Palladium catalysed tandem cyclisation–anion capture. Part 8: Cascade hydrostannylation—cyclisation–anion capture and cascade hydroboration—cyclisation–anion capture on solid phase

Up to four bonds and five stereocentres are created, in five component processes (five point diversity), utilising resin bound aryl iodides by hydroboration or hydrostannylation of alkynes, followed by cyclisation–anion capture involving Suzuki or Stille reactions. Three small libraries were prepared to validate the chemistry.     

Highly regio- and stereoselective hydrostannylation of alkynols with a new Lewis acidic hydrostannane

[reaction: see text] Bu2Sn(OTf)H (1a), easily prepared from Bu2SnH2 and TfOH, was found to be very valuable for highly regio- and stereoselective hydrostannylation of various propargyl alcohols leading to (Z)-gamma-stannylated allyl alcohols. The stannylation with 1a is applicable to the synthesis of hydroxy-substituted (Z)-vinylstannanes from terminal alkynes bearing a hydroxy group at the homoallylic or bishomoallylic position. The coordination of the hydroxy group to the Lewis acidic tin center plays an important role for the observed regio- and stereochemistry.     

Palladium-catalyzed hydrostannylations of highly hindered acetylenes in hexane

Hexane is particularly favorable as a solvent for hydrostannylation of hindered internal alkynes by minimizing the competing formation of H₂ and Bu₃SnSnBu₃. The optimum conditions involve Pd(OAc)₂ and a donor monophosphine (PCy₃) in hexane at 23°C.     

On the Hydrostannylation of Aryl Propargylic Alcohols and Their Derivatives: Remarkable Differences in Both Regio‐ and Stereoselectivity in Radical‐ and Nonradical‐Mediated Transformations

Herein, we describe a highly regio‐ and stereoselective radical‐mediated and molecular‐oxygen (O₂)‐dependent hydrostannylation of phenyl propargylic alcohols and their derivatives. There is a significant steric effect on the stereoselectivity of the tin‐radical addition. Further, the uncatalyzed regio‐ and stereoselective hydrostannylation of aryl propargylic alcohols with nBu₃SnH and Ph₃SnH is also described and occurs with near titration kinetics. Although the uncatalyzed addition with nBu₃SnH gave a remarkable γ‐regioselectivity irrespective of the electronic nature of the aryl moiety, addition with Ph₃SnH appears to be driven by the electronic nature of the aryl alkynes.     

经由三丁基锡化氢、炔基砜和炔基溴的锡氢化-Stille串联反应“一锅”立体选择合成( Z)-2-砜基取代的1,3-烯炔

炔基砜和三丁基锡化氢在四(三苯基膦)钯催化下于苯中室温下进行锡氢化反应4 h,经溶剂转换成DMF后,再在CuI助催化剂存在下与炔基溴化物于室温进行Stille偶联反应,以良好产率且立体选择性地合成了( Z)-2-砜基取代的1,3-烯炔。该“一锅”合成法具有起始原料易得、反应条件温和、操作简便、钯催化剂利用率高和产率好等优势。     

Ligand-free copper(Ι)-catalyzed Sonogashira-type coupling of arylboronic acids with terminal alkynes

An efficient ligand-free CuI-catalyzed Sonogashira-type coupling reaction of arylboronic acids with terminal alkynes under air is described. The electron-deficient alkynes gave the desired cross-coupling products in good yields. Thus, it represents a simple and alternative method for the traditional Sonogashira reaction.     

Silver‐catalyzed Glaser coupling of alkynes

Excellent yields were obtained from the silver nitrate‐catalyzed homocoupling reaction of alkynes in N,N‐dimethylformamide using triphenylphosphine as ligand. This safe and simple silver catalytic system has been employed in a safe and efficient protocol for the synthesis of various 1,3‐diyne products from the corresponding aromatic or aliphatic alkynes with good air stability and absence of side products. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis, characterization and primary evaluation of the synthetic efficiency of supported vinyltins and allyltins

Supported vinyltins and allyltins grafted to an insoluble cross-linked polystyrene matrix were prepared using methods usually employed in solution, like hydrostannylation of alkynes, transmetallation of a tin halide with organomagnesium or organozinc reagents, and substitution of an allyl halide by a supported stannylanion or S_N2′ substitution of a supported β-stannylacrolein acetal by cyanocopper reagents in the presence of boron trifluoride etherate. The insoluble grafted organotin reagents were analysed by HRMAS NMR, allowing an unambiguous assignment of their isomeric distribution or the identification of side products. When involved in Stille cross-coupling reactions (vinyltins) or in addition on aldehydes (allyltins), these supported reagents exhibit similar reactivity and similar stereoselectivity when compared to the tributyltin analogues, with the advantage to prevent problems due to the contamination by tin residues.     

