Synthesis and Applications of HexaPHEMP, a Novel Biaryl Diphosphine Ligand

Abstract

The novel biaryldiphosphine ligand 1 (HexaPHEMP) has been prepared in five steps from commercially available 3,4,5‐trimethylphenol using a concise synthetic route. This approach also allows fine tuning of the ligand's stereoelectronic properties through the variation of the aromatic groups on the ligating phosphorus atoms. In certain asymmetric hydrogenation processes, catalysts containing this ligand were found to have enhanced activity and selectivity over other biaryldiphosphine‐containing catalysts.

Enantioselective Hydrogenation of Aromatic Ketones Catalyzed by Ru Complex Using a New Bipyridyl Diphosphine

“…The preliminary results demonstrate that opposite results were obtained in different bases [KOH or (CH 3 ) 3 COK] when complexes 9a and 9c were used as catalysts (Table 1, Entries 1,2 vs. 4,5). In the solution of (CH 3 ) 3 COK higher enantioselectivity was achieved than in the solution of KOH when 9c was used as catalyst ( 16 Ru(S-MeO-P-Phos)(S,S-DPEN)Cl 2 afforded almost the same ee value as Ru(S-P-Phos)(S,S-DPEN)Cl 2 , but higher enantioselectivity was obtained with Ru(S-MeO-P-Phos)(S-DAIPEN)Cl 2 , Chiral diamine played a more significant role than chiral diphosphine in the asymmetric hydrogenation of acetophenone.…”

Asymmetric Hydrogenation of Quinoxalines Catalyzed by Iridium/PipPhos

“…The use of THF slightly increased the enantioselectivity to 73% yet the reaction was slower (entry 5). Finally, the best results were obtained in dichloromethane with ees up to 96% (entries [6][7][8]. It is clear that the presence of piperidine hydrochloride affects the enantioselectivity of this reaction in dichloromethane (entries 6 and 7).…”

“…[7] In 2003 Henschke et al reported the use of a diverse library of ruthenium Noyori-type precatalysts (RuPPNNCl 2 ) in the enantioselective hydrogenation of imines. [8] The highest enantioselectivity in the hydrogenation of 2-methylquinoxaline (73% ee) was obtained using (S)-Xyl-HexaPHEMP as ligand with the addition of (S,S)-cyclohexanediamine and potassium tert-butoxide as base. The use of a tethered BIPHEP-type ligand in combinatioin with [Ir-A C H T U N G T R E N N U N G (COD)Cl] 2 and I 2 was reported by Chan, who achieved up to 80% ee in the asymmetric hydrogenation of 1a.…”

Adventure in Asymmetric Hydrogenation: Synthesis of Chiral Phosphorus Ligands and Asymmetric Hydrogenation of Heteroaromatics

“…In 2003, Henschke group reported asymmetric hydrogenation of 2-methylquinoxaline by using Noyori's catalytic system RuCl 2 (diphosphine)(diamine) with moderate enantioselectivity [98,99]. Chan group reported the hydrogenation of 2-methylquinoxaline using the Ir-PQ-Phos complex as catalyst with up to 80% ee in the presence of iodine [67].…”