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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.


Related in: MedlinePlus

Enantioselective Steglich-type reactions of various substrates promoted by catalyst 1j.A wide range of substrates may be subjected to enantioselective acyl rearrangement processes that afford quaternary carbon stereogenic centres in quantitative yield and in up to 98:2 er. The level of enantioselectivity can depend on the nature of the substituents within the oxindole ring. Reactions were performed on a 0.1 or 0.2 mmol (10b, 10d and 10l) scale in THF (0.4 M) under an argon atmosphere. Yields are of isolated and purified products after silica gel chromatography (±2%). Er values (±1%) were determined by high-performance liquid chromatography (HPLC) analysis.
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f5: Enantioselective Steglich-type reactions of various substrates promoted by catalyst 1j.A wide range of substrates may be subjected to enantioselective acyl rearrangement processes that afford quaternary carbon stereogenic centres in quantitative yield and in up to 98:2 er. The level of enantioselectivity can depend on the nature of the substituents within the oxindole ring. Reactions were performed on a 0.1 or 0.2 mmol (10b, 10d and 10l) scale in THF (0.4 M) under an argon atmosphere. Yields are of isolated and purified products after silica gel chromatography (±2%). Er values (±1%) were determined by high-performance liquid chromatography (HPLC) analysis.

Mentions: A variety of different substrates can be used in the enantioselective Steglich rearrangement process (Fig. 5 and Supplementary Figs 42–66). Thus, 3-alkyl-, 3-allyl- or 3-propargyl-substituted oxindole products 10b−f were isolated in quantitative yields and in 96:4–99:1 er. Higher catalyst loading (3.0 versus 0.5 mol%) and temperature (25 versus –20 °C) was required in the case of 10c, probably as a result of the presence of the more sterically demanding iso-propyl group. The stereochemical identity of 10c was established through an X-ray structure (Supplementary Fig. 67). Transformation with substrates that contain an alkyl chain that bears a functionalizable polar group, such as an amide (10g), a silyl ether (10h) or a cyano unit (10i) proved to be exceptionally efficient (>98% yield) and highly enantioselective (91:9–97:3 er). Rearrangements involving 3-phenyl- (10j) or 3-thienyl-substituted oxindoles (10k) were more sluggish (3.0 mol % 1j at −20 °C was needed) likely due to their sizeable nature, but were also less enantioselective than the previous examples (79:21–84:16 er). Efficient and enantioselective preparation of bromo-substituted 10l (>98% yield, 92:8 er) and N-Me oxindole 10m (>98% yield, 87:13 er) further illustrates the scope of the catalytic process.


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)

Enantioselective Steglich-type reactions of various substrates promoted by catalyst 1j.A wide range of substrates may be subjected to enantioselective acyl rearrangement processes that afford quaternary carbon stereogenic centres in quantitative yield and in up to 98:2 er. The level of enantioselectivity can depend on the nature of the substituents within the oxindole ring. Reactions were performed on a 0.1 or 0.2 mmol (10b, 10d and 10l) scale in THF (0.4 M) under an argon atmosphere. Yields are of isolated and purified products after silica gel chromatography (±2%). Er values (±1%) were determined by high-performance liquid chromatography (HPLC) analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Enantioselective Steglich-type reactions of various substrates promoted by catalyst 1j.A wide range of substrates may be subjected to enantioselective acyl rearrangement processes that afford quaternary carbon stereogenic centres in quantitative yield and in up to 98:2 er. The level of enantioselectivity can depend on the nature of the substituents within the oxindole ring. Reactions were performed on a 0.1 or 0.2 mmol (10b, 10d and 10l) scale in THF (0.4 M) under an argon atmosphere. Yields are of isolated and purified products after silica gel chromatography (±2%). Er values (±1%) were determined by high-performance liquid chromatography (HPLC) analysis.
Mentions: A variety of different substrates can be used in the enantioselective Steglich rearrangement process (Fig. 5 and Supplementary Figs 42–66). Thus, 3-alkyl-, 3-allyl- or 3-propargyl-substituted oxindole products 10b−f were isolated in quantitative yields and in 96:4–99:1 er. Higher catalyst loading (3.0 versus 0.5 mol%) and temperature (25 versus –20 °C) was required in the case of 10c, probably as a result of the presence of the more sterically demanding iso-propyl group. The stereochemical identity of 10c was established through an X-ray structure (Supplementary Fig. 67). Transformation with substrates that contain an alkyl chain that bears a functionalizable polar group, such as an amide (10g), a silyl ether (10h) or a cyano unit (10i) proved to be exceptionally efficient (>98% yield) and highly enantioselective (91:9–97:3 er). Rearrangements involving 3-phenyl- (10j) or 3-thienyl-substituted oxindoles (10k) were more sluggish (3.0 mol % 1j at −20 °C was needed) likely due to their sizeable nature, but were also less enantioselective than the previous examples (79:21–84:16 er). Efficient and enantioselective preparation of bromo-substituted 10l (>98% yield, 92:8 er) and N-Me oxindole 10m (>98% yield, 87:13 er) further illustrates the scope of the catalytic process.

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