Metal-Free Synthetic Shortcut to Octahydro-Dipyrroloquinoline Skeletons from 2,5-Cyclohexadienone Derivatives and l-Proline.

The tandem decarboxylative condensation-dimerization reaction of l-proline with 2,5-cyclohexadienones including p-quinone monoacetals, p-quinol ethers, and p-quinols is reported to provide a concise and rapid synthesis of octahydro-dipyrroloquinoline compounds. The reaction features the use of cost-effective and readily available starting materials, high efficiency, metal-free and green reaction conditions. The reaction is applied to the synthesis of incargranine B aglycone. The discovery of this reaction may suggest a biosynthetic pathway from 2,5-cyclohexadienones and proline for natural ingredients containing pyrroloquinoline moieties.

Three-Component Reactions of α-Amino Acids, p-Quinone Monoacetals, and Diarylphosphine Oxides to Selectively Afford 3-(Diarylphosphinyl)anilides and N-Aryl-2-diarylphosphinylpyrrolidines.

The three-component reactions of α-amino acids, p-quinone monoacetals (or p-quinol ethers), and diarylphosphine oxides have been developed for the synthesis of 3-(diarylphosphinyl) anilides and N-aryl-2-diarylphosphinylpyrrolidines. The transformations may involve the in situ generation of conjugated azomethine ylides or 2-azaallyl anion species from the reaction of α-amino acids and p-quinone monoacetals, which are further trapped by diarylphosphine oxides.

Zinc-catalyzed regioselective C-P coupling of p-quinol ethers with secondary phosphine oxides to afford 2-phosphinylphenols.

The zinc triflate-catalyzed highly regioselective C-P cross coupling reaction of p-quinol ethers with secondary phosphine oxides is reported. The reaction provides a facile alternative method for the synthesis of 2-phosphinylphenols in good to high yields. Mechanistically, zinc triflate may serve as an oxophilic σ-Lewis acid to activate the C-O bond in p-quinol ether first. Then the regioselective attack of the phosphorus nucleophile at the α-carbon position takes place to form the C-P bond and give the product. In addition, α-alkynyl substituted p-quinol ethers also react with secondary phosphine oxides in the same reaction mode to give 6-alkynyl 2-phosphinylphenols in the presence of the zinc catalyst.

Synthesis of benzooxepane-fused cyclobutene derivatives via Pd-catalyzed cascade reactions of haloarenes and diynylic ethers.

A tandem palladium-catalyzed Sonogashira coupling, propargyl-allenyl isomerization, and [2+2] cycloaddition sequence between electron-deficient haloarenes and 1,8-diynylic ethers is developed. The reaction shows good functional tolerance and proceeds under mild conditions to provide a new profile of benzooxepane-fused cyclobutene derivatives in moderate to high yields with high selectivity. The reaction mechanism is validated both by experimental studies and DFT calculations.

Pd-catalyzed reaction of aryl halides and propargyl furylmethyl ethers: a novel pathway to functionalized dihydroisobenzofurans.

An interesting sequential reaction involving Sonogashira coupling, propargyl-allenyl isomerization, intramolecular [4 + 2] cycloaddition, and bridged oxa-ring opening has been realized, providing a facile method for the synthesis of functionalized dihydroisobenzofurans from easily accessible starting materials with a decent diastereoselectivity.

Highly selective 1,4- and 1,6-addition of P(O)-H compounds to p-quinones: a divergent method for the synthesis of C- and O-phosphoryl hydroquinone derivatives.

The reaction of P(O)-H compounds with p-quinones could proceed through either 1,4- or 1,6-addition pathways by employing different additives to selectively give the corresponding C- and O-phosphoryl hydroquinone derivatives in good yields. Oxidative double 1,4-addition of P(O)-H compounds to p-quinones was also achieved by tuning the solvent, affording a facile synthesis of bis-substituted hydroquinones with phosphorus functionality. Further studies on these reactions by using optically active H-phosphinates showed that all addition reactions took place stereospecifically with retention of configuration at the phosphorus center. The findings lead to the establishment of a divergent method for the synthesis of C- and O-phosphoryl hydroquinone derivatives from easily available P(O)-H compounds.

