Alkynes hydroalkoxylation

An iridium(m) hydride catalyzed intramolecular alkyne hydroalkoxylation can be used to construct isochromans 545 bearing a C(3)-spiroacetal moiety (Equation 226) <2005OL5437>. Novel isochromans bearing an array of C(3)-spiroacetal moieties are accessible via the hydroboration of alkynediols with disiamylborane followed by treatment of the resulting alkenylboron compounds with alkaline hydrogen peroxide <1998CL81>. 

The hydroalkoxylation of an internal alkyne to afford a spiroacetal was first described by Utimoto in 1983 [85]. Using PdCl2 or PdCl2(PhCN)2 as catalyst, the spiroacetals 158 were obtained in high yield (Scheme 39). The method was not adopted as a general tool for the synthesis of spiroacetals for some time, with only a few reports exploiting the approach [86, 87]. Recent applications of palladium-catalyzed intramolecular alkyne hydroalkoxylation include syntheses of spirolaxine methyl ether [88] and enantiomers of the natural cephalosporoUdes [89]. 

R = n-Bu, isobutenyl, n-CgHij, Ph(CH2)4. cyclohexyl Scheme 49 Alkynes hydroalkoxylation... 

Li X, Chianese AR, Vogel T, Crabtree RH (2005) Intramolecular alkyne hydroalkoxylation and hydroamination catalyzed by iridium hydrides. Org Lett 7 5437-5440... 

Moreover, spiroketals are produced from tandem hydroalkoxylation of 4-alkynols (Scheme 15) [130]. Starting from diynediols, bis-spiroketals are obtained using Au (I) as catalysts [131]. Furthermore, Barluenga et al. reported the formation of spirocychc compounds in a tandem alkyne hydroalkoxylation [4 -1- 2] cycloaddition reaction [132, 133], together with a tandem intramolecular hydroalkoxylation of a triple bond followed by a Prins-type cyclization [129]. 

NHC-Pd(ll) complexes have also been used in tandem reactions involving a Sonogashira couphng and hydroalkoxylation of the resulting alkyne for the synthesis of benzofurans [131] as well as sequential Heck-Sonogashira couphngs [132] (Scheme 6.44). 

A large number of examples of the intramolecular hydroalkoxylation reaction of alkynes bearing pendant alcohols have been reported. In the reactions of enynols, the cyclization process has typically been accompanied by isomerization of the resulting enol ethers to give rise to furan or pyran products. These processes have been achieved using Pd(ll),294-297 Ru(n),298,299 Au(i),300 Au(m)286,300,301 Ir(i)302 Ir(m) 303 and Ag(i) 304 catalysts. Some examples are shown in Equations (83)-(87). 

Aside from alcohols, other oxygen nucleophiles have also participated in hydroalkoxylation reactions with alkynes. The most common of these are 1,3-dicarbonyl compounds, whose enol oxygens are readily available to add to alkynes. Cyclization reactions of this type have been carried out under Pd(0) catalysis with various aryl or vinyl iodides or triflates, often in the presence of CO, affording the corresponding furan derivatives (Equation (95)).337-340 A similar approach employing cyclic 1,3-diketones has also been reported to prepare THFs and dihydropyrans under Pd, Pt, or W catalysis.341 Simple l-alkyn-5-ones have also been isomerized to furans under the influence of Hg(OTf)2.342... 

Alkoxides that arise from simple carbonyl additions have also functioned as excellent in situ nucleophiles for intramolecular hydroalkoxylation reactions. Garbinols derived from the addition of allyltin reagents have proved to be potent nucleophiles in reactions of this type (Equation (99)),349 and this approach has also been used for the combined addition-cyclization of alkynals under Pd(n)350 or Cu(i)351 catalysis, and alkynones under Pd(n) catalysis.352... 

A few examples have recently appeared in the literature where epoxides can function as nucleophiles for the hydroalkoxylation of alkynes. Both AuC 353 and HgO354 in an acidic medium have been used as catalysts for this purpose (Equation (100)). 

Hydration and Hydroalkoxylation of Alkynes Gold compounds were first applied to catalyze these types of reactions by Utimoto et al. in 1991, when they studied the use of Au(III) catalysts for the effective activation of alkynes. Previously, these reactions were only catalyzed by palladium or platinum(II) salts or mercury(II) salts under strongly acidic conditions. Utimoto et al. reported the use of Na[AuCI41 in aqueous methanol for the hydration of alkynes to ketones [13]. 

A novel gold catalyzed example of three-component addition was recently reported by Shi et al. (Equation 8.44) [106]. Terminal aryl alkynes, alcohols and 2-(arylmethy-lene) cyclopropylcarbinols provided an intermolecular tandem hydroalkoxylation/ Prins-type reaction to form 3-oxabicyclo[3.1.0]hexanes from simple materials and under mild conditions, catalyzed by the system AuClPPh3/AgOTf. The proposed mechanism for this reaction is shown in Scheme 8.19. 

