Scope and limitations of diastereoselective aziridination reactions using stabilised ammonium ylides or α-bromo carbonyl nucleophiles

Aichhorn, Stefan; Gururaja, Guddeangadi N.; Reisinger, Michael; Waser, Mario

doi:10.1039/c3ra40429c

Cited by 28 publications

(22 citation statements)

References 36 publications

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“…Electrophilic and nucleophilic Parr functions are local descriptors to study local reactivity in the polar reactions. Such descriptors are resulted from the excess of spin electron density reached via the GEDT process from the nucleophile toward the electrophile . Indeed, the most electrophilic site in an electrophile species is that comprising the largest electrophilic

P_{k}^{+}

Parr function value while the most nucleophilic site of the nucleophile species corresponds to that site possessing the largest nucleophilic

P_{k}^{-}

Parr function value.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective cyclopropanation of olefins through ammonium ylides: A molecular electron density theory study

Amiri

Emamian

Hosseini

et al. 2019

J of Physical Organic Chem

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The highly trans stereoselective formation of cyclopropane derivative trans‐CP 6 via the reaction of ammonium salt (AS 2) with methyl vinyl ketone (MVK) in the presence of Na2CO3 was theoretically investigated within Molecular Electron Density Theory (MEDT) at the B3LYP/6‐31G(d) computational level to probe energetics, selectivities, and molecular mechanism. This domino reaction starts by nucleophilic substitution reaction between 1,4‐diazabicyclo[2.2.2]octane (DABCO) and phenacyl chloride (PC) to form AS 2 followed by a proton abstraction from AS 2 in the presence of Na2CO3 to yield ammonim ylide (AY 3). Subsequently, AY 3 nucleophilically attacks to the MVK to produce gauche betaine‐like intermediate IN‐Tg 2, which is converted into anti betaine‐like intermediate IN‐Ta through a C–C single bond rotation. Finally, trans‐CP 6 is generated along a ring‐closure step. Analysis of the relative Gibbs free energies shows that nucleophilic attack of AY 3 to MVK is the rate‐determining step (RDS). An analysis of the density functional theory (DFT)‐based reactivity indices permits that AY 3 and MVK are, respectively, classified as a strong nucleophile and as a strong electrophile, in clear agreement with the high polar character of the additional step while exploring of the electrophilic as well as nucleophilic Parr functions computed at the reactive sites of reagents elucidates the regioselectivity within the C1–C4 single bond formation process.

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P_{k}^{+}

Parr function value while the most nucleophilic site of the nucleophile species corresponds to that site possessing the largest nucleophilic

P_{k}^{-}

Parr function value.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective cyclopropanation of olefins through ammonium ylides: A molecular electron density theory study

Amiri

Emamian

Hosseini

et al. 2019

J of Physical Organic Chem

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“…Very recently, Emamian et al reported a molecular electron density theory (MEDT) study to analyze stereoselective aziridination of aromatic aldimines through stabilized ammonium ylides. Their investigation showed that the reaction under study progress at highly trans ‐stereoselectivity, in excellent agreement with experimentally findings, and its ring closer step is the rate‐determining step (RDS).…”

Section: Introductionmentioning

confidence: 99%

Stereoselective aziridination of imines via ammonium ylides: A molecular electron density theory study

Jalali

Hosseini

Ali‐Asgari

et al. 2019

Journal of Heterocyclic Chem

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The highly trans-stereoselective reaction of ammonium salt (AS 2) toward (E)-Nbenzylidene-4-methylbenzenesulfonamide (IM 4) in the presence of Na 2 CO 3 leading to an aziridine derivative, trans-Az 6, was theoretically studied using Molecular Electron Density Theory (MEDT) at the B3LYP/6-31G(d) computational level to probe energy transformation, selectivities, and molecular mechanism. The reaction starts by a nucleophilic substitution reaction between 1,4diazabicyclo [2.2.2]octane (DABCO) and phenacyl bromide (PB) to form AS 2 which undergoes a proton abstraction by Na 2 CO 3 to produce Ammonium Ylide (AY 3). Subsequently, nucleophilic addition of AY 3 to the double bond in IM 4 leads to form a betaine-like intermediate, namely, IN-Ta which named IN-Ta. Finally, trans-Az 6 is produced as a result of the nucleophilic attack of the negatively charged nitrogen atom on the carbon atom bearing DABCO in IN-Ta.Analysis of the relative Gibbs free energies shows that the ring closure step is the rate-determining step (RDS). By an investigation of the conceptual density functional theory, CDFT reactivity indices AY 3 and IM 4 are classified as a strong nucleophilic molecular system and as a strong electrophilic molecular system, respectively, which implies that the addition step of AY 3 to IM 4 has a high polar character. An analysis of the calculated electrophilic and nucleophilic Parr functions at the reactive sites of reagents clarifies the regioselectivity observed experimentally within the C 1 -C 2 bond creation process.

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“…The use of easily available ammonium ylides [1] has emerged as a powerful alternative to classically used sulfonium ylides [2] for the synthesis of three-membered ring compounds like epoxides [3–11], aziridines [12, 13], and cyclopropanes [14–16]. These reactions usually benefit from very high and predictable diastereoselectivities and broad application scopes [3–16], as illustrated for epoxidation reactions using amide-based ylides 1 with different aldehydes 2 (Scheme 1a) [7].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the use of chiral amines often allows for highly enantioselective protocols. However, some limitations were observed: While the use of Cinchona alkaloids as chiral amine leaving groups was found to be a very versatile strategy for enantioselective cyclopropanation reactions [14, 15], these simple naturally occurring chiral amines were not suited for epoxidations and aziridinations [6, 11, 13]. Our group has for years been interested in the development of new catalytic [17, 18] and auxiliary-based methods [8, 11] for the synthesis of chiral heterocycles.…”

Section: Introductionmentioning

confidence: 99%

On the origin of the stereoselectivity in chiral amide-based ammonium ylide-mediated epoxidations

2016

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Detailed DFT studies provide an in-depth mechanistic understanding for the use of chiral amide-based ammonium ylides in epoxidation reactions. It is shown that the used chiral auxiliary efficiently shields one face of the ylide, which thus results in an extraordinarily high stereoselectivity giving only one trans-isomer with perfect control of the absolute configuration.Graphical abstract Electronic supplementary materialThe online version of this article (doi:10.1007/s00706-016-1866-8) contains supplementary material, which is available to authorized users.

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Scope and limitations of diastereoselective aziridination reactions using stabilised ammonium ylides or α-bromo carbonyl nucleophiles

Cited by 28 publications

References 36 publications

Stereoselective cyclopropanation of olefins through ammonium ylides: A molecular electron density theory study

Stereoselective cyclopropanation of olefins through ammonium ylides: A molecular electron density theory study

Stereoselective aziridination of imines via ammonium ylides: A molecular electron density theory study

On the origin of the stereoselectivity in chiral amide-based ammonium ylide-mediated epoxidations

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