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A three-component coupling protocol has been developed for the generation of 3-oxo-3-(hetero)arylpropanenitriles via a carbonylative palladium-catalyzed α-arylation of tert-butyl 2-cyanoacetates with (hetero)aryl bromides followed by an acid-mediated decarboxylation step. Through the combination of only a stoichiometric loading of carbon monoxide and mild basic reaction conditions such as MgCl2 and dicyclohexylmethylamine for the deprotonation step, an excellent functional group tolerance was ensured for the methodology. Through the use of (13)C-labeled carbon monoxide generated from (13)COgen, the corresponding (13)C-isotopically labeled β-ketonitriles were obtained, and these products could subsequently be converted into cyanoalkynes and 3-cyanobenzofurans with site specific (13)C-isotope labeling.

A general approach to N-arylation and N-alkenylation of all five DNA/RNA nucleobases at the nitrogen atom normally attached to the sugar moiety in DNA or RNA has been developed. Various protected or masked nucleobases engaged readily in the copper-mediated Chan-Lam-Evans-modified Ullmann condensation with a range of different boronic acids at room temperature and were subsequently converted to the corresponding deprotected or unmasked adducts. Different N(3)-protecting groups were examined in the case of thymine, where the benzoyl group afforded the highest yields. A 4-alkylthio-substituted pyrimidin-2(1H)-one served as both a cytosine and a uracil precursor and was N-arylated and N-alkenylated in high yields. Adenine was efficiently and selectively N-arylated and N-alkenylated at the N(9) position by employing a bis-Boc-protected adenine derivative, while a bis-Boc-protected 2-amino-6-chloropurine served as guanine precursor and could also be selectively N(9)-arylated and N(9)-alkenylated.

The Lewis acid-mediated addition of silyl enolates to easily accessible homochiral N-acylhydrazones derived from 3-amino-2-oxazolidinones proceeded in yields up to 71% and diastereomeric ratios of 99:1. In most cases, optimal reaction conditions entailed the simple use of ZnCl(2) in acetonitrile at room temperature. Hydrazones derived from phenyl-, isopropyl-, and benzyl-substituted 2-oxazolidinones were examined in the reaction in terms of yield and diastereoselectivity. The facile SmI(2)-mediated N-N bond cleavage of the formed hydrazines was demonstrated yielding a beta-amino acid derivative. Hence, the overall reaction sequence constitutes an efficient asymmetric Mannich-type reaction. The sense of diastereoselectivity was explained by a preferential attack on the less shielded Si face of the chiral hydrazones and confirmed by means of X-ray crystallography.

Addition of ketene acetals to sulfinimines derived from homochiral N-tert-butanesulfinamide using various Lewis acids furnishes derivatives of aspartic acid in diastereomeric ratios up to 97:3. Following an easy removal of the N-tert-butanesulfinyl chiral auxiliary, optical active beta-amino esters are obtained.

A series of C4-keto-functionalized 1-[(benzoyloxy)(ethoxycarbonyl)methyl]-2-azetidinones were prepared and studied for their tendency to undergo a Reformatsky-type cyclization to fused bicyclic or tricyclic beta-lactams with the single-electron reducing agent samarium diiodide. Whereas the azetidinone 21a underwent reductive cyclization, affording the potent antibiotic sanfetrinem's tricyclic [4.5.6] core structure as the major component, all other examples tested resulted in cyclization followed by an N to O acyl migration involving cleavage of the beta-lactam ring as the favored pathway. Highly functionalized proline derivatives were therefore accessed as single diastereomers through the reductive cyclization of benzoates 21b, 22, 23a,b, 24b, and 25-28. Pertinent for the success of these cyclizations was the addition of 1 equiv of tert-butyl alcohol, allowing for the protonation of the basic amide derivative obtained after the acyl migration step. The diastereoselectivities of these reactions deviate from those of similar cyclizations involving the corresponding lithium enolate. This divergence could be rationalized by the coordination of the metal ion of the samarium(III) enolate intermediate to the beta-lactam amide functionality in the cyclization step, which may not be possible for lithium enolates.