Branched aldehydes as linchpins for the enantioselective and stereodivergent synthesis of 1,3-aminoalcohols featuring a quaternary stereocentre

Trost, Barry M.; Hung, Chao‐I Joey; Saget, Tanguy; Gnanamani, Elumalai

doi:10.1038/s41929-018-0093-6

Cited by 63 publications

(34 citation statements)

References 42 publications

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“…α‐Branched aldehydes 143 were also found to be competent nucleophiles to generate a range of chiral β‐amino aldehydes 144 . The adducts 144 can subsequently react with a second nucleophile, including nitromethane, ynones, acetophenones, and acetylenes, in the same‐pot to access 1,3‐aminoalcohols 145 with complex stereotriads (Scheme ).…”

Section: Catalytic Asymmetric Addition To Iminesmentioning

confidence: 99%

“…Reviews a-Branched aldehydes 143 were also found to be competent nucleophiles to generate a range of chiral b-amino aldehydes 144. [66] The adducts 144 can subsequently react with a second nucleophile, including nitromethane, ynones, acetophenones, and acetylenes, in the same-pot to access 1,3aminoalcohols 145 with complex stereotriads (Scheme 34). More importantly, good to excellent catalyst-control was observed during the second addition, allowing diastereodivergent access to the final products by either utilizing the same catalyst for both steps or simply switching to the other enantiomer of the catalyst for the second step.…”

Section: Angewandte Chemiementioning

confidence: 99%

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Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

2019

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The ProPhenol ligand is a member of the chiral aza‐crown family that spontaneously forms a bimetallic complex upon treatment with alkyl metal reagents, such as Et2Zn and Bu2Mg. The resulting complex features Lewis acidic and Brønsted basic sites, enabling simultaneous activation of both nucleophile and electrophile in the same chiral environment. Since the initial report in 2000, metal‐ProPhenol catalysts have been used to facilitate a broad range of asymmetric transformations, including aldol, Mannich, and Henry reactions, as well as alkynylations and conjugation additions. By promoting such a diverse array of reactions, these complexes provide rapid and atom‐economical access to valuable complex building blocks. In this Review, we describe in detail the development and synthetic applications of these versatile catalysts with a special focus on recent efforts to improve reactivity and selectivity through ligand design and structural modification.

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Section: Catalytic Asymmetric Addition To Iminesmentioning

confidence: 99%

Section: Angewandte Chemiementioning

confidence: 99%

Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

2019

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“…α‐Verzweigte Aldehyde 143 stellten gleichfalls reaktionsfähige Nukleophile dar, um eine Reihe chiraler β‐Aminoaldehyde 144 zu synthetisieren . Anschließend können die Addukte 144 im Eintopf mit einem zweiten Nukleophil wie Nitromethan, Inonen, Acetophenon und Acetylenen zur Reaktion gebracht werden, um so 1,3‐Aminoalkohole 145 mit komplexen Stereotriaden zu erhalten (Schema ).…”

Section: Katalytische Asymmetrische Addition An Imineunclassified

“…a-Verzweigte Aldehyde 143 stellten gleichfalls reaktionsfähige Nukleophile dar, um eine Reihe chiraler b-Aminoaldehyde 144 zu synthetisieren. [66] Anschließend kçnnen die Addukte 144 im Eintopf mit einem zweiten Nukleophil [67] Im Unterschied zu den meisten anderen bekannten Systemen erfordert dieser Prozess keine Präaktivierung der Butenolide als Siloxyfurane. [68] Zudem erwiesen sich a,b-wie auch b,g-Butenolide als gleichermaßen reaktionsfähige Nukleophile mit einer großen Substituentenvielfalt an den 4-und 5-Posi-tionen, im Unterschied zu einer Limitierung auf eine einfache Methylgruppe oder Wasserstoff.…”

Section: Katalytische Enantioselektive Mannich-reaktionunclassified

Zweikernige Metall‐ProPhenol‐Katalysatoren: Entwicklung und Anwendungen in der Synthese

2019

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ProPhenol‐Moleküle gehören zur Gruppe der chiralen Azakronen‐Verbindungen und bilden bei Umsetzung mit Alkylmetall‐Reagenzien wie Et2Zn und Bu2Mg spontan einen bimetallischen Komplex. Dieser Komplex hat Lewis‐saure und Brønsted‐basische Reaktionszentren, die eine simultane Aktivierung eines Nukleophils und eines Elektrophils in derselben chiralen Umgebung erlauben. Seit dem ersten Bericht im Jahr 2000 haben Metall‐ProPhenol‐Katalysatoren eine große Bandbreite asymmetrischer Umwandlungen wie Aldol‐, Mannich‐ und Henry‐Reaktionen sowie Alkinylierungen und konjugierte Additionen ermöglicht. Aufgrund der vielfältigen Einsatzmöglichkeiten bei unterschiedlichen Reaktionen erlauben diese Komplexe einen schnellen und atomökonomischen Zugang zu wertvollen komplexen Baugruppen. In diesem Aufsatz beschreiben wir detailliert die Entwicklung und synthetischen Anwendungen dieser vielseitigen Katalysatoren, mit besonderem Blick auf kürzliche Bemühungen, Reaktivität und Selektivität durch Ligandendesign und strukturelle Veränderungen zu verbessern.

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“…ntroduction of substituents with predictable stereoselectivity is crucial for rational synthetic design of functional molecules. Despite the already advanced toolbox for practitioners of synthetic chemistry, it is still challenging to access any and every stereoisomer of contiguous acyclic stereodiads in a predictable fashion, particularly for substrates that contain only hydrocarbon groups [1][2][3][4][5] . For example, electrophilic α alkylation of an enolate is one of the most fundamental textbook transformation.…”

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confidence: 99%

A unified approach for divergent synthesis of contiguous stereodiads employing a small boronyl group

Zhan

Ding

et al. 2020

Nat Commun

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Acyclic contiguous stereocenters are frequently seen in biologically active natural and synthetic molecules. Although various synthetic methods have been reported, predictable and unified approaches to all possible stereoisomers are rare, particularly for those containing non-reactive hydrocarbon substituents. Herein, a β-boronyl group is employed as a readily accessible handle for predictable α-functionalization of enolates with either syn or anti selectivity depending on reaction conditions. Contiguous tertiary-tertiary and tertiaryquaternary stereocenters are thus accessed in generally good yields and diastereoselectivity. Based on experimental and computational studies, mechanism for syn selective alkylation is proposed, and Bpin (pinacolatoboronyl) behaves as a smaller group than most carboncentered groups. The synthetic utility of this methodology is demonstrated by preparation of several key intermediates for bioactive molecules.

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Branched aldehydes as linchpins for the enantioselective and stereodivergent synthesis of 1,3-aminoalcohols featuring a quaternary stereocentre

Cited by 63 publications

References 42 publications

Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

Zweikernige Metall‐ProPhenol‐Katalysatoren: Entwicklung und Anwendungen in der Synthese

A unified approach for divergent synthesis of contiguous stereodiads employing a small boronyl group

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