Asymmetric Radical Process for General Synthesis of Chiral Heteroaryl Cyclopropanes

Wang, Xiaoxu; Ke, Jing; Zhu, Yiling; Deb, Arghya; Xu, Youren; Zhang, X. Peter

doi:10.1021/jacs.1c04655

Cited by 48 publications

(33 citation statements)

References 94 publications

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“…Scheme shows examples of asymmetric cyclopropanation of aromatic, aliphatic, electron-rich, and electron-deficient olefins under mild reaction conditions. ,,− These cyclopropanation reactions are dominated by reactions involving mostly styrenes and alkenes bearing electron withdrawing and radical-stabilizing substituents. With some exceptions, ,,− most of these reactions involve diazo compounds (or their tosylhydrazone precursors) containing a single substituent at the carbenoid carbon atom.…”

Section: Substrate Orientation By Hydrogen Bondingmentioning

confidence: 99%

Transition Metal Catalysis Controlled by Hydrogen Bonding in the Second Coordination Sphere

et al. 2022

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Transition metal catalysis is of utmost importance for the development of sustainable processes in academia and industry. The activity and selectivity of metal complexes are typically the result of the interplay between ligand and metal properties. As the ligand can be chemically altered, a large research focus has been on ligand development. More recently, it has been recognized that further control over activity and selectivity can be achieved by using the “second coordination sphere”, which can be seen as the region beyond the direct coordination sphere of the metal center. Hydrogen bonds appear to be very useful interactions in this context as they typically have sufficient strength and directionality to exert control of the second coordination sphere, yet hydrogen bonds are typically very dynamic, allowing fast turnover. In this review we have highlighted several key features of hydrogen bonding interactions and have summarized the use of hydrogen bonding to program the second coordination sphere. Such control can be achieved by bridging two ligands that are coordinated to a metal center to effectively lead to supramolecular bidentate ligands. In addition, hydrogen bonding can be used to preorganize a substrate that is coordinated to the metal center. Both strategies lead to catalysts with superior properties in a variety of metal catalyzed transformations, including (asymmetric) hydrogenation, hydroformylation, C–H activation, oxidation, radical-type transformations, and photochemical reactions.

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Section: Substrate Orientation By Hydrogen Bondingmentioning

confidence: 99%

Transition Metal Catalysis Controlled by Hydrogen Bonding in the Second Coordination Sphere

et al. 2022

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“…(Hetero)aryl iodides and alkenyl triflates proved most compliant; 66 in the case of highly activated coupling partners such as p -O 2 NC 6 H 4 X, even the chloride, bromide, and triflate furnished good results. In addition to the “late-stage” diversity aspect mentioned in the Introduction section, this procedure provides opportunities with regard to functional groups that would be difficult to manage otherwise.…”

Section: Resultsmentioning

confidence: 99%

From Serendipity to Rational Design: Heteroleptic Dirhodium Amidate Complexes for Diastereodivergent Asymmetric Cyclopropanation

et al. 2022

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A heteroleptic dirhodium paddlewheel complex comprising three chiral carboxylate ligands and one achiral acetamidate ligand has recently been found to be uniquely effective in catalyzing the asymmetric cyclopropanation of olefins with α-stannylated (silylated and germylated) α-diazoacetate derivatives. A number of control experiments in combination with detailed computational studies provide compelling evidence that an interligand hydrogen bond between the −NH group of the amidate and the ester carbonyl group of the reactive rhodium carbene intermediate plays a quintessential role in the stereodetermining transition state. The penalty for distorting this array outweighs steric arguments and renders two of the four conceivable transitions states unviable. Based on this mechanistic insight, the design of the parent catalyst is revisited herein: placement of appropriate peripheral substituents allows high levels of diastereocontrol to be imposed upon cyclopropanation, which the original catalyst lacks. Because the new complexes allow either trans- or cis-configured stannylated cyclopropanes to be made selectively and in excellent optical purity, this transformation also marks a rare case of diastereodivergent asymmetric catalysis. The products are amenable to stereospecific cross coupling with aryl halides or alkenyl triflates; these transformations appear to be the first examples of the formation of stereogenic quaternary carbon centers by the Stille reaction; carbonylative coupling is also achieved. Moreover, tin/lithium exchange affords chiral lithium enolates, which can be intercepted with a variety of electrophilic partners. The virtues and inherent flexibility of this new methodology are illustrated by an efficient synthesis of two salinilactones, extremely scarce bacterial metabolites with signaling function involved in the self-regulatory growth inhibition of the producing strain.

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“…During the Co(II)-catalyzed cyclopropanation, the initially generated α-metalloalkyl radical intermediates from metalloradical activation of diazo compounds, which are centrally situated inside the pocketlike environment of the chiral porphyrin ligands, can be precisely governed to perform a sequence of homolytic reactions such as radical addition and radical substitution with olefin substrates, leading to productive formation of cyclopropanes with effective control of diastereoselectivity and enantioselectivity. Except for a few recent examples of using α-aryldiazomethanes, Co(II)-based radical cyclopropanation has so far been mostly involved with the use of acceptor- and acceptor/acceptor-substituted diazo compounds as metalloradicophiles . In all the previous cases, the key α-Co(III)-supported C-centered radical intermediates are stabilized by C(sp 2 )-based carbonyl or aryl substituents through potential H-bonding interactions with the amide units of the catalyst, facilitating the reactivity and stereoselectivity of the catalytic radical process.…”

Section: Introductionmentioning

confidence: 99%

Metalloradical Activation of In Situ-Generated α-Alkynyldiazomethanes for Asymmetric Radical Cyclopropanation of Alkenes

Lee

Wang

et al. 2022

J. Am. Chem. Soc.

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α-Alkynyldiazomethanes, generated in situ from the corresponding sulfonyl hydrazones in the presence of a base, can serve as effective metalloradicophiles in Co(II)-based metalloradical catalysis (MRC) for asymmetric cyclopropanation of alkenes. With D 2 -symmetric chiral amidoporphyrin 2,6-DiMeO-QingPhyrin as the optimal supporting ligand, the Co(II)-based metalloradical system can efficiently activate different α-alkynyldiazomethanes at room temperature for highly asymmetric cyclopropanation of a broad range of alkenes. This catalytic radical process provides a general synthetic tool for stereoselective construction of alkynyl cyclopropanes in high yields with high both diastereoselectivity and enantioselectivity. Combined computational and experimental studies offer several lines of evidence in support of the underlying stepwise radical mechanism for the Co(II)-catalyzed olefin cyclopropanation involving a unique α-metalloradical intermediate that is associated with two resonance forms of α-Co(III)-propargyl radical and γ-Co(III)-allenyl radical. The resulting enantioenriched alkynyl cyclopropanes, as showcased with several stereospecific transformations, may serve as valuable chiral building blocks for stereoselective organic synthesis.

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Asymmetric Radical Process for General Synthesis of Chiral Heteroaryl Cyclopropanes

Cited by 48 publications

References 94 publications

Transition Metal Catalysis Controlled by Hydrogen Bonding in the Second Coordination Sphere

Transition Metal Catalysis Controlled by Hydrogen Bonding in the Second Coordination Sphere

From Serendipity to Rational Design: Heteroleptic Dirhodium Amidate Complexes for Diastereodivergent Asymmetric Cyclopropanation

Metalloradical Activation of In Situ-Generated α-Alkynyldiazomethanes for Asymmetric Radical Cyclopropanation of Alkenes

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