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Parts-per-million level loading organocatalysed enantioselective silylation of alcohols.

Park SY, Lee JW, Song CE - Nat Commun (2015)

Bottom Line: Similar to metal catalysis, extremely low catalyst loading (p.p.m. or p.p.b. levels) is the ultimate goal of the organocatalysis community.Herein we report a remarkable contribution in this context: 1 p.p.m. loading of a simple 1,1'-bi-2-naphthol-based organocatalyst was enough to achieve highly enantioselective silylation reactions of alcohols.The unprecedented TONs and excellent enantioselectivity are ascribed to the robustness of the catalyst and systematic cooperative hydrogen-bonding organocatalysis in a densely confined chiral space.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, Korea.

ABSTRACT
The field of organocatalysis has blossomed over the past few decades, becoming an alternative to transition-metal catalysis or even replacing the realm of transition-metal catalysis. However, a truly powerful organocatalyst with a high turnover number (TON) and turnover frequency (TOF) while retaining high enantioselectivity is yet to be discovered. Similar to metal catalysis, extremely low catalyst loading (p.p.m. or p.p.b. levels) is the ultimate goal of the organocatalysis community. Herein we report a remarkable contribution in this context: 1 p.p.m. loading of a simple 1,1'-bi-2-naphthol-based organocatalyst was enough to achieve highly enantioselective silylation reactions of alcohols. The unprecedented TONs and excellent enantioselectivity are ascribed to the robustness of the catalyst and systematic cooperative hydrogen-bonding organocatalysis in a densely confined chiral space.

No MeSH data available.


Related in: MedlinePlus

Substrate scope of the silylative kinetic resolution of racemic alcohol 2 catalysed by 1e.The reactions were performed in the presence of 1 equiv of KF and 0.8 equiv of Amberlite CG 50 (CG 50). *Using catalyst 1c (X=Cl, 16.8% conv., s=20), catalyst 1d (X=Br, 36.7% conv., s=48), catalyst 1f (X=CF3, 50.8% conv., s=50) and catalyst 1g (X=C2F5, 34.1% conv., s=30). †Using catalyst 1d (X=Br). e.r., enantiomeric ratio.
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f4: Substrate scope of the silylative kinetic resolution of racemic alcohol 2 catalysed by 1e.The reactions were performed in the presence of 1 equiv of KF and 0.8 equiv of Amberlite CG 50 (CG 50). *Using catalyst 1c (X=Cl, 16.8% conv., s=20), catalyst 1d (X=Br, 36.7% conv., s=48), catalyst 1f (X=CF3, 50.8% conv., s=50) and catalyst 1g (X=C2F5, 34.1% conv., s=30). †Using catalyst 1d (X=Br). e.r., enantiomeric ratio.

Mentions: With the optimized reaction conditions in hand, the substrate scope of our protocol was investigated, and the results are shown in Fig. 4. Various simple acyclic 1-arylalkanols 2a–2r without any secondary binding functionality were successfully resolved with excellent selectivity factors. Both the electron-withdrawing and electron-donating substituents on the aromatic ring were tolerated under the reaction conditions. Sterically demanding ortho-substituted substrates were also smoothly and selectively converted to TMS-protected alcohols with excellent s-factors. Notably, the s-factors for the silylation of the sterically bulky alcohol 2p increased from 21 to 104 by changing the catalyst 1e (X=I) to 1d (X=Br), a sterically less demanding catalyst, indicating that stereoselectivity can be controlled by tuning the cage size of the catalyst3435. However, 1-cyclohexylethanol, which does not contain an aromatic moiety, exhibited a poor selectivity factor (s=1.4, Supplementary Fig. 4), indicating that the π–π interaction between catalyst and substrate might play an important role in obtaining high stereoselectivity, as shown in Fig. 2.


Parts-per-million level loading organocatalysed enantioselective silylation of alcohols.

Park SY, Lee JW, Song CE - Nat Commun (2015)

Substrate scope of the silylative kinetic resolution of racemic alcohol 2 catalysed by 1e.The reactions were performed in the presence of 1 equiv of KF and 0.8 equiv of Amberlite CG 50 (CG 50). *Using catalyst 1c (X=Cl, 16.8% conv., s=20), catalyst 1d (X=Br, 36.7% conv., s=48), catalyst 1f (X=CF3, 50.8% conv., s=50) and catalyst 1g (X=C2F5, 34.1% conv., s=30). †Using catalyst 1d (X=Br). e.r., enantiomeric ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4557389&req=5

f4: Substrate scope of the silylative kinetic resolution of racemic alcohol 2 catalysed by 1e.The reactions were performed in the presence of 1 equiv of KF and 0.8 equiv of Amberlite CG 50 (CG 50). *Using catalyst 1c (X=Cl, 16.8% conv., s=20), catalyst 1d (X=Br, 36.7% conv., s=48), catalyst 1f (X=CF3, 50.8% conv., s=50) and catalyst 1g (X=C2F5, 34.1% conv., s=30). †Using catalyst 1d (X=Br). e.r., enantiomeric ratio.
Mentions: With the optimized reaction conditions in hand, the substrate scope of our protocol was investigated, and the results are shown in Fig. 4. Various simple acyclic 1-arylalkanols 2a–2r without any secondary binding functionality were successfully resolved with excellent selectivity factors. Both the electron-withdrawing and electron-donating substituents on the aromatic ring were tolerated under the reaction conditions. Sterically demanding ortho-substituted substrates were also smoothly and selectively converted to TMS-protected alcohols with excellent s-factors. Notably, the s-factors for the silylation of the sterically bulky alcohol 2p increased from 21 to 104 by changing the catalyst 1e (X=I) to 1d (X=Br), a sterically less demanding catalyst, indicating that stereoselectivity can be controlled by tuning the cage size of the catalyst3435. However, 1-cyclohexylethanol, which does not contain an aromatic moiety, exhibited a poor selectivity factor (s=1.4, Supplementary Fig. 4), indicating that the π–π interaction between catalyst and substrate might play an important role in obtaining high stereoselectivity, as shown in Fig. 2.

Bottom Line: Similar to metal catalysis, extremely low catalyst loading (p.p.m. or p.p.b. levels) is the ultimate goal of the organocatalysis community.Herein we report a remarkable contribution in this context: 1 p.p.m. loading of a simple 1,1'-bi-2-naphthol-based organocatalyst was enough to achieve highly enantioselective silylation reactions of alcohols.The unprecedented TONs and excellent enantioselectivity are ascribed to the robustness of the catalyst and systematic cooperative hydrogen-bonding organocatalysis in a densely confined chiral space.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, Korea.

ABSTRACT
The field of organocatalysis has blossomed over the past few decades, becoming an alternative to transition-metal catalysis or even replacing the realm of transition-metal catalysis. However, a truly powerful organocatalyst with a high turnover number (TON) and turnover frequency (TOF) while retaining high enantioselectivity is yet to be discovered. Similar to metal catalysis, extremely low catalyst loading (p.p.m. or p.p.b. levels) is the ultimate goal of the organocatalysis community. Herein we report a remarkable contribution in this context: 1 p.p.m. loading of a simple 1,1'-bi-2-naphthol-based organocatalyst was enough to achieve highly enantioselective silylation reactions of alcohols. The unprecedented TONs and excellent enantioselectivity are ascribed to the robustness of the catalyst and systematic cooperative hydrogen-bonding organocatalysis in a densely confined chiral space.

No MeSH data available.


Related in: MedlinePlus