Enantioselective Rhodium‐Catalyzed Addition of Arylboronic Acids to Trifluoromethyl Ketones

Abstract

A new C 2 -symmetrical, chiral bisphosphorus ligand proved to be efficient for the rhodiumcatalyzed nucleophilic addition of arylboronic acids to trifluoromethyl ketones, providing a series of chiral trifluoromethyl-substituted tertiary alcohols in high yields (up to 93%) and excellent enantioselectivities (> 99%).

Highly Enantioselective Rhodium‐Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram

“…Low enantioseletivities were reported for either chiral nickel or rhodium catalysts (a Ni/chiral N‐heterocyclic carbene ligand: 36 % ee , a Rh/chiral bisphosphine: 38 % ee , a Rh/chiral diene: 68 % ee ) . A low yield was also observed in our previous study, albeit with an improved enantioselectivity (25 % yield, 95 % ee ) . To our knowledge, both excellent enantioselectivities and yields are yet to be achieved for intermolecular asymmetric additions of aryl boron reagents to simple ketones.…”

“…To further demonstrate the importance of ( R , R , R , R )‐WingPhos for both yield and enantioselectivity of this addition, L2 and L3 were also employed for this reaction under otherwise identical reaction conditions and both provided inferior yields and ee values (entries 22 and 23). A low conversion was also observed with L4 as the ligand, thus further demonstrating the superior reactivity of ( R , R , R , R )‐WingPhos as the ligand (entry 24).…”

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

“…Apart from α‐keto carbonyl compounds, trifluoromethyl ketones are also popular substrates for asymmetric arylation as the corresponding trifluoromethylated tertiary alcohols are widely present in biologically active compounds and drugs. 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.…”

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

“… [a] All reactions were conducted using 0.67 mmol of the ketone, 1.34 mmol of the arylboronic acid, 2.01 mmol of KF, 5 mol% of ligand 1 or 3 , and 2.5 mol% of [Rh(C 2 H 4 ) 2 Cl] 2 under reflux in diethyl ether for 3 h. The absolute configuration was determined by comparison with literature values ,. and on the basis of similar stereochemical models. [b] Isolated product. [c] Determined by chiral stationary phase HPLC. [d] In brackets are given the yields and ees obtained with Sulfolefin 1 .…”