Hexafluoroisopropanol (HFIP) assisted transition-metal-free C-heteroatom bond forming reactions

Abstract

One of the main focuses of the present thesis is to carry out various C-heteroatom bond forming reactions under transition-metal-free condition.

Chapter 1: Introduction To pursue the above thought process, a detailed literature studies as well as vigorous surveys of previous reports on C–heteroatom bond forming reactions was carried out in chapter 1, introduction part. Due to the presence of C–heteroatom bond containing molecules in several natural products and pharmaceutical molecules, the construction of C–heteroatom bonds have drawn a notable attention from synthetic chemists. This chapter features; a) important metal-free chemistry, b) various C–heteroatom bond forming techniques, c) several imperative characteristics of HFIP, d) use of a strong H-bond-donor solvent 1,1,1,3,3,3-Hexafluoro isopropanol (HFIP) to conduct the above-mentioned transformation in a metal-free way, e) HFIP assisted various functional group activation and their concomitant reactions, f) detailed reactivity and basic chemistry of nitrosoarene in C–N/C–O bond formation.

Chapter 2: Regiodivergent Aromatic Electrophilic Substitution Using Nitrosoarenes in Hexafluoroisopropanol: A Gateway for Diarylamines and p-Iminoquinone Synthesis In this chapter, we have exploited the dual electrophilic nature of nitrosoarene and conducted electrophilic aromatic substitution reaction towards the synthesis of diarylamines and p-iminoquinones via C–N and C–O bond formation respectively. For the amination purpose, HFIP was used as a sole promoter, which activates the O-atom of nitroso functionality selectively to facile the C–N bond forming reaction. Alongside, TfOH was used as the acid additive to obtain the p-iminoquinone products via C– O bond formation in HFIP. Interestingly, when less electron-rich arene nucleophilic partners are employed, the p-iminoquinone formation was encountered in the absence of any acid additive. This can be attributed by the mild Brønsted acidic character of HFIP. Protonation at the more basic nitrogen centre by acid triggers iminoquinone formation.

Chapter 3: Nitrosoarene-Catalyzed Regioselective Aromatic C–H Sulfinylation with Thiols under Aerobic Conditions In this chapter, we have represented regioselective aromatic C–H sulfinylation of aromatics using thiol under aerobic condition. We have demonstrated the catalytic utility of nitrosoarene for the first time in organic synthesis. Here nitrosoarene acts as a redox catalyst to conduct the transformation following a radical reaction mechanism in HFIP. For the terminal oxidation of hydroxylamine species to revive active nitrosoarene, aerobic oxygen plays a crucial role.

Chapter 4: Nitrosoarene-Catalyzed HFIP-Assisted Transformation of Arylmethyl Halides to Aromatic Carbonyls under Aerobic Conditions In this chapter, an extension work of nitrosoarene catalysis was portrayed. Here, we have used the C–halogen bond activation property of HFIP to synthesize aromatic carbonyls from arylmethyl halides under aerobic conditions. HFIP polarizes the C–halogen bond by forming a strong H-bonding network with benzyl halides and generates a benzyl carbocation intermediate. The nucleophilic nitrosoarene catalyst attacks the benzyl carbocation intermediate and after the α-deprotonation of nitrosonium ion and hydrolysis of nitrone species, the aromatic carbonyls were yielded. Here also aerobic oxygen was found to be a critical oxidant for the terminal oxidation of hydroxylamine to nitrosoarene.

Chapter 5: Transition-Metal-Free Regioselective Intermolecular Hydroamination of Conjugated 1,3-Dienes with Heterocyclic Amines In this last chapter, a transition-metal-free Brønsted acid catalyzed HFIP assisted regioselective intermolecular Markovnikov selective 4,3-hydroamination of conjugated 1,3-dienes was carried out using rarely explored amine sources (heterocyclic amines). The molecular aggregation between HFIP and Brønsted acid (HNTf2) enhances the acidity and readily protonates heterocyclic amines (pyrazole, triazole, indazole). Thereafter, the transfer of proton to the dienes and nucleophilic attack by the heterocyclic amines afforded the regioselective allylic amines.