Metal-catalyzed hydrofunctionalization reactions of alkynes, i.e., the addition of Y–H units (Y = heteroatom or carbon) across the carbon–carbon triple bond, have attracted enormous attention for decades since they allow the straightforward and atom-economic access to a wide variety of functionalized olefins and, in its intramolecular version, to relevant heterocyclic and carbocyclic compounds. Despite conjugated 1,3-diynes being considered key building blocks in synthetic organic chemistry, this particular class of alkynes has been much less employed in hydrofunctionalization reactions when compared to terminal or internal monoynes. The presence of two C≡C bonds in conjugated 1,3-diynes adds to the classical regio- and stereocontrol issues associated with the alkyne hydrofunctionalization processes’ other problems, such as the possibility to undergo 1,2-, 3,4-, or 1,4-monoadditions as well as double addition reactions, thus increasing the number of potential products that can be formed. In this review article, metal-catalyzed hydrofunctionalization reactions of these challenging substrates are comprehensively discussed.
AbstractOver the past two decades, catalytic alkyne alkoxylation-initiated Claisen rearrangement has proven to be a practical and powerful strategy for the rapid assembly of a diverse range of structurally complex molecules. The rapid development of Claisen rearrangements triggered by transition-metal-catalyzed alkyne alkoxylation has shown great potential in the formation of carbon–carbon bonds in an atom-economic and mild way. However, metal-free alkyne alkoxylation-triggered Claisen rearrangement has seldom been exploited. Recently, Brønsted acids such as HNTf2 and HOTf have been shown to be powerful activators that promote catalytic alkyne alkoxylation/Claisen rearrangement, leading to the concise and flexible synthesis of valuable compounds with high efficiency and atom economy. Recent advances on the Brønsted acid catalyzed alkyne alkoxylation/Claisen rearrangement are introduced in this Account, in which both intramolecular and intermolecular tandem reactions are discussed.
AbstractTrivalent-phosphorus-containing molecules are widely used in fields ranging from catalysis to materials science. Efficient catalytic methods for their modifications, providing straightforward access to novel hybrid structures with superior catalytic activities, are highly desired to facilitate reaction improvement or discovery. We have recently developed new methods for synthesizing polyfunctional phosphines by C–C cross-couplings through rhodium-catalyzed C–H bond activation. These methods use a native P(III) atom as a directing group, and can be used in regioselective late-stage functionalization of phosphine ligands. Interestingly, some of the modified phosphines outperform their parents in Pd-catalyzed cross-coupling reactions.1 Introduction2 Early Examples of Transition-Metal-Catalyzed P(III)-Directed C–H Bond Activation/Functionalizations3 Synthesis of Polyfunctional Biarylphosphines by Late-Stage Alkylation: Application in Carboxylation Reactions4 Synthesis of Polyfunctional Biarylphosphines by Late-Stage Alkenylation: Application in Amidation Reactions5 Conclusion
Nitrogen-containing heterocycles are important scaffolds for a large number of compounds with biological, pharmaceutical, industrial and optoelectronic applications. A wide range of different methodologies for the preparation of N-heterocycles are based on metal-catalyzed cyclization of suitable substrates. Due to the growing interest in Green Chemistry criteria over the past two decades, the use of supported metal catalysts in the preparation of N-heterocycles has become a central topic in Organic Chemistry. Here we will give a critical overview of all the solid supported metal catalysts applied in the synthesis of N-heterocycles, following a systematic approach as a function of the type of support: (i) metal catalysts supported on inorganic matrices; (ii) metal catalysts supported on organic matrices; (iii) metal catalysts supported on hybrid inorganic-organic matrices. In particular, we will try to emphasize the effective heterogeneity and recyclability of the described metal catalysts, specifying which studies were carried out in order to evaluate these aspects.
The mechanism of metal-catalyzed spiroketalization of propargyl acetonide is explored by employing DFT with the B3LYP/6-31+G(d) method. Acetonide is used as a regioselective regulator in the formation of monounsaturated spiroketal. The energies of transition states, intermediates, reactants and products are calculated to provide new insight into the mechanism of the reaction. The energetic features, validation of the observed trends in regioselectivity are conferred in terms of electronic indices via FMO analysis. The presence of acetonide facilitates a stepwise spiroketalization as it masks the competing nucleophile, and thus hydroxyl group present, exclusively acts as a nucleophile. The vinyl gold intermediate 3 is formed from 2 via activation barrier TS1. This is the first ring formation, which is 6-exo-dig cyclization. The intermediate 3 is converted into allenyl ether 4, which isomerizes to the intermediate oxocarbenium ion 5 via activation barrier TS2. The intermediate 5 cyclizes to 6 via TS3. This is the second ring formation. The intermediate 6 on protodeauration turns into 6,6-monounsaturated spiroketal 7. It is concluded that acetonide as a protecting group serves the purpose, and thus a wide range of spiroketals can be prepared, regioselectivity.
Synthetic access to poly(indazolyl)methanes has limited their study despite their structural similarity to the highly investigated chelating poly(pyrazolyl)methanes and their potentially important indazole moiety. Herein is presented a high yielding, one-pot synthesis for the 3d-metal catalyzed formation of bis(1H-indazol-1-yl)methane from 1H-indazole utilizing dimethylsulfoxide as the methylene source. Complete characterization of bis(1H-indazol-1-yl)methane is given with 1H and 13C NMR, UV/Vis, FTIR, high resolution mass spectrometry and for the first time, single crystal X-ray diffraction. This simple, inexpensive pathway to yield exclusively bis(1H-indazol-1-yl)methane provides synthetic access to further investigate the coordination and potential applications of the family of bis(indazolyl)methanes.
Optically active indole derivatives are ubiquitous in natural products and widely recognized as privileged components in pharmacologically relevant compounds. Therefore, developing catalytic asymmetric approaches for constructing indole derivatives is highly desirable. In this short review, transition-metal-catalyzed enantioselective synthesis of indoles from 2-alkynylanilines is summarized.
2 Aminometalation triggered asymmetric cross-coupling reaction/insertion
2.1 Asymmetric Cross-Coupling Reaction
2.2 Asymmetric insertion of C=O, C=C and C≡N bonds
3 Asymmetric relay catalysis