Doctor of Philosophy

dissertationDuring the past few decades, one-pot multicomponent reactions have attracted significant attention because of their ability to install multiple carbon-carbon or carbonheteroatom bonds in a single step. However, the development of these reactions is a challenge because of the generation of many side products arising from undesired reaction pathways. Hence, optimization for the formation of desired products is difficult. Our group has been involved in developing such multicomponent reactions that take advantage of the stability of π-allyl/benzyl palladium species to generate biologically relevant and synthetically challenging products in an efficient manner. Herein, I describe the development of three novel multicomponent transformations to achieve difunctionalization of cheap olefins such as ethylene and dienes. First, a Pd(II)-catalyzed three-component coupling involving ethylene, alkenyl triflates, and aryl boronic acids is described, where 1,1-vinylarylated products can be obtained in high yields and good to high selectivity. The crucial factor for an efficient reaction is cationic Pd(II)-intermediates, which prevent side products such as Suzuki products and Heck products. In general, the scope of the reaction is good as both electronrich and electron-withdrawing boronic acids are tolerated. Heteroaromatic cross-coupling partners are also compatible under the reaction conditions. However, the scope is limited to six-membered alkenyl electrophiles, which bias the selectivity towards the formation of 1,1-vinylarylated products. Second, the scope of this three-component reaction was extended to aryl electrophiles such as aryl diazonium salts. The reaction can also be used to couple allylic carbonates as the olefin source instead of ethylene to afford a wider range of 1,1-diarylalkanes. Also, deuterium labeling study and cross-over experiment revealed useful information regarding the mechanistic aspect of the reaction. Finally, 1,2-hydrovinylation of terminal 1,3-dienes was achieved with alkenyl triflates/nonaflates and a hydride source. The reaction can be used to couple a variety of triflates derived from natural products to generate complex molecules in a mild fashion. Additionally, configurationally-defined alkenyl triflates (i.e., E/Z) can be coupled efficiently to generate synthetically useful tri- and tetrasubstituted alkenes

Transition-Metal Free Allylic Fluorination of Acyclic Olefins

one step allylic fluorination of alkenes is reported which furnishes the products in a highly regioselective manner via allylic rearrangement. The reaction proceeds efficiently under mild conditions with the use of trisubstituted alkenes as olefin partner and Selectfluor as an electrophilic fluorinating agent without the need of any transitionmetal catalyst or pre-functionalized substrate

Synthesis of Highly Functionalized Tri- and Tetrasubstituted Alkenes via Pd-Catalyzed 1,2-Hydrovinylation of Terminal 1,3-Dienes

An efficient method for the construction of Csp²–Csp³ bond in a regio- and stereoselective fashion involving 1,3-terminal dienes, enol triflates/nonaflates, and sodium formate under Pd(0)-catalysis is described. The three component assembly allows trapping of a π-allyl intermediate, after the initial migratory insertion of the diene, by a hydride source that leads to structurally complex and synthetically challenging tri- and tetrasubstituted alkene building blocks

Development and Analysis of a Pd(0)-Catalyzed Enantioselective 1,1-Diarylation of Acrylates Enabled by Chiral Anion Phase Transfer.

Enantioselective 1,1-diarylation of terminal alkenes enabled by the combination of Pd catalysis with a chiral anion phase transfer (CAPT) strategy is reported herein. The reaction of substituted benzyl acrylates with aryldiazonium salts and arylboronic acids gave the corresponding 3,3-diarylpropanoates in moderate to good yields with high enantioselectivies (up to 98:2 er). Substituents on the benzyl acrylate and CAPT catalyst significantly affect the enantioselectivity, and multidimensional parametrization identified correlations suggesting structural origins for the high stereocontrol

Development and Analysis of a Pd(0)-Catalyzed Enantioselective 1,1-Diarylation of Acrylates Enabled by Chiral Anion Phase Transfer

The enantioselective 1,1-diarylation of terminal alkenes is reported herein enabled by the combination of palladium catalysis with a chiral anion phase-transfer strategy. The reaction of substituted benzyl acrylates with aryldiazonium salts and arylboronic acids gave the corresponding 3,3-diaryl propanoates in moderate to good yields and high enantioselectivies (up to 98:2 er). Substituents on the benzyl acrylate and chiral anion phase-transfer catalyst significantly affect the enantioselectivity, and multidimensional parameterization identified correlations suggesting structural origins for high stereocontrol

