Triarylaminium salt facilitated Friedel–Crafts reaction of indoles with enamides and vinyl ethers

Commercially available stable radical cation triarylaminium salt can be used as an efficient initiator for Friedel–Crafts reaction of indoles with enamides to regioselectively construct complex indole derivatives and for double Friedel–Crafts reaction of indoles with vinyl ethers to offer 3,3′-Bis(indolyl)alkane derivatives. The ready availability of the starting materials and the usefulness of the products make this strategy attractive.     

Direct alkylation of indoles and amines by tert-enamides: facile access to pharmaceutically active 2-oxo-1-pyrrolidine analogues

Direct alkylation of indoles and amines by tertiary enamides for the synthesis of pharmaceutically active 2-oxo-1-pyrrolidine analogues was described. With only a 0.5 mol% catalyst loading, molecular iodine was demonstrated to be efficiently enough to promote the reaction under neat condition. Only Markovnikov addition product was obtained indicating that the reactions proceeded with excellent regioselectivity.     

Copper‐Catalyzed Oxidative Amination and Allylic Amination of Alkenes

Enamines and enamides are useful synthetic intermediates and common components of bioactive compounds. A new protocol for their direct synthesis by a net alkene C? H amination and allylic amination by using catalytic Cu^II in the presence of MnO₂ is reported. Reactions between N‐aryl sulfonamides and vinyl arenes furnish enamides, allylic amines, indoles, benzothiazine dioxides, and dibenzazepines directly and efficiently. Control experiments further showed that MnO₂ alone can promote the reaction in the absence of a copper salt, albeit with lower efficiency. Mechanistic probes support the involvement of nitrogen‐radical intermediates. This method is ideal for the synthesis of enamides from 1,1‐disubstituted vinyl arenes, which are uncommon substrates in existing oxidative amination protocols.     

On a Facile Synthesis of Melatonin and Other Related Indoles

An efficient laboratory synthesis for melatonin and other related indoles utilising enamides and enecarbamates is described.     

TFA-catalyzed C–N bond activation of enamides with indoles: efficient synthesis of 3,3-bisindolylpropanoates and other bisindolylalkanes

An efficient TFA-catalyzed cleavage of C–N bonds in alkylation of indoles by tertiary enamides was described. A variety of bisindolylalkane derivatives, especially 3,3-bisindolylpropanoates, were expeditiously synthesized in good yields.     

One‐Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides

A general and efficient one‐pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper‐catalyzed alkyne and azide cycloaddition to N‐sulfonyl‐1,2,3‐triazole, rhodium‐catalyzed selective insertion of α‐iminocarbenes onto the C3?H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH₃ or palladium catalyst, in one‐pot. The reaction also showed excellent functional‐group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one‐pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro‐β‐carboline and tryptoline.     

Nucleophilicity parameters of enamides and their implications for organocatalytic transformations

The kinetics of the reactions of eleven substituted enamides with benzhydrylium ions (diarylcarbenium ions) were determined in acetonitrile solution. The second-order rate constants follow the correlation log k(2) (20 °C)=s(N)(E+N), which allowed us to derive reactivity parameters N and s(N). With 4.6相似文献   

Direct C?H Functionalization of Enamides and Enecarbamates by Using Visible‐Light Photoredox Catalysis

