Tunable Gold-catalyzed Reactions of Propargyl Alcohols and Aryl Nucleophiles

Gold-catalyzed transformations of 1,3-diarylpropargyl alcohols and various aryl nucleophiles were studied. Selective tunable synthetic methods were developed for 1,1,3-triarylallenes, diaryl-indenes and tetraaryl-allyl target products by C3 nucleophilic substitution and subsequent intra- or intermolecular hydroarylation, respectively. The reactions were scoped with regards to gold(I)/(III) catalysts, solvent, temperature, and electronic and steric effects of both the diarylpropargyl alcohol and the aryl nucleophiles. High yields of triaryl-allenes and diaryl-indenes by gold(III) catalysis were observed. Depending on the choice of aryl nucleophile and control of reaction temperature, different product ratios have been obtained. Alternatively, tetraaryl-allyl target products were formed by a sequential one-pot tandem process from appropriate propargyl substrates and two different aryl nucleophiles. Corresponding halo-arylation products (I and Br; up to 95 % 2-halo-diaryl-indenes) were obtained in a one-pot manner in the presence of the respective N-halosuccinimides (NIS, NBS).     

Enantiodivergent Chemoenzymatic Dynamic Kinetic Resolution: Conversion of Racemic Propargyl Alcohols into Both Enantiomers

Natural lipases typically recognize enantiomers of alcohols based on the size differences of substituents near the carbinol moiety and selectively react with the R enantiomers of secondary alcohols. Therefore, lipase-catalyzed dynamic kinetic resolution (DKR) of racemic secondary alcohols produces only R enantiomers. We report herein a method for obtaining S enantiomers by DKR of secondary 3-(trialkylsilyl)propargyl alcohols by using a well-known R-selective Pseudomonas fluorescens lipase in combination with a racemization catalyst VMPS4, in which the silyl group reverses the size relationship of substituents near the carbinol moiety. We have already reported R-selective DKR of the corresponding propargyl alcohols without substituents on the ethynyl terminal carbon, and the presence of an easily removable silyl group has enabled us to produce both enantiomers of propargyl alcohols in high chemical yields and with high enantiomeric excess. In addition, immobilization of the lipase on Celite was found to be important for achieving a high efficiency of the DKR.     

Cyclisation versus 1,1‐Carboboration: Reactions of B(C6F5)3 with Propargyl Amides

A series of propargyl amides were prepared and their reactions with the Lewis acidic compound B(C₆F₅)₃ were investigated. These reactions were shown to afford novel heterocycles under mild conditions. The reaction of a variety of N‐substituted propargyl amides with B(C₆F₅)₃ led to an intramolecular oxo‐boration cyclisation reaction, which afforded the 5‐alkylidene‐4,5‐dihydrooxazolium borate species. Secondary propargyl amides gave oxazoles in B(C₆F₅)₃ mediated (catalytic) cyclisation reactions. In the special case of disubstitution adjacent to the nitrogen atom, 1,1‐carboboration is favoured as a result of the increased steric hindrance (1,3‐allylic strain) in the 5‐alkylidene‐4,5‐dihydrooxazolium borate species.     

Gold‐Catalyzed Cyclization of Furan‐Ynes bearing a Propargyl Carbonate Group: Intramolecular Diels–Alder Reaction with In Situ Generated Allenes

Gold‐catalyzed cyclization of various furan‐ynes with a propargyl carbonate or ester moiety results in the formation of a series of polycyclic aromatic ring systems. The reactions can be rationalized through a tandem gold‐catalyzed 3,3‐rearrangement of the propargyl carboxylate moiety in furan‐yne substrates to form an allenic intermediate, which is followed by an intramolecular Diels–Alder reaction of furan and subsequent ring‐opening of the oxa‐bridged cycloadduct. It was found that the steric and electronic properties of phosphine ligands on the gold catalyst had a significant impact on the reaction outcome. In the case of 1,5‐furan‐yne, the cleavage of the oxa‐bridge in the cycloadduct with concomitant 1,2‐migration of the R¹ group occurs to furnish anthracen‐1(2H)‐ones bearing a quaternary carbon center. For 1,4‐furan‐yne, a facile aromatization of the cycloadduct takes place to give 9‐oxygenated anthracene derivatives.     

