Development of Ar‐BINMOL‐Derived Atropisomeric Ligands with Matched Axial and sp³ Central Chirality for Catalytic Asymmetric Transformations

Abstract

Recently, academic chemists have renewed their interest in the development of 1,1'-binaphthalene-2,2'-diol (BINOL)-derived chiral ligands. Six years ago, a working hypothesis, that the chirality matching of hybrid chirality on a ligand could probably lead to high levels of stereoselective induction, prompted us to use the axial chirality of BINOL derivatives to generate new stereogenic centers within the same molecule with high stereoselectivity, obtaining as a result sterically favorable ligands for applications in asymmetric catalysis. This Personal Account describes our laboratory's efforts toward the development of a novel class of BINOL-derived atropisomers bearing both axial and sp(3) central chirality, the so-called Ar-BINMOLs, for asymmetric synthesis. Furthermore, on the basis of the successful application of Ar-BINMOLs and their derivatives in asymmetric catalysis, the search for highly efficient and enantioselective processes also compelled us to give special attention to the BINOL-derived multifunctional ligands with multiple stereogenic centers for use in catalytic asymmetric reactions.

Catalytic Enantioselective Addition of Organozirconium Reagents to Aldehydes

“…Provided with both axial and tetrahedral chirality, 1,1-binaphthalene-2-α-arylmethan-2-ols (Ar-BINMOLs)—developed by Kiyooka, Lai, and Xu [ 102 , 103 , 104 , 105 ]—have recently emerged as very efficient ligands for the titanium-assisted catalytic addition of organometallic reagents to carbonyl compounds [ 21 , 23 , 30 , 36 , 37 ]. Here, we started our investigations by evaluating the use of the very versatile Ph-BINMOL [ 23 , 102 , 103 , 104 , 105 ] ligand in the addition of 1-hexene to benzaldehyde ( Table 1 ). Following known procedures [ 97 , 98 , 99 ], the treatment of 1-hexene with 2.0 eq.…”

Catalytic Synthesis of Enantiopure Chiral Alcohols via Addition of Grignard Reagents to Carbonyl Compounds

“…In 2011, the straightforward synthesis of 1,1′-binaphthalene-2-alfa-arylmethan-2′-ols (Ar-BINMOLs) by Xu and co-workers encouraged Maciá and Yus et al to investigate the catalytic activity of those ligands for the direct addition of Grignard reagents to carbonyl compounds. Good results were obtained for the addition of alkylmagnesium bromides to aldehydes in the presence of Ti­(O i Pr) 4 (15 equiv) and the chiral ligand ( S a , R )-Ph-BINMOL L5 (20 mol %) at −40 °C (Scheme ).…”

Synthesis of atropisomeric phosphino-triazoles and their corresponding gold(i) complexes

“…[1][2][3] Atropisomerism is present in many compounds with several natural products, ligands and organocatalysts incorporating restricted rotation. [4][5][6] Phosphine ligands for transition metals that rely on atropisomerism to engender chirality into products are well established, with compounds such as BINAP and the phosphoramidite family commonly being employed in a variety of asymmetric catalytic applications (Fig. 1a).…”