European Journal of Organic Chemistry

The cover picture illustrates, in a small comic strip, the difficulties of designing vetiver odorants from scratch. While vetiver oil is indispensible in perfumery, no synthetic vetiver odorant is yet available on the perfumer's palette. An empirical rule linked the olfactory properties of khusimone, the odorous principle of vetiver oil, to the distance between its α-branched carbonyl osmophore and the bulky gem-dimethyl moiety. Thus, 7,8-seco-khusimone was envisaged as a synthetic target, allegedly easier to synthesize than the natural lead. But life is not safe from frustration even if you reach your synthetic target, and the vetiver rule proved to be wrong as is further discussed in the article by P. Kraft and N. Denizot on p. 49 ff.

Biaryl coupling through nickel catalysis has been known for a few decades. The topic has recently resurfaced in synthetic chemistry, however, thanks to its use of ideal coupling partners such as simple arenes (Ar–H) and phenol derivatives (Ar–OR). In this microreview, recent achievements in nickel-catalyzed biaryl coupling are summarized.

The Mannich addition reaction of different N-protected imines with β-keto esters and 1,3-diketones is efficiently performed by using the gold IPrAuNTf₂ complex under mild conditions.

The silver-catalyzed cycloisomerization of readily available N-(prop-2-yn-1-ylamino)pyridines is a new and practical method for the synthesis of differently substituted 3-methylimidazo[1,2-a]pyridines, suitable intermediates for further synthetic transformations and modulation, that proceeds under mild reaction conditions to give good-to-high yields and excellent regioselectivity.

2-Methyleneaziridines proved to be good substrates for the cycloaddition with isocyanates, for which a tin iodide system, Bu₂SnI₂–LiI, was employed as an effective catalyst. Products were derived from N-attack of the ring-opened metalloenamine intermediate.

Diels–Alder reactions of substituted cyclobutadiene–AlCl₃ complexes with methyl phenylpropynoate provide Dewar benzenes, which undergo further transformations, including hydrolysis, photochemical rearrangement, intramolecular Friedel–Crafts reaction, and reduction, to provide 1,2,3,4-alkylfluorenones and -fluorenes. A Ru complex with 1,2,3,4-tetraethylfluorenone is prepared.

Dissecting the bond between the methylene and the gem-dimethyl unit of khusimone leads to a spirocycle of almost identical shape, which was synthesized by 1,4-conjugate addition of a vinyl Gilman reagent, Mukaiyama aldol condensation of a bromo aldehyde prepared by Ireland–Claisen rearrangement of allyl isovalerate, and subsequent cyclization.

Four 2,7-dioxygenated carbazole alkaloids, clausine O, clausine H (clauszoline-C), and the anti-HIV active 7-methoxy-O-methylmukonal and clausine K (clauszoline-J), have been synthesized by using an iron-mediated approach for the construction of the carbazole framework.

Two tripodal receptors based on a triethylbenzene scaffold substituted with trihydroxybenzoyl groups have been synthesised, and their conformational preferences and carbohydrate-binding ability have been evaluated. One of them has a pre-organisation that allows the recognition, in DMSO, of mannose-containing polysaccharides that mimic the envelope or cell-wall polysaccharides of certain pathogens. These results open attractive perspectives for the development and potential application of 2 or compounds derived thereof in future antiinfective strategies.

The total syntheses of the natural product 3-O-methylfunicone and its derivatives has been accomplished. The key reactions are TMPZnCl·LiCl-mediated iodination and a carbonylative Stille cross-coupling reaction. In addition, the inhibitory effect of the synthesized compounds have been evaluated against Y-family DNA polymerases κ and η by primer extension experiments.

Two donor–acceptor metal-free organic dyes, CR29 and CR52, featuring two isomeric benzodithiophene (BDT₁ or BDT) π-spacers have been synthesized. The dyes display good extinction coefficients in the visible spectral region 400–650 nm and promising performance in DSSC. Theoretical and experimental investigations established that in such architectures, the BDT₁-based dye outperformed the BDT-based dye.

