(R)‐BINOL‐6,6’‐bistriflone: Shortened Synthesis, Characterization, and Enantioselective Catalytic Applications

Abstract

The title compound, characterized by X‐ray crystallography, was accessed in 4 steps with 92 % ee. and 25 % yield from an O‐protected (R)‐BINOL precursor. This revised synthetic route relied on a chlorosulfonylation reaction, as a shortcut to a previously developed sequence requiring the use of toxic SO2 gas and bromine. The strongly electron‐impoverished (R)‐6,6′‐Tf2‐BINOL proved an effective ligand in metal‐catalyzed enantioselective transformations such as a Zr‐based Mannich‐type reaction. The catalytic species was characterized by X‐ray crystallography as a unique tetrameric metal cluster. The 6,6′‐bistriflone groups also allowed to exalt the H‐bond donor capacity of the BINOL moiety, as illustrated in an organocatalyzed Morita‐Baylis‐Hillman transformation. Theoretical study indicated that the 6,6′‐bistriflone groups induce a drop of the phenol acidity of 5 pKa units in DMSO. Overall, this work simplified the access, completed the characterization, and confirmed the potential of (R)‐6,6′‐Tf2‐BINOL as a promising platform to further elaborate activated chiral metal ligands or organocatalysts.

Regioselective Substitution of BINOL

“…Reaction of (R)-BINOL dihexyl ether with chlorosulfonic acid (12 equiv) in CHCl 3 at 0 °C to room temperature gave the 6,6′-dichlorosulfonyl product (R)-49 in 40% yield. 134 (R)-49 was then converted to (R)-50 to catalyze asymmetric reactions such as an alkyne addition to aldehydes, a Zr-based Mannich-type reaction and an organocatalyzed Morita−Baylis−Hillman transformation. The macrocycle (S)-51 was synthesized from (S)-49 (R = n C 4 H 9 ) and used for enantioselective extraction of phenylglycine from aqueous solution to chloroform.…”

“…( S )- 48 was used to form an ionic polymer with a chiral quaternary ammonium salt to catalyze the asymmetric alkylation of a glycine ester. Reaction of ( R )-BINOL dihexyl ether with chlorosulfonic acid (12 equiv) in CHCl 3 at 0 °C to room temperature gave the 6,6′-dichlorosulfonyl product ( R )- 49 in 40% yield . ( R )- 49 was then converted to ( R )- 50 to catalyze asymmetric reactions such as an alkyne addition to aldehydes, a Zr-based Mannich-type reaction and an organocatalyzed Morita–Baylis–Hillman transformation.…”

Cascade Alkenylation/Intramolecular Friedel–Crafts Alkylation: High Selectivity at the C7-Position of BINOL

“…4 Therefore, site-selective modification strategies to generate various BINOL derivatives have aroused great interest. 5 Up to the last two decades, the transition-metal-catalyzed C− H activation has opened sustainable synthetic methodologies to achieve a site-selective transformation. 5,6 Consequently, the C− H activation shows great potential in the regioselective study of BINOL derivatives.…”

“…It is worth mentioning that BINOL skeletons have gained a thriving popularity owing to their rigid structure and chelation with various metal centers . Therefore, site-selective modification strategies to generate various BINOL derivatives have aroused great interest …”

“…Up to the last two decades, the transition-metal-catalyzed C–H activation has opened sustainable synthetic methodologies to achieve a site-selective transformation. , Consequently, the C–H activation shows great potential in the regioselective study of BINOL derivatives. For example, 3,3′-biaryl, alkenyl, alkyl, and amination BINOLs have been synthesized out (Scheme , eq 1), which appears as a common and conventional ortho-site.…”