No abstract

(3 + 2)-Annulation of donor-acceptor cyclopropanes to alkynes induced by both Lewis and Brønsted acids has been developed. The reaction provides a rapid approach to functionalized indenes displaying intense visible emission (λmax = 430 nm, Φ = 0.28-0.34).

Copper-catalyzed 1,3-dipolar cycloaddition reactions are used for the synthesis of a series of bis(1,2,3-triazole)-containing macrocycles possessing acyclic, aromatic and steroidal fragments. The influence of the nature of the substituents on the diazides, and the length of the dialkyne-linking chain, in the substrates, on the product yields is studied. Macrocycles containing steroidal fragments are prepared via reactions of bis(cholane)-24,24¢-diazides with aliphatic dipropargyl esters, or bis(cholane)-24,24¢-dipropargyl esters with aromatic diazides, or by cyclization-dimerization of bile acid derivatives possessing both azide and acetylene groups in the same molecule.Macrocycles containing bile acid fragments are of substantial interest because such compounds can be used for modeling biological systems and for molecular recognition. 1 The rigid lipophilic skeleton of the steroid molecule, together with the presence of several endocyclic hydroxy groups, imparts macrocycles derived from bile acids with high selectivity towards cations, anions and neutral molecules. 2 Chola-crown ethers produced from bile acids readily form complexes with alkali metal ions. 3 Ester, amide and ether fragments have been used as linkers to bind two bile acid units. We have reported previously that palladium-catalyzed amination reactions can be employed for the synthesis of macrocyclic derivatives of bile acids in unexpectedly high yields. 4 This was explained by the fact that the final macrocyclization step proceeds within the coordination sphere of the transition metal, which enables favorable orientation of the two reacting fragments of the intermediate during macrocycle formation. In addition, metathesis has been proposed for the synthesis of steroid-containing macrocycles. 5Following reports of the catalytic effect of copper(I) in the Huisgen reaction, interest in the synthesis of complexing agents possessing a 1,2,3-triazole moiety has increased significantly. 6 This approach has several attractive features including a simple synthetic procedure, the stability of triazoles towards many reagents, and the ability of the triazole group to act both as an inert linker and a complexant for cations 7 and anions. 8 The synthesis of macrocycles possessing triazole groups is of interest because, in addition to above-mentioned properties, the formation of triazole rings is substantially exothermic 9 which can lead to increased product yields. To date, triazole units have been introduced into macrocycles via peptides and glycopeptides, 10 sugars 11 and steroids. 8 Copper-catalyzed syntheses of compounds containing several triazole rings conjugated to an aromatic ring is limited to only a few examples. 7b,12 No reports of aromatic diazides as easily available precursors to such conjugated systems were found in the literature.Herein we report a new approach to triazole-containing macrocycles which employs a copper-catalyzed 1,3-dipolar cycloaddition. We used aromatic 1a-e, aliphatic 1f-h, and cholane-containing 1i diazides in reactions wit...

An efficient direct approach to triazole-fused sultams has been developed. The key step of the proposed strategy is base-mediated cyclization of sulfonamide-tethered 5-iodo-1,2,3-triazoles which are readily available via an improved protocol for Cu-catalyzed 1,3-dipolar cycloaddition. The annulation of the sultam fragment to the triazole ring proceeds smoothly under transition-metal-free conditions in the presence of Cs2CO3 in dioxane at 100 °C and affords fused heterocycles in high yields up to 99%. The favorability of an SNAr-like mechanism for the cyclization was supported by DFT calculations. The applicability of the developed procedure to modification of natural compounds was demonstrated by preparation of a deoxycholic acid derivative.

Cu-catalyzed Pd-free Sonogashira coupling has been proposed as a straightforward and convenient route to valuable steroidal enynes. A biligand catalyst system based on Ph3P and TMEDA has been designed. The protocol was utilized for the efficient coupling of iodosteroids with diverse terminal alkynes and 1-trimethylsilylalkynes. A possible role of an auxiliary ligand as a phase-transfer catalyst for a sparingly soluble inorganic base (K2CO3) was revealed.