Synthesis of 1,1,4,5-Tetrasubstituted Phthalans via Pd-Catalyzed Three-Component Reactions of Haloarenes, Alkynes, and Protic Nucleophiles.

A novel approach for the synthesis of 1,1,4,5-tetrasubstituted phthalans is developed via a tandem palladium-catalyzed Sonogashira coupling/propargyl-allenyl isomerization/pentadehydro-Diels-Alder cyclization/regioselective nucleophilic addition sequence. The reaction shows good functional tolerance and provides a wide variety of substituted phthalans in moderate to high yields from haloarenes, triynes, and protic nucleophiles, such as amines and alcohols, under very mild conditions.

Facile regio- and stereoselective hydrometalation of alkynes with a combination of carboxylic acids and group 10 transition metal complexes: selective hydrogenation of alkynes with formic acid.

A facile, highly stereo- and regioselective hydrometalation of alkynes generating alkenylmetal complex is disclosed for the first time from a reaction of alkyne, carboxylic acid, and a zerovalent group 10 transition metal complex M(PEt(3))(4) (M = Ni, Pd, Pt). A mechanistic study showed that the hydrometalation does not proceed via the reaction of alkyne with a hydridometal generated by the protonation of a carboxylic acid with Pt(PEt(3))(4), but proceeds via a reaction of an alkyne coordinate metal complex with the acid. This finding clarifies the long proposed reaction mechanism that operates via the generation of an alkenylpalladium intermediate and subsequent transformation of this complex in a variety of reactions catalyzed by a combination of Brϕnsted acid and Pd(0) complex. This finding also leads to the disclosure of an unprecedented reduction of alkynes with formic acid that can selectively produce cis-, trans-alkenes and alkanes by slightly tuning the conditions.

Stereospecific coupling of H-phosphinates and secondary phosphine oxides with amines and alcohols: a general method for the preparation of optically active organophosphorus acid derivatives.

The reaction of H-phosphinates and secondary phosphine oxides with amines and alcohols proceeds highly stereospecifically to give the corresponding coupling products with inversion of configuration at the phosphorus center under the Atherton-Todd reaction conditions. This finding leads to the establishment of a general and efficient method for the synthesis of a variety of optically active organophosphorus acid derivatives from the easily available chiral H-phosphinates and secondary phosphine oxides.

Stereospecific halogenation of P(O)-H bonds with copper(II) chloride affording optically active Z1Z2P(O)Cl.

A general and efficient method for the preparation of optically active Z1Z2P(O)Cl from the easily prepared optically active H-phosphinates and H-phosphine oxides was reported. H-Phosphinates and H-phosphine oxides react stereospecifically with CuCl2 to produce the corresponding optically active Z1Z2P(O)Cl with retention of configuration at the phosphorus center. Optically active Z1Z2P(O)Cl reacts easily with a variety of nucleophiles to produce other chiral organophosphorus acid derivatives with inversion of configuration at phosphorus.

Unexpected Pd-catalyzed coupling, propargyl-allenyl isomerization and alder-ene reaction: facile synthesis of some not readily available 2,3-dihydrofuran derivatives.

An interesting sequential reaction involving Pd-catalyzed coupling, propargyl-allenyl isomerization, and Alder-ene cycloaddition is reported, providing a facile synthesis of some not readily available 2,3-dihydrofurans from electron-deficient vinyl or aromatic halides and 1-aryl-prop-2-ynyl 3'-methylbut-2'-enyl ethers.

Metal-Free Denitrogenative C-C Couplings of Pyridotriazoles with Boronic Acids To Afford α-Secondary and α-Tertiary Pyridines.

Pyridotriazoles are utilized as robust building blocks to access α-secondary and α-tertiary pyridines via the development of a simple yet practically useful metal-free denitrogenative C-C cross-coupling with boronic acids. The reaction shows a high level of functional tolerance, broad substrate scope, and facile scalability. The synthetic potential of the method is demonstrated by the strurctural modification of a bioactive molecule and concise synthesis of pheniramine analogs.