Kinetic versus Thermodynamic Stereoselectivity in the Hydrostannylation of Propargylic Alcohol Derivatives Using AIBN and Et(3) B as Promotors

Et(3) B versus AIBN: Equally radical? The stereoselectivity of hydrostannylation of internal propargyl alcohol derivatives has been studied by using both 2-2'-azobisisobutyronitrile (AIBN) and Et(3) B as promoters. With silyl-protected alcohols, complete Z selectivity of the resultant vinylstannane has been achieved with Et(3) B, whereas AIBN shows zero stereoselectivity. Evidence suggests that, despite decades of acceptance, the hydrostannylation mechanisms employing Et(3) B and AIBN appear to be mechanistically distinct.     

Stille couplings catalytic in tin: the "Sn-O" approach.

A one-pot tandem Pd-catalyzed hydrostannylation/Stille coupling protocol for the stereoselective generation of vinyltins and their subsequent union, employing only catalytic amounts of tin, is described. By recycling the organotin halide Stille byproduct back to organotin hydride, a hydrostannylation/cross-coupling sequence can be carried out with catalytic amounts of tin. Such a process is most effective with Me(3)SnCl serving as the tin source. This protocol allows a 94% reduction of the tin requirement, while maintaining good yields (up to 90%) for a variety of Stille products. Furthermore, since one cycle requires the tin to undergo at least four transformations, each moiety of trialkyltin is experiencing a minimum of 60 reactions over the course of the hydrostannylation/Stille sequence.     

原子经济反应:氢氧化铯催化下二硒醚与端炔反应合成炔硒醚

氢氧化铯是无机超强碱,它能夺去端炔上的氢而产生稳定炔负离子,这种炔负离子与亲电的酮、醛反应生成相应的炔醇,但是与亲电的杂原子反应形成碳杂键的研究尚未见报道,碳杂键的形成是合成杂原子有机化合物的主要途径,所以研究无机超强碱催化下的碳杂键形成反应,有可能开辟-个合成杂原子有机化合物的新领域,不论在理论上还是在应用上都具有重要意义。     

DABCO作为高效配体促进钯催化末端炔烃自偶联反应研究

发展了一种以DABCO(1,4-diaza-bicyclo[2.2.2]octane)为配体高效钯催化末端炔烃自偶联反应方法.在醋酸钯(2 mol%)、碘化亚铜(2 mol%)、DABCO(4 mol%)、醋酸钠(3 mmol)、乙腈(5 mL)和空气氛等条件下,1 mmol的末端炔烃可以顺利发生自偶联反应生成相应的二炔化合物,产率为中等到良好.     

CuI‐catalyzed homocoupling of terminal alkynes to 1,3‐diynes

A simple and efficient protocol for CuI‐catalyzed oxidative homocoupling reaction of terminal alkynes to symmetrical 1,4‐disubstituted 1,3‐diynes was reported. The reaction can be carried out in the open air, using NaOAc as a base in the absence of any other additives. A variety of terminal alkynes were converted to the corresponding 1.3‐diynes in good to excellent yields without any side product formation. Copyright © 2010 John Wiley & Sons, Ltd.     

Iron/copper promoted oxidative homo-coupling reaction of terminal alkynes using air as the oxidant

An inexpensive catalytic system, which used a readily available Fe(acac)₃ and trace quantity of Cu(acac)₂ as the co-catalyst and air as the oxidant for the homo-coupling of terminal alkynes, has been developed. The catalytic system could also apply to the cross-coupling reaction of two different terminal alkynes.     

Ready access to organoiodides: Practical hydroiodination and double-iodination of carbon-carbon unsaturated bonds with I2

By using I₂ or I₂/H₃PO₃ system, various alkenes and alkynes were converted to the corresponding alkyl and alkenyl iodides in good yields. In the presence of I₂, alkynes could be di-iodinated using H₂O as the solvent in air at room temperature. This method also features the simple work-up procedure since the pure product could be obtained by extraction. Additionally, for the first time, combining with the non-toxic and cheap phosphonic acid H₃PO₃, alkenes and alkynes were also hydroiodinated successfully, which provides a simple and practical approach for synthesis of organoiodides.     

