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3 pages, 192 KiB

Open AccessEditorial

Stereogenic Centers

by Alejandro Baeza

Molecules 2018, 23(11), 2964; https://doi.org/10.3390/molecules23112964 - 13 Nov 2018

Viewed by 2380

Abstract

The demand for chiral organic entities for different industrial purposes has grown exponentially in the last decades. [...] Full article

(This article belongs to the Special Issue Stereogenic Centers)

Research

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16 pages, 1742 KiB

Open AccessFeature PaperCommunication

First Organocatalytic Asymmetric Synthesis of 1-Benzamido-1,4-Dihydropyridine Derivatives

by Fernando Auria-Luna, Eugenia Marqués-López and Raquel P. Herrera

Molecules 2018, 23(10), 2692; https://doi.org/10.3390/molecules23102692 - 19 Oct 2018

Cited by 13 | Viewed by 5561

Abstract

Preliminary results concerning the first asymmetric synthesis of highly functionalized 1-benzamido-1,4-dihydropyridine derivatives via the reaction of hydrazones with alkylidenemalononitriles in the presence of β-isocupreidine catalyst are reported. The moderate, but promising, enantioselectivity observed (40–54% ee), opens the door to a new area of [...] Read more.

Preliminary results concerning the first asymmetric synthesis of highly functionalized 1-benzamido-1,4-dihydropyridine derivatives via the reaction of hydrazones with alkylidenemalononitriles in the presence of β-isocupreidine catalyst are reported. The moderate, but promising, enantioselectivity observed (40–54% ee), opens the door to a new area of research for the asymmetric construction of new chiral 1,4-dihydropyridine derivatives, whose enantioselective catalytic preparation are still very limited. Moreover, the use of hydrazones for the enantioselective construction of chiral 1,4-dihydropyridines has been overlooked in the literature so far. Therefore, our research represents a pivotal example in this field which remains still unexplored. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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11 pages, 2026 KiB

Open AccessArticle

Asymmetric Synthesis of (−)-6-Desmethyl-Fluvirucinine A₁ via Conformationally-Controlled Diastereoselective Lactam-Ring Expansions

by Hyunyoung Moon, Hojong Yoon, Changjin Lim, Jaebong Jang, Jong-Jae Yi, Jae Kyun Lee, Jeeyeon Lee, Younghwa Na, Woo Sung Son, Seok-Ho Kim and Young-Ger Suh

Molecules 2018, 23(9), 2351; https://doi.org/10.3390/molecules23092351 - 14 Sep 2018

Cited by 3 | Viewed by 3514

Abstract

The versatile synthesis of (−)-6-desmethyl-fluvirucinine A₁ was accomplished at a 24% overall yield through a thirteen-step process from a known vinylpiperidine. The key part involved the elaboration of the distal stereocenters and a macrolactam skeleton via conformationally-induced diastereocontrol and the iterative aza-Claisen [...] Read more.

The versatile synthesis of (−)-6-desmethyl-fluvirucinine A₁ was accomplished at a 24% overall yield through a thirteen-step process from a known vinylpiperidine. The key part involved the elaboration of the distal stereocenters and a macrolactam skeleton via conformationally-induced diastereocontrol and the iterative aza-Claisen rearrangements of lactam precursors. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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7 pages, 1250 KiB

Open AccessFeature PaperCommunication

One-pot Fluorination and Organocatalytic Robinson Annulation for Asymmetric Synthesis of Mono- and Difluorinated Cyclohexenones

by Xin Huang, Weizhao Zhao, Xiaofeng Zhang, Miao Liu, Stanley N. S. Vasconcelos and Wei Zhang

Molecules 2018, 23(9), 2251; https://doi.org/10.3390/molecules23092251 - 4 Sep 2018

Cited by 8 | Viewed by 4862

Abstract

A one-pot fluorination and organocatalytic Robinson annulation sequence has been developed for asymmetric synthesis of 6-fluoroyclohex-2-en-1-ones and 4,6-difluorocyclohex-2-en-1-ones. The reactions promoted by cinchona alkaloid amine afforded products bearing two or three stereocenters in good to excellent yields with up to 99% ee and [...] Read more.

