Conversion of α-Haloaldehydes into Acylating Agents by an Internal Redox Reaction Catalyzed by Nucleophilic Carbenes

Reynolds, Nathan T.; Alaniz, Javier Read de; Rovis, Tomislav

doi:10.1021/ja046991o

Cited by 372 publications

(124 citation statements)

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“…(1) and (2) in Scheme 131]. [447] In these cases, the oxidation is effected by displacement of the a substituent with concomitant formation of an enolate. Proton transfer then generates an active acylating agent that reacts with an alcohol to yield the product.…”

Section: Methodsmentioning

confidence: 99%

Lewis Base Catalysis in Organic Synthesis

2008

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The legacy of Gilbert Newton Lewis (1875-1946) pervades the lexicon of chemical bonding and reactivity. The power of his concept of donor-acceptor bonding is evident in the eponymous foundations of electron-pair acceptors (Lewis acids) and donors (Lewis bases). Lewis recognized that acids are not restricted to those substances that contain hydrogen (Brønsted acids), and helped overthrow the "modern cult of the proton". His discovery ushered in the use of Lewis acids as reagents and catalysts for organic reactions. However, in recent years, the recognition that Lewis bases can also serve in this capacity has grown enormously. Most importantly, it has become increasingly apparent that the behavior of Lewis bases as agents for promoting chemical reactions is not merely as an electronic complement of the cognate Lewis acids: in fact Lewis bases are capable of enhancing both the electrophilic and nucleophilic character of molecules to which they are bound. This diversity of behavior leads to a remarkable versatility for the catalysis of reactions by Lewis bases.

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Section: Methodsmentioning

confidence: 99%

Lewis Base Catalysis in Organic Synthesis

2008

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“…[10] To our delight, benzoin (1) in combination with an excess of trifluoroacetophenone (2) as reactive electrophilic ketone component led chemoselectively to the crossed acyloin product 3 in high yield, employing 20 mol% of the bicyclic triazolium salt 4 [11] as precatalyst in the presence of 20 mol% DBU in THF at room temperature (Scheme 1).…”

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confidence: 99%

A Direct Intermolecular Cross‐Benzoin Type Reaction: N‐Heterocyclic Carbene‐Catalyzed Coupling of Aromatic Aldehydes with Trifluoromethyl Ketones

Enders

Henseler

2009

Adv Synth Catal

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A direct intermolecular cross-benzointype condensation catalyzed by an N-heterocyclic carbene has been developed. The cross-coupling of commercially available aromatic aldehydes and trifluoromethyl ketones results in a-hydroxy-a-trifluoromethyl ketones bearing a quaternary stereocenter with excellent chemoselectivity and good to excellent yields.Keywords: cross-benzoin reaction; N-heterocyclic carbenes; organocatalysis; trifluoromethyl substitution; umpolungIn their pioneering and historic paper on the benzoyl compounds of 1832 [1] Wçhler and Liebig not only started the chemistry of aromatic compounds, such as benzaldehyde, benzoic acid, benzoyl chloride and benzamide, but also reported the cyanide-catalyzed (bitter almond oil) formation of benzoin, which in a sense can be seen as the start of organocatalysis. Since these early days of organic chemistry, the cyanide-and later carbene-catalyzed coupling of two aldehyde molecules to form the corresponding a-hydroxy ketones (benzoin, acyloin) has been investigated extensively. [2] Although significant progress has been made with enantioselective and intramolecular versions in recent years, [3] there still are limitations in the intermolecular coupling of two different aldehydes and of aldehydes with ketones. In these cases the outcome is typically a mixture of all possible symmetrical and unsymmetrical acyloins, with the chemoselectivity strongly depending on the relative thermodynamic stability of the corresponding products.[4] In order to overcome this problem several research groups have made excellent contributions by developing enzymatic approaches [5] or utilizing acylsilanes [6] and acylphosphonates [7] as acyl anion equivalents in cyanide-catalyzed transformations. In addition, very recently Scheidt et al. reported intermolecular cross-acyloin reactions by fluoride-promoted addition of O-silylthiazolium salts.[8] However, to the best of our knowledge, there is no precedent for a direct organocatalytic intermolecular coupling of aldehydes with ketones, which we would like to report in this communication.Based on our mechanistic proposal for the Stetter reaction, which relies on a reversible formation of the benzoin product prior to the Stetter product formation, [9] we envisaged to use benzoins as masked aldehyde equivalents.[10] To our delight, benzoin (1) in combination with an excess of trifluoroacetophenone (2) as reactive electrophilic ketone component led chemoselectively to the crossed acyloin product 3 in high yield, employing 20 mol% of the bicyclic triazolium salt 4[11] as precatalyst in the presence of 20 mol% DBU in THF at room temperature (Scheme 1).Since the crossed acyloin product 3 containing a tertiary alcohol seemed to be energetically preferred relative to benzoin (1) a simpler and more practical version of this concept would be to employ the aldehyde component directly in this transformation (Scheme 2). Under the reaction conditions given (10 mol% carbene precursor 4 and 10 mol% DBU), it was indeed possible to obtain the cross-co...

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“…Intermediates similar to I-2 have been hypothesized by many authors, [11,15,64,65] but never isolated. It cannot be excluded that product 6 is an artefact of the column chromatography used trying to isolate possible addition products.…”

Section: Resultsmentioning

confidence: 98%

Investigation of the Role of Electrogenerated N-Heterocyclic Carbene in the Staudinger Synthesis in Ionic Liquid

Feroci¹

2011

IJOC

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Electrogenerated N-heterocyclic carbene (NHC), obtained by cathodic reduction of Bmim-BF 4 , behaves as organocatalyst and base in the Staudinger synthesis from an acyl chloride and a deactivated imine in ionic liquid to yield -lactams. The effect of many parameters (temperature, amount of electricity, substituents, presence of an external base) has been evaluated and a tentative mechanism for the Staudinger synthesis in a very polar medium like the ionic liquid reported. The yields of isolated -lactams are good, starting from non-electrophilic imines, and predominantly trans lactams are obtained with a good diastereomeric ratio.

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Conversion of α-Haloaldehydes into Acylating Agents by an Internal Redox Reaction Catalyzed by Nucleophilic Carbenes

Cited by 372 publications

References 19 publications

Lewis Base Catalysis in Organic Synthesis

Lewis Base Catalysis in Organic Synthesis

A Direct Intermolecular Cross‐Benzoin Type Reaction: N‐Heterocyclic Carbene‐Catalyzed Coupling of Aromatic Aldehydes with Trifluoromethyl Ketones

Investigation of the Role of Electrogenerated N-Heterocyclic Carbene in the Staudinger Synthesis in Ionic Liquid

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