enzymatic and catalytic kinetic resolution of racemic alcohols through acylation or deacylation has been extensively studied [91][92][93][94][95]. Effective oxidative kinetic resolution of racemic alcohols has been reported by Sigman's and Stoltz's groups which involves the aerobic oxidative kinetic resolution of secondary alcohols catalyzed by (-)-sparteine/Pd(II) to conveniently access enantiomerically enriched secondary alcohols [96][97][98][99].…”

“…Although the enantioselective oxidation of sulfides catalyzed by chiral complexes of transition metals, such as titanium [130][131][132], vanadium [133,134], iron [135], manganese [136], has been extensively studied, Kagan method and its improvements are mainly used in the large scale preparations of sulfoxides. The kinetic resolution of racemic sulfoxides and oxidation of sulfides accompanying kinetic resolution catalyzed by titanium-binol (Scheme 6) often gave high ee values of sulfoxides, but low yields [91,137]. Recently, Chan developed a one-pot, titanium-catalyzed tandem sulfoxidation and kinetic resolution process, which proceeded at different temperatures and gave very high ee values and acceptable yields of chiral sulfoxides [138].…”