Direct C? H functionalization of various enamides and enecarbamates was realized through visible‐light photoredox catalyzed reactions. Under the optimized conditions using [Ir(ppy)₂(dtbbpy)PF₆] as photocatalyst in combination with Na₂HPO₄, enamides such as N‐vinylpyrrolidinone could be easily functionalized by irradiation of the reaction mixture overnight in acetonitrile with visible light. The scope of the reaction with respect to enamide and enecarbamate substrates by using diethyl 2‐bromomalonate for the alkylation reaction was explored, followed by an investigation of the scope of alkylating reagents used to react with the enamides and enecarbamates. The results indicated that reaction takes place with quite broad substrate scope, however, tertiary enamides with an internal C?C double bond in the E configuration could not be alkylated. Alkylation of N‐vinyl tertiary enamides and enecarbamates gave monoalkylated products exclusively in the E configuration. Alkylation of N‐vinyl secondary enamides gave doubly alkylated products. Double bond migration was observed in the reaction of electron‐deficient bromides such as 3‐bromoacetyl acetate with N‐vinylpyrrolidinone. A mechanism is proposed for the reaction that is different from reported reactions of SOMOphiles with a nonfunctionalized C?C double bond. Further tests on the trifluoromethylation and arylation of enamides and enecarbamates under similar conditions showed that the reactions could serve as a mild, practical, and environmentally friendly approach to various functionalized enamides and enecarbamates.     

Sequential N-acylamide methylenation-enamide ring-closing metathesis: construction of benzo-fused nitrogen heterocycles

The dimethyltitanocene methylenation of N-acylamides derived from ortho-vinylanilines, ortho-allylaniline, and ortho-vinylbenzylamine provides the corresponding enamides, which upon exposure to the second generation Grubbs ruthenium catalyst give access to indoles, 1,4-dihydroquinolines, and 1,2-dihydroisoquinolines, respectively. This sequential protocol also allows the synthesis of dihydrobenzoazepines, although the ring-closing metathesis (RCM) step is complicated by the alkene isomerization processes. From certain substrates, the direct annulation is observed in the titanium-mediated step, which is likely to occur through an olefin metathesis-intramolecular olefination sequence.     

Reversal of nucleophilicity of enamides in water: control of cyclization pathways by reaction media for the orthogonal synthesis of dihydropyridinone and pyrrolidinone Clausena alkaloids

A highly efficient, metal-free, and divergent method for the synthesis of 3,4-dihydropyridin-2-one and pyrrolidin-2-one Clausena alkaloids and their analogs is reported. While the oxirane-containing enamides underwent the TFA-mediated 6-endo-enamide-epoxide cyclization reaction in Bu(t)OH to produce homoclausenamides, an unprecedented nucleophilic reaction occurred at the alpha-carbon of enamides in water to yield 5-endo-enamide-epoxide cyclization products in excellent yields. The reversal of nucleophilicity of enamides in intramolecular cyclization is discussed in terms of steric and electronic effects of the oxirane-containing enamides.     

Copper‐Promoted Oxidative Coupling of Enamides and Alkynes for the Synthesis of Substituted Pyrroles

An efficient copper‐promoted oxidative coupling of enamides with alkynes has been developed for the synthesis of substituted pyrroles. The reaction proceeded through C?H and N?H bond functionalization of enamides under mild conditions.     

Regioselective and Enantioselective Synthesis of β‐Indolyl Cyclopentenamides by Chiral Anion Catalysis

The regioselective and enantioselective synthesis of β‐indolyl cyclopentenamides, a versatile chiral building block, by asymmetric addition of indoles to α,β‐unsaturated iminium intermediates has been achieved through chiral anion catalysis. Key to the success of this methodology is the generation of a chiral anion‐paired ketone‐type α,β‐unsaturated iminium intermediate from α‐hydroxy enamides. Preliminary mechanistic studies and DFT calculations are consistent with a mechanism involving multiple, concurrent pathways for isomerization of the initially formed azaallylcation into the key α,β‐unsaturated iminium intermediate, all mediated by the phosphoric acid catalyst.     

Palladium(II)-catalyzed direct alkenylation of nonaromatic enamides

A mild and efficient method for the direct alkenylation of nonaromatic enamides was achieved through a palladium(II)-catalyzed C-H functionalization. The reaction scope includes cyclic and acyclic enamides and a range of activated alkenes. This approach represents the first successful direct C(3)-functionalization of nonaromatic cyclic enamides.     

