Enantioselective Synthesis of Tropanes: Brønsted Acid Catalyzed Pseudotransannular Desymmetrization

Rodríguez, Sebastián Figueroa; Uria, Uxue; Reyes, Efraím; Carrillo, Luisa; Tejero, Tomás; Merino, Pedro; Vicario, José L.

doi:10.1002/anie.202000650

Cited by 15 publications

(11 citation statements)

References 56 publications

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“…In 2020, Vicario et al illustrated an innovative approach for the asymmetric synthesis of tropanes, based on intramolecular desymmetrization of meso-epoxides. 70 The central scaffold of tropane alkaloids, namely, the 8azabicyclo[3.2.1]octane core, has been recurrently targeted 71 since the pivotal synthesis of tropinone reported by Robinson in 1917. 72 meso-4,5-Epoxycycloheptylamines 11 were screened with different chiral phosphoric acids, and finally VAPOLderived organocatalyst 13 proved to be the most effective at 5 mol % loading in either toluene or chlorobenzene as the solvents at −20 °C.…”

Section: Desymmetrization Of Meso-epoxidesmentioning

confidence: 99%

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Epoxides: Small Rings to Play with under Asymmetric Organocatalysis

Meninno

Lattanzi

2022

ACS Org. Inorg. Au

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Optically pure epoxides are recognized as highly valuable products and key intermediates, useful in different areas from pharmaceutical and agrochemical industries to natural product synthesis and materials science. The predictable fate of the ringopening process, in terms of stereoselectivity and often of regioselectivity, enables useful functional groups to be installed at vicinal carbon atoms in a desired manner. In this way, products of widespread utility either for synthetic applications or as final products can be obtained. The advent of asymmetric organocatalysis provided a new convenient tool, not only for their preparation but also for the elaboration of this class of heterocycles. In this review, we focus on recent developments of stereoselective organocatalytic ringopening reactions of meso-epoxides, kinetic resolution of racemic epoxides, and Meinwald-type rearrangement. Examples of asymmetric organocatalytic processes toward specific synthetic targets, which include ring opening of an epoxide intermediate, are also illustrated.

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Section: Desymmetrization Of Meso-epoxidesmentioning

confidence: 99%

“…In 2020, Vicario et al illustrated an innovative approach for the asymmetric synthesis of tropanes, based on intramolecular desymmetrization of meso -epoxides …”

Section: Desymmetrization Of Meso-epoxidesmentioning

confidence: 99%

Epoxides: Small Rings to Play with under Asymmetric Organocatalysis

Meninno

Lattanzi

2022

ACS Org. Inorg. Au

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“…In 2020, Vicario and co‐workers reported the desymmetrization of meso 1‐aminocyclohept‐4‐ene derived epoxides 111 enabled by a VAPOL‐derived CPA catalyst ( CPA‐19 ) through the pseudotransannular intramolecular ring opening reaction, which produced a series of tropane derivatives 112 in high yields, diastereoselectivities and enantioselectivities (Scheme 36). [50] The synthetic utilities of these reactions were fully demonstrated by the facile asymmetric synthesis of two natural products (including the two‐steps synthesis of (−)‐α‐tropanol ( 113 ) from chiral product 112 a ). In addition, both experimental and computational mechanistic studies supported that the Ts group at the nucleophilic amine group is critically important to the reactivities and stereoselectivities of these reactions, which may be attributed to the requirement of forming H‐bonding with CPA catalyst and the contribution of stabilizing C−H⋅⋅⋅O=S interactions in the asymmetric transition state.…”

Section: Chiral Phosphoric Acids Catalyzed Enantioselective Desymmetr...mentioning

confidence: 99%

Recent Advances in (Dynamic) Kinetic Resolution and Desymmetrization Catalyzed by Chiral Phosphoric Acids

Liu

Yang

2021

Asian J Org Chem

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Kinetic resolution, dynamic kinetic resolution and desymmetrization are practical methods to produce enantioenriched products from relatively simple racemic or achiral starting materials, which are also sometimes difficult to be accessed by other asymmetric methods. Chiral phosphoric acids, which have been recognized as one of the most powerful chiral organocatalysts to date, have also been extensively applied in the above-mentioned research fields.In this minireview, we summarized the tremendous development of kinetic resolution, dynamic kinetic resolution and desymmetrization reactions enabled by chiral phosphoric acids since the year of 2016, which were not included in the two previous outstanding reviews by Petersen et al and Dixon et al. A number of examples involving the use of CPA as cooperative catalyst are also included in this review.Scheme 1. KR of β-amino alcohols via CPA-catalyzed p-methoxybenzylations.

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“…Since the seminal work of Akiyama and Terada in 2004, as powerful and versatile Brønsted acid catalysts, chiral phosphoric acids (CPAs) have been shown to facilitate a vast number of stereoselective examples to enantiopure molecules under catalytic conditions without requiring additional expensive, unstable, and hard accessible transition-metal catalysts . In particular, recently, the CPAs with a BINOL (1,1′-bi-2-naphthol) or a SPINOL (1,1′-spirobiindane-7,7′-diol) skeleton have emerged as privileged organocatalysts for a plethora of asymmetric transformations. − , In general, BINOL-based CPAs have been demonstrated to be capable of imparting exceptionally high enantioselectivities in arylation, Passerini reaction, and Ugi reactions . The spirocyclic backbone has higher rigidity than the binaphthyl skeleton, and hence, SPINOL-based phosphoric acids have drawn increasing attention .…”

Section: Introductionmentioning

confidence: 99%

Insights into the Chiral Phosphoric Acid-Catalyzed Dynamic Kinetic Asymmetric Hydroamination of Racemic Allenes: An Allyl Carbocation/Phosphate Pair Mechanism

2021

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Computational studies of chiral phosphoric acid (CPA)-catalyzed dynamic kinetic asymmetric hydroamination (DyKAH) of racemic allenes show that the reaction proceeds through a catalytic asymmetric model involving a highly reactive π-allylic carbocationic intermediate, generated from a racemic allene through an intermolecular proton transfer mediated by CPA, which also results in a high E/Z selectivity. Moreover, the distortion–interaction, atom in molecule, and electrostatic interaction analyses and space-filling models are employed on the basis of the DyKAH catalyzed by (S)-A5 (reaction 1) or (R)-A2 (reaction 2) to explain the high enantioselectivity and the controlling effects of SPINOL scaffolds on the signs of enantioselectivity. Our calculations indicate that the enantioselectivity of reactions 1 and 2 can be mainly ascribed to the favorable noncovalent interactions within the stronger chiral electrostatic environment created by the phosphoric acid in the preferential transition states. Finally, the effect of (S/R)-SPINOL-based CPAs on the signs of enantioselectivity can be explained by the different combination modes of substrates into the chiral binding pocket of the catalyst controlled by the chirality of SPINOL backbones. Overall, the new insights into the reaction rationalize the outcome and these key factors that affect the product enantioselectivity are important to guide the DyKAHs.

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Enantioselective Synthesis of Tropanes: Brønsted Acid Catalyzed Pseudotransannular Desymmetrization

Cited by 15 publications

References 56 publications

Epoxides: Small Rings to Play with under Asymmetric Organocatalysis

Epoxides: Small Rings to Play with under Asymmetric Organocatalysis

Recent Advances in (Dynamic) Kinetic Resolution and Desymmetrization Catalyzed by Chiral Phosphoric Acids

Insights into the Chiral Phosphoric Acid-Catalyzed Dynamic Kinetic Asymmetric Hydroamination of Racemic Allenes: An Allyl Carbocation/Phosphate Pair Mechanism

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