Ruthenium‐Catalyzed Functionalization of Pyrroles and Indoles with Propargyl Alcohols

Several ruthenium‐catalyzed atom‐economic transformations of propargyl alcohols with pyrroles or indoles leading to alkylated, propargylated, or annulated heteroaromatics are reported. The mechanistically distinct reactions are catalyzed by a single ruthenium(0) complex containing a redox‐coupled dienone ligand. The mode of activation regarding the propargyl alcohols determines the reaction pathway and depends on the alcohols’ substitution pattern. Secondary substrates form alkenyl complexes by a 1,2‐hydrogen shift, whereas the transformation of tertiary substrates involves allenylidene intermediates. 1‐Vinyl propargyl alcohols are converted by a cascade allylation/cyclization sequence. The environmentally benign processes are of broad scope and allow the selective synthesis of highly functionalized pyrroles and indoles generating water as the only waste product.     

Ruthenium-catalyzed functionalization of pyrroles and indoles with propargyl alcohols

Several ruthenium-catalyzed atom-economic transformations of propargyl alcohols with pyrroles or indoles leading to alkylated, propargylated, or annulated heteroaromatics are reported. The mechanistically distinct reactions are catalyzed by a single ruthenium(0) complex containing a redox-coupled dienone ligand. The mode of activation regarding the propargyl alcohols determines the reaction pathway and depends on the alcohols' substitution pattern. Secondary substrates form alkenyl complexes by a 1,2-hydrogen shift, whereas the transformation of tertiary substrates involves allenylidene intermediates. 1-Vinyl propargyl alcohols are converted by a cascade allylation/cyclization sequence. The environmentally benign processes are of broad scope and allow the selective synthesis of highly functionalized pyrroles and indoles generating water as the only waste product.     

Zirconyl triflate, [ZrO(OTf)2], as a new and highly efficient catalyst for ring-opening of epoxides

A highly efficient method for the ring opening of epoxides catalyzed by ZrO(OTf)₂ was adopted. This catalyst efficiently catalyzed alcoholysis, acetolysis and hydrolysis of epoxides and the corresponding alkoxy alcohols, acetoxy alcohols and 1,2- diols were obtained in excellent yields. Conversion of epoxides to 1,2-diacetetes, thiiranes and 1,3-dioxolanes was also performed in the presence of catalytic amounts of ZrO(OTf)₂, and the corresponding products were obtained in high to excellent yields. The high catalytic activity of ZrO(OTf)₂ is due to the replacement of Cl with OTf, which makes the ZrO(OTf)₂ as efficient Lewis acid.     

Sc(OTf)3‐Catalyzed Bicyclization of o‐Alkynylanilines with Aldehydes: Ring‐Fused 1,2‐Dihydroquinolines

A Sc(OTf)₃‐catalyzed cascade Prins‐type cyclization reaction of o‐alkynylanilines, bearing a hydroxy or amine functionality, with aldehydes affords 1,2‐dihydroquinoline derivatives having an extra fused ring efficiently under mild reaction conditions. It is interesting to observe the reversed reactivity in the highly selective formation of 1,2‐dihydroquinoline derivatives instead of the formation of the usually favored indole derivatives.     

Gold(I)‐Catalyzed Furan‐yne Cyclizations Involving 1,2‐Rearrangement: Efficient Synthesis of Functionalized 1‐Naphthols and Its Application to the Synthesis of Wailupemycin G

Gold‐catalyzed cascade cyclization/1,2‐rearrangement of 1‐(2‐furanyl)phenyl propargyl alcohols has been developed, which provides a rapid and efficient access to multisubstituted 1‐naphthols bearing an enal or enone moiety with high stereoselectivity. The (Z)‐ or (E)‐stereochemistry can be easily controlled by choosing protected‐ or non‐protected substrates. The utility of the methodology has been illustrated in the first total synthesis of wailupemycin G.     

Zn(II)/amine-catalyzed coupling reaction of alkylidenemalonates with propargyl alcohol: a one-pot synthesis of methylenetetrahydrofurans

[reaction: see text] A metal-catalyzed tandem 1,4-addition/cyclization between propargyl alcohol and a Michael acceptor, such as alkylidene malonate, has been developed. In the presence of catalytic amounts of zinc triflate [Zn(OTf)(2)] and triethylamine (Et(3)N), various 2-alkylidene-1,3-dicarbonyl compounds reacted with propargyl alcohol to give 3- or 4-methylene tetrahydrofurans in excellent yields.     