A one-pot fluorination and organocatalytic Robinson annulation sequence has been developed for asymmetric synthesis of 6-fluoroyclohex-2-en-1-ones and 4,6-difluorocyclohex-2-en-1-ones. The reactions promoted by cinchona alkaloid amine afforded products bearing two or three stereocenters in good to excellent yields with up to 99% ee and 20:1 dr. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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7 pages, 1914 KiB

Open AccessCommunication

Oxidative Asymmetric Formal Aza-Diels–Alder Reactions of Tetrahydro-β-carboline with Enones in the Synthesis of Indoloquinolizidine-2-ones

by Xiang Wu, Shi-Bao Zhao, Lang-Lang Zheng and You-Gui Li

Molecules 2018, 23(9), 2228; https://doi.org/10.3390/molecules23092228 - 1 Sep 2018

Cited by 8 | Viewed by 4664

Abstract

Ru-catalyzed tandem amine oxidative dehydrogenation/formal aza-Diels–Alder reaction for enantio- and diastereoselective synthesis of indoloquinolizidine-2-ones from tetrahydro-β-carbolines and α,β-unsaturated ketones is described. The reaction proceeds via tandem ruthenium-catalyzed amine dehydrogenation using tert-butyl hydroperoxide (TBHP) as the oxidant and a chiral thiourea-catalyzed formal aza-[4 + [...] Read more.

Ru-catalyzed tandem amine oxidative dehydrogenation/formal aza-Diels–Alder reaction for enantio- and diastereoselective synthesis of indoloquinolizidine-2-ones from tetrahydro-β-carbolines and α,β-unsaturated ketones is described. The reaction proceeds via tandem ruthenium-catalyzed amine dehydrogenation using tert-butyl hydroperoxide (TBHP) as the oxidant and a chiral thiourea-catalyzed formal aza-[4 + 2] cycloaddition, providing a step-economical strategy for the synthesis of these valuable heterocyclic products. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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8 pages, 2707 KiB

Open AccessArticle

Direct Asymmetric Reductive Amination for the Synthesis of (S)-Rivastigmine

by Guorui Gao, Shaozhi Du, Yang Yang, Xue Lei, Haizhou Huang and Mingxin Chang

Molecules 2018, 23(9), 2207; https://doi.org/10.3390/molecules23092207 - 31 Aug 2018

Cited by 18 | Viewed by 6162

Abstract

In this article we demonstrate how asymmetric total synthesis of (S)-rivastigmine has been achieved using direct asymmetric reductive amination as the key transformation in four steps. The route started with readily available and cheap m-hydroxyacetophenone, through esterification, asymmetric reductive amination, [...] Read more.

In this article we demonstrate how asymmetric total synthesis of (S)-rivastigmine has been achieved using direct asymmetric reductive amination as the key transformation in four steps. The route started with readily available and cheap m-hydroxyacetophenone, through esterification, asymmetric reductive amination, N-diphenylmethyl deprotection and reductive amination, to provide the final (S)-rivastigmine in 82% overall yield and 96% enantioselectivity. In the asymmetric reductive amination, catalysed by the iridium–phosphoramidite ligand complex and helped by some additives, the readily prepared 3-acetylphenyl ethyl(methyl)carbamate directly reductively coupled with diphenylmethanamine to yield the chiral amine product in 96% ee and 93% yield. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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19 pages, 5429 KiB

Open AccessArticle

Kinetic Resolution of Racemic 2-Hydroxyamides Using a Diphenylacetyl Component as an Acyl Source and a Chiral Acyl-Transfer Catalyst

by Takatsugu Murata, Tatsuya Kawanishi, Akihiro Sekiguchi, Ryo Ishikawa, Keisuke Ono, Kenya Nakata and Isamu Shiina

Molecules 2018, 23(8), 2003; https://doi.org/10.3390/molecules23082003 - 10 Aug 2018

Cited by 10 | Viewed by 4526

Abstract

Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can [...] Read more.

Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity (22 examples; s-value reaching over 250). The resulting chiral compounds could be transformed into other useful structures while maintaining their chirality. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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9 pages, 877 KiB

Open AccessArticle

One-Dimensional ¹³C NMR Is a Simple and Highly Quantitative Method for Enantiodiscrimination

by Peter P. Lankhorst, Jozef H. J. Van Rijn and Alexander L. L. Duchateau

Molecules 2018, 23(7), 1785; https://doi.org/10.3390/molecules23071785 - 20 Jul 2018

Cited by 16 | Viewed by 5776

Abstract

The discrimination of enantiomers of mandelonitrile by means of 1D ¹³C NMR and with the aid of the chiral solvating agent (S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol (TFAE) is presented. ¹H NMR fails for this specific compound because proton signals either overlap with the signals of [...] Read more.

