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The β-ketoester structural motif continues to intrigue chemists with its electrophilic and nucleophilic sites. Proven to be a valuable tool within organic synthesis, natural product, and medicinal chemistry, reports on chiral β-ketoester molecular skeletons display a steady increase. With the reignition of organocatalysis in the past decade, asymmetric methods available for the synthesis of this structural unit has significantly expanded, making it one of the most exploited substrates for organocatalytic transformations. This review provides comprehensive information on the plethora of organocatalysts used in stereoselective organocatalyzed construction of β-ketoester-containing compounds.

Herein, we report a convenient synthesis of aryl-substituted (E)-vinylic NH-sulfoximines via the Horner–Wadsworth–Emmons reaction without the use of protection–deprotection group strategies.

Herein, we report an efficient, ligand-free, and additive-free Suzuki–Miyaura coupling that is compatible with the aromatic sulfonyl fluoride functional group. The protocol proceeds at room temperature, on water, and offers facile access to a wide range of biaryl sulfonyl fluorides as bioorthogonal “click” reagents.

Asymmetric Michael addition of ketoproline derivative (I) to nitrostyrenes affords the title products with excellent diastereoselectivities and high enantioselectivities.

N′-Vinyl sulfonimidamides have been synthesized through a Pd-catalyzed C–N cross coupling between the N′-(imine nitrogen) of N′-deprotected sulfonimidamides and vinyl bromides. The hitherto unreported products were obtained in moderate to excellent yield, and the C–C double bond geometry of the vinylic substrates were retained during the course of reaction. Single crystal X-ray crystallographic analysis confirmed the product structure. Furthermore, we demonstrate that the formed N′-vinyl sulfonimidamides could undergo hydrogenation with Pd–C/H2 to provide N′-alkyl sulfonimidamides.

A mild and efficient Cu(OAc)2-catalyzed protocol for the oxidative C—N cross-coupling of terminal alkynes and N-deprotected sulfonimidamides is reported.

The carbapenem (β-lactam antibiotic) scaffold serves as a useful nucleophile in organocatalytic diarylprolinol trimethylsilyl ether mediated α-heterofunctionalization reactions leading to the formation of diverse products that bear multiple stereocenters in high diastereoselectivity and moderate to good yields.

A Pd(0)-catalyzed process for the amidocarboxylation of sulfonimidamide nucleophiles with Mo(CO)6 as CO-source and vinyl halides and triflates as well as aryl triflates is developed.

An efficient diastereoselective synthesis of carbapenem Mannich bases was developed using organocatalysis. This method also provides a route to new highly functionalized diazabicyclo[4.2.1]nonanes of proposed biological significance.

Herein, we report the development of mild, organocatalyzed routes to novel β-lactam carbapenem derivatives through Michael type C C bond forming reactions. The same methodology, followed by a retro-Dieckmann reaction, provides a pathway to novel and highly functionalized monobactam derivatives, another class of valuable β-lactam antibiotics.

A convenient and mild procedure for the N-arylation of sulfonimidamides with various boronic acids is presented.

Novel carbapenam derivatives are prepared through organocatalyzed aldol, Mannich and Michael C—C bond forming reactions.

This novel methodology, employing sulfonimidamides as nucleophiles and CO gas released in situ from solid Mo(CO)6 in a sealed two-chamber system, shows high functional group tolerance affording a wide range of carbamate protected sulfonimidamides in good to excellent yields.

The new and facile title reaction affords the novel 1,3-diols (III) with excellent enantioselectivities and moderate diastereoselectivities.

The presented ligand shows the best activity of the novel synthesized ligands for the title reaction.

Novel Lewis base N-oxide organocatalysts possessing tetrahydroisoquinoline as a readily tunable backbone are synthesized and evaluated in asymmetric allylation reactions of aromatic and α,β-unsaturated aldehydes.

Three novel aryl sulfonamides derived from (2S)-indoline-2-carboxylic acid have been obtained and used as organocatalysts. The catalysts incorporate diverse functionality on the phenyl ring, enabling steric, and electronic fine tuning of the catalysts. The catalysts facilitate the reaction between a range of α,β-unsaturated aldehydes and sulfur ylides, thus providing cyclopropane products in enantiomeric excesses of up to 99%.

This thesis deals with synthetically modified chiral molecules and their application in asymmetric catalysis. The first part of the thesis describes the use of commercially available chiral diamine ligands in the iridium catalyzed transfer hydrogenation of aromatic ketones. The chiral diamine ligands were mixed with an appropriate transition-metal complex, which after addition of suitable base provided a chiral transition metal complex capable of reducing a range of different aromatic ketones in high yields and enantioselectivities. The developed methodology constitutes a cost effective and readily available procedure for transfer hydrogenation reactions. The following chapters in the thesis are completely devoted to rational design of small organic molecules acting as catalyst in various organocatalytic transformations. Organocatalytic methodology, represent a new and complementary approach to asymmetric organic synthesis, as compared to e.g. transition metal based methodology. Advantages of this methodology typically include mild and less stringent reaction conditions. This, in combination with the lack of toxic transition metal by-products, makes the process more environmentally benign; the organocatalytic methodology, therefore represent a promising approach towards implementation of green chemistry in organic synthesis. Despite this promise, typical drawbacks of the current methodology are long reaction times and the need for high catalyst loadings. Thus, a large demand exists for enhancing reactivity and increasing selectivity in organocatalytic reactions. The present thesis describes several efforts where we have tried to rationally design improved catalysts for various enantioselective organocata-lytic reactions. First, a structurally modified L-proline, incorporating a 1H-tetrazolic acid, was synthesized and evaluated in the direct asymmetric organocatalytic aldol reaction. As shown in Paper II, the catalyst displayed very high reactivity and subsequent studies were initiated in order to rationalize the reactivity enhancement (Paper III). Delightfully, the design principle of a 1H-tetrazolic acid as replacement for a carboxylic acid has since been widely used in the community, including our own efforts in organocatalytic asymmetric cyclopropanations (Paper V)and Diels-Alder reactions (Paper VII). Novel catalysts, including other functionalizations, were also designed for organocatalytic asymmetric addition of nitroalkanes to α,β-unsaturated aldehydes (Paper IV) and for cyclopropanations (Paper VI).

A highly efficient and environmentally friendly synthesis of Fmoc-N-methyl α- and β-amino acids from the corresponding Fmoc-amino acid, via intermediate oxazolidinones/oxazinanones, has been developed. Microwave heating for 3 min was required for the synthesis of the oxazinanones, while their Lewis acid catalyzed reductive opening only needed 1 min for completion. Hence, Fmoc-N-methyl-amino acids, suitable for, for example, solid phase peptide synthesis, can be readily prepared from the corresponding Fmoc amino acid in less than 1 h including purification. Fmoc-β3-homophenyl alanine showed unanticipated reactivity, and provided a one-step route to the highly useful Fmoc-protected 1,2,3,4-tetrahydroisoquinolineaceticacid, that is a β-hTic analogue.