Intramolecular hydroalkoxylation

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). 

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... 

The Trost group has disclosed two methods of rhodium vinylidene-mediated hydrofunctionalization (i) intramolecular hydroalkoxylation of alkynols and... 

Lee and coworkers went on to show that the concept of alkenylidene formation and functionalization by a single catalyst can be applied to other transformations. Under conditions similar to those reported by Trost and coworkers for vmylidene-mediated catalytic intramolecular hydroalkoxylation (see Section 9.2.3), alcohol 111 was transformed into a mixture of enol ethers with moderate selectivity for three-component coupling (Equation 9.9). 

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... 

Electron-rich phenols react with isoprene in ionic liquids and with added Sc(OTf)3 to give 2,2-dimethylchromans <07SL3050>. Ionic liquids also promote the one-pot synthesis of 4-arylchromans from benzaldehydes, phenols and allyl bromide which involves sequential Barbier allylation, Friedel-Crafts alkylation and an intramolecular hydroalkoxylation <07SL1357>. 

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]... 

For example, the bimetallic Au catalyst 36 was shown to catalyse the intramolecular hydroalkoxylation of allene alcohols with exceptional enantios-electivity (>93% ee) (Scheme 15c). 

FIGURE 7.15 Intramolecular hydroalkoxylation of unactivaled hydroxy olefins promoted by the hexameric capsule of resorcin[4]arene through encapsulation compared to triflic acid... 

Catti L, Tiefenbacher K. Intramolecular hydroalkoxylation catalyzed inside a self-assembled cavity of an enzyme-like host structure. Chem Commun 2015 51 892-4. 

Ln[N(SiMe3)2]3 (Ln = La, Sm, Y, Lu) can serve as effective precatalysts for the rapid, exoselective, and highly regioselective intramolecular hydroalkoxylation/cyclization of primary and secondary aUcynyl alcohols to yield the... 

Dzudza, A. and Marks, T.J., Efficient intramolecular hydroalkoxylation of unactivated alkenols mediated by recyclable lanthanide triflate ionic liquids scope and mechanism, Chem. Eur. J. 16, 3403-3422 (2010). 

Scheme 31.2 (a) General scheme for the intramolecular hydroalkoxylation of inactivated hydroxyl olefins and (b) substrate selectivity imposed by the 6e hexamer on the reaction [54b]... 

Recently, Pt DENs were used as an electrophilic catalyst in an intramolecular addition of phenols to alkynes (intramolecular hydroalkoxylation), as shown in Fig. 4.13b [100], The Pt DENs were supported on a mesoporous silica material known as SBA-15 (Fig. 4.13a). Since the as-synthesized SBA-15 consists of micrometer-sized particles, the supported Pt DENs can be easily separated from the reaction solution by centrifugation. This reaction has only been catalyzed by homogeneous catalysts (e.g., PtCy before this report. The use of the supported Pt DENs to catalyze this reaction was the first demonstration that a heterogeneous catalyst could also catalyze this conversion. It was also found that adding an oxidation agent, PhICF, would dramatically increase the benzofuran yield from 10 to 98 %, as shown in Fig. 4.13b. The authors proposed that PhICl2 could render the surface of the Pt nanoparticles more electrophilic, which is required for the Pt DENs to be active for the hydroalkoxylation reaction. 

The authors also designed and performed extensive experiments, such as three-phase and catalyst filtration tests, to prove the heterogeneous nature of the SBA-15 supported Pt DENs in the intramolecular hydroalkoxylation reaction. No leaching of the active catalytic species was detected in these tests. PVP-capped Pt nanoparticles were also tested for use in this reaction, but they could not be recycled. 

Pd DENs also catalyzed the same intramolecular hydroalkoxylation reaction [101]. SBA-15 supported Pd DENs achieved 95 % yield of benzofuran in 15 h at 20 °C, while PdBr2 and PdCla only achieved 10 % yield under the same conditions. Even at 100 °C, PdCl2 only gave 25 % yield of benzofuran after 15 h. After proving that there is no leaching of Pd during the reaction, the SBA-15 supported Pd DENs were applied in a continuous flow reactor. It was found that the presence of 5 tnM... 

Scheme 2.13 Tandem ring-opening isomerization/intramolecular hydroalkoxylation.

E. Perez-Mayoral, I. Matos, P. NachfigaU, M. Polozij, 1. Fonseca, D. Vitvarova- Prochazkova, J. Cejka, Intramolecular hydroalkoxylation of non-activated C=C bonds catalysed by zeolites an experimental and theoretical study, ChemSusChem 6 (2013) 1021-1030. 

SCHEME 2.85 Gold-catalyzed intramolecular hydroalkoxylation of internal alkynes [125]. 

Activity of a (CH3)3PAu cation as a catalyst of intramolecular hydroalkoxylation of allenes became eight times higher upon its encapsulation within the cavity of the Ga4Lg coordination capsule 575. This allowed performing these reactions in water up to 67 catalytic turnovers by the caged catalyst have been observed in [34]. 

An efficient total synthesis of bruguierol A was accomplished from commercially available (S)-epichlorydrin (Scheme 18.57) [47]. The key step is a catalytic tandem intramolecular hydroalkoxylation/hydroarylation reaction to construct a 2,3-benzofused 8-oxobicyclo[3.2.1]octane system. Bruguierol A belongs to a family of compounds termed bruguierol A to C, isolated from the stem of the Bruguiera gym-morrhiza tree. 

A gold-catalyzed benzylic C-H functionalization for the synthesis of IH-isochromene derivatives 34 was disclosed by Hashmi and coworkers in their study of the intramolecular hydroalkoxylation of alkynes (Scheme 12.15) [19]. A proposed mechanism for this reaction is shown in Scheme 12.16. The reaction... 

Bartolome C, Garcia-Cuadrado D, Ramiro Z, Espinet P. Synthesis and catalytic activity of gold chiral nitrogen acycHc carbenes and gold hydrogen bonded heterocyclic carbenes in cyclopropanation of vinyl arenes and in intramolecular hydroalkoxylation of allenes. Inorg Chem. 2010 49 9758-9764. 

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