The discrimination of enantiomers of mandelonitrile by means of 1D ¹³C NMR and with the aid of the chiral solvating agent (S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol (TFAE) is presented. ¹H NMR fails for this specific compound because proton signals either overlap with the signals of the chiral solvating agent or do not show separation between the (S)-enantiomer and the (R)-enantiomer. The ¹³C NMR method is validated by preparing artificial mixtures of the (R)-enantiomer and the racemate, and it is shown that with only 4 mg of mandelonitrile a detection limit of the minor enantiomer of 0.5% is obtained, corresponding to an enantiomeric excess value of 99%. Furthermore, the method shows high linearity, and has a small relative standard deviation of only 0.3% for the minor enantiomer when the relative abundance of this enantiomer is 20%. Therefore, the ¹³C NMR method is highly suitable for quantitative enantiodiscrimination. It is discussed that ¹³C NMR is preferred over ¹H NMR in many situations, not only in molecules with more than one chiral center, resulting in complex mixtures of many stereoisomers, but also in the case of molecules with overlapping multiplets in the ¹H NMR spectrum, and in the case of molecules with many quaternary carbon atoms, and therefore less abundant protons. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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10 pages, 3100 KiB

Open AccessArticle

Chiral 2-Aminobenzimidazole as Bifunctional Catalyst in the Asymmetric Electrophilic Amination of Unprotected 3-Substituted Oxindoles

by Llorenç Benavent, Alejandro Baeza and Megan Freckleton

Molecules 2018, 23(6), 1374; https://doi.org/10.3390/molecules23061374 - 6 Jun 2018

Cited by 12 | Viewed by 4262

Abstract

The use of readily available chiral trans-cyclohexanediamine-benzimidazole derivatives as bifunctional organocatalysts in the asymmetric electrophilic amination of unprotected 3-substituted oxindoles is presented. Different organocatalysts were evaluated; the most successful one contained a dimethylamino moiety (5). With this catalyst under optimized [...] Read more.

The use of readily available chiral trans-cyclohexanediamine-benzimidazole derivatives as bifunctional organocatalysts in the asymmetric electrophilic amination of unprotected 3-substituted oxindoles is presented. Different organocatalysts were evaluated; the most successful one contained a dimethylamino moiety (5). With this catalyst under optimized conditions, different oxindoles containing a wide variety of substituents at the 3-position were aminated in good yields and with good to excellent enantioselectivities using di-tert-butylazodicarboxylate as the aminating agent. The procedure proved to be also efficient for the amination of 3-substituted benzofuranones, although with moderate results. A bifunctional role of the catalyst, acting as Brønsted base and hydrogen bond donor, is proposed according to the experimental results observed. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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12 pages, 3684 KiB

Open AccessFeature PaperCommunication

Catalytic Enantioselective Addition of Organozirconium Reagents to Aldehydes

by Ricard Solà, Marcos Veguillas, María José González-Soria, Nicholas Carter, M. Angeles Fernández-Ibáñez and Beatriz Maciá

Molecules 2018, 23(4), 961; https://doi.org/10.3390/molecules23040961 - 20 Apr 2018

Cited by 4 | Viewed by 6005

Abstract

A catalytic enantioselective addition reaction of alkylzirconium species to aromatic aldehydes is reported. The reaction, facilitated by a chiral nonracemic diol ligand complex with Ti(OⁱPr)₄, proceeds under mild and convenient conditions, and no premade organometallic reagents are required since [...] Read more.

A catalytic enantioselective addition reaction of alkylzirconium species to aromatic aldehydes is reported. The reaction, facilitated by a chiral nonracemic diol ligand complex with Ti(OⁱPr)₄, proceeds under mild and convenient conditions, and no premade organometallic reagents are required since the alkylzirconium nucleophiles are generated in situ by hydrozirconation of alkenes with the Schwartz reagent. The methodology is compatible with functionalized nucleophiles and a broad range of aromatic aldehydes. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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13 pages, 1803 KiB

Open AccessArticle

Asymmetric Conjugate Addition of α,α-Disubstituted Aldehydes to Nitroalkenes Organocatalyzed by Chiral Monosalicylamides from trans-Cyclohexane-1,2-Diamines

by José R. Martínez-Guillén, Jesús Flores-Ferrándiz, Cecilia Gómez, Enrique Gómez-Bengoa and Rafael Chinchilla

Molecules 2018, 23(1), 141; https://doi.org/10.3390/molecules23010141 - 11 Jan 2018

Cited by 9 | Viewed by 4546

Abstract

Primary amine-salicylamides derived from chiral trans-cyclohexane-1,2-diamines are used as organocatalysts for the enantioselective conjugate addition of α,α-disubstituted aldehydes to arylated and heteroarylated nitroalkenes. The reaction is performed in the presence of 4-dimethylaminopyridine as an additive in dichloromethane as a solvent at room [...] Read more.

