- Regioselectivity Influences in Platinum-Catalyzed Intramolecular Alkyne O-H and N-H Additions
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The steric and electronic drivers of regioselectivity in platinum-catalyzed intramolecular hydroalkoxylation are elucidated. A branch point is found that divides the process between 5-exo and 6-endo selective processes, and enol ethers can be accessed in good yields for both oxygen heterocycles. The main influence arises from an electronic effect, where the alkyne substituent induces a polarization of the alkyne that leads to preferential heteroatom attack at the more electron-deficient carbon. The electronic effects are studied in other contexts, including hydroacyloxylation and hydroamination, and similar trends in directionality are predominant although not uniformly observed.
- Costello, Jeff P.,Ferreira, Eric M.
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supporting information
p. 9934 - 9939
(2019/12/24)
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- Catalytic and metal-free intramolecular hydroalkoxylation of alkynes
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Benzyltrimethylammonium hydroxide act as an efficient metal-free catalyst for the intramolecular hydroalkoxylation of alkynes. Notably, the use of microwave irradiation allowed reaction to operate in only two minutes. Under optimized reaction conditions, linear alkynes bearing aryl and heteroaryl substituents were successfully cyclized with good level of stereoselectivity.
- Jean, Alexandre,Rouden, Jacques,Maddaluno, Jacques,De Paolis, Micha?l,Blanchet, Jér?me
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p. 534 - 537
(2019/01/19)
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- S-Block cooperative catalysis: Alkali metal magnesiate-catalysed cyclisation of alkynols
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Mixed s-block metal organometallic reagents have been successfully utilised in the catalytic intramolecular hydroalkoxylation of alkynols. This success has been attributed to the unique manner in which these reagents can overcome the challenges of the reaction: namely OH activation and coordination to and then addition across a CC bond. In order to optimise the reaction conditions and to garner vital catalytic system requirements, a series of alkali metal magnesiates were enlisted for the catalytic intramolecular hydroalkoxylation of 4-pentynol. In a prelude to the main investigation, the homometallic magnesium dialkyl reagent MgR2 (where R = CH2SiMe3) was utilised. This reagent was unsuccessful in cyclising the alcohol into 2-methylenetetrahydrofuran 2a or 5-methyl-2,3-dihydrofuran 2b, even in the presence of multidentate Lewis donor molecules such as N,N,N′,N′′,N′′-pentamethyldiethylenetriamine (PMDETA). Alkali metal magnesiates MIMgR3 (when MI = Li, Na or K) performed the cyclisation unsatisfactorily both in the absence/presence of N,N,N′,N′-tetramethylethylenediamine (TMEDA) or PMDETA. When higher-order magnesiates (i.e., MI2MgR4) were employed, in general a marked increase in yield was observed for MI = Na or K; however, the reactions were still sluggish with long reaction times (22-36 h). A major improvement in the catalytic activity of the magnesiates was observed when the crown ether molecule 15-crown-5 was combined with sodium magnesiate Na2MgR4(TMEDA)2 furnishing yields of 87% with 2a:2b ratios of 95:5 after 5 h. Similar high yields of 88% with 2a:2b ratios of 90:10 after 3 h were obtained combining 18-crown-6 with potassium magnesiate K2MgR4(PMDETA)2. Having optimised these systems, substrate scope was examined to probe the range and robustness of 18-crown-6/K2MgR4(PMDETA)2 as a catalyst. A wide series of alkynols, including terminal and internal alkynes which contain a variety of potentially reactive functional groups, were cyclised. In comparison to previously reported monometallic systems, bimetallic 18-crown-6/K2MgR4(PMDETA)2 displays enhanced reactivity towards internal alkynol-cyclisation. Kinetic studies revealed an inhibition effect of substrate on the catalysts via adduct formation and requiring dissociation prior to the rate limiting cyclisation step.
- Fairley, Michael,Davin, Laia,Hernán-Gómez, Alberto,García-álvarez, Joaquín,O'Hara, Charles T.,Hevia, Eva
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p. 5821 - 5831
(2019/06/18)
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- Organothorium-catalyzed hydroalkoxylation/cyclization of alkynyl alcohols. Scope, mechanism, and ancillary ligand effects
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Organothorium complexes bearing amide or alkyl proligands are active toward the highly selective hydroalkoxylation/cyclization of alkynyl alcohols. Substrates include primary and secondary alcohols, as well as terminal and internal alkynes. Catalysts with strongly binding ligation such as pentamethylcyclopentadienyl (Cp* = C5Me5) or constrained geometry catalysts (CGC = Me2Si(η 5-Me4C5)(tBuN)) remain soluble throughout the reaction, with the more sterically open (CGC)Th(NMe 2)2 (1) exhibiting higher activity than Cp*2Th(CH2TMS)2 (2). The use of precatalyst [(Me3Si)2N]2Th[κ2- (N,C)-CH2Si(CH3)2N(SiMe3)] (3) leads to precipitation upon the addition of alcohol substrates, although catalytic activity is retained. The substrate scope for 1 includes primary and secondary alcohols as well as terminal and internal alkynes. In situ1H NMR spectroscopic monitoring indicates that the rate law is zero-order in [substrate] and first-order in [catalyst]. The rates of primary alcohols and terminal alkynes are significantly more rapid than their more sterically hindered counterparts, suggesting that steric demands dominate the hydroalkoxylation/cyclization transition state. Turnover frequencies as high as 49 h-1 at 60 C are observed, producing exclusively the exo-methylene products. For internal alkyne substrates, alkenes with E-orientation are formed with complete selectivity. Activation parameters ΔH? = 27.9(0.4) kcal/mol, ΔS? = -3.0(1.1) eu, and E a = 28.6(0.4) kcal/mol are largely in accord with observations for other f-element-mediated insertive hydroelementation processes, and an ROH/ROD kinetic isotope effect of 0.97(0.02) is observed. The reactivity patterns, kinetics, and activation parameters are consistent with a pathway proceeding via turnover-limiting alkyne insertion into the Th-O bond, with subsequent, rapid Th-C protonolysis, regenerating the initial Th-OR species.
