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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

Synthesis of binaphthyl-based chiral nucleophilic catalyst candidates.(a) Catalyst libraries containing C2- and C1-symmetic catalyst with different substitution pattern were used in the Steglich rearrangement of O-acylated oxindole derivatives. (b) C2-symmetric catalyst with polar functional group at 3,3′-positions of binaphthyl moiety can be prepared by a synthesis scheme that is high yielding and is readily amenable to scale-up with minimal column chromatography purification, as the representative example clearly illustrates. AIBN, 2,3′-azodiisobutyronitrile; NBS, N-bromosuccinimide; NDMBA, N,N′-dimethylbarbituric acid; RuPhos, 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1'-biphenyl.
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f3: Synthesis of binaphthyl-based chiral nucleophilic catalyst candidates.(a) Catalyst libraries containing C2- and C1-symmetic catalyst with different substitution pattern were used in the Steglich rearrangement of O-acylated oxindole derivatives. (b) C2-symmetric catalyst with polar functional group at 3,3′-positions of binaphthyl moiety can be prepared by a synthesis scheme that is high yielding and is readily amenable to scale-up with minimal column chromatography purification, as the representative example clearly illustrates. AIBN, 2,3′-azodiisobutyronitrile; NBS, N-bromosuccinimide; NDMBA, N,N′-dimethylbarbituric acid; RuPhos, 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1'-biphenyl.

Mentions: We began by preparing a series of enantiomerically pure DMAP derivatives (1a−p) that contain a 1,1′-binaphthyl unit with different substituents pattern at their C3 and C3′ sites with reference to chiral quaternary ammonium salt syntheses from BINOL (refs 39, 40; Fig. 3a, Supplementary Figs 1–26 and Supplementary Methods). The representative route for synthesis of catalyst 1j is presented in Fig. 3b. Ortho-lithiation of MOM-protected compound 2 derived from (S)-BINOL with n-BuLi, followed by quenching with ethyl chloroformate, and deprotection of MOM group under acidic conditions gave the desired BINOL with 3,3′-diesters 3 in 98% yield over 2 steps (78.9 mmol scale). Then, two hydroxy groups of 3 were converted to the corresponding ditriflate, and subjected to Migita–Kosugi–Stille coupling reaction in the presence of tetra n-butyl ammonium chloride and lithium chloride as additives to afford 5 in 83% yield. Our studies revealed that Migita–Kosugi–Stille coupling reaction using a Pd nanoparticle generated in situ was found to be superior to Negishi coupling reaction40 in large scale reaction because Me2Zn is costly and pyrophoric reagent. The benzylic positions of 5 were brominated using N-bromosuccinimide in the presence of 2,2′-azodiisobutyronitrile to give the desired dibromide 6 in 97% yield. Seven-membered ring formation from dibromide 6 using allylamine gave rise to the formation of amine 7 in 82% yield, and deprotection of ally group afforded amine 8 in 95% yield. Installation of pyridine ring was accomplished by using Buchwald–Hartwig amination of 4-bromopyridine hydrochoride with amine 8 to provide the key intermediate 1e in 70% yield. The formation of bis-tertiary alcohols 1j was readily accomplished by the addition of ArLi to bis-ester 1e in 91% yield. All transformations can be easily carried out in large scale (>10 g scale for 1e from BINOL throughout the whole process, and >1 g scale for 1j from 1e), and overall yield of 1j from (S)-BINOL was 38% (10 steps, >90% average yield for each step) with only 4 times of silica gel column chromatography purifications. The present synthetic route sufficiently secures facile accessibility to the key catalyst. The structures of 1e and 1g were identified by X-ray single-crystal analysis (Supplementary Figs 27 and 28).


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)

Synthesis of binaphthyl-based chiral nucleophilic catalyst candidates.(a) Catalyst libraries containing C2- and C1-symmetic catalyst with different substitution pattern were used in the Steglich rearrangement of O-acylated oxindole derivatives. (b) C2-symmetric catalyst with polar functional group at 3,3′-positions of binaphthyl moiety can be prepared by a synthesis scheme that is high yielding and is readily amenable to scale-up with minimal column chromatography purification, as the representative example clearly illustrates. AIBN, 2,3′-azodiisobutyronitrile; NBS, N-bromosuccinimide; NDMBA, N,N′-dimethylbarbituric acid; RuPhos, 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1'-biphenyl.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Synthesis of binaphthyl-based chiral nucleophilic catalyst candidates.(a) Catalyst libraries containing C2- and C1-symmetic catalyst with different substitution pattern were used in the Steglich rearrangement of O-acylated oxindole derivatives. (b) C2-symmetric catalyst with polar functional group at 3,3′-positions of binaphthyl moiety can be prepared by a synthesis scheme that is high yielding and is readily amenable to scale-up with minimal column chromatography purification, as the representative example clearly illustrates. AIBN, 2,3′-azodiisobutyronitrile; NBS, N-bromosuccinimide; NDMBA, N,N′-dimethylbarbituric acid; RuPhos, 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1'-biphenyl.
Mentions: We began by preparing a series of enantiomerically pure DMAP derivatives (1a−p) that contain a 1,1′-binaphthyl unit with different substituents pattern at their C3 and C3′ sites with reference to chiral quaternary ammonium salt syntheses from BINOL (refs 39, 40; Fig. 3a, Supplementary Figs 1–26 and Supplementary Methods). The representative route for synthesis of catalyst 1j is presented in Fig. 3b. Ortho-lithiation of MOM-protected compound 2 derived from (S)-BINOL with n-BuLi, followed by quenching with ethyl chloroformate, and deprotection of MOM group under acidic conditions gave the desired BINOL with 3,3′-diesters 3 in 98% yield over 2 steps (78.9 mmol scale). Then, two hydroxy groups of 3 were converted to the corresponding ditriflate, and subjected to Migita–Kosugi–Stille coupling reaction in the presence of tetra n-butyl ammonium chloride and lithium chloride as additives to afford 5 in 83% yield. Our studies revealed that Migita–Kosugi–Stille coupling reaction using a Pd nanoparticle generated in situ was found to be superior to Negishi coupling reaction40 in large scale reaction because Me2Zn is costly and pyrophoric reagent. The benzylic positions of 5 were brominated using N-bromosuccinimide in the presence of 2,2′-azodiisobutyronitrile to give the desired dibromide 6 in 97% yield. Seven-membered ring formation from dibromide 6 using allylamine gave rise to the formation of amine 7 in 82% yield, and deprotection of ally group afforded amine 8 in 95% yield. Installation of pyridine ring was accomplished by using Buchwald–Hartwig amination of 4-bromopyridine hydrochoride with amine 8 to provide the key intermediate 1e in 70% yield. The formation of bis-tertiary alcohols 1j was readily accomplished by the addition of ArLi to bis-ester 1e in 91% yield. All transformations can be easily carried out in large scale (>10 g scale for 1e from BINOL throughout the whole process, and >1 g scale for 1j from 1e), and overall yield of 1j from (S)-BINOL was 38% (10 steps, >90% average yield for each step) with only 4 times of silica gel column chromatography purifications. The present synthetic route sufficiently secures facile accessibility to the key catalyst. The structures of 1e and 1g were identified by X-ray single-crystal analysis (Supplementary Figs 27 and 28).

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