An Improved and Safer Synthesis of (R)‐ and (S)‐4,4′‐Diaminomethyl‐BINAP

Abstract

(R)‐ and (S)‐4,4′‐diaminomethyl‐BINAP were prepared in three steps from enantiomerically pure BINAPO in a global yield of 52 %. A regioselective bromination of BINAPO with NBS in HMimPF6 gave the desired 4,4′‐dibromo‐BINAPO in quantitative yield, and the recyclability of the ionic liquid was demonstrated. Copper cyanide cyanation of 4,4′‐dibromo‐BINAPO gave the 4,4′‐dicyano‐BINAPO in 70 % yield. Both enantiomers were characterized by NMR spectroscopy and HPLC analysis, and the structures were confirmed by X‐ray crystallography. The cyano and phosphane oxide groups of the resulting 4,4′‐dicyano‐BINAPO were reduced in one step to the corresponding 4,4′‐diaminomethyl‐BINAP by using tetramethyldisiloxane/Ti(OiPr)4 in 75 % yield.

Lewis Base-Catalyzed Enantioselective Conjugate Reduction of β,β-Disubstituted α,β-Unsaturated Ketones with Trichlorosilane: E/Z-Isomerization, Regioselectivity, and Synthetic Applications

“…We then screened a variety of chiral Lewis bases at −40 °C (entries 3–6 and Figure ). Compared to a bulkier catalyst (xylyl-BINAPO) or more Lewis basic catalysts (SEGPHOSO and p -tol-DIOPO) (entries 3–5), 4,4′-dibromo-BINAPO (Br 2 -BINAPO) provided higher regio- and enantioselectivities (entry 6). Both selectivities were improved (to 99:1 regioselectivity and 92% ee) when the reaction temperature was further lowered to −78 °C using Br 2 -BINAPO (entry 7).…”

“…( S )-BINAPO, ( S )-xylyl-BINAPO, and ( S )-SEGPHOSO were prepared by oxidation of the corresponding diphosphine with hydrogen peroxide in acetone . ( R , R )- p -tolyl-DIOPO and ( S )-Br 2 -BINAPO were prepared according to the literatures. Enones 1a – 1c , 1d – 1e , 1f , 1l – 1s , and ar -atlantone ( 1t ) were prepared according to the literature.…”

“…After the product was obtained by column chromatography on silica gel, the catalyst (Br 2 -BINAPO) was recovered quantitatively by eluting with CH 2 Cl 2 /MeOH (10:1) and reused after recrystallization …”

Synthesis of binaphthyl based phosphine and phosphite ligands

“…Furthermore, Lemaire described several reports on the synthesis of BINAP diphosphines bearing ammonium quaternised substituents in various positions of the binaphthyl skeleton, in order to enhance their solubilisation in water. 160,164,[238][239][240] In general, the cyano-BINAP derivatives were reduced with LiAlH 4 to give the corresponding amino-BINAP compounds. Simple aqueous HBr addition transformed these ligands into the desired bromide ammonium quaternised water soluble salts 137-140 (Fig.…”

“…Catalysts could be recycled several times by extraction of the product with pentane with practically no loss of activity and just a slight decrease in the enantioselectivity. 160,239,240 Reetz and Gavrilov 241 described the synthesis of a new class of P-monodentate phosphite ligands bearing ionic liquid fragments (Fig. 66) by reaction of (S)-BINOL phosphochloridite with an equimolar solution of imidazolium based ionic liquid and triethylamine, in dichloromethane, giving 141 in 40% isolated yield.…”