C-M bond addition, for C-C bond formation, 10, 403-491 iridium additions, 10, 456 nickel additions, 10, 463 niobium additions, 10, 427 osmium additions, 10, 445 palladium additions, 10, 468 rhodium additions, 10, 455 ruthenium additions, 10, 444 Sc and Y additions, 10, 405 tantalum additions, 10, 429 titanium additions, 10, 421 vanadium additions, 10, 426 zirconium additions, 10, 424 Carbon-oxygen bond formation via alkyne hydration, 10, 678 for aryl and alkenyl ethers, 10, 650 via cobalt-mediated propargylic etherification, 10, 665 Cu-mediated, with borons, 9, 219 cycloetherification, 10, 673 etherification, 10, 669, 10, 685 via hydro- and alkylative alkoxylation, 10, 683 via inter- andd intramolecular hydroalkoxylation, 10, 672 via metal vinylidenes, 10, 676 via SnI and S Z processes, 10, 684 via transition metal rc-arene complexes, 10, 685 via transition metal-mediated etherification, overview,... 

Intramolecular geometries, database studies, 1, 597 Intramolecular hydroalkoxylation, and etherification, 10, 672 Intramolecular pinacol coupling to cyclic 1,2-diols, 11, 51 with samarium reagents, 11, 60 Intramolecular silylformylation, alkynes and alkenes, 11, 489 Intramolecular solvomercuration alkenes, 2, 436 alkynes, 2, 439... 

Iridium(ni) hydrides, such as (98), proved to be air-stable active catalysts for intramolecular hydroalkoxylation and hydroamination of internal alkynes with proximate nucleophiles (e.g. 96). The cyclization follows the 6-endo-dig pathway with high preference (when regioselectivity is an issue).125... 

The transition metal-catalyzed addition of alcohols to unsaturated systems has not been widely investigated. Reports on addition of alcohols to 1,3-diene [24] or allene [25] have appeared but have very limited scope. We recently reported the palladium/benzoic acid-catalyzed inter- and intramolecular addition of alcohols to alkynes in which various acyclic and cyclic allylic ethers are produced [26], The Pd-catalyzed addition of alcohols to alkylidenecyclopropanes proceeds smoothly providing a powerful tool for synthesis of allylic ethers [27a]. An intramolecular version of the hydroalkoxylation has been demonstrated in which the phenol-tethered alkylidenecyclopropanes undergo facile cyclization to give exomethylene products [27b],... 

Transition metal-catalyzed addition of heteroatom-hydrogen bonds to alkynes in syntheses of cyclic amines and pyrroles by hydroamination reactions, in syntheses of O-heterocycles by hydroalkoxylation of alkynes, and in syntheses of S- and Se-heterocycles 04CRV3079. 

We reported that the intramolecular hydroamina-tion and hydroalkoxylation of the alkynes 285 in the presence of palladium/benzoic acid catalysts produced... 

Hydroalkoxylation of alkynes, or the addition of alcohol to alkynes, is a fundamental reaction in organic chemistry that allows the preparation of enol ethers and a variety of oxygen-containing heterocycles such as furan, pyran, and benzofuran derivatives. Bergbreiter et al. found that a Mnear poly-(A-isopropylacrylamide) (PNIPAM) polymer exhibited inverse temperature solubility in water (i.e., soluble in cold water but insoluble in hot water). A recoverable homogeneous palladium catalyst was prepared based on the polymer. The PNIPAM-bound Pd(0) catalyst was effective for the reaction of 2-iodophenol with phenylacetylene in aqueous THE media to give the target product... 

For alkynes (and in part, allenes), synthetically useful protocols for Markovnikov and anti-Markovnikov selective hydrations, hydroalkoxylations (mainly intramolecular), and hydrocarboxylations are available and find increasing applications in organic synthesis. In the past decade, the research focus on cationic gold(l) complexes has led to new additions to the catalysis toolbox. It can be predicted that a further refining of such tools for alkyne functionalization with respect to catalytic activity and functional group tolerance will take place. 

Catalyzed reactions of alkynes in water (particularly, s5mtheses of O-het-erocycles by hydroalkoxylation, N-heterocycles by hydroamination, syntheses of triazoles, imidazoles, furans, and hetero [2 + 2 + 2] tri-merizations) 06ASCI 459. 

Gold-catalyzed organic reactions, particularly, olefin epoxydation and hydroamination or hydroalkoxylation of alkynes to give N- or O-het-... 

Phenyl-1-propyne (55) underwent facile formal intermolecular hydroamination, affording the allylic amine 56 in high yield at 0 "C in the presence of AcOH or benzoic acid. In this reaction, at first, Pd-catalyzed isomerization of 55 to pheny-lallene (57) occurs by addition-elimination of H-Pd-OAc to internal alkyne 55, and then the allene 57 is converted to jr-allylpalladium intermediate 58 by hydropal-ladation. The final step is a well-known amination to produce the allylic amine 56. As an intramolecular version, 2-(2-phenylpropenyl)pyrrole (60) was obtained from l-phenyl-7-amino-l-hexyne 59 [16,16a]. Similarly Pd/benzoic acid-catalyzed hydroalkoxylation of 55 with (—)-menthol (61) afforded the allylic ether 62 [17]. 

Another very short route to racemic olean comes from Jef De Brabander, and is based on the platinum-catalysed intramolecular hydroalkoxylation of internal alkynes. Under optimised conditions, the 6-exo-dig/7-endo-dig ratio is more than 100 1. [218]... 

Representative procedure for the gold-catalyzed hydroalkoxylation of alkynes. Trans-2,5-dimethyl-2,5-dimethoxy-l, 4-dioxane ... 

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