- Wobser, Stephen D.,Marks, Tobin J.
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p. 2517 - 2528
(2013/06/27)
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- Alkaline earth catalysis of alkynyl alcohol hydroalkoxylation/cyclization
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Heavier alkaline earth bis(trimethylsilyl)amides [Ae{N(SiMe 3)2}2]2 (Ae = Ca, Sr, Ba) are shown to act as effective precatalysts for the regioselective intramolecular hydroalkoxylation/cyclization of a wide range of alkynyl and allenyl alcohols. In the majority of cases, cyclization of alkynyl alcohols produces mixtures of the possible endo- and exocyclic enol ether products, rationalized as a consequence of alkynylalkoxide isomerization to the corresponding allene derivatives. Cyclization rates for terminal alkynyl alcohols were found to be significantly higher than for substrates bearing internal alkynyl substituents, while the efficacy of cyclization was in general found to be determined by a combination of stereoelectronic influences and the thermochemical viability of the specific alkaline earth metal catalysis, which we suggest is determined by the individual M-O bond strengths. Kinetic studies have provided a rate law pertaining to a pronounced catalyst inhibition with increasing [substrate], indicating that turnover-limiting insertion of C-C unsaturation into the M-O bond requires the dissociation of substrate molecules away from the Lewis acidic alkaline earth center.
- Brinkmann, Christine,Barrett, Anthony G. M.,Reid, Stephanie,Hill, Michael S.,Procopiou, Panayiotis A.
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p. 7287 - 7297,11
(2020/09/02)
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- Intramolecular hydroalkoxylation/cyclization of alkynyl alcohols mediated by lanthanide catalysts. Scope and reaction mechanism
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Lanthanide-organic complexes of the general type Ln[N(SiMe 3)2]3 (Ln = La, Sm, Y, Lu) serve as effective precatalysts for the rapid, exoselective, and highly regioselective intramolecular hydroalkoxy- lation/cyclization of primary and secondary alkynyl alcohols to yield the corresponding exocyclic enol ethers. Conversions arehighly selective with products distinctly different from those generall y produced by conventional transition metal catalysts, and turnover frequencies as high as 52.8 h-1 at 25 °C are observed. The rates of terminal alkynl alcohol hydroalkoxylation/cyclization are significantly more rapid than those of internal alkynyl alcohols, arguing that steric demands dominate the cyclization transition state. The hydroalkoxylation/cyclization of internal alkynyl alcohols affords excellent E -selectivity. The hydroalkoxylation/ cyclization of the SiMe3-terminated internal alkynyl alcohols reveals interesting product profiles which include the desired exocyclic ether, a SiMe3-eliminatedexocyclic ether, and the SiMe3-O- functionalized substrate. The rate law for alkynyl alcohol hydroalkoxylation/ cyclization is first -order in [catalyst] and zero-order in [alkynyl alcohol], as observed inthe intramolecular hydroamination/cyclization of aminoalkenes, aminoalk ynes, and aminoallenes. An ROH/ROD kinetic isotope effect of 0.95(0.03) is observed for hydroalkoxy- lation/cyclization. These mechanistic data implicate turnover-limiting insertion of C-C unsaturation into the Ln-O bond, involving a highly organized transition state, with subsequent, rapid Ln-C protonolysis.
- Seo, SungYong,Yu, Xianghua,Marks, Tobin J.
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supporting information; experimental part
p. 263 - 276
(2009/06/28)
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- Intramolecular meta photocycloaddition of conformationally restrained 5-phenylpent-1-enes. Part II: Steric and electronic effects caused by 4-mono- and 4-disubstitution
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The meta photocycloaddition of 4-substituted 5-phenylpent-1-enes. 10-18, has been studied. The monosubstituted derivatives always prefer 2,6 addition, independent of the size of the substituent. For 2,6 addition two basic conformations are possible. Disubstituted compounds yield predominantly 1,3 addition with the sterically more demanding group exo. Except for the methoxymethyl and THF derivative the oxygen is found exo as a result of repulsion, while the monohydroxy derivative gives also endo which might be explained by hydrogen bonding. The products from compound 11 change from mainly endo-OH in cyclohexane to chiefly exo-OH in methanol. Much similarity is found with Diels-Alder cycloaddition.
- Barentsen, Helma M.,Sieval, Alex B.,Cornelisse, Jan
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p. 7495 - 7520
(2007/10/02)
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- The Preparation of (α-Alkylidene)tetrahydrofuran by Tungsten Catalyzed Decarboxylation of Aldol Precursors
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A series of substituted (α-alkylidene)tetrahydrofurans was prepared by tungsten catalyzed reaction of substituted hydroxyfuroic acids.These reactions likely involve β-lactone intermediates which decarboxylate under the reaction conditions, and rates for o
- Tanzawa, Tomoya,Schwartz, Jeffrey
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p. 6783 - 6786
(2007/10/02)
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- Intramolecular Oxypalladation and Cross-Coupling of Acetylenic Alkoxides
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Stereodefined 2-alkylidenetetrahydrofurans and pyrans were synthesized by treatment of alkyl or aryl acetylenic alcohols with n-BuLi in THF at 0 deg C followed by addition of a solution of 10 mol percent of Pd(OAc)2 or PdCl2 and PPh3 in THF and 1 equiv of
- Luo, Fen-Tair,Schreuder, Inessa,Wang, Ren-Tzong
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p. 2213 - 2215
(2007/10/02)
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