Insights into the Molecular Recognition Process in Organocatalytic Chemoselective Monoacylation of 1,5‐Pentanediol

Imayoshi, Ayumi; Yamanaka, Masahiro; Sato, Makoto; Yoshida, Keisuke; Furuta, Takumi; Ueda, Y.; Kawabata, Takeo

doi:10.1002/adsc.201600010

Cited by 17 publications

(11 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further reversal of the chemoselectivity of acylation was observed in sterically more demanding alcohol 12. These results and other results regarding chemoselective acylation observed in our laboratory [18][19][20][21] suggest that catalyst 1f and its analogues can promote chemoselective acylation of a hydroxy group located at a certain distance (~5 Å) from the nitrogen atom of the NHNs group.…”

Section: Designed Strategysupporting

confidence: 80%

Discrimination of Mobile Supramolecular Chirality: Kinetic Resolution of Mechanically Planar Chiral Rotaxanes by Organocatalysis

Imayoshi

2021

Discrimination of Mobile Supramolecular Chirality

Self Cite

View full text Add to dashboard Cite

Among the fields of asymmetric synthesis approaching the mature science, asymmetric discrimination and catalytic synthesis of chiral supramolecules still stand as unsolved problems. Supramolecules such as rotaxanes and catenanes are known to possess mechanical chirality when each of the axis and/or ring components has dissymmetry (Fig. 3.1) (Frisch and Wasserman in J Am Chem Soc 83: 3789-3795, 1961, [1]; Schill in Catenanes, rotaxanes and knots, Academic Press, New York, 1971, [2]). The extreme difficulty in asymmetric synthesis of such supramolecules may be resulting from conformational diversity and movability of mechanically chiral supramolecules. I have achieved the first example of highly enantioselective synthesis of mechanically planar chiral rotaxanes by acylative kinetic resolution of the racemate. In the presence of catalyst 1c, an acylative kinetic resolution of a racemic rotaxane 10 afforded a mechanically planar chiral rotaxane 10 with perfect enantiopurity (>99% ee) in 29% yield (the theoretical maximum yield of kinetic resolution of racemate is 50%) (Fig. 3.2). The catalysts enabled to discriminate mobile mechanical chirality of the rotaxanes with the excellent selectivity in up to 16. KeywordsCatalytic synthesis of chiral supramolecules • Rotaxanes and catenanes • Mechanically chiral supramolecules • Mobile supramolecular chirality • Acylative kinetic resolution by organocatalysis • Enantiopure rotaxane BackgroundsA field of asymmetric synthesis has extensively developed during the last few decades. The construction of ubiquitous chiral molecules involving conventional chiral elements such as central, axial or planer chirality has already been adequately realized. With the current state of chemical science, asymmetric synthesis of such fixed chirality over covalent bond is reaching a level of mature science. Chiral supramolecules with additional chiral elements such as central [3,4], axial [5,6], planer [7] or helical [8] chirality on their ring or axis component, have already been actively synthesized (Fig. 3.3).

show abstract

Section: Designed Strategysupporting

confidence: 80%

Discrimination of Mobile Supramolecular Chirality: Kinetic Resolution of Mechanically Planar Chiral Rotaxanes by Organocatalysis

Imayoshi

2021

Discrimination of Mobile Supramolecular Chirality

Self Cite

View full text Add to dashboard Cite

show abstract

“…The enhanced conformational flexibility by one-carbon elongation could also be responsible for the diminished selectivity. Based on these results and previously proposed transition state models for site-selective acylation with catalyst 2 and the related catalysts 24 – 27 , 32 , 34 , we propose A as a possible transition state model for remote asymmetric acylation (Fig. 4b ).…”

Section: Discussionsupporting

confidence: 63%

“…2c) that consists of a structurally dissymmetric axis component with a hydroxy group and a structurally dissymmetric ring component with an NHNs (Ns = -SO 2 -2-NO 2 -C 6 H 4 ) group. According to our previous studies [24][25][26][27] , we hypothesized that use of a substrate alcohol with an NHNs group in the presence of catalyst 3 (Fig. 2d) and the analogous catalysts are the key to achieve remote asymmetric acylation.…”

Section: Resultsmentioning

confidence: 98%

“…After finding that catalyst 2 is the most effective for the acylative kinetic resolution of mechanically planar chiral rotaxanes, we re-investigated the reaction parameters, including the solvents, acylating agents, auxiliary bases and concentrations (Supplementary Table 1). We employed acid anhydrides as acyl donors throughout the screening because carboxylate anion generated from the anhydride and the nucleophilic catalyst was expected to be critically important for both selectivity and acceleration of the site-selective acylation 26 , 27 , 31 , 32 . It was found that selectivity of the acylation was strongly dependent on the substrate concentration.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Enantioselective preparation of mechanically planar chiral rotaxanes by kinetic resolution strategy

et al. 2021

Self Cite

View full text Add to dashboard Cite

Asymmetric synthesis of mechanically planar chiral rotaxanes and topologically chiral catenanes has been a long-standing challenge in organic synthesis. Recently, an excellent strategy was developed based on diastereomeric synthesis of rotaxanes and catenanes with mechanical chirality followed by removal of the chiral auxiliary. On the other hand, its enantioselective approach has been quite limited. Here, we report enantioselective preparation of mechanically planar chiral rotaxanes by kinetic resolution of the racemates via remote asymmetric acylation of a hydroxy group in the axis component, which provides an unreacted enantiomer in up to >99.9% ee in 29% yield (the theoretical maximum yield of kinetic resolution of racemate is 50%). While the rotaxane molecules are expected to have conformational complexity, our original catalysts enabled to discriminate the mechanical chirality of the rotaxanes efficiently with the selectivity factors in up to 16.

