Highly Efficient Silylative Kinetic Resolution of Racemic trans‐2‐Alkyl‐1‐indanols Catalyzed by Chiral Guanidine

Abstract

Chiral guanidine catalyzed silylative kinetic resolution of racemic trans-2-alkyl-1-indanols using Ph 3 SiCl was achieved with high s-values. A variety of substrates bearing alkyl groups at the C-2 position and substituents on the aromatic rings of the indanol moiety were applicable in the reaction achieving good to high selectivity, irrespective of the type of substituent present. In addition to exhibiting high selectivity, the guanidine catalyst was found to be highly active and the reactions could be performed using a catalyst loading of only 0.5 mol %. It was revealed that the relative stereochemistry of the stereogenic centers of the substrates was important and that the reaction using cis-substrates did not proceed at all, whereas the reaction can be selectively carried out using trans-substrates.

Two-Step Kinetic Resolution of Racemic Secondary Benzylic Alcohols Using the Combination of Enantioselective Silylation and Acylation: One-Pot Procedure Catalyzed by Chiral Guanidine

“…Since we did not examine the same substrate in former studies, as a preliminary examination, rac -1-phenyl-1-propanol ( rac - 2 ) was used for both acylative and silylative kinetic resolutions (Scheme ). We observed that under previously optimized reaction conditions , (Scheme a,b), both the silylative and acylative kinetic resolutions of rac - 2 produced high s values. This confirmed our assumption that the obtained silylated compound 3 and the acylated compound 4a had opposite sense of the stereochemistry.…”

“…Different solvents and amounts of silyl chloride were separately applied to verify their effects on the reactivity of the silylative kinetic resolution (Table ). The reactions were carried out in THF, CH 2 Cl 2 , EtOAc, and toluene as solvents (entries 1–4), as they were shown to give good results in our previous studies . Certainly, good conversions were achieved (45–54%), and the reactions in THF, CH 2 Cl 2 , and EtOAc produced moderate s values (entries 1–3), while toluene showed the highest value (entry 4).…”

“…On the other hand, we recently reported that chiral guanidine compound 1 and its derivatives were found to function as efficient catalysts for the acylative and silylative kinetic resolutions of a variety of racemic alcohols with good s values . During these investigations, we observed that acylated and silylated compounds may have opposite stereochemistry based on the phenyl ring on the benzylic alcohol substrates.…”

Chiral Cyclopropenimine‐catalyzed Asymmetric Michael Addition of Bulky Glycine Imine to α,β‐Unsaturated Isoxazoles

“…[27] In fact, triethylamine (Et 3 N), 1,4-Diazabicyclo[2.2.2]octane (DABOC), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) were used as achiral organosuperbases in many reactions. In recent decade, several types of chiral organosuperbases [28,29] including amidine, [30][31][32] guanidine, [33][34][35][36][37][38][39][40][41] cyclopropenimine, [42][43][44][45][46][47] iminophosphorane, [48][49][50][51][52][53][54][55][56] and azaphosphatrane [57][58][59][60] have been developed and used as catalysts for direct deprotonation of substrates with high pK a values in asymmetric Michael reaction, Mannich reaction, amination, oxidation, aldol reaction and [3 + 2] cycloaddition. Benzophenone-protected glycine t-butyl ester 1 a bearing not only high pK a but also bulky group was regarded as a challenging substrate for asymmetric Michael addition.…”

One out of Four: Kinetic Resolution of Stereoisomeric Mixtures of Secondary Alcohols with a Quaternary Carbon Atom in the β-Position by Cu–H-Catalyzed Enantioselective Silylation

“… 19 We found this substance class particularly promising to probe their stereoselective kinetic resolution ( Scheme 1 , bottom). 20 , 21 The synthesis of similar acyclic alcohols with a vicinal quaternary stereocenter is mainly achieved by reagent- and catalyst-controlled carbonyl allylation to arrive at the corresponding homoallylic alcohols. 22 − 31 In this Letter, we present an enantio- and diastereoselective Cu–H-catalyzed silylation of stereoisomeric mixtures of those alcohols that enriches the fastest-reacting stereoisomer as the silyl ether.…”