Enantioselective Additions of Aryltitanium Tris(isopropoxide) to Ketones: Structure of [(i‐PrO)₂Ti{μ‐(S)‐BINOLate}(μ‐O‐i‐Pr)TiPh(O‐i‐Pr)₂], Study of Mechanistic and Stereochemical Insights

Abstract

Aryl addition reactions of ArTi(O‐i‐Pr)3 to aromatic, heteroaromatic, or α,β‐unsaturated ketones are described, producing tertiary alcohols in good to excellent enantioselectivities of up to 97% ee. The structure of the dititanium complex [(i‐PrO)2Ti{μ‐(S)‐BINOLate}(μ‐O‐i‐Pr)TiPh(O‐i‐Pr)2] [(S)‐4] that simultaneously bears a chiral directing ligand and a nucleophile is reported. Complex (S)‐4 possesses a pocket structure and has been illustrated as the key active species for addition reactions of both aldehydes and ketones. Mechanistic and stereochemical insights concerning addition reactions of organometallic reagents to organic carbonyls are rationalized based on the pocket structure and pocket size of (S)‐4.

Enhancement of the Catalytic Activity of Chiral H8‐BINOL Titanium Complexes by Introduction of Sterically Demanding Groups at the 3‐Position

“…First, the aryl (Ar) group on ArTi(O i Pr) 3 is transferred to complex IA to generate complex 4 . The X‐ray crystal structure of a closely relevant [(BINOLate)Ti 2 (O i Pr) 5 (Ph)] complex has been reported recently by Gau et al . Complex 4 is then coordinated by an aldehyde to form the activated complex 5 , which undergoes arylation to give intermediate 6 enantioselectively .…”

“…[20] First, the aryl (Ar) group on ArTi(OiPr) 3 is transferredt oc omplex IA to generate complex 4.T he X-ray crystal structure of ac losely relevant [(BI-NOLate)Ti 2 (OiPr) 5 (Ph)] complex has been reported recently by Gau et al [21] Complex 4 is then coordinated by an aldehyde to form the activated complex 5,w hich undergoes arylation to give intermediate 6 enantioselectively. [20] First, the aryl (Ar) group on ArTi(OiPr) 3 is transferredt oc omplex IA to generate complex 4.T he X-ray crystal structure of ac losely relevant [(BI-NOLate)Ti 2 (OiPr) 5 (Ph)] complex has been reported recently by Gau et al [21] Complex 4 is then coordinated by an aldehyde to form the activated complex 5,w hich undergoes arylation to give intermediate 6 enantioselectively.…”

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

“…Catalytic asymmetric nucleophilic addition of arylmetallic reagents to ketones is a simple and efficient method to construct optically active monoaryl, diaryl and/or triaryl tertiary alcohols ,. In 2013, Gau and co‐workers reported the arylation of ketones with ArTi(O‐ i‐ Pr) 3 in the presence of 10 mol% of ( S )‐BINOL 3a and 50 mol% of Ti(O‐ i‐ Pr) 4 (Scheme ) . High yields and excellent enantioselectivities were observed with aromatic, heteroaromatic and α,β‐unsaturated ketones, while aliphatic ketones gave less satisfactory enantiocontrol (e.g., product 4d , 32% ee ).…”

Development of Highly Active Chiral Titanium Catalysts for the Enantioselective Addition of Various Organometallic Reagents to Aldehydes

“…First, the aryl group on ArTi(O i Pr) 3 is transferred to 35 to generate complex 37 . Recently, the isolation and X‐ray crystal analysis of the ( S )‐BINOL derivative ( 37 ; Ar = Ph, R = H) has been reported by Gau et al55 Complex 37 is then coordinated by an aldehyde to form activated complex 38 , which undergoes facile arylation to give intermediate 39 enantioselectively. In complex 38 , substituent R at the 3‐position is located distal to the reaction center, which is consistent with the fact that the substituents are not influential on the inherent enantioselectivity of the 3‐aryl H 8 ‐BINOL derivatives.…”