Functionalized BINOL Derivatives as Ligands for Enantioselectively Catalyzed Aldol Additions: Highly Enantioselective Synthesis of Chiral β-Hydroxy Thioesters

Abstract

A series of 3,3¢-disubstituted and 6,6¢-disubstituted BINOL derivatives was synthesized and examined in typical titanium(IV) promoted aldol reactions. The model reaction of S-ketene silyl acetal 13 and aldehydes 12a and 12b revealed that 6,6¢-dibromo-BINOL derivative (R)-6 is the ligand of choice for these transformations. Up to 97% yield with excellent enantioselectivity (ee > 97%) could be achieved. Scope and limitations were demonstrated using a series of aldehydes as substrates, which were generally transformed into their aldol adducts by the (R)-6/Ti(Oi-Pr) 4 catalyst with good efficacy and high enantioselectivity.

Quinoid BINOL-type compounds as a novel class of chiral ligands

“…The ethoxy-groups were removed after the iodination in positions 3,3 0 with BBr 3 in CH 2 Cl 2 to yield compound (R)-18 15 quantitatively. Sonogashira-coupling with trimethylsilyl acetylene and subsequent cleavage of the TMS-groups under basic conditions gave bisalkynes (R)-19 16 and (R)-20 17 in quantitative yields, respectively. Although quantitative consumption of the alkyne was observed, unfortunately, no product arising from the double benzannulation of (R)-20 and pentacarbonyl[methoxy(phenyl)carbene]chromium could be isolated after in situ oxidation with CAN.…”

“…After removing the solvent under reduced pressure, the remaining residue was dried in vacuo to give compound 19 (0.34 g, 99%) as a white solid; the spectroscopic and chiroptical data were in agreement with those reported in the literature. 16 4.14. (R)-3,3 0 -Diethynyl-2,2 0 -dihydroxy-1,1 0 -binaphthyl, 20…”

In the Arena of Enantioselective Synthesis, Titanium Complexes Wear the Laurel Wreath

“…416 A screening of different BINOL derivatives showed that varying the electronic properties of substitutents at the 6 position had a remarkable influence on the enantioselectivity and the chemical yield, with the best BINOL being the ligand 90ax, which could perform the aldol reaction in the absence of any additive with a wide scope of different functionalized aldehydes (for instance 57%, 92% for compound 307b). 417 However, substituents at the 3 position of ligands had a detrimental effect.…”

An Enantioselective Mukaiyama Aldol Reaction as the Key Step towards the Tetrahydropyran Core of Psymberin via a γ-Butyrolactone Intermediate

“…The catalytic system worked best at 0°C by using 20 mol% of catalyst (Table 2, entry 2). The dibromobinaphthol ligand D 18 furnished moderate to good yields (23-84%) and the enantiomeric excess was consistently superior (≥96%; Table 2, entries 5-7). Best results were obtained running the reaction at 0°C: An excellent enantiomeric excess of 98% and 84% yield were obtained using 20 mol% of catalyst (Table 2, entry 6).…”