Asymmetric Kulinkovich Hydroxycyclopropanation of Alkenes Mediated by Titanium(IV) TADDOLate Complexes

Iskryk, Marharyta; Barysevich, Maryia V.; Ošeka, Maksim; Adamson, Jasper; Kananovich, Dzmitry G.

doi:10.1055/s-0037-1611709

Cited by 16 publications

(8 citation statements)

References 12 publications

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“…43d,62−64 Aside from their activated nature, which enables them to undergo nucleophilic addition by compounds bearing hydroxyl groups or by various amines without the presence of coupling agents, they also lead to higher enantioselectivities in the asymmetric Kulinkovich cyclopropanation. 64 As a testament to the practical value of this system, the synthesis of 19a was performed on a 10 mmol scale (Scheme 4). Because of the larger scale, more time than necessary was purposefully allocated to each step.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The reaction time required for complete solvolysis was significantly less than 16 h ( vide infra ); however, we determined that since the products did not undergo decomposition, it was simpler to let reactions stir for a longer time as a general protocol. It should be noted that hexafluoroisopropyl esters have been shown to be useful synthons. ,− Aside from their activated nature, which enables them to undergo nucleophilic addition by compounds bearing hydroxyl groups or by various amines without the presence of coupling agents, they also lead to higher enantioselectivities in the asymmetric Kulinkovich cyclopropanation …”

Section: Resultsmentioning

confidence: 99%

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Hexafluoroisopropanol (HFIP) as a Multifunctional Agent in Gold-Catalyzed Cycloisomerizations and Sequential Transformations

et al. 2023

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Despite the unique position of gold catalysis in contemporary organic synthesis, this area of research is notorious for requiring activators and/or additives that enable catalysis by generating cationic forms of gold catalysts. Cycloisomerization reactions occupy a significant portion of the gold-catalyzed reaction space, while they represent a diverse family of reactions that are frequently utilized in synthesis. Herein, hexafluoroisopropanol (HFIP) is shown to be a uniquely simple tool for gold-catalyzed cycloisomerizations, rendering the use of external activators obsolete and leading to highly active catalytic systems with ppm levels of catalyst loading in certain cases. HFIP assumes a dual role as a solvent and an activator, operating via the dynamic activation of the Au−Cl bond through hydrogen bonding, which initiates the catalytic cycle. This special mode of catalysis can enable efficient and scalable cyclization reactions of propargylamides and ynoic acids with simple [AuCl(L)] complexes. A thorough screening of ancillary ligands and counter anions has been performed, establishing this methodology as an alternative to elaborate ligand/catalyst design and to the use of activators. Additionally, this concept is applied in C−C bond-forming cycloisomerization reactions leading to 2H-chromenes and to the design of catalytic systems for sequential or one-pot transformations leading to activated ketoesters, a functionalized N-heterocyclic carbene (NHC) precursor salt, and a compound bearing the bioactive indole core, among others. Importantly, through mechanistic investigations, including a "snapshot" of the species of interest in the solid state, we were able to unambiguously detect the key H-bonding interaction between HFIP and the gold catalyst, shedding light on the intermolecular mode of activation that enables catalysis. In the cases examined herein, HFIP is not only an excellent solvent but also a potent activator and a valuable synthetic handle when incorporated into functional groups of products.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Hexafluoroisopropanol (HFIP) as a Multifunctional Agent in Gold-Catalyzed Cycloisomerizations and Sequential Transformations

et al. 2023

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Section: Accepted Manuscriptmentioning

confidence: 99%

Gram-Scale Preparation of Acyl Fluorides and Their Reactions with Hindered Nucleophiles

Tryniszewski

Barbasiewicz

2021

Synthesis

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A series of acyl fluorides was synthesized at 100 mmol scale using phase transfer catalyzed halogen exchange between acyl chlorides and aqueous bifluoride solution. The convenient procedure consists of vigorous stirring of the biphasic mixture at rt, followed by extraction and distillation. Isolated acyl fluorides (usually 7 g to 20 g) display excellent purity, and can be transformed into sterically hindered amides and esters, when treated with lithium amide bases and alkoxides under mild conditions.

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“…Finally, as these compounds are also able to perform α-H abstraction, the competitive study between these two mechanisms will be performed, particularly in terms of activation energy. In addition to its fundamental aspect, the understanding of the formation of titanacyclopropanes would be useful for the development of new metallacyclopropane complexes and their use in organic synthesis, particularly in the case of asymmetric versions where the stereogenic center is created during the titanacyclopropane formation step. , …”

Section: Introductionmentioning

confidence: 99%

From Dialkyltitanium Species to Titanacyclopropanes: An Ab Initio Study

Bertus

2019

Organometallics

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Although the dialkoxytitanacyclopropanes are presented as important reagents in organic synthesis, the mechanism of their generation from dialkyltitanium species is not firmly established, as shown by the various propositions cited in the literature. An ab initio study of these transformations was investigated, namely, β-H elimination, β-H abstraction, epimetalation, as well as the related α-H abstraction. The results tend to show that the formation of a titanium hydride intermediate is unlikely, but, most probably, a direct hydrogen transfer (β-H abstraction) would occur. Compared to titanocene analogues, the α-H and β-H abstraction reactions were less favorable with dialkoxytitanium complexes. The overall reaction was found to be more favorable in the case of dialkoxydialkyltitanium complexes by the prior formation of bimetallic intermediates, underlining the importance of titanium ate complexes in this chemistry. A prior agostic interaction between the ethyl moiety and the metal was found to facilitate the hydrogen transfer and the formation of the metallacyclopropane. This phenomenon was illustrated by an easier β-H abstraction from a complex bearing an agostic interaction in its ground state. The intrinsic bond orbital method was used throughout this work to better visualize the electronic processes involved in these transformations.

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Asymmetric Kulinkovich Hydroxycyclopropanation of Alkenes Mediated by Titanium(IV) TADDOLate Complexes

Cited by 16 publications

References 12 publications

Hexafluoroisopropanol (HFIP) as a Multifunctional Agent in Gold-Catalyzed Cycloisomerizations and Sequential Transformations

Hexafluoroisopropanol (HFIP) as a Multifunctional Agent in Gold-Catalyzed Cycloisomerizations and Sequential Transformations

Gram-Scale Preparation of Acyl Fluorides and Their Reactions with Hindered Nucleophiles

From Dialkyltitanium Species to Titanacyclopropanes: An Ab Initio Study

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