show abstract

“…18,19) The amide side chains at C(2) and C(5) of the pyrrolidine ring are assumed to be responsible for the molecular recognition process. Therefore, preparation of all four possible isomers of C 2 -symmetric PPY catalysts with dual chiral amide side chains at C(2) and C(5) such as 1, 1a, ent-1, and ent-1a seemed to be meaningful for optimizing the conditions for the targeted site-selective molecular transformation (Fig.…”

Section: )mentioning

confidence: 99%

A Concise Access to <i>C</i><sub>2</sub>-Symmetric Chiral 4-Pyrrolidinopyridine Catalysts with Dual Functional Side Chains

Mishiro

Takeuchi

Furuta

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

A practical method was developed for the preparation of a diastereomeric library of C 2 -symmetric chiral 4-pyrrolidinopyridine catalysts with dual amide side chains. Use of a racemic precursor is the key to the concise production of catalysts with diverse stereochemisty.Key words organocatalyst; C 2 -symmetry; pyrrolidinopyridine; catalyst library; racemic precursor Various chiral 4-dimethylaminopyridine (DMAP) and 4-pyrrolidinopyridine (PPY) derivatives have been developed and extensively employed in asymmetric acyl transfer and the related reactions.1-6) Especially, C 2 -symmetric-2,5-disubstituted PPY is a privileged structure for site-and chemoselective molecular transformation. For example, catalyst 1 was found to be effective for site-selective acylation of glycopyranoside derivatives, 7-11) chemoselective monoacylation of linear diols, 12) and site-selective acylation of a cardiac glycosides, digitoxin 13) and lanatoside C (5) 14) (Fig. 1). Highly geometryselective acylation of tetra-substituted α,α′-alkenediols has been also achieved by employing catalyst 2a.15) Catalyst 2b was found to be effective for chemoselective acylation of sterically hindered secondary alcohols in the presence of otherwise more reactive primary alcohols.16) Asymmetric desymmetrization of meso-diols has been performed by catalyst 3 17) (Fig. 1). All of these C 2 -symmetric PPY catalysts have been prepared from versatile precursor 4. 7)For the above-mentioned site-and chemoselective molecular transformations, precise molecular recognition process between the catalysts and the substrates seems to be involved. 18,19) The amide side chains at C(2) and C(5) of the pyrrolidine ring are assumed to be responsible for the molecular recognition process. Therefore, preparation of all four possible isomers of C 2 -symmetric PPY catalysts with dual chiral amide side chains at C(2) and C(5) such as 1, 1a, ent-1, and ent-1a seemed to be meaningful for optimizing the conditions for the targeted site-selective molecular transformation (Fig. 2). For example, site-selective acylation of lanatoside C (5) took place at the C(4⁗)-OH in 86% site-selectivity among eight hydroxy groups in the different micro environments in the presence of catalyst 1 14) (Fig. 2). On the other hand, the diastereomeric and enantiomeric catalysts 1a, ent-1, and ent-1a gave the C(4⁗)-, C(3⁗)-, and C(3⁗)-O-acylates as the major acylate in 73, 62, and 80% site-selectively, respectively. Accordingly, site-selectivity of the acylation was critically affected by the nature and stereochemistry of the amide side chains at C(2) and C(5) of the pyrrolidine ring of the PPY catalysts.These four diastereomeric catalysts have been prepared from versatile precursor 4 and its enantiomer. We have reported a method for the preparation of 4 starting from L-pyroglutamic acid (6) via tedious five-step sequence in 16% overall yield 7) (Fig. 3A). Large-scale preparation of 4 has been often problematic because of poor reproducibility of the transformation from 7 to 8 with catalytic amount of CuI....

show abstract

Insights into the Molecular Recognition Process in Organocatalytic Chemoselective Monoacylation of 1,5‐Pentanediol

Cited by 17 publications

References 10 publications

Discrimination of Mobile Supramolecular Chirality: Kinetic Resolution of Mechanically Planar Chiral Rotaxanes by Organocatalysis

Discrimination of Mobile Supramolecular Chirality: Kinetic Resolution of Mechanically Planar Chiral Rotaxanes by Organocatalysis

Enantioselective preparation of mechanically planar chiral rotaxanes by kinetic resolution strategy

A Concise Access to <i>C</i><sub>2</sub>-Symmetric Chiral 4-Pyrrolidinopyridine Catalysts with Dual Functional Side Chains

Contact Info

Product

Resources

About