Platinum‐Catalyzed Multi‐Step Reaction of Propargyl Alcohols with N‐Heteroaromatics

N‐Methyl indole reacts with but‐2‐yn‐1‐ol in the presence of PtCl₂ in MeOH giving indole derivatives having a substituted 3‐oxobutyl group at the 3‐position in good yield. Under the reaction conditions, various substituted indoles and substituted propargyl alcohols are successfully involved in the reaction giving the corresponding addition products in good to moderate yields. The catalytic reaction can be further extended to N‐phenyl pyrrole. In the present multi‐step reaction, PtCl₂ likely plays dual roles: as the catalyst for the rearrangement of propargyl alcohols to the corresponding alkenyl ketones and as the catalyst for the addition of indoles to the alkenyl ketones. Experimental evidence is provided to support the proposed mechanism.     

Cyclization Reactions of Aryl Propargyl Acetates with Tethered Epoxide Induced by Ruthenium Complex

Reactions of the ruthenium complex [Ru]Cl ([Ru]=Cp(PPh₃)₂Ru; Cp=η⁵‐C₅H₅) with several aryl propargyl acetates, each with an ortho ‐substituted chain of various length containing an epoxide on the aromatic ring and with or without methyl substitutents on the epoxide ring, bring about novel cyclizations. The cyclization reactions of HC≡CCH(OAc)(C₆H₄)CH₂(RC₂H₂O) (R=H, 6 a ; R=CH₃, 6 b , where RC₂H₂O is an epoxide ring) in MeOH give the vinylidene complexes 5 a – b , respectively, each with the Cβ integrated into a tetrahydro‐5H ‐benzo[7]annulen‐6‐ol ring. A C−C bond formation takes place between the propargyl acetate and the less substituted carbon of the epoxide ring. Further cyclizations of 5 a – b induced by HBF₄ give the corresponding vinylidene complexes 8 a – b each with a new 8‐oxabicyclo‐[3.2.1]octane ring by removal of a methanol molecule in high yield. For similar aryl propargyl acetates with a shorter epoxide chain, the cyclization gives a mixture of a vinylidene complex with a tetrahydronaphthalen‐1‐ol ring and a carbene complex with a tricyclic indeno‐furan ring. For the cyclization of 18 , with a longer epoxide chain, opening of the epoxide is required to afford the vicinal bromohydrin 22 , then tandem cyclization occurs in one pot. Products are characterized by spectroscopic methods as well as by XRD analysis.     

Gold(I)‐Catalyzed 1,2‐Acyloxy Migration/[3+2] Cycloaddition of 1,6‐Diynes with an Ynamide Propargyl Ester Moiety: Highly Efficient Synthesis of Functionalized Cyclopenta[b]indoles

A gold‐catalyzed cycloisomerization of 1,6‐diynes containing an ynamide propargyl ester or carbonate moiety has been developed that provides an attractive route to a diverse‐substituted 3‐acyloxy‐1,4‐dihydrocyclopenta[b]indoles. Mechanistic studies indicate that the reaction likely proceeds through a competitive 1,2‐OAc migration followed by [3+2] cycloaddition of the vinyl gold–carbenoid intermediate with the pendant triple bond. The synthetic utility of the obtained cyclopenta[b]indole products was demonstrated by their efficient transformations by deprotection or double‐bond isomerization reactions.     

