Synlett最新文献

The impetuous development of the pharmaceutical industry and material science stimulates the search for new synthetic approaches and new methods for the synthesis and functionalization of aza-heterocycles; these are some of the key objectives of modern organic chemistry. As a result, an advanced method towards the synthesis of functionalized N-heterocycles that circumvents the limitations associated with traditional methods needs to be devised. In recent decades, rearrangement/reorganization reactions have emerged as a powerful tool for the efficient synthesis of the aza-heterocycle. In this illustration, we summarize some our recent efforts in the development of few complex aza-heterocyclic cores.

1 Introduction

2 Skeletal Rearrangement of Small Heterocycles via Domino Ring-Opening and Ring-Closing (DROC) Strategy

3 Ru(II)-Catalyzed Skeletal Rearrangement of the Quinazoline Ring

4 Lewis Acid Catalyzed Skeletal Rearrangement of Furans to Indolizine Cores

5 Skeletal Rearrangement of Donor–Acceptor Cyclopropanes via Domino Ring-Opening and Ring-Closing (DROC) Strategy

6 Lewis Acid Mediated Skeletal Rearrangement of Donor–Acceptor Spirocyclopropylpyrazolones

7 Skeletal Rearrangement through Ring Distortion Strategy

8 Conclusion

The synthesis of short phosphorodiamidate morpholino oligonucleotides (PMOs) has been successfully achieved using azidoaryl carbamate protected chlorophosphoramidate monomers. The deprotection step carried out in a neutral medium with triphenylphosphine-based reagents avoids the need for chlorinated solvents. This method uses a meticulously tailored combination of resin support, solvents, deblocking agents, and coupling reagents to ensure efficient synthesis. Additionally, the azidoaryl carbamate protecting group has been adapted as an orthogonal protection, enabling the development of bi- and trifunctionalized PMOs for bioconjugation. These advancements are expected to broaden the potential applications of PMOs in biomedical research.

We report a useful synthetic approach to assemble in/in epoxide, in/out epoxide, and out/out epoxide in cage systems using the Corey–Chaykovsky reaction and the Peterson olefination as key steps. In this regard, a variety of pentacycloundecane (PCUD) based cage compounds containing oxirane rings with diverse stereochemical disposition were synthesized via a simple synthetic sequence. Five cage diones were used for this purpose, and the starting cage diones were prepared with easily accessible starting materials such as 1,4-hydroquinone derivatives and cyclopentadiene. Here, we have used the Diels–Alder (DA) reaction, a [2+2] photocycloaddition, the Corey–Chaykovsky reaction, and the Peterson olefination as crucial steps to prepare the target molecules.

A sequential Cu-catalyzed amidation and hydroxylation of p-dihalobenzenes is applied to synthesize acetaminophen. This method allows the direct introduction of acetamido and hydroxy groups under acid-free conditions without forming other regioisomers. By using a one-pot process, acetaminophen can be prepared with an overall yield of up to 74%.

This review summarizes various strategies that combine metathesis with diverse named and unnamed reactions to create molecular diversity in producing carbocycles, macrocycles, and heterocycles.

1 Introduction

2 Olefinations

3 Rearrangement

4 Allylation

5 Cycloadditions

6 Coupling Reactions

7 Grignard Reaction

8 Radical reactions

9 Conjugate Addition–Metathesis

10 Multicomponent Reactions

11 Miscellaneous

12 Conclusions

Here, we report the NiCo₂O₄-nanoparticle-catalyzed dehydrogenative direct oxidation of primary alcohols to carboxylic acid in the presence of KOH under microwave irradiation in the absence of any oxidant in good to excellent yields (75–99%) within a short reaction time (5–10 min). The polycrystalline cubic spinel phase of NiCo₂O₄ nanoparticles (NPs) with an average size of 25 nm were synthesized by the co-precipitation method and analyzed properly by using powder X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and transmission electron microscopy measurements. The NiCo₂O₄ NPs were stable under the reaction conditions and reused for up to eight cycles without appreciable loss in the yield of benzoic acid. According to mechanistic insight, the KOH acts as a second oxygen source and is essential for the synthesis of carboxylic acid from alcohols. The hydrogen gas was found to be the only byproduct of this method detected by chemical reactions.

Methanol is gaining popularity as a transfer-hydrogenating agent in catalytic reduction reactions because of its bulk-scale production and inexpensive nature. Current research interests include the utilization of methanol as a safe and sustainable hydrogen source for chemical synthesis and drug development. In particular, the chemoselective reduction of α,β-unsaturated ketones is of great interest because of their prevalence in many natural products. We investigated the potential application of acridine-derived SNS-Ru pincer complexes in methanol activation for chemoselective reduction of chalcones. Our developed catalytic system showed broad substrate tolerance, including substrates containing reducible functional groups. Control experiments and postsynthetic applications are also highlighted.

Dearomatization of indole derivatives offers a straightforward approach to accessing the indoline framework. However, highly efficient dearomatization of indoles bearing electron-deficient groups remains underdeveloped. Herein, a nickel-catalyzed intermolecular hydroalkylative dearomatization reaction of indoles with simple alkyl bromides through a single-electron-transfer process is reported. A wide variety of indole derivatives bearing various functional groups were compatible with this protocol and reacted with primary, secondary, or tertiary alkyl bromides to afford a series of indolines in good yields (up to 82%) and with excellent diastereoselectivity (up to >20:1). Notably, a nickel-mediated hydrogen-atom-transfer process was observed when terminal alkyl bromides were employed as the radical precursors, which resulted in branched products.

A Fe(OTf)₃ and γ-cyclodextrin-catalyzed hydroarylation of alkenes with 1-naphthols or 2-naphthols is demonstrated. This efficient and general method delivers a wide range of benzylic naphthols from readily available starting materials with high chemo- and regioselectivity in up to 99% yield, with no need for a strong base or additive.

We describe effective development of the highly diastereoselective synthesis of double helical tetraamine 2-H₂-C₂ and propose a mechanism for its formation. The resolution of 2-H₂-C₂ is facilitated by a high racemization barrier of 43 kcal mol^–1 and it is implemented via either a chiral auxiliary or preparative supercritical fluid chromatography. This enables preparation of the first high-spin neutral diradical, with spin density delocalized within an enantiomeric double helical π-system. The presence of two effective 3-electron C–N bonds in the diradical leads to: (1) the triplet (S = 1) high-spin ground state with a singlet-triplet energy gap of 0.4 kcal mol^–1 and (2) the long half-life of up to 6 days in 2-MeTHF at room temperature. The diradical possesses a racemization barrier of at least 26 kcal mol^–1 in 2-MeTHF at 293 K and chiroptical properties, with an absorption anisotropy factor |g| ≈ 0.005 at 548 nm. These unique magnetic and optical properties of our diradical form the basis for the development of next-generation spintronic devices.

1 Introduction

2 Synthesis and Resolution of the C₂-Symmetric Double Helical Tetraamine 2-H₂-C₂

3 Synthesis and Characterization of Neutral High-Spin Aminyl Diradical 2^2•-C₂

4 Conclusion