Dehydroacetic acid Derived Schiff base as Selective and Sensitive Colorimetric Chemosensor for the Detection of Cu(II) ions in Aqueous Medium

14 The deficiency, as well as overconsumption of essential metal ions, has serious health 15 implications. Hence, the design and synthesis of sensors for accurate detection of such ionic 16 species are of great significance. We report the synthesis and characterization of a yellow-17 coloured Dehydroacetic acid-based chemosensor DHB ((E)-N-(1-(2-hydroxy-6-methyl-4-oxo-18 4H-pyran-3-yl) ethylidene) benzohydrazide for a quick and affordable copper detection. A 19 naked-eye visible colour transition from light yellowish to bluish green was observed instantly 20 following Cu 2+ addition. DHB did not yield colour change with any other ionic species indicating 21 its specificity. The binding of DHB to Cu 2+ caused a blue shift accompanied by an increased 22 intensity due to an intramolecular charge transfer (ICT). No interference from competitive ionic 23 species reiterated the selectivity of this probe. The outcomes of single-crystal X-ray analysis, 24 titration studies, and Job's plot indicated a 1:2 stoichiometry between Cu 2+ and DHB. The 25 experimental results matched well with the theoretical results obtained from Density Functional 26 Theory (DFT) calculations. The practical applicability of the probe for Cu 2+ estimation was 27 further determined using water samples from various sources. The sensor could detect copper as 28 low as 0.156 í µí¼M in an aqueous media which is very less than the permissible value of 20 í µí¼M in 29 water. 30 31 32 33

Pd(0)-Catalyzed 1,1-Diarylation of Ethylene and Allylic Carbonates

An efficient protocol for the one-step synthesis of biologically relevant 1,1-diarylalkanes has been described. This reaction introduces two different aryl groups across the terminal end of simple feedstock alkenes such as ethylene and allylic carbonates. The propensity to generate π-benzylpalladium intermediates dictates the exclusive 1,1-regioselectivity observed in the product

The Development and Mechanistic Investigation of a Palladium- Catalyzed 1,3-Arylfluorination of Chromenes

A mild palladium-catalyzed ligand-controlled regioselective 1,3-arylfluorination of 2[H]-chromenes has been developed. The products with a syn-1,3 substitution pattern were obtained with high enantiomeric excess using a PyrOx ligand, wherein the utility of these pyranyl-fluorides was further demonstrated through their participation in a diastereoselective C‒C bond forming reaction. Ligand dependent divergent formation of both the 1,3- and 1,2- alkene difunctionalization products was observed. The nature of this bifurcation was investigated through experimental studies in combination with computational and statistical analysis tools. Ultimately, the site selectivity was found to rely on ligand denticity and metal electrophilicity, the electronics of the boronic acid, and the donor ability of the directing group in the substrat

Extraction and characterization of ultrasound assisted extraction: improved functional quality of pectin from jackfruit (Artocarpus heterophyllus Lam.) peel waste

Jackfruit peels are potential waste for valorization and extraction of pectin and quality of pectin is a function of extraction conditions. Present study evaluates the effect of low temperature (LT) extraction; mediated through ultrasonication on the quality of pectin from jackfruit peel waste (JP). We first optimized ultrasound assisted extraction (UAE) process through response surface methodology (RSM) based on a Box-Behnken design (BBD) and arrived at optimal extraction conditions with maximum pectin yield and galacturonic acid content (GalA). Pectin extracted at LT and conventional high temperature (HT) referred as UAE-P and CE-P respectively were compared for their technological and structural properties. GalA content ranged between 65.53 and 68.65% in CE-P and UAE-P respectively. UAE-P had methoxyl content (5.58), protein (1.69%), molecular weight (149.67), total phenolic content (1645 mg GAE/100 g), and antioxidant capacity (123.76 µmol TE/g). There were significant (p < 0.05) differences in the Arabinose (Ara) content, FTIR spectra and functionality of pectin extracted at LT and HT. The Ara content was ~ twofold higher while antioxidant activity was ~ 1.66-fold higher in LT extracted UAE-P pectin. Hypoglycemic activity as determined by in vitro α–amylase and α–glucosidase inhibitory activity was significantly higher (p < 0.05) in UAE-P in comparison to CE-P. The DE value of UAE-P (38.11%) was low (< 50%) thus it was categorized as low methoxyl pectin. Results suggests that the UAE is potential efficient green method to obtain high quality food grade pectin with higher yield and functionality in short duration