Development and application of latent hydrosilylation catalysts [2]—Control of catalytic activity of platinum catalyst by polystyrene derivatives having propargyl moieties

A new thermal latent hydrosilylation catalyst on the basis of H₂PtCl₆ and polystyrene derivatives having propargyl moieties is described. The polystyrene derivatives having various propargyl moieties were obtained by the reaction of propargyl alcohols with poly(p‐chloromethylstyrene) or its copolymer with styrene. The polymer‐supported platinum catalysts were prepared by aging H₂PtCl₆ with these polymers in tetrahydrofuran at 30 °C for 12 h. In the presence of the polymers, the hydrosilylation activity of H₂PtCl₆ was found to be controlled thermally in the model reaction of trimethylsilane and triethylvinylsilane. Effective control of the crosslinking reaction of silicone resin was also achieved by using these latent catalyst systems. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 35–42, 2000     

Ruthenium‐Catalyzed Cascade Annulation of Indole with Propargyl Alcohols

Cascade transformations forming multiple bonds and one‐pot procedures provide rapid access to natural‐product‐like scaffolds from simple precursors. These atom‐economic processes are valuable tools in organic synthesis and drug discovery. Herein, we report on ruthenium‐catalyzed cascade annulations of indole with readily available propargyl alcohols. These provide rapid access to diverse carbazoles, cyclohepta[b]indoles, and further fused polycycles with high selectivity. A bifunctional ruthenium complex featuring a redox‐coupled cyclopentadienone ligand acts as a common catalyst for the different cascade processes.     

锡-铟促进和微波辐射辅助下醛和炔丙基溴的炔丙基化反应

A rapid and regioselective preparation of homopropargyl alcohols was reported. In the presence of SnCl2C6HsMe3NBr and microwave irradiation, the mixture of tin-indium and propargyl bromide reacted quickly with aldehydes in aqueous media to produce the homopropargyl alcohols exclusively in high yields. For benzaldehydes bearing different substituents, electronic effect of the substituents affected the reaction, the electron-withdrawing groups promoting the reaction and the electron-donating groups impeding the reaction. The reactions of benzaldehydes bearing an ortho substituent group on the phenyl ring with propargyl bromide may yield a mixture of regioisomers （homopropargyl and homoallenyl alcohols） or a single homoallenic alcohol due to the steric effect.     

New Application of N-Halosuccinimide/PPh3 for the Halogenation of Propargyl Alcohols to Haloallenes

An efficient and convenient new method has been developed for the preparation of haloallenes from propargyl alcohols by a reagent combination of N-halosuccinimide and triphenylphosphine. Chloroallenes 2 and bromoallenes 3 were obtained exclusively in moderate to good yields with regioselectivity.     

激发态Ti＋(3d14s2)与丙炔醇气相反应理论研究

用量子化学密度泛函(DFT)方法研究了激发态Ti^＋(3d¹4s²)与丙炔醇(PPA)气相反应的机理. 在B3LYP/DZVP水平上, 优化了反应的两个通道的反应物、中间体、过渡态和产物的几何构型, 并在MP4/[6-311＋G**(C,H,O)＋Lanl2dz (Ti)]水平上计算了各驻点的单点能量. 为了确证过渡态的真实性, 在B3LYP/DZVP水平上进行了内禀坐标(IRC)计算和频率分析, 获得了二重态反应势能面, 确定了反应机理. 研究结果表明生成产物为[C₃H₃O]^＋和Ti—H的通道是主要反应途径.     

