Azoacetylenes for the Synthesis of Arylazotriazole Photoswitches.

We report a modular approach toward novel arylazotriazole photoswitches and their photophysical characterization. Addition of lithiated TIPS-acetylene to aryldiazonium tetrafluoroborate salts gives a wide range of azoacetylenes, constituting an underexplored class of stable intermediates. In situ desilylation transiently leads to terminal arylazoacetylenes that undergo copper-catalyzed cycloadditions (CuAAC) with a diverse collection of organoazides. These include complex molecules derived from natural products or drugs, such as colchicine, taxol, tamiflu, and arachidonic acid. The arylazotriazoles display near-quantitative photoisomerization and long thermal Z-half-lives. Using the method, we introduce for the first time the design and synthesis of a diacetylene platform. It permits implementation of consecutive and diversity-oriented approaches linking two different conjugants to independently addressable acetylenes within a common photoswitchable azotriazole. This is showcased in the synthesis of several photoswitchable conjugates, with potential applications as photoPROTACs and biotin conjugates.

Recent Advances of the Halogen-Zinc Exchange Reaction.

For the preparation of zinc organometallics bearing highly sensitive functional groups such as ketones, aldehydes or nitro groups, especially mild halogen-zinc exchange reagents have proven to be of great potential. In this Minireview, the latest research in the area of the halogen-zinc exchange reaction is reported, with a special focus lying on novel dialkylzinc reagents complexed with lithium alkoxides. Additionally, the preparation and application of organofluorine zinc reagents and transition-metal-catalyzed halogen-zinc exchange reactions are reviewed.

A Predictive Model Towards Site-Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl⋠LiCl.

The development of a predictive model towards site-selective deprotometalation reactions using TMPZnCl⋅LiCl is reported (TMP=2,2,6,6-tetramethylpiperidinyl). The pKa values of functionalized N-, S-, and O-heterocycles, arenes, alkenes, or alkanes were calculated and compared to the experimental deprotonation sites. Large overlap (>80 %) between the calculated and empirical deprotonation sites was observed, showing that thermodynamic factors strongly govern the metalation regioselectivity. In the case of olefins, calculated frozen state energies of the deprotonated substrates allowed a more accurate prediction. Additionally, various new N-heterocycles were analyzed and the metalation regioselectivities rationalized using the predictive model.

Lewis Acid Directed Regioselective Metalations of Pyridazine.

Mono- or bidentate boron Lewis acids trigger a regioselective magnesiation or zincation of pyridazine in position C3 (ortho product) or C4 (meta product). The regioselectivity of the metalation was rationalized with the help of calculated pKa values of both pyridazine and pyridazine/Lewis acid complexes.

Preparation of Polyfunctional Arylzinc Organometallics in Toluene by Halogen/Zinc Exchange Reactions.

A wide range of polyfunctional diaryl- and diheteroarylzinc species were prepared in toluene within 10 min to 5 h through an I/Zn or Br/Zn exchange reaction using bimetallic reagents of the general formula R'2 Zn⋅2 LiOR (R'=sBu, tBu, pTol). Highly sensitive functional groups, such as a triazine, a ketone, an aldehyde, or a nitro group, were tolerated in these exchange reactions, enabling the synthesis of a plethora of functionalized (hetero)arenes after quenching with various electrophiles. Insight into the constitution and reactivity of these bimetallic mixtures revealed the formation of highly active lithium diorganodialkoxyzincates of type [R'2 Zn(OR)2 Li2 ].

Zn-, Mg-, and Li-TMP Bases for the Successive Regioselective Metalations of the 1,5-Naphthyridine Scaffold (TMP=2,2,6,6-Tetramethylpiperidyl).

A set of successive regioselective metalations and functionalizations of the 1,5-naphthyridine scaffold are described. A combination of Zn-, Mg-, and Li-TMP (TMP=2,2,6,6-tetramethylpiperidyl) bases and the presence or absence of a Lewis acid (BF3 ⋅OEt2 ) allows the introduction of up to three substituents to the 1,5-naphthyridine core. Also, a novel "halogen dance" reaction was discovered upon metalation of an 8-iodo-2,4-trifunctionalized 1,5-naphthyridine allowing a fourth regioselective functionalization. Additionally, reactions leading to key 1,5-naphthyridines for the preparation of OLED materials and a potential antibacterial agent were performed.

Localised and delocalised excitons in star-like squaraine homo- and heterotrimers.

