Synthetic potential of the tertiary-amine-catalysed reaction of activated vinyl carbanions with aldehydes

Coumarins fused with other aromatic units have recently emerged as a hot topic of research. Their synthesis is partly based on classical methodologies such as Pechmann reaction or Knoevenagel condensation, but it also sparked the discovery of completely new pathways. In very recent years so-called vertically expanded coumarins were synthesized, effectively expanding the portfolio of existing architectures. A subtle relationship exists between the structure of fused coumarins and their optical properties. Although absorption of UV-radiation and light is a unifying theme among these π-expanded coumarins, the fluorescence properties strongly depend on the structure. The mode of fusion, the type of additional ring and the presence of electron-donating and electron-withdrawing substituents all influence the photophysical parameters. Recent advances made it possible to modulate their absorption from 300 nm to 550 nm, resulting in new coumarins emitting orange light. This review serves as a guide through both synthesis strategies and structure–property relationship nuances. Strong intramolecular charge-transfer character made it possible to reach suitable values of two-photon absorption cross-section. Photophysical advantages of π-expanded coumarins have been already utilized in fluorescent probes and two-photon excited fluorescence microscopy.

https://oasis.postech.ac.kr/bitstream/2014.oak/13024/1/OAIR003795.pdf

π-Expanded coumarins: synthesis, optical properties and applications

In a patent application published in 1972, Baylis and Hillman reported the reaction of acetaldehyde with ethyl acrylate and acrylonitrile in the presence of catalytic amounts of 1,4-diazabicyclo[2.2.2]octane to give the α-hydroxyethylated products in good yields. No structure proof was given. The assignment eventually was shown to be correct, but since the initial disclosure was not followed by a journal publication, this remarkably simple, atom-efficient, and useful reaction was ignored for a number of years, and it has been only fairly recently that its potential has begun to be explored. The transformation is now commonly referred to as the Baylis–Hillman reaction. This is unfortunate because credit for its invention clearly belongs to Morita, who five years earlier, in patents and a brief paper reported the same reaction with the exception that tertiary phosphines were used as the catalysts; he also proposed the currently accepted mechanism. Baylis and Hillman made reference to Morita's work in their patent application. It is true that tertiary amines in general are cheaper, less toxic, and more readily removed than tertiary phosphines. However, the latter sometimes give higher yields in shorter reaction times, and there are a number of examples where they are the only useful catalysts.



The DABCO-catalyzed reaction is slow, and reaction times at room temperature of days or even weeks are common. Attempts to remedy this situation by use of other amine catalysts, change of reaction temperature, high pressure, or microwave irradiation have been partially successful. Activated olefins other than acrylonitrile and acrylic esters that have now been shown to undergo the reaction include α,β-unsaturated aldehydes and ketones, vinyl sulfoxides, vinyl sulfones, vinylsulfonates, and vinylphosphonates. β-Substituted activated olefins do not normally react. Among electrophiles other than aldehydes, unactivated ketones undergo the Morita–Baylis–Hillman reaction only under high pressure, but activation such as in α-halo ketones, α-keto esters, α-keto lactones, and nonenolizable α-diketones often produces very reactive substrates. Imines also can be employed, provided they carry a sufficiently electronegative group on nitrogen.



This chapter covers catalyzed α-hydroxyalkylations and α-aminoalkylations of activated olefins. Transition metal catalyzed reactions of this type, are also included even though they proceed by a different mechanism. Transformations that require stoichiometric amounts of reagents or more than one step are summarized in the section on Comparison With Other Methods but are not included in the Tabular Survey. The Morita–Baylis–Hillman reaction has been reviewed before.


Keywords:

catalysts;
hydroxyalklyation;
aminoalkylation;
activated olefin;
acrylates;
allenic esters;
acrylamides;
acrylonitrile;
acrolein;
unsaturated ketones;
vinyl sulfoxides;
vinyl sulfones;
vinylsulfonates;
vinylphosphonates;
substituted activated olefins;
electrophile;
intramolecular reactions;
side reactions;
aldehydes;
diketones;
keto esters;
keto lactones;
imines;
iminium salts;
Aldol and Michael reactions;
Morita-Baylis-Hillman reaction;
comparison of methods;
synthetic utility;
experimental conditions;
experimental procedures;
tabular survey

The Catalyzed α‐Hydroxyalkylation and α‐Aminoalkylation of Activated Olefins (The Morita—Baylis—Hillman Reaction)

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF recptor TrkA.

Compositions of protein receptor tyrosine kinase inhibitors

The Rh(II)-catalyzed reaction of 1-acetyl-1-(diazoacetyl)cyclopropane and ethyl 3-(1-acetyl-cyclopropyl)-2-diazo-3-oxopropiolate with various dipolarophiles afforded dipolar cycloadducts in good yield. The reaction involves the formation of a rhodium carbenoid and subsequent transannular cyclization of the electrophilic carbon onto the adjacent keto group to generate a five-membered cyclic carbonyl ylide which undergoes a subsequent dipolar cycloaddition reaction. The regiochemical results encountered can be rationalized on the basis of FMO considerations. For carbonyl ylides, the HOMO dipole is dominant for reactions with electron deficient dipolarophiles, while the LUMO becomes important for cycloaddition to more electron rich species. A short synthesis of several members of the pterosin family of sesquiterpenes is described in which the key step involves a dipolar cycloaddition using a carbonyl ylide. The Rh(II)-catalyzed reaction of 1-acetyl-1-(diazoacetyl)cyclopropane with cyclopentenone afforded a d...

K. Sunitha

Papers

A reinvestigation of the claisen rearrangement of methyl γ-aryloxycrotonates a convenient synthesis of 3-ethylidenebenzofuran-2(3H)-ones

Thermal rearrangement of α-(aryloxy)methylacrylic acids: a facile synthesis of 3-methylcoumarins

Studies in claisen rearrangement : Novel thermal transformation of α-aryloxymethylacrylic acids and their derivatives

A new route to the synthesis of 3-methylenecoumarins-via Lewis acid catalyzed rearrangement of methyl α-aryloxymethylacrylates

Synthesis of 3-substituted coumarins via sequential pericyclic transformations of δ-aryloxymethylacrylic acids and enophiles