Asymmetric Grignard Synthesis of Tertiary Alcohols through Rational Ligand Design

A simple, general and practical method is reported for highly enantioselective construction of tertiary alcohols through the direct addition of organomagnesium reagents to ketones. Discovered by rational ligand design based on a mechanistic hypothesis, it has an unprecedented broad scope. It utilizes a new type of chiral tridentate diamine/phenol ligand that is easily removed from the reaction mixture. It is exemplified by application to a formal asymmetric synthesis (>95:5 d.r.) of vitamin E.     

Reactivity of ortho‐Substituted Aryl–Palladium Complexes towards Carbodiimides,Isothiocyanates, Nitriles,and Cyanamides

Complexes [Pd(C₆H₃XH‐2‐R′‐5)Y(N^N)] (X=O, NH; Y=Br, I; R′=H, NO₂; N^N=N,N,N′,N′‐tetramethylethylenediamine (tmeda), 2,2′‐bipyridine (bpy), 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine (dtbbpy)) react with RN?C?E (E=NR, S) or RC≡N (R=alkyl, aryl, NR′′₂) and TlOTf (OTf=CF₃SO₃) to give, respectively, 1) products of the insertion of the C?E group into the C? Pd bond, protonation of the N atom, and coordination of X to Pd, [Pd{κ²‐X,E‐(XC₆H₃{EC(NHR)}‐2‐R′‐4)}(N^N)]OTf or [Pd(κ²‐X,N‐{ZC₆H₃(NH?CR)‐2‐R′‐4})(N^N)]OTf, or products of the coordination of carbodiimides and OH addition, [Pd{κ²‐C,N‐(C₆H₄{OC(NR)}NHR‐2)}(bpy)]OTf; or 2) products of the insertion of the C≡N group to Pd and N‐protonation, [Pd(κ²‐X,N‐{XC₆H₃(NH?CR)‐2‐R′‐4})(N^N)]OTf.