Direct alkenylation of non-aromatic enamides via palladium-catalyzed oxidative coupling: Synthetic developments and applications

Direct C(3) alkenylation of non-aromatic enamides through palladium(II)-catalyzed Fujiwara–Moritani cross-coupling was developed. The reaction scope includes a range of cyclic enamides as well as activated alkenes. The utility of this methodology is illustrated by the synthesis of octa- or tetrahydroquinoline cores obtained from conjugated enamides via Diels–Alder cycloaddition.     

Selective hydroalkoxycarbonylation of enamides to N-acyl amino acid esters: synthetic applications and theoretical studies

N-acyl amino acid esters are easily accessible from enamides by cobalt-catalyzed hydroalkoxycarbonylation in moderate to excellent yield. An important reaction parameter for selective carbonylation is the use of low hydrogen partial pressure, which prevents hydrogenation as a side reaction. The reported method is applicable to various enamides and alcohols. A DFT calculation of the catalytic cycle explains the preferred pathway of this reaction.     

A new and concise way to enamides by fluoroalkanosulfonyl fluoride mediated Beckmann rearrangement of α,β-unsaturated ketoximes

The reaction of α,β-unsaturated ketoximes with fluoroalkanosulfonyl fluorides in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) underwent the Beckmann rearrangement smoothly to afford the corresponding acid-sensitive enamides in moderate to excellent yields, which provides a new efficient method for the preparation of acid-sensitive enamides.     

Aqueous metal-free hydrothiolation of enamides and enecarbamates

An efficient and metal-free, anti-Markovnikov selective, hydrothioaltion reaction of enamides and enecarbamates in an aqueous medium is presented. This protocol is operationally simple, mild, and atom-economical. This process provides access to thioethers from available thiols and a variety of enamides and enecarbamates.     

Rhodium(III)-catalyzed arene and alkene C-H bond functionalization leading to indoles and pyrroles

Recently, the rhodium(III)-complex [Cp*RhCl(2)](2) 1 has provided exciting opportunities for the efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C-H bond functionalization event. In the present report, the use of complexes 1 and its dicationic analogue [Cp*Rh(MeCN)(3)][SbF(6)](2) 2 have been employed in the formation of indoles via the oxidative annulation of acetanilides with internal alkynes. The optimized reaction conditions allow for molecular oxygen to be used as the terminal oxidant in this process, and the reaction may be carried out under mild temperatures (60 °C). These conditions have resulted in an expanded compatibility of the reaction to include a range of new internal alkynes bearing synthetically useful functional groups in moderate to excellent yields. The applicability of the method is exemplified in an efficient synthesis of paullone 3, a tetracyclic indole derivative with established biological activity. A mechanistic investigation of the reaction, employing deuterium labeling experiments and kinetic analysis, has provided insight into issues of reactivity for both coupling partners as well as aided in the development of conditions for improved regioselectivity with respect to meta-substituted acetanilides. This reaction class has also been extended to include the synthesis of pyrroles. Catalyst 2 efficiently couples substituted enamides with internal alkynes at room temperature to form trisubstituted pyrroles in good to excellent yields. The high functional group compatibility of this reaction enables the elaboration of the pyrrole products into a variety of differentially substituted pyrroles.     

Palladium-catalyzed oxidative cyclopropanation of enamides and norbornenes initiated by C–H activation

A novel palladium-catalyzed oxidative cyclopropanation of enamides and norbornenes has been developed. The reaction proceeded through palladium-catalyzed vinyl C–H bond activation of enamides followed by two migratory insertions, β-(N)H elimination and hydrolyzation cascade steps. The reaction tolerates a range of functional groups and provides an effective method for the synthesis of cyclopropane-fused norbornanes in good yields under mild conditions.     

Synthesis and reactivity of an alpha-stannyl beta-silyl enamide

We describe here an unprecedented approach to the synthesis of stereodefined 1,2-bis-substituted enamides. Starting from bis-metallated enamides, a palladium-copper coupling reaction allows the introduction of various groups at C1, whilst iododesilylation affords a new entry for the functionalization at C2.