Axial-Chiral Biisoquinoline N,N′-Dioxides Bearing Polar Aromatic C-H Bonds as Catalysts in Sakurai-Hosomi-Denmark Allylation

Abstract

The design, synthesis, and evaluation of axial-chiral biisoquinolines bearing polar aromatic C-H bonds as Lewis base catalysts are reported. Lewis bases containing the 3,5-bis(trifluoromethyl)phenyl group were found to be significantly more enantioselective for a wider range of substrates than those bearing aromatic residues that are not strongly electron-deficient in the allylation of aldehydes with allyltrichlorosilane. Also, optically pure 3,3'-dibromo-1,1'-biisoquinoline N, N'-dioxide that has not been previously reported was synthesized as a common catalyst precursor to facilitate the study.

C(sp2)−H Hydrogen‐Bond Donor Groups in Chiral Small‐Molecule Organocatalysts

“…With respect to the stereochemical aspects of these transformations, the relative orientation of the chiral Lewis base, reacting substrates, and chlorine atoms (i. e., ligand configuration of such a hypervalent silicon complex) plays a central role for the enantioselectivity, however, the control of such a ligand configuration remains largely elusive and significantly challenging. In this context, Takenaka and co‐workers conceived a conceptually new strategy to selectively generate the trans ‐Cl complex ( 23 ) by internal hydrogen bonding from a catalyst (Scheme ) . More specifically, it was envisioned that not only the trans ‐Cl complex could be selectively generated over the other competing diastereomeric complexes but also the expected complex adopts a Λ‐ cis ‐α structure by virtue of hydrogen‐bonding in which chirality is at the Si atom (the reaction center) and its two coordination sites for substrates (L and E) are identical (two C 2 symmetric sites).…”

“…While Schreiner and co‐workers have clearly demonstrated the hydrogen‐bond donor ability of the ortho C−H bonds of the 3,5‐bis(trifluoromethyl)phenyl group (Figure ), and transition‐metal‐bound chlorines are known to accept hydrogen‐bonds, the extent to which peripheral Cl atoms of a hypervalent chlorosilane accept hydrogen‐bonds is not easily discerned without computational analysis. Therefore, Takenaka initiated a computational study in collaboration with the Peverati group . They began their computational investigation by performing a preliminary energy minimization of the complex of chiral Lewis base 24 and SiCl 4 in the gas phase.…”

Heteroaromatic N-Oxides in Asymmetric Catalysis: A Review

“…Axially-chiral symmetrically substituted 2,2 -biquinoline N,N'-dioxide derivatives were developed by Takenaka and Peverati. Simple transformations allowed to receive the new Lewis base catalysts 8 (see Figure 1) with yields up to 99% [36]. Their catalytic utility was tested in allylation of 4-metoxybenzaldehyde with allyltrichlorosilane.…”

“…The authors noticed that 8a is less reactive and less selective for the halogen-substituted aldehydes. Considering the fact, that electron-rich Lewis base catalysts are usually more reactive in reaction with halosilane compounds, they decided to prepare compound 8g, having two phenyl rings double substituted with CF 3 groups, suitable for aldehydes with halogen groups [36]. Application of 8g increased the yield, unfortunately with unchanged or only slightly increased enantioselectivity.…”

“…The allylations of benzaldehyde, p-methoxybenzaldehyde and p-trifluoromethylbenzaldehyde using 34, described in this report, were performed using 0.5 mol% of the catalyst [54]. Comparing them with the same reactions applying 1mol% of the catalyst [36] allows the conclusion that reducing the loading does not affect enantioselectivity. Only in case of p-trifluorobenzaldehyde the yield slightly decreased using (S,R)-enantiomer, while with use (R,R)-enantiomer, the yield apparently decreased, when half amount of catalyst has been used.…”