Enantioselective acyl transfer catalysis by a combination of common catalytic motifs and electrostatic interactions

Catalysts that can promote acyl transfer processes are important to enantioselective synthesis and their development has received significant attention in recent years. Despite noteworthy advances, discovery of small-molecule catalysts that are robust, efficient, recyclable and promote reactions with high enantioselectivity can be easily and cost-effectively prepared in significant quantities (that is, >10 g) has remained elusive. Here, we demonstrate that by attaching a binaphthyl moiety, appropriately modified to establish H-bonding interactions within the key intermediates in the catalytic cycle, and a 4-aminopyridyl unit, exceptionally efficient organic molecules can be prepared that facilitate enantioselective acyl transfer reactions. As little as 0.5 mol% of a member of the new catalyst class is sufficient to generate acyl-substituted all-carbon quaternary stereogenic centres in quantitative yield and in up to 98:2 enantiomeric ratio (er) in 5 h. Kinetic resolution or desymmetrization of 1,2-diol can be performed with high efficiency and enantioselectivity as well.

. HPLC spectra for product 10d of Steglich rearrangement with catalyst 1j (see Figure 5) Supplementary Figure 59. HPLC spectra for product 10f of Steglich rearrangement with catalyst 1j (see Figure 5)  Figure 60. HPLC spectra for product 10g of Steglich rearrangement with catalyst 1j (see Figure 5)  Figure 61. HPLC spectra for product 10h of Steglich rearrangement with catalyst 1j (see Figure 5)  Figure 62. HPLC spectra for product 10i of Steglich rearrangement with catalyst 1j (see Figure 5)  Figure 63. HPLC spectra for product 10j of Steglich rearrangement with catalyst 1j (see Figure 5)   We conducted several screening in order to explore the optimal reaction conditions. After screening of catalyst (Figure 4a), we carried out screening of solvent (Supplementary Table 1). Various solvents could be used in these reaction to afford the product 10a with complete conversions (>98% conv) and a high enantioselectivity (>95:5 er, entries 17) except in the case of hexane and t-amyl alcohol (entries 8 and 9). In addition, the t-amyl alcohol significantly decreased the enantioselectivity (64:36 er) which might be stem largely from inhibition of hydrogen bonding network between the catalyst 1j and substrate 9a in the transition state. Since the highest enantiomeric ratio (98:2 er) was achieved in the reaction in THF (entry 1), we selected THF as an optimal solvent.  The screening of the reaction temperature for the explore of optimal reaction conditions Next, we also carried out the reaction at various temperature (Supplementary Table 2). The reaction at above -40 °C proceeded smoothly (>98% conv; >96:4 er; entries 14), whereas below -60 °C decreased the reaction conversions with maintaining almost the same enantiomeric ratios (99:1 er, entries 5 and 6). Interestingly, synthetically useful enantioselectivity (96:4 er) was also maintained even if the reaction at 25 °C. The catalyst 1j, however, could be used and tolerated in various solvents and the reaction temperature to deliver the desired product 10a with a high enantiomeric ratio. Judging from practicality and efficiency of the reaction, the reaction at -20 °C was determined to be optimal in the enantioselective Steglich rearrangement of oxindoles.
Supplementary Table 3. The screening of the migrating and N-protected group for the explore of optimal reaction conditions We carried out the reaction with different migrating group (Supplementary Table 3). As a result, phenyl carbonate gave the best enantioselectivity (98:2 er, entry 1). Therefore phenyl carbonate thought to be the O OPh optimal migrating group, and was used for further screening. The procedures and the compounds data were shown in the later part of this supporting information.
Supplementary Table 4. The screening of the catalyst loading for the explore of optimal reaction conditions We carried out the reaction in the presence of various catalyst loading (Supplementary Table 4). The reaction with at least 0.5 mol % of catalyst 1j also proceeded smoothly, and the desired product 10a was obtained in >98% conv with 98:2 er (entries 14). The use of less than 0.3 mol % of 1j in the reaction decreased the conversion of 9a after 12 h but still maintaining high enantioselectivities (entries 5 and 6).   ntary Table   ee Energies

General procedure for the Steglich rearrangement of oxindole derivatives
When the catalytic amounts was less than 0.5 mol %, a solution of the catalyst in THF (50.0 mM) was prepared in advance and this stock solution was used the following reaction.
To a solution of substrate 9b−r in THF was added a catalyst or a solution of the catalyst at −20 ºC. The reaction mixture was stirred for 5 h and then 1 M aqueous HCl was added. The resulting mixture was extracted with EtOAc, dried over MgSO 4 and concentrated in vacuo. The purification of the crude product by flash column chromatography on a short pad of silica gel (eluent: hexane/Et 2 O = 1/1, v/v) gave the corresponding product 10b−m (>98% yield). The enantiomeric ratio was determined by chiral HPLC analysis.
The absolute configuration of the product 10j was assigned to be (S)-configuration according to Vedejs's paper 9 and 10b, 10d-l and 10n-p were assigned to be (S)-configuration according to our previous paper (10k; (R)-configuration) 10 . For product 10c, the absolute configuration was determined by single crystal X-ray structure analysis (Supplementary Figure 67).