An Efficient and Practical Method for the Enantioselective Synthesis of Tertiary Trifluoromethyl Carbinols

Abstract

An efficient sulfinamide/olefin based chiral ligand, MetSulfolefin, has been developed for the enantioselective rhodium-catalysed addition of aryl-boronic acids to trifluoromethyl ketones. This shelf-stable ligand is insensitive to air, oxygen and moisture, and it is obtained in only two high yielding steps from cheap commercially available (R)-tert-butanesulfinamide. The new ligand tolerates the use of hindered boronic acids and leads to the formation of a series of chiral trifluoromethylsubstituted tertiary carbinols in high yields and excellent enantioselectivities (up to > 99% ee).

Carbene‐Catalyzed Enantioselective Decarboxylative Annulations to Access Dihydrobenzoxazinones and Quinolones

“…Tr ifluoromethyl ketones (2)w ith para and meta substituents of varying electronic and steric parameters were all suitable substrates for the reaction. Reactions attempted using ortho-substituted aryl trifluoromethyl ketones, [17] alkyl-trifluoromethyl ketones, [18] or a-keto esters gave the desired products with diminished yields,whereas isatins did not react under the current conditions ( To first gain insight into the origins of the stereocontrol, we analyzed the cycloaddition transition structures involving catalyst E,anhydride 1a,and trifluoromethyl ketone 2a with the wB97XD/6-31G(d)/SMD(Toluene) level of theory at 323 Kt om atch experimental conditions (Figure 1). Ther eactions of 3,5-substituted ketones also provided the desired products 3i and 3j in moderate yields and high stereoselectivity (56 %, 97:3 er and 77 %, 95:5 er, respectively).…”

Diastereoselective Pd-Catalyzed Decarboxylative Allylation To Construct Quaternary Stereocenters Using Sulfinimine as the ­Directing Group

“…In the presence of Pd 2 (dba) 3 and dppf, the sulfinamine group acted as the in-ner chiral directing group to chelate with Pd, thus causing the intramolecular steric hindrance. 27 As a result, nucleophilic attack could only occur at the back side. However, it is worth noting that Pd tends to chelate with the 'O' atom of sulfoxide group instead of 'S' atom.…”

Recent Advances in Catalytic Asymmetric Synthesis of Tertiary Alcohols via Nucleophilic Addition to Ketones

“…In 2013, Tang's group reported a [Rh(C 2 H 4 ) 2 Cl] 2 ‐catalyzed addition of arylboronic acids to trifluoromethyl ketones in the presence of the chiral bisphosphorus ligand 10a (3.6 mol%) containing a deep pocket (Scheme ) . A variety of CF 3 ‐substituted tertiary alcohols 11 was obtained in 31–93% yields and 81–99% ee s. Shortly thereafter, Khiar and Fernández disclosed that the same reaction could be catalyzed by a chiral complex of [Rh(C 2 H 4 ) 2 Cl] 2 and ligand 6a or 6b , but ligand 6b turned out to be more efficient and showed much better enantioselectivities.…”