Zn/Y双金属接力催化:一锅法分子内环异构化/分子间阿尔德-烯反应构建α-羟基酰胺噁唑衍生物

报道了一种新型的Zn/Y双金属接力催化的串联反应,该方法通过Zn(OTf)₂和Y(OTf)₃接力催化,一锅法进行分子内环异构化/分子间阿尔德-烯反应构建α-羟基酰胺噁唑衍生物.产物的形成主要是由Zn(OTf)₂活化炔丙基酰胺的叁键发生分子内的环化反应构建噁唑啉中间体,由Y(OTf)₃催化1-苄基吲哚啉-2,3-二酮类化合物,继而由噁唑啉中间体与1-苄基吲哚啉-2,3-二酮类化合物发生分子间阿尔德-烯反应,实现了α-羟基酰胺噁唑衍生物的合成.优化部分的对比实验证实,Zn(OTf)₂和Y(OTf)₃的存在对于该串联反应都是必须条件.所有反应都是将各反应物和试剂一次性加入,在空气氛围下100℃加热进行反应.该方法反应条件简单、原子经济性高、官能团兼容性好,对噁唑衍生物合成具有重要的意义.     

Mercuric triflate-catalyzed reaction of propargyl acetates with water leading vinyl ketones

[reaction: see text]. Reaction of propargyl acetate with water catalyzed by Hg(OTf)2 afforded vinyl ketone as the major product along with a dimeric vinyl mercuric product and normal hydration products in small amounts. The reaction is an alternative to the Meyer-Schuster and Rupe rearrangement applicable to primary alcohols, although the mechanism is entirely different.     

Sequential allenylidene/vinylidene cyclization for stereoselective construction of bicyclic carbocycles from propargyl alcohol

Consecutive cyclization reactions of phenyl propargyl alcohols 1 and 2 are catalyzed by [Ru]NCCH(3)(+) ([Ru] = Cp(PPh(3))(2)Ru) in cosolvent CHCl(3)/MeOH at 60 °C, to afford the fused cyclic compounds 11a (R = Me) and 10a (R = Me), respectively.     

1,2-联烯基酮的合成与反应

1,2-联烯基酮可以通过2-丙炔基酮异构化反应,相应有机金属试剂中间体与酯、酰氯或酰胺的反应,[2,3]或[3,3]迁移反应,Wittig反应,消除反应,2,3-联烯醇氧化等方法合成。由于联烯酮上含有吸电子基团羰基,它可发生亲核加成、环加成、环化反应。     

Allenylphosphonates/allenylphosphine oxides as intermediates/precursors for intramolecular cyclization leading to phosphorus-based indenes, indenones, benzofurans, and isochromenes

Utilizing internally available functional groups, a simple protocol for the efficient synthesis of phosphorus-based indenes, indenones, benzofurans, and isochromenes via intramolecular cyclization of allene intermediates/precursors is generated; the latter intermediates/precursors are conveniently obtained through aldehyde-, alkylidene-, and hydroxyl-functionalized propargyl alcohols and P(III)-Cl precursors. The structures of key products have been unequivocally confirmed by X-ray crystallography.     

Zirconyl triflate: A new, highly efficient and reusable catalyst for acetylation and benzoylation of alcohols, phenols, amines and thiols with acetic and benzoic anhydrides

Highly efficient acetylation and benzoylation of alcohols, phenols, amines and thiols with acetic and benzoic anhydrides catalyzed by new and reusable zirconyl triflate, ZrO(OTf)₂, is reported. The high catalytic activity of electron deficient ZrO(OTf)₂ can be used for the acetylation and benzoylation of not only primary alcohols but also sterically-hindered secondary and tertiary alcohols with acetic and benzoic anhydrides. Acetylation of phenols with acetic and benzoic anhydrides was achieved to afford the desired acetates and benzoates efficiently. This catalyst also efficiently catalyzed the acetylation and benzoylation of amines and thiols whereby the corresponding amides and thioesters were obtained in good to excellent yields. This catalyst can be reused several times without loss of its activity.     

Cascade synthesis of 3-quinolinecarboxylic ester via benzylation/ propargylation-cyclization

Reactions of 2-amino-aryl alcohols with beta-ketoesters catalyzed by a catalytic amount of FeCl3 via tandem benzylation-cyclization produce the corresponding 3-quinolinecarboxylic esters in good to high yields. Extending this methodology to propargylation-cyclization, 2-nitrophenyl propargyl alcohols with beta-ketoesters catalyzed by FeCl3 and SnCl2 also produce the 4-alkyne-3-quinolinecarboxylic esters. The mechanistic details of this benzylation/propargylation and cyclization cascade process are also discussed.     

