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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

Initial consideration and options in catalyst design.The basic design of the new acyl transfer catalysts, their projected advantages and the possible means by which electrostatic interactions can facilitate transformation. R1, FG, various functional groups.
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f2: Initial consideration and options in catalyst design.The basic design of the new acyl transfer catalysts, their projected advantages and the possible means by which electrostatic interactions can facilitate transformation. R1, FG, various functional groups.

Mentions: According to our continuous efforts for the development of chiral nucleophilic catalysts171819 to design an efficient and highly enantioselective acyl transfer catalyst that can be prepared in significant quantities without the need for expensive and/or specialized techniques, we envisioned chiral DMAP derivatives that might contain a binaphthyl unit at C4 position of a pyridine ring (Fig. 2). We reasoned that this blueprint would have several noteworthy advantages. First, either enantiomeric form of 1,1′-bi-2-naphthol (BINOL) is inexpensively available, thus obviating resolution procedures. Second, the catalyst platform allows synthesis and screening of C1- and C2-symmetric variants from a common intermediate. Third, the proposed catalyst construct easily lends to steric and/or electronic modification through the use of well-established protocols3940. Finally, the absence of substituents at the C2 or C3 sites of the pyridyl ring (cf. Fig. 1b,c) would ensure that efficiency levels remain high. The suggested line of attack poses several significant challenges, however. One is that because the source of stereogenicity is somewhat distal from the pyridine ring, an attribute can result in minimal enantioselectivity. Thus, appropriate structural modification would be needed if the stereochemical bias inherent in the binaphthyl moiety is to exert a meaningful role in the acyl bond forming event. Towards this end, preliminary examination of molecular models implied that the substituents (functional group) at C3 and C3′ positions of the binaphthyl moiety are located sufficiently proximal to the reaction site, offering an attractive option for influencing enantioselectivity through catalyst structure alteration. Thus, we surmised that attractive interactions (for example, π–π stacking, cation-π affinity2741 or hydrogen-bonding26) between an appropriate unit within the catalyst structure and counteranion of N-acylpyridinium salt (design option 1, Fig. 2), or the nucleophile (design option 2, Fig. 2) might give rise to enhancement of enantioselectivity and perhaps reaction efficiency. Below, we outline the successful realization of the above plan.


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)

Initial consideration and options in catalyst design.The basic design of the new acyl transfer catalysts, their projected advantages and the possible means by which electrostatic interactions can facilitate transformation. R1, FG, various functional groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Initial consideration and options in catalyst design.The basic design of the new acyl transfer catalysts, their projected advantages and the possible means by which electrostatic interactions can facilitate transformation. R1, FG, various functional groups.
Mentions: According to our continuous efforts for the development of chiral nucleophilic catalysts171819 to design an efficient and highly enantioselective acyl transfer catalyst that can be prepared in significant quantities without the need for expensive and/or specialized techniques, we envisioned chiral DMAP derivatives that might contain a binaphthyl unit at C4 position of a pyridine ring (Fig. 2). We reasoned that this blueprint would have several noteworthy advantages. First, either enantiomeric form of 1,1′-bi-2-naphthol (BINOL) is inexpensively available, thus obviating resolution procedures. Second, the catalyst platform allows synthesis and screening of C1- and C2-symmetric variants from a common intermediate. Third, the proposed catalyst construct easily lends to steric and/or electronic modification through the use of well-established protocols3940. Finally, the absence of substituents at the C2 or C3 sites of the pyridyl ring (cf. Fig. 1b,c) would ensure that efficiency levels remain high. The suggested line of attack poses several significant challenges, however. One is that because the source of stereogenicity is somewhat distal from the pyridine ring, an attribute can result in minimal enantioselectivity. Thus, appropriate structural modification would be needed if the stereochemical bias inherent in the binaphthyl moiety is to exert a meaningful role in the acyl bond forming event. Towards this end, preliminary examination of molecular models implied that the substituents (functional group) at C3 and C3′ positions of the binaphthyl moiety are located sufficiently proximal to the reaction site, offering an attractive option for influencing enantioselectivity through catalyst structure alteration. Thus, we surmised that attractive interactions (for example, π–π stacking, cation-π affinity2741 or hydrogen-bonding26) between an appropriate unit within the catalyst structure and counteranion of N-acylpyridinium salt (design option 1, Fig. 2), or the nucleophile (design option 2, Fig. 2) might give rise to enhancement of enantioselectivity and perhaps reaction efficiency. Below, we outline the successful realization of the above plan.

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