Pd-catalyzed sequential reactions via allene intermediate for the synthesis of polycyclic frameworks containing 2,3-dihydrofuran units.

A stepwise process involving Sonogashira coupling, propargyl allenyl isomerization, and consecutive [4 + 2] cyclization has been realized, leading to an efficient synthesis of polycyclic compounds containing a 2,3-dihydrofuran unit. Most attractive for synthetic interest is the finding that up to four stereogenic centers could be generated in one step with high stereoselectivity.

Convenient synthesis of allenylphosphoryl compounds via Cu-catalysed couplings of P(O)H compounds with propargyl acetates.

A novel Cu-catalysed substitution reaction of propargyl acetates with P(O)H compounds is developed to afford allenylphosphoryl compounds via C-P bond coupling in high yields under mild conditions. A plausible mechanism involving the nucleophilic interception of the Cu-allenylidene intermediates is proposed.

Cu-Catalyzed hydrophosphorylative ring opening of propargyl epoxides: highly selective access to 4-phosphoryl 2,3-allenols.

A novel CuI-catalyzed cross-coupling of propargyl epoxides with P(O)H compounds is disclosed. The reaction proceeded efficiently under mild conditions to give 4-phosphoryl 2,3-allenols in good to high yields with excellent selectivity. The utility of the products was demonstrated and a plausible mechanism was also proposed.

Highly stereoselective generation of complex oxy-bicyclic scaffolds via an atom-economic Pd(II)-catalyzed hydroalkynylation, isomerization and Diels-Alder cycloaddition sequence.

An atom-economic tandem Pd(II)-catalyzed hydroalkynylation, alkyne-allene isomerization, and Diels-Alder cycloaddition is reported. The reaction employs readily available starting substrates, proceeds in a highly ordered fashion, features high regio- and stereoselectivity, and tolerates a wide range of functionality and structural motifs, thus offering an attractive strategy for producing new molecular complexity and diversity from easily available starting materials. A mechanistic study with density functional theoretical calculations was conducted to rationalize the observed stereoselectivity.

Copper-catalyzed coupling reaction of unactivated secondary alkyl iodides with alkyl Grignard reagents in the presence of 1,3-butadiene as an effective additive.

Cu-catalyzed cross-coupling of unactivated secondary alkyl iodides with alkyl Grignard reagents in the presence of 1,3-butadiene as a ligand precursor was developed. The use of 1,3-butadiene resulted in improved yields of alkyl-alkyl products with improved selectivities.

A new oxapalladacycle generated via ortho C-H activation of phenylphosphinic acid: an efficient catalyst for Markovnikov-type additions of E-H bonds to alkynes.

A new oxapalladacycle 3 can be conveniently prepared via direct ortho palladation of diphenylphosphinic acid with palladium acetate. Catalysts derived from 3 can efficiently catalyze Markovnikov-type additions of E-H bonds (P(O)-H, S-H and spC-H) to alkynes via a unique catalytic cycle.

Unexpected multiple electrophilic addition reaction of (Z)-alk-2-en-4-ynoates with N,N-dibromo-p-toluenesulfonamide (TsNBr(2)): a highly diastereoselective synthesis of densely functionalized aziridines.

A novel electrophilic addition reaction of (Z)-alk-2-en-4-ynoates and TsNBr(2) is reported, providing a facile and highly stereoselective synthesis of densely functionalized aziridine derivatives.

Reaction of 2,3-allenoates with TsNBr2 in the presence of base: a facile highly stereoselective synthesis of (1E,2E)-3-bromo-4-oxo-N'-tosyl-2-alkenoxylimidic acid ethyl esters.

A novel reaction pathway of 2,3-allenoates with an electrophile (TsNBr2) in the presence of K2CO3 to produce (1E,2E)-3-bromo-4-oxo-N'-tosyl-2-alkenoxylimidic acid ethyl esters is reported. The reaction proceeds in a highly stereoselective fashion. A plausible mechanism to rationalize this reaction is also proposed.