Synthesis and neurotropic activity of silyl propargyl alcohols and sulfides

New silicon derivatives of hetaryl propargyl sulfides and propargyl alcohols were synthesized using phase‐transfer catalytic and organometallic methods. These compounds were tested for acute toxicity and neurotropic activity in the pentylenetetrazole test, and for phenamine hypothermia, phenamine hyperactivity and passive avoidance response tests. We have found that the silyl propargyl alcohols and sulfides are low toxicity compounds, the LD₅₀ being 700–1300 mg kg^?1. In the PAR test, the synthesized compounds exerted some memory‐improving activity. For di‐1‐(3‐methyl‐3‐hydroxybutyn‐1‐yl)methyl(3‐iodopropyl)silane ( 16 ) the effect was statistically significant and amounted to 250% of the control level. In the pentylenetetrazole test, all compounds possessed anticonvulsant activity, the most active compounds being 3‐(benzoxazolylthio)‐1‐propynyl(trimethyl)silane ( 6 ) and di‐[2‐(1‐hydroxycyclohexyl)ethynyl]methyl(3‐iodopropyl)silane ( 17 ). The phenamine‐induced hyperactivity was significantly elevated after treatment with (3‐trimethylsilyl‐2‐propynyl)thiobenzene ( 1 ) or di‐[1‐(3‐methyl‐3‐hydroxybutyn‐1‐yl)diphenylsilane ( 12 ). Our data show that these silicon derivatives of hetaryl propargyl sulfides and propargyl alcohols possess certain memory improving and anticonvulsant activity that should be studied in detail to evaluate the receptor systems involved. Copyright © 2004 John Wiley & Sons, Ltd.     

Reversal of Regioselectivity of Nitrone Cycloadditions by Lewis Acids

The regio‐ and stereoselectivity of cycloadditions of the nitrone 1a and the chiral, sugar‐derived nitrones 13a and 13b with 3‐(prop‐2‐enoyl)‐1,3‐oxazolidin‐2‐one ( 2 ) depends on the nature of the Lewis acid catalyst used. Addition of Lewis acid reverses the regioselectivity of the cycloaddition, and improves the anti‐diastereoselectivity in the case of chiral nitrones. The sterically favored isoxazolidin‐5‐yl‐substituted adducts 3, 4 , and 14 – 17 are produced as the major products in the absence of Lewis acid, while the electronically favored regioisomers with isoxazolidin‐4‐yl substituents ( 5, 6 , and 18 – 21 , respectively) are obtained as major products in the [Ti(OⁱPr)₂Cl₂] catalyzed reactions. The reactions of nitrone 13b with 2 in the presence of other Lewis acids such as ZnCl₂, ZnBr₂, ZnI₂ and MgI₂/I₂ gave both regioisomeric pairs of the diastereoisomers, favoring the 4‐substituted congeners. The diastereoisomeric isoxazolidines 3a – 6a were reduced with NaBH₄ in THF/H₂O with subsequent desilylation to yield the separable diols 9 – 12 . Reduction of the diastereoisomeric isoxazolidines 19a and 18a afforded the chiral alcohols 23 and 22 , the latter of which was analyzed by X‐ray crystallography.     

Preparation of Propargyl-terminated Polylactide by the Bulk Ring-opening Polymerization

Propargyl-terminated polylactide was prepared by bulk ring-opening polymerization of L-lactide (LLA) at 105°C in the presence of 3-methyl-1-pentyn-3-ol as the initiator and Sn(Oct)₂ as the catalyst. A significant decline of the alkynes chain-end functionality was observed by ¹H NMR even at the early stage of the polymerization. The most probable reason is the intermolecular oxidative coupling of the propargyl end groups. Propargyl-terminated polylactide having higher chain-end functionality (f = 86%) and low polydispersity (PDI = 1.22) was prepared with the addition of N,N,N′,N″,N″-pentamethyldiethylenetriamine, whose huge steric hindrance provides the protective effect of propargyl groups.     

Silver(I)‐Promoted Radical Sulfonylation of Allyl/Propargyl Alcohols: Efficient Synthesis of γ‐Keto Sulfones

An efficient Ag₂CO₃‐promoted sulfonylation of allyl/propargyl alcohols with sodium sulfinates has been developed. The reaction tolerates a wide range of functional groups to deliver γ‐keto sulfones in high yields (up to 93 %). Propargyl alcohols furnished trimerization product 1,3,5‐triaroylbenzenes in the presence of sodium methanesulfinate under the standard conditions. A mechanism involving a sulfonyl radical was suggested.     

