Chemoselectivity Improvement via Partial Shielding of an Imidazole Active Site in Branched/Dendritic Homogeneous Catalysts of the Baylis–Hillman Reaction

Abstract

While comparing analogousp olystyrenesupported and homogeneous catalysts for the Baylis-Hillmanr eaction, we hypothesized that the hydrophobice nvelopment of the imidazole catalytic sites of the former is responsible for the significantly better chemoselectivity exhibited by the heterogeneous catalysts compared to theirh omogeneousc ounterparts.I no rder to test this hypothesis,w ep repared as eries of branched/dendritic homogeneousc atalysts,w ith an imidazole active site near the focal point andf lexiblet ails of various lengthsa nd polarities,c apable of providing partials hieldingo ft his site.T he design of the catalysts was based on a5 -hydroxyisophthalate scaffold,a nd they were prepared throughanumber of multistep synthetic pathways. Thec omparison of the catalysts under av arietyo f conditions in am odel Baylis-Hillman reactiond emonstrated that long hydrophobic tales enhance the chemoselectivity parameter of the catalysis,w hile reducing the rate of the consumptiono ft he substrates, and that the chemoselectivity is further improvedb y the presence of af ree phenolic moiety in the vicinity of the catalytic imidazole unit. Moreover, in secondgeneration catalysts,t he peripherall ong tails could be either hydrophobic or polar, since the dendritic inner backbone itself presumably partially provides the necessary isolation of the catalytic site.T hus,e xperimental results support our hypothesis.Synthesis of 1,3-bis(methoxymethyl)-5-(methoxymethoxy)benzene: Thec ompound was prepared according to the typical procedure for the benzylic alcohol alkylation, using the followingq uantities:i odomethane (1.68 mL, 28.0 mmol, 4.0 equiv.), [5-(methoxymethoxy)-1,3-phenylene]dimethanol

Design and Synthesis of BODIPY-Cored Near IR-emitting Lipophilic and Water-Soluble Dendritic Platforms

“…One of the most promising methods for introducing water solubility of BODIPY‐based dyes and related compounds, seems to be the introduction of oligo‐ or polyethyleneglycol appendages ,,,. Accordingly and in the light of abovementioned, we proposed to capitalize on our experience in constructing branched monomers and aryl‐benzyl ether dendrons with functionizable aromatic moiety at the focal point and various terminal functional groups, in particular long aliphatic and oligoethyleneglycol tails . Furthermore, we speculated that the use of such building blocks will add potential conjugation sites to the dye, in addition to altering its solubility properties and absorption/emission profile.…”

“…Initially, a lipophilic series of dyes was constructed. For this synthesis dodecyl‐bearing first‐ and second‐generation dendrons were prepared via the synthetic sequences similar to those previously reported (compounds 4 , 7 , Scheme b) . The first‐generation dendron was subjected to Duff formylation, while for the second‐generation building block the formylation was carried out under milder conditions using paraformaldehyde/triethylamine/magnesium chloride mixture .…”

The Use of Lewis Acids for Repairing Chemoselectivity of the Organocatalyzed Morita‐Baylis‐Hillman Reaction

“…Whereas slow catalytic reactions could be enhanced by proper adjustment of reaction time, temperature or the catalyst loading, catalytic processes suffering from low selectivity frequently has to be repaired by other, more sophisticated means. In the past few years we demonstrated that the MBH reaction between methyl vinyl ketone (MVK) and 4‐nitrobenzaldehyde suffers from multiple byproduct formation when promoted by simple homogeneous catalyst, but can be substantially improved chemoselectivity‐wise by immobilization of the catalyst on polystyrene support or by partial shielding of the catalytic site in the interior of dendrimer‐like homogeneous catalysts ,. Herein we report an alternative way to repair the chemoselectivity of this model reaction by concurrent action of a Lewis acid, operating in concert with an organocatalyst, which incorporates a coordination site for the acid.…”

Chemoselective α-Methylenation of Aromatic Ketones Using the NaAuCl4/Selectfluor/DMSO System

“… Ethacrynic acid 1 is a loop diuretic that can treat high blood pressure and the swelling caused by diseases like congestive heart failure, liver failure, and kidney failure; Oridonin 2 , a diterpenoid isolated from Rabdosia rubescens, displays anti-inflammatory, antibacterial, and antitumor effects and has been used for the treatment of human esophageal carcinoma, and penicillic acid 3 is a polyketide mycotoxin used to study the genotoxicity of hepatocytes . Moreover, these types of compounds are important intermediates for many organic reactions such as Diels–Alder reaction, Michael addition, Morita–Baylis–Hillman reaction, Heck coupling, etc . Therefore, the synthesis of 1,2-disubstituted propenones has attracted extensive attention .…”