Synthetic Efforts Towards Carbon-Heteroatom Bond Generations Employing Dearomatization, Alkene and Alkyne Intrigues

Abstract

Carbon-hetero bond generation has been a core interest of synthetic chemists throughout the past. The modern approach to develop these attempts in environmentally benign condition with atom economy has emerged as a frontier goal in organic synthesis. Particularly, dearomatization of cheaply available planar arenes and molecular gymnastics with alkenes and alkynes precursors has opened a new avenue for chemists with regard to efficiency and versatility. The present thesis covers some of our attempts in the generation of carbon-heteroatom bonds via dearomatization of planar phenols and pyridine derivatives in the first part, delivering the multi-functionalized spiro, indolizine molecules employing our own tri-bromides (TBrs), visible light and copper(I) catalysis. The second part of the thesis focuses on strategies like isomerisations of alkenes or alkynes, free radical reactions and multi-component reactions to synthesize these biologically important motifs.
Chapter-I:
In this chapter, we have discussed a metal free one-pot stereoselective synthesis of para-quinone monoketals and their derivatives have been reported in this present work. Tri-bromides (TBrs) have been employed as an effective reagent for intramolecular spiro-cyclizations leading to excellent yields of the monoketals. The TBrs are slowly turning out to be an important reagent for oxidative dearomatization which is further attested in the presented work. In addition, the obtained substituted para-quinone monoketals and their derivatives were readily transformed into more complex products by reaction with Pd/C under hydrogen atmosphere leading to saturated para-monoacetal, which are important building blocks in organic synthesis.
Chapter-II:
In this chapter, we metal free one pot approach towards a highly stereoselective synthesis of N-substituted spiro azacyclodienones, dihydro spiro-azacyclodienones and spiro-lactams has been reported in this present work. Phenyl tri-methyl ammonium tri-bromide (PTAB) as an effective reagent has been implied for intramolecular spiro-cyclizations via the key oxidative dearomatization reaction. Interestingly, the obtained substituted N-substituted spiro azacyclodienones was readily transformed into strained cyclopropanated spirocycles.
Chapter-III:
In this chapter, a visible light assisted dearomative selenylative carbo-spirocyclisation of aromatic homologated-ynones has been reported. The ynones deliver selenylative spiro-cyclohexadienones and spiro-diepoxides at varied temperatures. The prescribed methodology is photo-catalyst free and scalable. The combination of visible light, molecular oxygen and the products synthesized delivers a uniqueness to the designed methodology.
Chapter-IV:
In this chapter, we have discussed an efficient two-component copper-catalyzed cyclization cascade approach towards highly functionalized indolizinone heterocycles have been developed from reactions of pyridine-, isoquinoline-, and quinoline ynones, via 5-exo-dig cyclization. The catalysis involves the activation by diorgano diselenide and diorgano disulphide and also their incorporation into the indolizinone core. In addition, the obtained substituted indolizinones were readily transformed into 1 (organochalcogenyl)indolizin-2-ols, which are important building blocks in organic synthesis.
Chapter-V:
In this chapter, we have discussed the radical induced cyclopropyl ring fragmentation with encompassed olefinic and cyclopropane environment has been carried out. Interestingly, the fragmentation has occasioned onto a stereoselective synthesis of trans-3-allyl-2,3 dihydrobenzofurans (TADHBs) with impressive yields. The trans-dihydrobenzofurans are present as central core in many molecules of medicinal interest and the present protocol deliver a straight forward access to the embedded molecular architecture.
Chapter-VI:
In this chapter, we have discussed about an efficient approach for the synthesis of α-allyl α-selanyl ketone and selanyl tetra-hydrofurans has been reported in this present work. The sodium methoxide (MeONa) mediated one pot three-component synthesis lead towards a good to an excellent yield of products with a wide substrate scope. The selenylated ketones can be important point towards important organic synthons.
Chapter-VII:
In this chapter, we have discussed about a facile hydrochloride promoted regioslective synthesis of isoxazoles and pyrazoles from 1,2-allenic ketones. The reaction has been scaled upto grams. A direct 8-endo-dig ring annulations towards the first synthesis of (Z)-2-methyl-7H benzo[b]pyrazolo[5,1-d][1,5]oxazocine has been developed.
Chapter-VIII:
In this chapter, we have discussed about revisit towards regioselective addition of insitu generated negative nucleophiles to allenic ketones in the presence of a base. A wide variety of allenic ketones as well as nucleophiles are viable in this transformation. A direct ring annulation towards the challenging benzodioxin skeleton synthesis has been developed. Environmentally benign protocol and wide substrate scope are the notable features of this methodology.
Chapter-IX:
In this chapter, we have discussed about addition of boron trifluoride etherate (BF3OEt2) to allenic ketones has lead to trapping of the isolated boron-difluoride enolate. The challenging single-crystal structure of the boron-enolate has been solved. The (Z) β-difluoroboryloxy ether derivatives undergo an unpreceedented C1-C10 migration, to deliver rearranged phenol derivatives which are functionalized to C-2 alkyl-chromenones. This has been the first example where isolated boron-enolates have exhibited significant anti-cancer properties.
Chapter-X:
In this chapter, we have discussed about an efficient copper-catalyzed cyclization cascade approach towards highly functionalized methylene 4-chromanol and aurone derivatives has been developed from reactions of ynols via 6-exo-dig and 5-exo-dig cyclization respectively. The catalysis involves the alkyne activation via diorgano-diselenides and also their regioselective incorporation into the methylene 4 chromanol and aurone derivatives core and is an open-air transformation.
Chapter-XI:
In this chapter, we have discussed about a direct metal-free approach for the synthesis of alpha-cyanoalkylboronic esters from bis-diboron ester and azobis-nitrile compound is reported under ambient temperature and pressure via a free radical procedure.