NMR Spectroscopic Investigations of Mixed Aggregates Underlying Highly Enantioselective 1,2-Additions of Lithium Cyclopropylacetylide to Quinazolinones

Parsons, Rodney L.; Fortunak, Joseph; Dorow, Roberta L.; Harris, Gregory D.; Kauffman, Goss S.; Nugent, William A.; Winemiller, Mark D.; Briggs, Timothy F.; Xiang, Bosong; Collum, David B.

doi:10.1021/ja0105616

Cited by 40 publications

(26 citation statements)

References 30 publications

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“…It may seem surprising that the polarity of the medium has only a minimal influence on reactions reputed to proceed via relatively ionic species 38. We hasten to add, however, that aromatic hydrocarbons can cause significant deviations from ideality in some cases 39…”

Section: Structure–reactivity Relationshipsmentioning

confidence: 99%

Lithium Diisopropylamide: Solution Kinetics and Implications for Organic Synthesis

2007

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Lithium diisopropylamide (LDA) is a prominent reagent used in organic synthesis. In this Review, rate studies of LDA-mediated reactions are placed in the broader context of organic synthesis in three distinct segments. The first section provides a tutorial on solution kinetics, emphasizing the characteristic rate behavior caused by dominant solvation and aggregation effects. The second section summarizes substrate- and solvent-dependent mechanisms that reveal basic principles of solvation and aggregation. The final section suggests how an understanding of mechanism might be combined with empirical methods to optimize yields, rates, and selectivities of organolithium reactions and applied to organic synthesis.

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Section: Structure–reactivity Relationshipsmentioning

confidence: 99%

Lithium Diisopropylamide: Solution Kinetics and Implications for Organic Synthesis

2007

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“…8 We previously studied amino alkoxides 2a and 3a using NMR spectroscopy and gleaned no useful information. 6,7 The current paper describes how a combination of 6 Li NMR spectroscopy and MCV allowed us to characterize 2a,b and 3a,b as stereochemically pure cubic tetramers 9a,b and 10a,b . Computational studies suggest that the S 4 -symmetric cubic core is inherently more stable than the D 2d core, a preference that is amplified by the substituents along the chelate backbone (eqs 4 and 5).…”

Section: Discussionmentioning

confidence: 99%

“…6 A subsequent Cornell–DuPont collaboration attributed the enantioselectivity in eq 2 to external attack of acetylide on 3:1 (ROLi) 3 (substrate) 1 mixed tetramer 6 . 7 In both reactions, aging the reaction near ambient temperature before addition at low temperature was key to attaining high selectivity.…”

Section: Introductionmentioning

confidence: 99%

Solution Structures of Lithium Amino Alkoxides Used in Highly Enantioselective 1,2-Additions

2014

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Lithium ephedrates and norcarane-derived lithium amino alkoxides used to effect highly enantioselective 1,2-additions on large scales have been characterized in toluene and tetrahydrofuran. The method of continuous variations in conjunction with 6Li NMR spectroscopy reveals that the lithium amino alkoxides are tetrameric. In each case, low-temperature 6Li NMR spectra show stereoisomerically pure homoaggregates displaying resonances consistent with an S4-symmetric cubic core rather than the alternative D2d core. These assignments are supported by density functional theory computations and conform to X–ray crystal structures. Slow aggregate exchanges are discussed in the context of amino alkoxides as chiral auxiliaries.

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“…Es erscheint überraschend, dass die Polarität des Mediums nur einen minimalen Einfluss auf Reaktionen ausübt, die über Spezies mit einem relativ ausgeprägten ionischen Charakter verlaufen 38. Wir müssen allerdings hinzufügen, dass aromatische Kohlenwasserstoffe in manchen Fällen zu erheblichen Abweichungen vom idealen Verhalten führen können 39…”

Section: Struktur‐reaktivitäts‐beziehungenunclassified

Lithiumdiisopropylamid: Reaktionskinetik in Lösung und Folgerungen für die organische Synthese

2007

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Lithiumdiisopropylamid (LDA) ist ein herausragendes Reagens in der organischen Synthese. Dieser Aufsatz diskutiert kinetische Untersuchungen von LDA‐vermittelten Reaktionen, wobei eine Unterteilung in drei Abschnitte vorgenommen wird. Der erste Teil gibt eine Einführung in die Reaktionskinetik von LDA‐Lösungen mit Schwerpunkt auf dem charakteristischen Reaktionsgeschwindigkeitsverhalten, das von Solvatations‐ und Aggregationseinflüssen bestimmt wird. Im zweiten Teil werden substrat‐ und solvensabhängige Mechanismen zusammengefasst, aus denen sich grundlegende Prinzipien der Solvatation und Aggregatbildung ableiten lassen. Im abschließenden Teil werden Vorschläge gemacht, wie sich Erkenntnisse zu den Reaktionsmechanismen mit empirischen Methoden kombinieren lassen, um Ausbeuten, Reaktionsgeschwindigkeiten und Selektivitäten von Organolithiumreaktionen zu optimieren.

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NMR Spectroscopic Investigations of Mixed Aggregates Underlying Highly Enantioselective 1,2-Additions of Lithium Cyclopropylacetylide to Quinazolinones

Cited by 40 publications

References 30 publications

Lithium Diisopropylamide: Solution Kinetics and Implications for Organic Synthesis

Lithium Diisopropylamide: Solution Kinetics and Implications for Organic Synthesis

Solution Structures of Lithium Amino Alkoxides Used in Highly Enantioselective 1,2-Additions

Lithiumdiisopropylamid: Reaktionskinetik in Lösung und Folgerungen für die organische Synthese

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