Exciton coupling of localised chromophore states within covalently bound superchromophores is a viable strategy to modify optical properties such as spectral broadening and red-shifting of absorption bands. These are desirable properties for e.g. organic photovoltaic applications. Attaching three squaraine dyes to a central nitrogen core in a star-shaped manner leads to the formation of superchromophores that may form localised and delocalised excitons upon photoexcitation. In this work we investigated two homotrimers, two heterotrimers and a heterodimer formed by the combination of two different squaraines SQA and SQB. Due to exciton coupling the two homotrimers display a red shift of the main absorption band by about 1000 cm(-1) compared to their monomeric reference compounds. On the other hand, the heterotrimers show a broadening of the absorption spectra with three peak maxima at the exciton manifold band. In fluorescence experiments the homotrimers display signals similar to the emission of the monomeric compounds but red shifted. However, the heterotrimers and the heterodimer show, beside emission from the delocalised lowest energy state, an additional signal that overlaps strongly with the absorption. Excitation and time-dependent emission spectra of the hetero compounds indicate that this emission stems from a localised higher energy state. This interpretation is corroborated by transient absorption measurements with fs-time resolution.

Cobalt-Catalyzed Aerobic Aminocyclization of Unsaturated Amides for the Synthesis of Functionalized γ- and δ-Lactams.

We report the cobalt-catalyzed aminocyclization of unsaturated N-acyl sulfonamides in the presence of oxygen to provide γ- and δ-lactam aldehydes. Use of an optically active cobalt catalyst resulted in the formation of enantiomerically enriched γ-and δ-lactam alcohols. The γ-lactam aldehydes and alcohols obtained were elaborated into useful building blocks.

Cobalt-Catalyzed Cyclization of Unsaturated N-Acyl Sulfonamides: a Diverted Mukaiyama Hydration Reaction.

The cycloisomerization of ß-, γ-, and δ-unsaturated N-acyl sulfonamides to N-sulfonyl lactams and imidates is reported. This transformation is effected in the presence of a CoIII(salen) catalyst using t-BuOOH or air as the oxidant. The method shows good functional group tolerance (alkyl, aryl, heteroaryl, ether, N-Boc) and furnishes an underexplored class of cyclic building blocks. The strong solvent dependence of the transformation is investigated, and the synthetic versatility of the N-sulfonyl imidate product class is highlighted.

Mn- and Co-Catalyzed Aminocyclizations of Unsaturated Hydrazones Providing a Broad Range of Functionalized Pyrazolines.

Manganese- and cobalt-catalyzed aminocyclization reactions of unsaturated hydrazones are reported. Whereas manganese catalysis provides access to pyrazoline and tetrahydropyridazine alcohols, cobalt catalysis for the first time paves the way for the selective formation of pyrazoline aldehydes. Furthermore, various functional groups including hydroperoxide, thiol derivatives, iodide, and bicyclopentane may be introduced via manganese-catalyzed ring-forming aminofunctionalization. A progesterone receptor antagonist was prepared using the aminocyclization protocol.

Synthesis of Functionalized Diaryl Sulfides by Cobalt-Catalyzed Coupling between Arylzinc Pivalates and Diaryl Disulfides.

An efficient protocol for the cobalt-catalyzed preparation of diaryl sulfides from solid organozinc pivalates and commercially available diaryl disulfides is reported. This cross-coupling proceeds at room temperature and displays a good functional group tolerance, allowing the preparation of a diversity of symmetrical or asymmetrical diaryl sulfides in 60-95% yield.

Amination of Phosphorodiamidate-Substituted Pyridines and Related N-Heterocycles with Magnesium Amides.

The amination of various phosphorodiamidate-substituted pyridines, quinolines, and quinoxaline with magnesium amides R2NMgCl·LiCl proceeds at room temperature within 8 h. Several pharmaceutically active amines were suitable substrates for this amination procedure, and also the antihistaminic tripelennamine was prepared. Additionally, several heterocyclic phosphorodiamidates underwent directed ortho-metalation (D oM) using TMPMgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) or TMP2Mg·2LiCl, followed by electrophilic functionalization prior to the amination step, which led to ortho-functionalized aminated N-heterocycles.

Regioselective Metalation and Functionalization of the Pyrazolo[1,5- a]pyridine Scaffold Using Mg- and Zn-TMP Bases.

A regioselective functionalization of the pyrazolo[1,5- a]pyridine scaffold using Mg- and Zn-TMP bases (TMP = 2,2,6,6-tetramethylpiperidyl) in the presence or absence of BF3·OEt2 is described. Also, various functionalized pyrazolo[1,5- a]pyridines bearing an ester function (and an NHBoc or ethyl group) are magnesiated and functionalized, leading to polysubstituted heterocycles. Additionally, a sulfoxide directed ortho-metalation, followed by the transition-metal-free amination of a pyrazolo[1,5- a]pyridine sulfoxide, using a magnesium amide, is reported.

Transition-Metal-Free Amination of Pyridine-2-sulfonyl Chloride and Related N-Heterocycles Using Magnesium Amides.

A new transition-metal-free amination of pyridine-2-sulfonyl chloride and related N-heterocycles using magnesium amides of type R2NMgCl·LiCl is reported. Additionally, the directed ortho-magnesiation of pyridine-2-sulfonamides using TMPMgCl·LiCl was investigated. Reaction of the magnesium intermediates with various electrophiles and subsequent amination using magnesium amides led to a range of 2,3-functionalized pyridines. Also, cyclization reactions providing an aza-indole and an aza-carbazole were carried out.