Vinyl Dihydropyrans and Dihydrooxazines: Cyclizations of Catalytic Ruthenium Carbenes Derived from Alkynals and Alkynones

A novel synthesis of 2‐vinyldihydropyrans and dihydro‐1,4‐oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles. Mechanistic aspects of the new cyclizations are discussed.     

Modular optimization of enantiopure epoxide-derived P,S-ligands for rhodium-catalyzed hydrogenation of dehydroamino acids

The optimization of P,S-ligands derived from enantiopure (2S,3S)-phenylglycidol for asymmetric rhodium-catalyzed hydrogenation of dehydroamino esters is described. The exceptionally high modular character of the (2S,3S)-phenylglycidol platform is demonstrated by systematic modification of the ether and thioether moieties, the skeletal aryl substituent and the stereo and regiochemistry of the ligands. An experimentally useful method for the monitoring of hydrogenation reactions is also described and used for obtaining relevant data of the catalytic systems studied.     

A multipurpose gold(I) precatalyst

[Au(tmbn)(2)](SbF(6)) is the first gold(I) complex supported by two nitrile ligands that is indefinitely stable at room temperature. This is a highly versatile precatalyst that can be used for the preparation of active and robust solid-supported gold(I) catalysts.     

New Route to N‐Alkylated trans‐Pyrrolidine Diols from 2,2,3,3‐Tetramethoxybutane‐Protected Dimethyl Tartrate

A short synthesis of some trans‐pyrrolidine diols is described starting from (2R,3R,5R,6R)‐5,6‐dimethoxy‐5,6‐dimethyl[1,4]dioxane‐2,3‐dicarboxylic acid dimethyl ester 3. The key step was the occurrence of a tandem azide reduction/cyclization sequence on mono‐azide intermediate 6 upon catalytic hydrogenation. This method afforded both (3R,4R)‐(+)‐1‐benzyl‐3,4‐pyrrolidinediol 9a and (3R,4R)‐(+)‐1‐allyl‐3,4‐pyrrolidinediol 9b starting from 3. Cytotoxicity tests were performed on compounds 9a and 9b using the brine shrimp bioassay, but each showed no activity, as were anti‐oxidant tests using the stable free radical diphenylpicrylhydrazyl (DPPH).     

Reaction of Alkynes and Azides: Not Triazoles Through Copper–Acetylides but Oxazoles Through Copper–Nitrene Intermediates

Well‐defined copper(I) complexes of composition [Tpm*^,BrCu(NCMe)]BF₄ (Tpm*^,Br=tris(3,5‐dimethyl‐4‐bromo‐pyrazolyl)methane) or [Tpa^*Cu]PF₆ (Tpa^*=tris(3,5‐dimethyl‐pyrazolylmethyl)amine) catalyze the formation of 2,5‐disubstituted oxazoles from carbonyl azides and terminal alkynes in a direct manner. This process represents a novel procedure for the synthesis of this valuable heterocycle from readily available starting materials, leading exclusively to the 2,5‐isomer, attesting to a completely regioselective transformation. Experimental evidence and computational studies have allowed the proposal of a reaction mechanism based on the initial formation of a copper–acyl nitrene species, in contrast to the well‐known mechanism for the copper‐catalyzed alkyne and azide cycloaddition reactions (CuAAC) that is triggered by the formation of a copper–acetylide complex.     

Cross‐Coupling Reactions of Organosilicon Compounds in the Stereocontrolled Synthesis of Retinoids

This paper presents a full account of the use of Hiyama cross‐coupling reactions in a highly convergent approach to retinoids in which the key step is construction of the central C10? C11 bond. Representatives of two families of oxygen‐activated dienyl silanes (ethoxysilanes and silanols) and of all reported families of “safety‐catch” silanols (siletanes, silyl hydrides, allyl‐, benzyl‐, aryl‐, 2‐pyridyl‐ and 2‐thienylsilanes) were regio‐ and stereoselectively prepared and stereospecifically coupled to an appropriate electrophile by treatment with a palladium catalyst and a nucleophilic activator. Both all‐trans and 11‐cis‐retinoids, and their chain‐demethylated analogues, were obtained in good yields regardless of the geometry (E/Z) and of the steric congestion in each fragment. This comprehensive study conclusively establishes the Hiyama cross‐coupling reaction, with its mild reaction conditions and stable, easily prepared, ecologically advantageous silicon‐based coupling partners, as the most effective route to retinoids reported to date.