The anti-selective Michael addition of allylic organometals to ethylidenemalonates and related compounds

Yamamoto, Yoshinori; Nishii, S.

doi:10.1021/jo00250a034

Cited by 46 publications

(11 citation statements)

References 2 publications

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“…Spectroscopic data are in agreement with published data. [131] (5S)-5-Phenyl-6-nitrohexan-3-one (7b): 1-Nitro-2-phenylheptan-4-one (7c): From propan-2-one 5c and nitrostyrene according to General Procedure 3 to obtain a mixture of 2 regioisomers: 3-(2-nitro-1-phenylethyl)pentan-2-one 6c and 7c as a colourless oil. The compound 6c was not isolated for analysis.…”

Section: Addition Of Unmodified Aldehydes or Ketones To Nitroolefins mentioning

confidence: 99%

The Use of N‐Alkyl‐2,2′‐bipyrrolidine Derivatives as Organocatalysts for the Asymmetric Michael Addition of Ketones and Aldehydes to Nitroolefins

Andrey¹,

Alexakis²,

Tomassini³

et al. 2004

Adv Synth Catal

254

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Abstract:The direct Michael addition of aldehydes and ketones to nitroolefins, catalyzed by N-i-Pr-2,2'-bipyrrolidine, is described. The desired 1,4-adducts are obtained in excellent yields with enantioselectivities up to 95% ee and dr up to 95 : 5 of the syn aldehyde addition product. An unexpected inversion of diastereoselectivity was observed for the addition of a-hydroxy ketones to b-arylnitroolefins with enantioselectivities up to 98% ee. The formation of an internal hydrogen bond between the OH group of the ahydroxy ketone and the tertiary nitrogen of the catalyst leads to the formation of a rigid cis enamine intermediate that accounts for the inversion of the expected diastereoselectivity and the very high ees.

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Section: Addition Of Unmodified Aldehydes or Ketones To Nitroolefins mentioning

confidence: 99%

The Use of N‐Alkyl‐2,2′‐bipyrrolidine Derivatives as Organocatalysts for the Asymmetric Michael Addition of Ketones and Aldehydes to Nitroolefins

Andrey¹,

Alexakis²,

Tomassini³

et al. 2004

Adv Synth Catal

254

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“…1 H NMR and 13 C NMR were consistent with those reported in the literature. 42 Anti isomer: t R (major) 10.52 min, t R (minor) 12.03 min; syn isomer: t R (minor) 13.42 min, t R (major) 18.80 min (Chiralcel AD; l = 254 nm; 1% i-PrOH-hexanes, 1 mL/min). 13 43 t R (minor) 9.06 min, t R (major) 11.78 min (Chiralcel AS; l 254 nm; 5% i-PrOHhexanes, 1.0 mL/min).…”

Section: -Methyl-5-nitro-4-phenylpentan-2-one (73)mentioning

confidence: 99%

Catalytic Direct Asymmetric Michael Reactions: Addition of Unmodified Ketone and Aldehyde Donors to Alkylidene Malonates and Nitro Olefins