Primary amine-salicylamides derived from chiral trans-cyclohexane-1,2-diamines are used as organocatalysts for the enantioselective conjugate addition of α,α-disubstituted aldehydes to arylated and heteroarylated nitroalkenes. The reaction is performed in the presence of 4-dimethylaminopyridine as an additive in dichloromethane as a solvent at room temperature. The corresponding enantioenriched γ-nitroaldehydes are obtained with enantioselectivities up to 95%. Theoretical calculations are used to justify the reasons of the stereoinduction. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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Review

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16 pages, 7307 KiB

Open AccessReview

Unsymmetrical Diboron Reagents: Application in Borylation Reactions of Unsaturated Bonds

by Siyi Ding, Liang Xu and Zongcheng Miao

Molecules 2019, 24(7), 1325; https://doi.org/10.3390/molecules24071325 - 4 Apr 2019

Cited by 22 | Viewed by 5105

Abstract

In the past decades, borylation reactions have received extensive research interest and have developed into effective tools in the synthesis of versatile organoboron compounds. Boranes and symmetrical diboron compounds are commonly utilized as borylating reagents in these transformations, especially in the borylation reactions [...] Read more.

In the past decades, borylation reactions have received extensive research interest and have developed into effective tools in the synthesis of versatile organoboron compounds. Boranes and symmetrical diboron compounds are commonly utilized as borylating reagents in these transformations, especially in the borylation reactions of unsaturated bonds. More recently, several types of unsymmetrical diboron reagents have been synthesized and applied in these borylation reactions, allowing for complementary chemo- and regioselectivity. This review aimed to highlight the recent development in this rising research field, focusing on new reactivity and selectivity that originates from the use of these unsymmetrical diboron reagents. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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17 pages, 4736 KiB

Open AccessReview

Recent Advances in the Catalytic Asymmetric Reactions of Oxaziridines

by Qiao Ren, Wen Yang, Yunfei Lan, Xurong Qin, Youzhou He and Lujiang Yuan

Molecules 2018, 23(10), 2656; https://doi.org/10.3390/molecules23102656 - 16 Oct 2018

Cited by 13 | Viewed by 5996

Abstract

Oxaziridines have emerged as powerful and elegant oxygen- and nitrogen-transfer agents for a broad array of nucleophiles, due to the remarkably high and tunable reactivities. However, the asymmetric catalysis involving oxaziridines is still in its infancy. Herein, this review aims to examine recent [...] Read more.

Oxaziridines have emerged as powerful and elegant oxygen- and nitrogen-transfer agents for a broad array of nucleophiles, due to the remarkably high and tunable reactivities. However, the asymmetric catalysis involving oxaziridines is still in its infancy. Herein, this review aims to examine recent advances in the catalytic asymmetric transformations of oxaziridines, including oxidation, amination, cycloaddition and deracemization. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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14 pages, 3938 KiB

Open AccessReview

Practical Enantioselective Reduction of Ketones Using Oxazaborolidine Catalysts Generated In Situ from Chiral Lactam Alcohols

by Yasuhiro Kawanami and Ryo C. Yanagita

Molecules 2018, 23(10), 2408; https://doi.org/10.3390/molecules23102408 - 20 Sep 2018

Cited by 13 | Viewed by 9343

Abstract

Oxazaborolidine catalyst (CBS catalyst) has been extensively used for catalytic borane reduction with a predictable absolute stereochemistry and high enantioselectivity. However, the use of isolated CBS catalyst sometimes has the drawback of low reproducibility due to the aging of the CBS catalyst during [...] Read more.

Oxazaborolidine catalyst (CBS catalyst) has been extensively used for catalytic borane reduction with a predictable absolute stereochemistry and high enantioselectivity. However, the use of isolated CBS catalyst sometimes has the drawback of low reproducibility due to the aging of the CBS catalyst during storage. Therefore, we investigated a more reliable and practical method for the reduction of a variety of ketones including challenging substrates, primary aliphatic ketones, α,β-enones, and trifluoromethyl ketones. This review surveys the developments in borane reduction using oxazaborolidine catalysts generated in situ from chiral lactam alcohols and borane. Full article

(This article belongs to the Special Issue Stereogenic Centers)

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