Semicyclic imides such as γ-lactam and isoxazolidinone derivatives are efficiently and selectivity reduced by the Cp₂ZrHCl agent. The energetic reaction pathways for endo and exo attack, computed at the DFT level including thermal effects, allow an exhaustive interpretation of current and previously reported experimental data.

Fully substituted 3-formyl-4-iodofurans are easily accessible under mild reaction conditions from readily available α-iodo β-alkoxy enones and terminal alkynes. The proposed two-step protocol combines a Sonogashira cross-coupling reaction and subsequent iodocyclization without the need to isolate the intermediate α-alkynyl β-alkoxy enone.

Diastereoselective ortho-lithiation of ferrocenyl(phenyl)methanamines was studied by ⁷Li NMR spectroscopy and DFT calculations. The configurations of the phosphane products were confirmed by X-ray crystallography. The different facial selectivities of the lithiation can be explained by the multicenter arrangement of the dilithium transition state, which features also Fe–Li interactions.

The cross-coupling reactions of 3,6-dihalopyridazines with triaryl- or triheteroarylbismuth compounds were performed under palladium catalysis. The reaction was highly chemoselective, affording functionalized aryl- or heteroarylpyridazinyl chlorides in moderate to good yields.

Polymethylhydrosiloxane (PMHS) is a practically convenient alternative to triethylsilane in a large set of synthetic elaborations entailing the quick generation of glycosyl iodides with a iodine/silane combined reagent.

A useful method for the regioselective introduction of the sulfenyl group into electron-rich aza-aromatics using S-alkyl- and S-arylthiophthalimides as sulfenylating agents is described. Catalytic amounts of CeCl₃·7H₂O/NaI are crucial to the promotion of this regioselective carbon–sulfur-bond-forming electrophilic aromatic substitution reaction.

Some proline amides are poor catalysts when aldehydes are used as substrates since the catalysts irreversibly form imidazolidinones. Proline amides with more basic amide groups form long-lived enamines, which allows catalysis to proceed. Proline sulfonamides only form imidazolidones, but these are unstable.

Treatment of 1-(trimethylsilyl)allene-1-carboxylates with Grignard reagents under iron catalysis conditions afforded stereodefined polysubstituted α-(methoxycarbonyl)allylsilanes in good to excellent yields. In addition, the products could be further applied to the stereocontrolled synthesis α,β-alkenoates, a β,γ-alkenoate, and an allylic fluoride.

An easy methodology for the synthesis of the piperazin-2-ones by one-pot reductive cyclization of PheΨ[CH(CN)NH]Gly pseudodipeptides is described. Study of the reactivity of the piperazin-2-one ring has shown that regioselective functionalization at the N¹ and N⁴ positions is possible, and hence great potential for molecular diversity generation

Three synthetic strategies have been developed for trichostatic acid and trichostatin A. Each strategy has a different key bond-forming step; a vinylogous Horner–Wadsworth–Emmons condensation, a Marshall propargylation, and coupling of a ketone enolate with various alkenyl halides. Two of the syntheses were efficient and able to produce analogues. Two of the syntheses were enantioselective.

The first total convergent synthesis of the naturally occurring (5-5′)/(8′-O-4″) dehydrotrimer of ferulic acid (A) has been achieved in 10 steps and in 18 % yield starting from commercially available vanillin using horseradish peroxidase mediated enzymatic aryl–aryl coupling, aldolization/crotonization, and Wittig olefination reactions as the key steps.

Synthesis of the AB-ring substructure of granaticin A was accomplished. The pyranolactone moiety was stereoselectively accessed by Sharpless asymmetric dihydroxylation and oxa-Pictet–Spengler cyclization. Ozonolysis of a hydroquinone led to pyranolactone anhydrides. Regioselective addition of a Grignard reagent to an unsymmetrical anhydride was observed. An alternative strategy was also investigated.

We report the total synthesis of taspine and its symmetrical analogue TAS2C. Both the synthesised compounds were tested by ESI-MS for their ability to bind different quadruplex and duplex DNA structures.