Indium (III) mediated Markovnikov addition of malonates and β-ketoesters to terminal alkynes and the formation of Knoevenagel condensation products

The indium(III) triflate mediated addition of active methylene compounds to terminal alkynes has been expanded to use malonates and low boiling terminal alkynes to form the Markovnikov addition products. Indium(III) chloride and indium(III) bromide were also found to be efficient catalysts. Knoevenagel condensation products were isolated when reactions involved a simple malonate or β-ketoester.     

Highly efficient and diastereoselective gold(I)-catalyzed synthesis of tertiary amines from secondary amines and alkynes: substrate scope and mechanistic insights

An efficient method for the synthesis of tertiary amines through a gold(I)‐catalyzed tandem reaction of alkynes with secondary amines has been developed. In the presence of ethyl Hantzsch ester and [{(tBu)₂(o‐biphenyl)P}AuCl]/AgBF₄ (2 mol %), a variety of secondary amines bearing electron‐deficient and electron‐rich substituents and a wide range of alkynes, including terminal and internal aryl alkynes, aliphatic alkynes, and electron‐deficient alkynes, underwent a tandem reaction to afford the corresponding tertiary amines in up to 99 % yield. For indolines bearing a preexisting chiral center, their reactions with alkynes in the presence of ethyl Hantzsch ester catalyzed by [{(tBu)₂(o‐biphenyl)P}AuCl]/AgBF₄ (2 mol %) afforded tertiary amines in excellent yields and with good to excellent diastereoselectivity. All of these organic transformations can be conducted as a one‐pot reaction from simple and readily available starting materials without the need of isolation of air/moisture‐sensitive enamine intermediates, and under mild reaction conditions (mostly room temperature and mild reducing agents). Mechanistic studies by NMR spectroscopy, ESI‐MS, isotope labeling studies, and DFT calculations on this gold(I)‐catalyzed tandem reaction reveal that the first step involving a monomeric cationic gold(I)–alkyne intermediate is more likely than a gold(I)–amine intermediate, a three‐coordinate gold(I) intermediate, or a dinuclear gold(I)–alkyne intermediate. These studies also support the proposed reaction pathway, which involves a gold(I)‐coordinated enamine complex as a key intermediate for the subsequent transfer hydrogenation with a hydride source, and reveal the intrinsic stereospecific nature of these transformations observed in the experiments.     

A Highly Efficient Dimeric Manganese‐Catalyzed Selective Hydroarylation of Internal Alkynes

We have developed a general and site‐predictable manganese‐catalyzed hydroarylation of internal alkynes in the presence of water, under an air atmosphere without the involvement of ligand. The unique catalytic feature of this reaction is highlighted by comparison with other widely used transition metal catalysts including palladium, rhodium, nickel, or copper. The simple operation, high efficiency and excellent functional group compatibility make this protocol practical for more than 90 structurally diverse internal alkynes, overcoming the influence of both electronic and steric effect of alkynes. Its exclusive regio‐ and chemoselectivity originates from the unique reactivity of the manganese‐based catalyst towards an inherent double controlled strategy of sterically hindered propargyl alcohols without the installing of external directing groups. Its synthetic robustness and practicality have been illustrated by the concise synthesis of bervastatin, a hypolipidemic drug, and late‐stage modification of complex alkynes with precise regioselectivity.     

A Highly Efficient Dimeric Manganese-Catalyzed Selective Hydroarylation of Internal Alkynes

We have developed a general and site-predictable manganese-catalyzed hydroarylation of internal alkynes in the presence of water, under an air atmosphere without the involvement of ligand. The unique catalytic feature of this reaction is highlighted by comparison with other widely used transition metal catalysts including palladium, rhodium, nickel, or copper. The simple operation, high efficiency and excellent functional group compatibility make this protocol practical for more than 90 structurally diverse internal alkynes, overcoming the influence of both electronic and steric effect of alkynes. Its exclusive regio- and chemoselectivity originates from the unique reactivity of the manganese-based catalyst towards an inherent double controlled strategy of sterically hindered propargyl alcohols without the installing of external directing groups. Its synthetic robustness and practicality have been illustrated by the concise synthesis of bervastatin, a hypolipidemic drug, and late-stage modification of complex alkynes with precise regioselectivity.     

Li+-catalyzed radical polymerization of simple terminal alkenes

Solutions of Li+ salts of highly alkylated derivatives of the monocarbadodecaborate anion in 1,2-dichloroethane catalyze the radical polymerization of simple terminal alkenes, dienes, and alkynes under ambient conditions, initiated by azoisobutyronitrile, di-tert-butyl peroxide, or atmospheric air.