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

Mandai H, Fujii K, Yasuhara H, Abe K, Mitsudo K, Korenaga T, Suga S - Nat Commun (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.

ABSTRACT
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.

No MeSH data available.


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Application of the catalyst with tert-alcohols at 3,3′-positions of a 1,1′-binaphthyl unit to intermolecular acylations.(a) Kinetic resolution of secondary carbinol with 5 mol% 1j. The reaction proceeded smoothly with moderate selectivity factor. Conversion values (±1%) and er values (±1%) were determined by high-performance liquid chromatography (HPLC) analysis. (b) Kinetic resolution of acyclic d,l-1,2-diol 13 with 0.5 mol % 1g. The reaction proceeded smoothly to afford (1S, 2S)-14 and (1R, 2R)-13 with high enantioselectivity. None of the di-acylated product was observed. Conversion values (±2%) were determined by 1H nuclear magnetic resonance (NMR) analysis of the unpurified reaction mixtures. Er values (±1%) were determined by HPLC analysis. (c) Desymmetrization of acyclic meso-1,2-diol 15 with 0.1 mol% 1g. Monoprotected diol (1S, 2R)-16 was obtained in 79% yield with high enantioselectivity (97:3 er). Small amount of di-acylated product 17 and meso-15 was obtained in 7 and 12% yield, respectively. Er values (±1%) were determined by HPLC analysis.
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f9: Application of the catalyst with tert-alcohols at 3,3′-positions of a 1,1′-binaphthyl unit to intermolecular acylations.(a) Kinetic resolution of secondary carbinol with 5 mol% 1j. The reaction proceeded smoothly with moderate selectivity factor. Conversion values (±1%) and er values (±1%) were determined by high-performance liquid chromatography (HPLC) analysis. (b) Kinetic resolution of acyclic d,l-1,2-diol 13 with 0.5 mol % 1g. The reaction proceeded smoothly to afford (1S, 2S)-14 and (1R, 2R)-13 with high enantioselectivity. None of the di-acylated product was observed. Conversion values (±2%) were determined by 1H nuclear magnetic resonance (NMR) analysis of the unpurified reaction mixtures. Er values (±1%) were determined by HPLC analysis. (c) Desymmetrization of acyclic meso-1,2-diol 15 with 0.1 mol% 1g. Monoprotected diol (1S, 2R)-16 was obtained in 79% yield with high enantioselectivity (97:3 er). Small amount of di-acylated product 17 and meso-15 was obtained in 7 and 12% yield, respectively. Er values (±1%) were determined by HPLC analysis.

Mentions: The utility of the present class of catalysts is not confined to Steglich rearrangements. For examples, as the representative data in Fig. 9 indicate, we find that binaphthyl-based DMAP derivatives with tert-alcohols at 3,3′-positions of a 1,1′-binaphthyl unit is not only effective in kinetic resolution of secondary carbinol and d,l-1,2-diol but in enantioselective desymmetrization of meso-1,2-diol as well. Initially, kinetic resolution of secondary carbinol rac-11 with an array of binaphthyl-based DMAP derivatives was performed. The reaction in the presence of 5 mol % 1j proceeded smoothly with moderate s-factor (s=11, Fig. 9a, and Supplementary Figs 69–72). We then turned our attention to 1,2-diol which might be more suitable than simple carbinols, expecting positive interactions between a substrate and a catalyst through the hydrogen bonding.


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

Mandai H, Fujii K, Yasuhara H, Abe K, Mitsudo K, Korenaga T, Suga S - Nat Commun (2016)

Application of the catalyst with tert-alcohols at 3,3′-positions of a 1,1′-binaphthyl unit to intermolecular acylations.(a) Kinetic resolution of secondary carbinol with 5 mol% 1j. The reaction proceeded smoothly with moderate selectivity factor. Conversion values (±1%) and er values (±1%) were determined by high-performance liquid chromatography (HPLC) analysis. (b) Kinetic resolution of acyclic d,l-1,2-diol 13 with 0.5 mol % 1g. The reaction proceeded smoothly to afford (1S, 2S)-14 and (1R, 2R)-13 with high enantioselectivity. None of the di-acylated product was observed. Conversion values (±2%) were determined by 1H nuclear magnetic resonance (NMR) analysis of the unpurified reaction mixtures. Er values (±1%) were determined by HPLC analysis. (c) Desymmetrization of acyclic meso-1,2-diol 15 with 0.1 mol% 1g. Monoprotected diol (1S, 2R)-16 was obtained in 79% yield with high enantioselectivity (97:3 er). Small amount of di-acylated product 17 and meso-15 was obtained in 7 and 12% yield, respectively. Er values (±1%) were determined by HPLC analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4835565&req=5

f9: Application of the catalyst with tert-alcohols at 3,3′-positions of a 1,1′-binaphthyl unit to intermolecular acylations.(a) Kinetic resolution of secondary carbinol with 5 mol% 1j. The reaction proceeded smoothly with moderate selectivity factor. Conversion values (±1%) and er values (±1%) were determined by high-performance liquid chromatography (HPLC) analysis. (b) Kinetic resolution of acyclic d,l-1,2-diol 13 with 0.5 mol % 1g. The reaction proceeded smoothly to afford (1S, 2S)-14 and (1R, 2R)-13 with high enantioselectivity. None of the di-acylated product was observed. Conversion values (±2%) were determined by 1H nuclear magnetic resonance (NMR) analysis of the unpurified reaction mixtures. Er values (±1%) were determined by HPLC analysis. (c) Desymmetrization of acyclic meso-1,2-diol 15 with 0.1 mol% 1g. Monoprotected diol (1S, 2R)-16 was obtained in 79% yield with high enantioselectivity (97:3 er). Small amount of di-acylated product 17 and meso-15 was obtained in 7 and 12% yield, respectively. Er values (±1%) were determined by HPLC analysis.
Mentions: The utility of the present class of catalysts is not confined to Steglich rearrangements. For examples, as the representative data in Fig. 9 indicate, we find that binaphthyl-based DMAP derivatives with tert-alcohols at 3,3′-positions of a 1,1′-binaphthyl unit is not only effective in kinetic resolution of secondary carbinol and d,l-1,2-diol but in enantioselective desymmetrization of meso-1,2-diol as well. Initially, kinetic resolution of secondary carbinol rac-11 with an array of binaphthyl-based DMAP derivatives was performed. The reaction in the presence of 5 mol % 1j proceeded smoothly with moderate s-factor (s=11, Fig. 9a, and Supplementary Figs 69–72). We then turned our attention to 1,2-diol which might be more suitable than simple carbinols, expecting positive interactions between a substrate and a catalyst through the hydrogen bonding.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus