Michael Additions of Benzotriazole-Stabilized Carbanions. A Review

1998 ◽  
Vol 63 (5) ◽  
pp. 599-613 ◽  
Author(s):  
Alan R. Katritzky ◽  
Ming Qi
Keyword(s):  
Steric Hindrance ◽  
Electronic Effect ◽  
Steric Effects ◽  
Unsaturated Ketone ◽  
Electronic Effects ◽  
Michael Additions ◽  
Unsaturated Aldehydes ◽  
Michael Acceptor ◽  
Michael Acceptors ◽  
Electron Withdrawing Group

The 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors is reviewed. The selectivity between 1,4- and 1,2-addition depends significantly on the electronic effect of the carbanion (usually lithium is the counterion), the type of the Michael acceptor, and steric effects. Steric hindrance of the benzotriazolyl group probably enhances the regioselectivity. Normally, 1,4-additions to α,β-unsaturated ketone or ester are observed for carbanions stabilized by a benzotriazolyl group and an electron-withdrawing group (e.g. aryl, vinyl, carbonyl). For α,β-unsaturated aldehydes as Michael acceptors, 1,2-addition is more likely, except where electronic effects are very strong. A review with 39 references.

scholarly journals On the nature of the electronic effect of multiple hydroxyl groups in the 6-membered ring – the effects are additive but steric hindrance plays a role too

2017 ◽  
Vol 15 (5) ◽  
pp. 1164-1173 ◽  
Author(s):  
Christian Marcus Pedersen ◽  
Mikael Bols
Keyword(s):  
Steric Hindrance ◽  
Electronic Effect ◽  
Membered Ring ◽  
Steric Effects ◽  
Hydroxyl Groups ◽  
Base Strength ◽  
Electronic And Steric Effects

Electronic and steric effects each play important roles in determining the base strength in piperidines.

Steric effects in quaternizations. Alkylation of pyridine, thiazole, isothiazole and some benzologues with methyl, ethyl and isopropyl iodides

1976 ◽  
Vol 29 (8) ◽  
pp. 1745 ◽  
Author(s):  
LW Deady ◽  
DC Stillman
Keyword(s):  
Steric Hindrance ◽  
Electronic Effect ◽  
Alkyl Halide ◽  
Steric Effects ◽  
Methyl Ethyl ◽  
Rate Retardation

Results of quaternization reactions in sulpholane at 65� are reported. A large steric hindrance is noted for quinoline relative to pyridine. A much smaller variation in rate with change in alkyl halide is seen in the benzothiazole/thiazole pair. Steric effects are very small and the rate retardation resulting from benzofusion is ascribed largely to an electronic effect. 2,l-Benzisothiazole reacts at essentially the same rate as isothiazole under these conditions.

Cyanoethylations and Michael additions. V. The synthesis of allylic cyclohexenols by γ-cyanoethylation of α,β-unsaturated aldehydes and ketones. Part V

1970 ◽  
Vol 48 (21) ◽  
pp. 3425-3439 ◽  
Author(s):  
Ch. R. Engel ◽  
V. S. Salvi ◽  
L. Ruest
Keyword(s):  
Reaction Time ◽  
Steric Hindrance ◽  
Carbonyl Compounds ◽  
Transfer Reaction ◽  
Main Reaction ◽  
Reaction Products ◽  
Enol Ethers ◽  
Michael Additions ◽  
Unsaturated Aldehydes ◽  
Aldehydes And Ketones

It is shown that the cyanoethylation of 3β-acetoxy-21-methyl-5α-pregn-17-en-21-one results in part in the addition of acrylonitrile to the γ-position, with concomitant cyclization, and that therefore the cyclo-γ-cyanoethylations of α,β-unsaturated carbonyl compounds reported previously were not confined to aldehydes. However, the main reaction products of the conjugated ketone were α-cyanoethylated derivatives. A variation of the reaction time did not affect the proportion of α- and γ-cyanoethylated products; the implications of this finding on mechanistic considerations are discussed; in particular, an explanation based on the assumption of an equilibrium between reactants and α- and γ-cyanoethylated products is ruled out. It is shown that the γ-additions observed, particularly in the case of α,β-unsaturated aldehydes, are not due to steric hindrance, neither to an abnormal charge distribution in the anion. It is further shown that in the presence of base the propionitrile moiety of oxygen-cyanoethylated α,β-unsaturated aldehydes with a suitable geometry is transferred to the γ-position of the original aldehyde and that cyclization occurs so that the same products are obtained from such cyano-enol ethers as in the direct cyanoethylation of the free aldehydes. On the basis of this finding, a mechanism for the cyclo-γ-cyanoethylations of α,β-unsaturated carbonyl compounds, involving such a transfer reaction, can be tentatively proposed.

scholarly journals Electron Rich Triarylphosphines as Nucleophilic Catalysts for Oxa-Michael Reactions

2021 ◽  
Author(s):  
Susanne Fischer ◽  
Simon Renner ◽  
Adrian Daniel Böse ◽  
Christian Slugovc
Keyword(s):  
Room Temperature ◽  
Oxidation Stability ◽  
Strong Impact ◽  
Michael Adduct ◽  
Michael Additions ◽  
Michael Reactions ◽  
Repeat Units ◽  
Michael Acceptor ◽  
Michael Acceptors ◽  
Reaction Speed

Herein, we study the activity of methoxysubstituted arylphosphines (4-methoxy-phenyl)diphenylphosphine (MMTPP) and tris(4-trimethoxyphenyl)phosphine (TMTPP) in catalyzing oxa-Michael additions in comparison to commonly used triphenylphosphine (TPP). Acrylonitrile, acryl amide and divinyl sulfone are used as Michael acceptors and propargyl alcohol, allyl alcohol, n-propanol and i-propanol are assessed as Michael donors. In many cases, catalyst loadings of only 1 mol% in respect to the Michael acceptor are sufficient to provide full conversion towards the Michael adduct in 24 h at room temperature. Generally, TMTPP is the most active catalyst in all cases. The experimental activity trend was rationalized by calculating the Michael acceptor affinities of all phosphine – Michael acceptor combinations. Besides this parameter, the acidity of the alcohol has a strong impact on the reaction speed. The oxidation stability of the phosphines was evaluated and electron richest TMTPP was found to be only slightly more sensitive to oxidation than TPP. Finally, the catalysts were employed in the oxa-Michael polymerization of 2-hydroxyethyl acrylate. With TMTPP polymers characterized by number average molar masses of about 1200 g/mol at room temperature are accessible. Polymerizations carried out at 80 °C resulted in macromolecules containing a considerable share of Rauhut-Currier type repeat units and consequently lower molar masses were obtained.

scholarly journals Electron Rich Triarylphosphines as Nucleophilic Catalysts for Oxa-Michael Reactions

2021 ◽  
Author(s):  
Susanne Fischer ◽  
Simon Renner ◽  
Adrian Daniel Böse ◽  
Christian Slugovc
Keyword(s):  
Room Temperature ◽  
Oxidation Stability ◽  
Strong Impact ◽  
Michael Adduct ◽  
Michael Additions ◽  
Michael Reactions ◽  
Repeat Units ◽  
Michael Acceptor ◽  
Michael Acceptors ◽  
Reaction Speed

Herein, we study the activity of methoxysubstituted arylphosphines (4-methoxy-phenyl)diphenylphosphine (MMTPP) and tris(4-trimethoxyphenyl)phosphine (TMTPP) in catalyzing oxa-Michael additions in comparison to commonly used triphenylphosphine (TPP). Acrylonitrile, acryl amide and divinyl sulfone are used as Michael acceptors and propargyl alcohol, allyl alcohol, n-propanol and i-propanol are assessed as Michael donors. In many cases, catalyst loadings of only 1 mol% in respect to the Michael acceptor are sufficient to provide full conversion towards the Michael adduct in 24 h at room temperature. Generally, TMTPP is the most active catalyst in all cases. The experimental activity trend was rationalized by calculating the Michael acceptor affinities of all phosphine – Michael acceptor combinations. Besides this parameter, the acidity of the alcohol has a strong impact on the reaction speed. The oxidation stability of the phosphines was evaluated and electron richest TMTPP was found to be only slightly more sensitive to oxidation than TPP. Finally, the catalysts were employed in the oxa-Michael polymerization of 2-hydroxyethyl acrylate. With TMTPP polymers characterized by number average molar masses of about 1200 g/mol at room temperature are accessible. Polymerizations carried out at 80 °C resulted in macromolecules containing a considerable share of Rauhut-Currier type repeat units and consequently lower molar masses were obtained.

Enantioselective Michael Addition of Malonates to Enones

2020 ◽  
Vol 24 (7) ◽  
pp. 746-773
Author(s):  
Péter Bakó ◽  
Tamás Nemcsok ◽  
Zsolt Rapi ◽  
György Keglevich
Keyword(s):  
Michael Addition ◽  
Activity Relationship ◽  
Chalcone Derivatives ◽  
Michael Additions ◽  
Michael Reactions ◽  
Structure Activity ◽  
Cyclic Enones ◽  
Michael Acceptors ◽  
Relationship Of ◽  
Enantioselective Catalysts

: Many catalysts were tested in asymmetric Michael additions in order to synthesize enantioenriched products. One of the most common reaction types among the Michael reactions is the conjugated addition of malonates to enones making it possible to investigate the structure–activity relationship of the catalysts. The most commonly used Michael acceptors are chalcone, substituted chalcones, chalcone derivatives, cyclic enones, while typical donors may be dimethyl, diethyl, dipropyl, diisopropyl, dibutyl, di-tert-butyl and dibenzyl malonates. This review summarizes the most important enantioselective catalysts applied in these types of reactions.

scholarly journals Theoretical Insight into the Reversal of Chemoselectivity in Diels-Alder Reactions of α,β-Unsaturated Aldehydes and Ketones Catalyzed by Brønsted and Lewis Acids

Organics ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 38-49
Author(s):  
Lakhdar Benhamed ◽  
Sidi Mohamed Mekelleche ◽  
Wafaa Benchouk
Keyword(s):  
Lewis Acids ◽  
Major Product ◽  
Diels Alder ◽  
Unsaturated Ketone ◽  
Unsaturated Aldehydes ◽  
Aldehydes And Ketones ◽  
Theoretical Insight ◽  
Insight Into ◽  
Good Agreement

Experimentally, a reversal of chemoselectivity has been observed in catalyzed Diels–Alder reactions of α,β-unsaturated aldehydes (e.g., (2E)-but-2-enal) and ketones (e.g., 2-hexen-4-one) with cyclopentadiene. Indeed, using the triflimidic Brønsted acid Tf2NH as catalyst, the reaction gave a Diels–Alder adduct derived from α,β-unsaturated ketone as a major product. On the other hand, the use of tris(pentafluorophenyl)borane B(C6F5)3 bulky Lewis acid as catalyst gave mainly the cycloadduct of α,β-unsaturated aldehyde as a major product. Our aim in the present work is to put in evidence the role of the catalyst in the reversal of the chemoselectivity of the catalyzed Diels–Alder reactions of (2E)-but-2-enal and 2-Hexen-4-one with cyclopentadiene. The calculations were performed at the ωB97XD/6-311G(d,p) level of theory and the solvent effects of dichloromethane were taken into account using the PCM solvation model. The obtained results are in good agreement with experimental outcomes.

scholarly journals New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, Thorectandra choanoides (CMB-01889)

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 97
Author(s):  
Shamsunnahar Khushi ◽  
Angela A. Salim ◽  
Ahmed H. Elbanna ◽  
Laizuman Nahar ◽  
Robert J. Capon
Keyword(s):  
Marine Sponge ◽  
Tissue Specificity ◽  
Spectroscopic Analysis ◽  
Transformation Products ◽  
Chemical Fractionation ◽  
Cancer Tissue ◽  
Michael Acceptor ◽  
Michael Acceptors ◽  
Stable Ring

Thorectandra choanoides (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (1), with the GNPS cluster revealing a halo of related alkaloids 1a–1n. In considering biosynthetic origins, we propose that Thorectandrachoanoides (CMB-01889) produces four well-known alkaloids, 6-bromo-1′,8-dihydroaplysinopsin (2), 6-bromoaplysinopsin (3), aplysinopsin (4), and 1′,8-dihydroaplysinopsin (10), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-like (IDO) enzyme to 1a–1n. Where the 1′,8-dihydroalkaloids 2 and 10 are fully transformed to stable ring-opened thorectandrins 1 and 1a–1b, and 1h–1j, respectively, the conjugated precursors 3 and 4 are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts 1c–1g, and 1k–1n, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For example, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme.

ChemInform Abstract: Steric and Electronic Effects on the Photochemical Reactivity of Oxime Acetates of β,γ-Unsaturated Aldehydes.

ChemInform ◽  
2010 ◽  
Vol 23 (15) ◽  
pp. no-no
Author(s):  
D. ARMESTO ◽  
W. M. HORSPOOL ◽  
M. G. GALLEGO ◽  
A. R. AGARRABEITIA
Keyword(s):  
Electronic Effects ◽  
Photochemical Reactivity ◽  
Unsaturated Aldehydes
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