Theoretical Study on the Mechanism of the Gas-phase Reaction of Sc＋ with Propargyl Alcohol

In order to elucidate the reaction mechanisms of reaction Sc^＋ with propargyl alcohol (PPA), the triplet potential energy surface for the reactions has been theoretically investigated using a DFT method. The geometries for the reactants, intermediates, transition states and products were completely optimized at B3LYP/DZVP level. The single point energy of each stationary point was calculated at MP4/(6-311＋G** for C, H, O and Lanl2dz for Sc^＋) level. All the transition states were verified by the vibrational analysis and the internal reaction coordinate (IRC) calculations. The present results show that the reaction takes an insertion-elimination mechanism both along the O—H and C—O bond activation branches, but the C—O bond activation is much more favorable in energy than the O—H bond activation. All theoretical results not only support the existing conclusions inferred from early experiment, but also complement the pathway and mechanism for this reaction.     

Construction of Optically Active Quaternary Propargyl Amines by Highly Enantioselective Zinc/BINOL‐Catalyzed Alkynylation of Ketoimines

A general and efficient method for the highly enantioselective alkynylation of ketoimines through a zinc/1,1′‐bi‐2‐naphthol (BINOL)‐catalyzed process has been developed. A variety of ketoimines, including α‐fluoroalkyl α‐imine esters, α‐aryl α‐imine esters, and trifluoromethyl aryl ketoimines, are applicable and provide their corresponding quaternary propargyl amines in excellent yields with high ee values (up to 99 % ee). Both the steric and electronic effects of substituents at the 3,3′ positions of BINOL are critical for the reaction efficiency and enantioselectivity. To demonstrate the usefulness of the method, (R)‐α‐CF₃ α‐proline has been prepared in a highly efficient manner. The notable features of this protocol are its broad substrate scope, high reaction efficiency (up to 99 %) and enantioselectivity (up to 99 % ee), low catalyst loading (5 mol % of BINOL derivative), and mild reaction conditions.     

Heterogeneous gold(I)-catalyzed three-component reaction of aldehydes,alkynes, and orthoformates toward propargyl ethers

Abstract

A novel and efficient heterogeneous gold(I)-catalyzed three-component reaction of aldehydes, alkynes, and orthoformates has been developed that proceeds smoothly in dichloroethane (DCE) at 83?°C in the presence of 5?mol% magnetic nanoparticles-anchored phosphine gold(I) complex (Fe₃O₄@SiO₂-P-AuOTf) and offers a general and practical approach for the preparation of a variety of propargyl ethers with good yields. This heterogeneous gold(I) catalyst can be facilely recovered by simply applying an external magnetic field and recycled at least eight times without any apparent decrease in the catalytic efficiency.     

Unprecedented Spectroscopic and Computational Evidence for Allenyl and Propargyl Titanocene(IV) Complexes: Electrophilic Quenching of Their Metallotropic Equilibrium

The synthesis and structural characterization of allenyl titanocene(IV) [TiClCp₂(CH=C=CH₂)] 3 and propargyl titanocene(IV) [TiClCp₂(CH₂?C≡C?(CH₂)₄CH₃)] 9 have been described for the first time. Advanced NMR methods including diffusion NMR methods (diffusion pulsed field gradient stimulated spin echo (PFG‐STE) and DOSY) have been applied and established that these organometallics are monomers in THF solution with hydrodynamic radii (from the Stokes–Einstein equation) of 3.5 and 4.1 Å for 3 and 9 , respectively. Full ¹H, ¹³C, Δ¹H, and Δ¹³C NMR data are given, and through the analysis of the Ramsey equation, the first electronic insights into these derivatives are provided. In solution, they are involved in their respective metallotropic allenyl–propargyl equilibria that, after quenching experiments with aromatic and aliphatic aldehydes, ketones, and protonating agents, always give the propargyl products P (when carbonyls are employed), or allenyl products A (when a proton source is added) as the major isomers. In all the cases assayed, the ratio of products suggests that the metallotropic equilibrium should be faster than the reactions of 3 and 9 with electrophiles. Indeed, DFT calculations predict lower Gibbs energy barriers for the metallotropic equilibrium, thus confirming dynamic kinetic resolution.