Stereoarrayed CF₃‐Substituted 1,3‐Diols by Dynamic Kinetic Resolution: Ruthenium(II)‐Catalyzed Asymmetric Transfer Hydrogenation

Abstract

CF3 -substituted 1,3-diols were stereoselectively prepared in excellent enantiopurity and high yield from CF3 -substituted diketones by using an ansa-ruthenium(II)-catalyzed asymmetric transfer hydrogenation in formic acid/triethylamine. The intermediate mono-reduced alcohol was also obtained in very high enantiopurity by applying milder reaction conditions. In particular, CF3 C(O)-substituted benzofused cyclic ketones underwent either a single or a double dynamic kinetic resolution during their reduction.

Stereoarrayed CF3‐Substituted 1,3‐Diols by Dynamic Kinetic Resolution: Ruthenium(II)‐Catalyzed Asymmetric Transfer Hydrogenation

“…value corresponds to the ratios of the four 19 FNMR signals,going in an upfield direction, corresponding to the diastereomers.X -ray analyses of 3j and 3s revealed their (1S,2S,1'S)a bsolute configuration. [12] This data demonstrates the manifestation of as econd DKR whereby the methine configuration (in the cycle) of 2 en route to 3 is inverted (Scheme 2f or 3i). [13] Thecreated stereochemistry at the benzylic carbon (C1) is governed by the handedness of D (see Figure 3), while the C2 configuration is impacted by outwards orientation of the peripheral CH(OH)CF 3 group,t hus minimizing the steric interference in the second transition state.…”

“…= 0:0:97.5:2.5, > 99.9 % ee (major)],r espectively.I nterestingly,( 1 S,2R,1'S)-3i [> 99 % de, > 99.9 % ee]was accessed by Me 4 NBH 4 /AcOH reduction in MeCN at À40 8 8Ca nd subsequent recrystallization from CHCl 3 /hexane.T heir absolute configurations were confirmed by X-ray analysis. [12] Note that in contrast to the double ATH/DKR of 1i employing either D or ent-D,t he methine configuration (in the cycle) of 2i en route to 3i is not inverted in these steps.…”

“…The absolute configuration was assigned by analogy to that of (2S*,1'S*)-2s as determined by X-ray analysis. [12] This stereochemistry can be rationalized by the attack of the ruthenium-(II) hydride on the CF 3 C(O) re-face,a nd formation of the equilibrium mixture wherein (2S,1'S)-2i is predominant. Notably,h eating the stereopure (2S,1'S)-2i at 40 8 8Ci n am ixture of HCO 2 H/Et 3 N( 5:2) and PhCl, in the absence of D resulted in a9 6:4m ixture of (2S,1'S)-2i and (2R,1'S)-2i.…”

Application of Hammett equation to intramolecular hydrogen bond strength in para-substituted phenyl ring of trifluorobenzoylacetone and 1-aryl-1,3-diketone malonates

“…Geometrical parameters of chelated ring are very important for explaining of IHB strength in the cis-enol forms of β-diketones, because the IHB strength in these molecules is explained by the resonance-assisted hydrogen bond [43][44][45][46][47]. Table 7 and Figure S3…”

trans-Diastereoselective Ru(II)-Catalyzed Asymmetric Transfer Hydrogenation of α-Acetamido Benzocyclic Ketones via Dynamic Kinetic Resolution

“…Relevant to our present work are 2-Z-1-indanones and -tetralones wherein Z = alkyl, (het)aryl, F, Cl, CO 2 R′, SO 2 Ph, C(O)Ph, SO 2 NHPh, and CH(OH)CF 3 , which furnish predominantly the corresponding enantiomeric cis -configured products under these reaction conditions. 7…”