3,3′-Substituted BINAP derivatives containing C-bound substituents: applications in asymmetric hydrogenation reactions

The synthesis and resolution of the first 3,3′-disubstituted BINAP ligands containing C-bonded substituents are described. An ortho-metallation/electrophile capture sequence was used to obtain the key trisubstituted naphthalene intermediate available and this intermediate was successfully converted into the desired ligands. Minor changes in the steric and stereoelectronic components of the 3,3′-substituents on the enantioselectivity and product enantiosense were also assessed in the context of the Rh-catalyzed asymmetric hydrogenation of enamides. A comparison of the absolute stereochemistry of the products derived from 3,3′-disubstituted BINAPs containing C-bonded substituents with their O-bound counterparts indicated that the product enantiosense could be dictated by increased steric bulk due to the 3 and 3′-substituents.

Graphical abstractThe synthesis and resolution of the first 3,3′-disubstituted BINAP derivatives containing C-bound substituents is described along with their use in the asymmetric hydrogenation of enamides.Figure optionsDownload full-size imageDownload as PowerPoint slide

(Sax)-2,2′-Bis-(diphenylphosphinoyl)-3,3′-bis-phenylethynyl-[1,1′]binaphthylC60H40O2P2Ee = >98%[α]D20=-137 (c 0.225, CHCl3)Source of chirality: co-crystallized with (–)-DTTA (di-p-toluoyl-l-tartaric acid monohydrate)Absolute configuration: (Sax)

(Sax)-2,2′-Bis-(diphenylphosphinoyl)-3,3′-bis-phenethyl-[1,1′]binaphthylC60H48O2P2Ee = >98%[α]D20=+95.5 (c 0.225, CHCl3)Source of chirality: derivative of (Sax)-2,2′-bis-(diphenylphosphinoyl)-3,3′-bis-phenylethynyl [1,1′]binaphthylAbsolute configuration: (Sax)

(Sax)-2,2′-Bis-(diphenylphosphino)-3,3′-bis-phenethyl-[1,1′]binaphthylC60H48P2Ee = >98%[α]D20=-137.1 (c 0.275, CHCl3)Source of chirality: derivative of (Sax)-2,2′-bis-(diphenylphosphinoyl)-3,3′-bis-phenylethynyl [1,1′]binaphthylAbsolute configuration: (Sax)

(Sax)-2,2′-(2,2′-Bis(diphenylphosphoryl)-[1,1′-binaphthalene]-3,3′-diyl)bis(1-phenylethane-1,2-dione)C60H48O6P2Ee = >98%[α]D20=-528 (c 0.195, CHCl3)Source of chirality: derivative of (Sax)-2,2′-bis-(diphenylphosphinoyl)-3,3′-bis-phenylethynyl [1,1′]binaphthylAbsolute configuration: (Sax)Sax confirmed by X-ray crystallography

(Sax)-2,2′-Bis-(diphenylphosphinoyl)-3,3′-bis-(hydroxymethyl)-[1,1′]binaphthylC60H36O4P2Ee = >98%[α]D20=+759 (c 0.205, CHCl3)Source of chirality: derivative of (Sax)-2,2′-bis-(diphenylphosphinoyl)-3,3′-bis-phenylethynyl [1,1′]binaphthylAbsolute configuration: (Sax)

(Sax)-2,2′-Bis-(diphenylphosphinoyl)-3,3′-bis-(phenoxymethyl)-[1,1′]binaphthylC58H44O4P2Ee = >98%[α]D20=+228 (c 0.265, CHCl3)Source of chirality: derivative of (Sax)-2,2’-bis-(diphenylphosphinoyl)-3,3′-bis-phenylethynyl [1,1′]binaphthylAbsolute configuration: (Sax)

(Sax)-2,2′-Bis-(diphenylphosphino)-3,3′-bis-(phenoxymethyl)-[1,1′]binaphthylC58H44O2P2Ee = >98%[α]D20=+129 (c 0.200, CHCl3)Source of chirality: derivative of (Sax)-2,2′-bis-(diphenylphosphinoyl)-3,3′-bis-phenylethynyl [1,1′]binaphthylAbsolute configuration: (Sax)