In the field of organic chemistry, the development of new catalytic methods for the synthesis of complex molecules from simple precursors is a top priority. The main focus of this thesis concerns the diastereoselective synthesis of heterocyclic compounds using main group elements as Lewis acid catalysts.

The first part of this thesis deals with an annulation reaction of nitrones with oxiranes, aziridines, and thiiranes using Al(III) or In(III) catalysts. From this protocol, 1,4,2-dioxazinanes, 1,2,4-oxadiazinanes, and 1,4,2-oxathiazinanes were obtained in moderate to high yields with excellent diastereoselectivity. The transformation was found to be stereospecific and proceed via an S_N2-mechanism.

The second and third parts concern the development of In(III)-catalyzed annulation of carbonyl compounds, amines, and alkynyl enones. InBr₃ was found to be an efficient catalyst for the activation of alkynyl enones in a multicomponent reaction with aldehydes and amines. The method affords cyclopenta[c]furans in high yields and in good to excellent diastereomeric ratios. Bicyclo[3.n.1]alkenone derivatives were formed via a double Michael addition reaction of cyclic ketones, amines, and alkynyl enones, in the presence of InCl₃. The utility of these protocols was also demonstrated by sequential transformations.

In the fourth part, AgOTf and CuI were found to be efficient catalysts for the activation of pyridine-substituted enynes towards enamines, providing indolizine derivatives in high yield and good diastereomeric ratios.

In the last part of the thesis, 1,2-aminoarylation of γ,δ-unsaturated oxime esters with arylboronic acids using Ni catalysis is discussed. The protocol demonstrates the potential of Ni-catalysts for the generation of iminyl radicals to furnish functionalized pyrroline derivatives. The utility of this protocol was exemplified by transforming the pyrroline products to the corresponding pyrrole and pyrrolidine derivatives. 

A diastereoselective metal-catalyzed reaction of 2-(2-enynyl)pyridines and cyclic enamines is reported. The method provides access to a variety of substituted indolizine derivatives by variation of the enyne component and the reaction conditions. Performing the reaction using a preformed enamine led to the formation of polycyclic indolizines. With in situ generated enamines, ketone-containing indolizine derivatives were obtained. An asymmetric reaction of 2-(2-enynyl)pyridines and enamines generated from an aldehyde and a catalytic amount of amine is presented.

The use of a well-chosen catalyst is instrumental for the development of more efficient, economical and environmentally friendly reactions. In recent decades, indium-based catalysts have proven to be competitive and useful alternatives to transition-metal catalysts such as silver and gold. In this short review, we present some of the recent advances in indium(III)-catalyzed transformations of alkynes, with a focus on cyclization reactions. 1 Introduction 2 Terminal Alkynes as Nucleophiles 3 Nucleophilic Additions to Alkynes 4 Carbo- and Heterocyclization Reactions 4.1 Carbocyclization 4.2 Oxygen-Based Heterocycles 4.3 Nitrogen-Based Heterocycles 4.4 Sulfur-Based Heterocycles 5 Conclusion

A nickel-catalyzed 1,2-aminoarylation of oximeester-tethered alkenes with boronic acids was developed. A variety of pyrroline derivatives were synthesized in good yields via the successive formation of C(sp(3))-N and C(sp(3))-C(sp(2)) bonds. For cyclobutanone-derived oxime esters, the reaction provided aliphatic nitriles incorporating an aromatic group in the gamma-position. A mechanism involving iminyl radical and carbon-centered radical intermediates was proposed.

An intermolecular cyclization of alkynyl enones with cyclic ketones for the synthesis of bicyclo[3.n.1]alkenones is reported. This protocol exhibits a high functional group tolerance and provides access to a variety of bicyclic systems found as skeletons in many natural products.

A diastereoselective three-component reaction between alkynyl enones, aldehydes and secondary amines is reported. With the aid of a benign indium catalyst, a range of highly substituted cyclopenta[c]furan derivatives can be obtained in a single-step procedure. The formation of the stereodefined heterocyclic motifs takes place via in situ generation of enamines followed by two sequential cyclization steps.

A highly selective Lewis acid catalyzed annulation of three-membered heterocycles with nitrones has been developed. Oxiranes, aziridines, and thiiranes were used as substrates for the synthesis of various six-membered heterocycles using Al or In catalysts. This catalytic protocol demonstrates a broad substrate scope and provides access to new structural motifs in high yields and in excellent selectivity under mild reaction conditions.

Copper-mediated trifluoromethylation of allylic chlorides and trifluoroacetates was performed using a convenient Cu-CF3 reagent. The reaction is suitable for selective synthesis of allyl trifluoromethyl species. Mechanistic studies indicate that the reaction proceeds via a nucleophilic substitution mechanism involving allyl copper intermediates. The analogous Cu-F reagent was suitable for fluorination of allyl chlorides. Stereodefined cyclic substrates reacted regio- and stereoselectively.