Formal total synthesis of (+)-lysergic acid via zinc(II)-mediated regioselective ring-opening reduction of 2-alkynyl-3-indolyloxirane

Asymmetric formal synthesis of (+)-lysergic acid was achieved with a reductive ring-opening reaction of chiral 2-alkynyl-3-indolyloxirane with NaBH(3)CN as the key step. With Zn(OTf)(2) as an additive, the ring-opening reaction proceeded regioselectively at the 3-position to give the corresponding propargyl alcohol, which was a precursor of the allenic amide for palladium-catalyzed domino cyclization to construct the ergot alkaloid core structure.     

Cu(I)-catalyzed cascade intramolecular cyclization of 2-propynol phenyl azides and diarylphosphine oxides for the synthesis of bisphosphorylated indole derivatives

The [Cu(OTf)]₂·C₆H₆ catalyzed cascade intermolecular addition–intramolecular cyclization reaction of easily prepared 2-propynol phenyl azides and diarylphosphine oxides was developed. This novel reaction leads to simultaneous formation of one C–N and two C–P bonds in a single step to give bisphosphorylated indole derivatives under mild conditions in moderate to good yields.     

Tuning the Reactivity of Isocyano Group: Synthesis of Imidazoles and Imidazoliums from Propargylamines and Isonitriles in the Presence of Multiple Catalysts

The reaction of propargyl amines with tert‐butylisonitrile in the presence of a catalytic amount of both Yb(OTf)₃ and AgOTf afforded imidazoles, whereas the same reaction with primary and secondary alkylisonitriles, as well as arylisonitriles, in the presence of three metal salts [Yb(OTf)₃/AgOTf/KOTf] resulted in the 1,3,4,5‐tetrasubstituted imidazoliums in excellent yields. Both chiral amines and chiral isonitriles can be used to provide corresponding chiral heterocycles without racemization. In this multiple catalytic system, Yb(OTf)₃ catalyzed the insertion of isonitriles to the N? H bond of amines, AgOTf catalyzed the 5‐exo‐dig cyclization of the resulting amidine nitrogen to the tethered triple bond, and KOTf promoted the salt metathesis, thus providing at the same time the counterion to the imidazolium. Against common knowledge, the isocyano group acted in these reactions as a polarized triple bond instead of conventional carbene‐like function.     

In(III)-catalyzed tandem reaction of chromone-derived Morita-Baylis-Hillman alcohols with amines

The reaction of chromone-derived cyclic Morita-Baylis-Hillman alcohols with amines catalyzed by In(OTf)(3) in a one pot process was developed for the convenient and efficient synthesis of 2-substituted-3-aminomethylenechromans. The tandem allylic amination/chromen ring-opening/Michael cyclization reactions were involved in this protocol.     

Solvent-free Zn(OTf)2-catalyzed dehydrative cross coupling of propargyl alcohols with diarylphosphine oxides to afford allenylphosphine oxides

Abstract

A less expensive and more environmentally friendly Zn(OTf)₂-catalyzed dehydrative coupling reaction of propargyl alcohols with diarylphosphine oxides is reported. The reaction takes place under mild and solvent free conditions, and features a high regioselectivity to provide an effective method for the synthesis of some diarylphosphinyl allenes in moderate to high yields.     

Regioselective annulation of propargyl alcohols with ambident-enols: A Ca(II)-catalyzed trisubstituted benzochromene synthesis

Highly regioselective, 6-endo cyclization between propargyl alcohols and ambident enols such as naphthols, 4-hydroxy coumarin, cyclohexane-1,3-dione, 5,5-dimethylcyclohexane-1,3-dione is described using Ca(OTf)₂ under solvent free conditions. The reaction proceeds through a cascade annulation which involves an etherification, Claisen type rearrangement, allene formation and endocyclization. Further, we extended this method to the synthesis of iodo-derivative and demonstrated the reactivity in cross-coupling reactions.     

Regio‐ and Chemoselective N‐1 Acylation of Indoles: Pd‐Catalyzed Domino Cyclization to Afford 1,2‐Fused Tricyclic Indole Scaffolds

A concise method for the synthesis of 1,2‐fused tricyclic indole scaffolds by domino cyclization involving a Pd‐catalyzed Sonogashira coupling, indole cyclization, regio‐ and chemoselective N‐1 acylation, and 1,4‐Michael addition is reported. This method provides straightforward access to tetrahydro[1,4]diazepino[1,2‐a]indole and hexahydro[1,5]diazocino[1,2‐a]indole scaffolds.