Betancort¹,

Sakthivel²,

Thayumanavan³

et al. 2004

Synthesis

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The Michael additions of a number of ketones and aldehydes to alkylidene malonates and nitro olefins were studied. The reactions employ small organic molecules as catalyst under mild reaction conditions and do not require preactivation of the carbonyl donors. These reactions afforded a variety of highly functionalized products in good yields with moderate to good enantioselectivity.The development of new methodologies in asymmetric synthesis is of tremendous importance given the increasing demand for optically active compounds. 1 Though remarkable advances have been made in the development of asymmetric catalysts containing metals, relatively few asymmetric transformations have been reported that employ small organic molecules as catalysts. As the field of enantioselective catalysis has evolved during the last few years, highly reliable methods that predictably generate products with known stereochemistry have been developed and demand has increased for environmentally benign and highly efficient catalytic processes. Enantioselective organocatalysis in which the reaction is mediated by a catalytic amount of a chiral organic molecule is emerging as a powerful tool within this context. 2 This approach is very attractive given the many advantages it provides ranging from operational simplicity and ease of handling to the use of inexpensive, nontoxic, and readilyavailable catalysts.Asymmetric carbon-carbon bond forming reactions are among the most challenging endeavors in organic synthesis. The Michael reaction is generally regarded as one of the most efficient and effective transformations, and studies concerning this reaction have played an important role in the development of modern synthetic organic chemistry. 3 Over many years, the scope of this reaction has been extended in both reactant structure and catalyst efficiency. Much progress has been made in the development of asymmetric variants of this reaction, providing for the preparation of Michael adducts with high enantiomeric purity. 4 Typically, carbon nucleophiles that contain an active methylene center such as malonic acid esters, b-keto esters, or nitroalkanes have been studied in the Michael reaction. 5 Carbonyl compounds, and ketones in particular, have generally been used as donors only following their pre-activation by conversion into a more reactive species such as enol or enamine equivalents. 6,7 In these cases, additional synthetic step(s), stoichiometric amounts of base, additional reagents, or chiral ligands are required. A potentially advantageous strategy in terms of atom economy would involve direct additions of unmodified carbonyl compounds to Research in our laboratories has recently focused on the concept of catalysis mediated by amino acids and amines. 9-21 These studies led to the development of amine-catalyzed direct asymmetric aldol and Mannich reactions, Robinson annulations, Diels-Alder cycloadditions, and a variety of asymmetric multicomponent or assembly reactions. The common feature of these reactions is the use of unmodified nuc...

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“…Several enantioselective Michael reactions using organic catalysts are known. Among them, the proline-catalyzed reactions studied by Seebach and Blarer in 1981 have received significant attention, and many related studies have been conducted since [2][3][4][5][6][7][8][9][10]. Seebach and Blarer reported the Michael reaction of an α, β-unsaturated nitroalkene using a chiral proline derivative [11,12].…”

Section: Introductionmentioning

confidence: 99%

Organocatalysis for the Asymmetric Michael Addition of Cycloketones and α, β-Unsaturated Nitroalkenes

et al. 2021

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Michael addition is one of the most important carbon–carbon bond formation reactions. In this study, an (R, R)-1,2-diphenylethylenediamine (DPEN)-based thiourea organocatalyst was applied to the asymmetric Michael addition of nitroalkenes and cycloketones to produce a chiral product. The primary amine moiety in DPEN reacts with the ketone to form an enamine and is activated through the hydrogen bond formation between the nitro group in the α, β-unsaturated nitroalkene and thiourea. Here, the aim was to obtain an asymmetric Michael product through the 1,4-addition of the enamine to an alkene to form a new carbon–carbon bond. As a result, the primary amine of the chiral diamine was converted into an enamine. The reaction proceeded with a relatively high level of enantioselectivity achieved using double activation through the hydrogen bonding of the nitro group and thiourea. Michael products with high levels of enantioselectivity (76–99% syn ee) and diastereoselectivity (syn/anti = 9/1) were obtained with yields in the range of 88–99% depending on the ketone.

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The anti-selective Michael addition of allylic organometals to ethylidenemalonates and related compounds

Cited by 46 publications

References 2 publications

The Use of N‐Alkyl‐2,2′‐bipyrrolidine Derivatives as Organocatalysts for the Asymmetric Michael Addition of Ketones and Aldehydes to Nitroolefins

The Use of N‐Alkyl‐2,2′‐bipyrrolidine Derivatives as Organocatalysts for the Asymmetric Michael Addition of Ketones and Aldehydes to Nitroolefins

Catalytic Direct Asymmetric Michael Reactions: Addition of Unmodified Ketone and Aldehyde Donors to Alkylidene Malonates and Nitro Olefins

Organocatalysis for the Asymmetric Michael Addition of Cycloketones and α, β-Unsaturated Nitroalkenes

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