Limits...
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

Kinetic studies in enantioselective Steglich rearrangement with catalyst 1j, 1j′ and DMAP.Kinetic profiles with catalyst 1j, 1j′ and DMAP in Steglich rearrangement of 9a under the optimal conditions. When 1j was used as catalyst, higher catalytic activity (k1j=1.22 h−1) and enantioselectivity (98:2 er) were observed compared with bis-methyl ether catalyst 1j′ (k1j′=2.62 × 10−2 h−1 and 66:34 er).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835565&req=5

f7: Kinetic studies in enantioselective Steglich rearrangement with catalyst 1j, 1j′ and DMAP.Kinetic profiles with catalyst 1j, 1j′ and DMAP in Steglich rearrangement of 9a under the optimal conditions. When 1j was used as catalyst, higher catalytic activity (k1j=1.22 h−1) and enantioselectivity (98:2 er) were observed compared with bis-methyl ether catalyst 1j′ (k1j′=2.62 × 10−2 h−1 and 66:34 er).

Mentions: To investigate the mechanism of the catalytic enantioselective rearrangement process, we performed a number of key experiments. First, cross-over studies (Fig. 6) between two marked substrates 9a and 9n clearly indicated that reactions proceed via an ion-pair complex, identifying the recovered starting material 9a and 9n (starting material); 9a′ and 9n′ (scrambled starting material) along with corresponding products 10a, 10n, 10a′ and 10n′ (Supplementary Fig. 68)44. Second, we carried out kinetic measurements (Fig. 7) with transformations promoted by catalyst 1j, the corresponding bis-methyl ether 1j′, and DMAP; oxindole 9a served as the substrate under the optimal conditions (0.5 mol% catalyst, THF (0.4 M), −20 °C, 5 h). In all cases, the reactions were found to be first-order with respect to the substrate (Supplementary Table 6). Moreover, substantially higher activity was observed with catalyst 1j (k1j=1.22 h−1) versus its derived bis-methyl ether 1j′ (k1j′=2.62 × 10−2 h−1), or DMAP (kDMAP=7.47 × 10−2 h−1). Thus, acyl rearrangement was nearly 50 times faster with 1j compared with 1j′ and 16 times faster than DMAP. Additionally, whereas the desired product was obtained in 98:2 er when 1j was use, there was hardly any enantiofacial selectivity when the hydroxyl units were protected (66:34 er with 1j′). The presence of tertiary alcohols clearly has a significant impact on the rate as well as enantioselectivity 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)

Kinetic studies in enantioselective Steglich rearrangement with catalyst 1j, 1j′ and DMAP.Kinetic profiles with catalyst 1j, 1j′ and DMAP in Steglich rearrangement of 9a under the optimal conditions. When 1j was used as catalyst, higher catalytic activity (k1j=1.22 h−1) and enantioselectivity (98:2 er) were observed compared with bis-methyl ether catalyst 1j′ (k1j′=2.62 × 10−2 h−1 and 66:34 er).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Kinetic studies in enantioselective Steglich rearrangement with catalyst 1j, 1j′ and DMAP.Kinetic profiles with catalyst 1j, 1j′ and DMAP in Steglich rearrangement of 9a under the optimal conditions. When 1j was used as catalyst, higher catalytic activity (k1j=1.22 h−1) and enantioselectivity (98:2 er) were observed compared with bis-methyl ether catalyst 1j′ (k1j′=2.62 × 10−2 h−1 and 66:34 er).
Mentions: To investigate the mechanism of the catalytic enantioselective rearrangement process, we performed a number of key experiments. First, cross-over studies (Fig. 6) between two marked substrates 9a and 9n clearly indicated that reactions proceed via an ion-pair complex, identifying the recovered starting material 9a and 9n (starting material); 9a′ and 9n′ (scrambled starting material) along with corresponding products 10a, 10n, 10a′ and 10n′ (Supplementary Fig. 68)44. Second, we carried out kinetic measurements (Fig. 7) with transformations promoted by catalyst 1j, the corresponding bis-methyl ether 1j′, and DMAP; oxindole 9a served as the substrate under the optimal conditions (0.5 mol% catalyst, THF (0.4 M), −20 °C, 5 h). In all cases, the reactions were found to be first-order with respect to the substrate (Supplementary Table 6). Moreover, substantially higher activity was observed with catalyst 1j (k1j=1.22 h−1) versus its derived bis-methyl ether 1j′ (k1j′=2.62 × 10−2 h−1), or DMAP (kDMAP=7.47 × 10−2 h−1). Thus, acyl rearrangement was nearly 50 times faster with 1j compared with 1j′ and 16 times faster than DMAP. Additionally, whereas the desired product was obtained in 98:2 er when 1j was use, there was hardly any enantiofacial selectivity when the hydroxyl units were protected (66:34 er with 1j′). The presence of tertiary alcohols clearly has a significant impact on the rate as well as enantioselectivity 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