Solvent-Dependent Stereoselectivity in a Still−Wittig Rearrangement:  An Experimental and ab Initio Study

Hart, Scott A.; Trindle, Carl; Etzkorn, Felicia A.

doi:10.1021/ol015764d

Cited by 21 publications

(38 citation statements)

References 18 publications

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“…During the synthesis of Pin1 inhibitors, [34] Etzkorn observed as olvent effect on the E/Z-selectivity. [35] When the Wittig-Still rearrangement of 49 was carried out in THF,the Z-isomer of 50 was obtained preferentially with a Z:E ratio of 75:25. When the reaction was performed in toluene,aswitch in the selectivity was observed and the E-isomer was obtained as the major product (Z:E = 25:75) (Scheme 11).…”

Section: Stereochemical Considerations:e /Z-selectivitymentioning

confidence: 99%

Applications of the Wittig–Still Rearrangement in Organic Synthesis

Rýček

Hudlický

2017

Angew Chem Int Ed

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This Review traces the discovery of the Wittig-Still rearrangement and its applications in organic synthesis. Its relationship to Wittig rearrangements is discussed along with detailed analysis of E/Z- and diastereoselectivity. Modifications of the products arising from the Wittig-Still rearrangement are reviewed in the context of increased complexity in intermediates potentially useful in target-oriented synthesis. Early applications of the Wittig-Still rearrangement to modifications of steroids are reviewed as are applications to various terpene and alkaloid natural product targets and miscellaneous compounds. To the best of our knowledge, the literature is covered through December 2016.

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Section: Stereochemical Considerations:e /Z-selectivitymentioning

confidence: 99%

Applications of the Wittig–Still Rearrangement in Organic Synthesis

Rýček

Hudlický

2017

Angew Chem Int Ed

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“…Bei der Synthese von Pin1‐Inhibitoren beobachtete Etzkorn einen Einfluss des Lösungsmittels auf die E / Z ‐Selektivität . Bei der Durchführung der Wittig‐Still‐Umlagerung von 49 in THF wurde bevorzugt das Z ‐Isomer von 50 mit einem Z : E ‐Verhältnis von 75:25 erhalten.…”

Section: Stereochemische Betrachtungen: E/z‐selektivitätunclassified

Anwendungen der Wittig‐Still‐Umlagerung in der organischen Synthese

Rýček

Hudlický

2017

Angewandte Chemie

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Dieser Aufsatz zeichnet die Entstehung der Wittig‐Still‐Umlagerung und deren Anwendung in der organischen Synthese nach. Ihre Beziehung zur Wittig‐Umlagerung wird diskutiert, einhergehend mit einer detaillierten Analyse der E/Z‐Selektivität und Diastereoselektivität. Modifikationen der in Wittig‐Still‐Umlagerungen gebildeten Produkte werden im Zusammenhang der gesteigerten Komplexität von Intermediaten mit potenziellem Nutzen für die zielorientierte Synthese erläutert. Frühe Anwendungen der Wittig‐Still‐Umlagerung zur Modifizierung von Steroiden werden ebenso besprochen wie Anwendungen in der Naturstoffsynthesen von Alkaloiden und Terpenen sowie der Synthese sonstiger Verbindungen. Nach unserem besten Wissen ist die Literatur bis Dezember 2016 abgedeckt.

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“…The regio-and stereoselectivity of these reactions depends on the precise structure of the carbanion, on the metal and solvent chosen [199], and on the structure of the electrophile [150,[200][201][202][203], and can be difficult to predict. The regio-and stereoselectivity of these reactions depends on the precise structure of the carbanion, on the metal and solvent chosen [199], and on the structure of the electrophile [150,[200][201][202][203], and can be difficult to predict.…”

Section: A-heteroatom Carbanionsmentioning

confidence: 99%

“…Convenient alternatives to direct deprotonation of ethers are tin-lithium exchange [199,[258][259][260][261], halogen-magnesium exchange [262], or reductive cleavage of O,Se-acetals [263,264]. Another synthetic equivalent of a-metalated ethers are (alkoxymethyl)phosphonium salts [265].…”

Section: A-nitrogen Carbanionsmentioning

confidence: 99%

The Alkylation of Carbanions

Dörwald

2004

Side Reactions in Organic Synthesis

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The deprotonation of organic compounds by strong, non-nucleophilic bases followed by C-alkylation with a suitable electrophile has become one of the most predictable and straightforward methods for formation of C-C bonds. The popularity of this chemistry is also a consequence of the often-seen close resemblance of feasible structural modifications by a deprotonation/alkylation strategy to an unsophisticated retrosynthetic analysis of a given target compound. Other reactions, which involve, for instance, substantial rearrangement of the carbon framework (e.g. Cope rearrangement, fragmentations, ring contractions or enlargements) are usually more difficult to take into account during retrosynthetic analysis.LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2]. Because the reactivity of an organometallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles.In this chapter the alkylation of carbanions with simple carbon electrophiles will be discussed, with special emphasis on the structure-reactivity relationship of the carbanion and on side reactions. In this context the term "carbanion" refers to an intermediate prepared by in-situ deprotonation of an organic compound, followed by optional cation exchange (transmetalation), which tends to be alkylated at carbon by soft electrophiles such as MeI or PhCHO. This type of reactivity is characteristic of enolates with an ionic M-O bond or for organometallic compounds with a strongly polarized or ionic M-C bond, M typically being an alkali metal, Mg, Cu, or Zn. Carbanions can, alternatively, also be prepared by halogen-metal exchange [3-8], sulfoxide-or sulfone-metal exchange [9-13], or by transmetalation of stannanes. The most suitable reagents for performing such metalating exchange reactions are organometallic compounds with a metal-bound secondary or tertiary alkyl group, such as tBuLi, sBuLi, iPr 2 Zn [14, 15], or iPrMgHal [6]. These reagents are thermodynamically less stable than organometallic compounds with primary alkyl 5 146 Scheme 5.1. Approximate relative rates of proton transfer in water at thermoneutrality (DpK a = 0) [35, 39, 51]. 147 Scheme 5.2. The effect of fluorine on the acidity of organic compounds [24, 62-65]. 148 Scheme 5.3. Dependence of the reactivity of carbanions on their basicity [68, 72-74]. Regioselectivity of Deprotonations and AlkylationsThe organic chemist is occasionally confronted with the problem that a compound has several differrent X-H groups of similar pK a . If only one of these is to be alkylated, one option would be to perform a regioselective deprotonation. This can sometimes be achieved by exploiting small differences be...

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Solvent-Dependent Stereoselectivity in a Still−Wittig Rearrangement: An Experimental and ab Initio Study

Cited by 21 publications

References 18 publications

Applications of the Wittig–Still Rearrangement in Organic Synthesis

Applications of the Wittig–Still Rearrangement in Organic Synthesis

Anwendungen der Wittig‐Still‐Umlagerung in der organischen Synthese

The Alkylation of Carbanions

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