Alkynes, activation hydroalkoxylation

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. 

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]. 

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... 

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. 

All these results seemed to indicate that this reaction was ideal for the con-stmction of the (—)-berkelic acid skeleton. However, a serious problem was still unresolved at this point how to constmct the additional pyran ring contained in the natural product. Nevertheless, our experience on cycloisomerization reactions led us to speculate on the possibility that a unique metal complex could promote the cycloisomerization of alkynol 15 to give the exo-cyclic enol ether 19 and also that the cycloisomerization of an alkynyl-substituted salicylaldehyde 23 would give 25. Thus, activation of the alkyne of 15 should promote a hydroalkoxylation reaction to give the exocyclic enol ether 19. On the other hand, activation of the alkyne in 23 should promote a cascade cyclization process to finally give the 8//-isochromen-8-one derivative 25. The formal [4-F 2]-cycloaddition reaction between intermediates 19 and 25 would result in the formation of the core structure of (—)-berkehc acid 24 in a very simple way (Scheme 7). 

As an alternative, iridium complexes show exciting catalytic activities in various organic transformations for C-C bond formation. Iridium complexes have been known to be effective catalysts for hydrogenation [1—5] and hydrogen transfers [6-27], including in enantioselective synthesis [28-47]. The catalytic activity of iridium complexes also covers a wide range for dehydrogenation [48-54], metathesis [55], hydroamination [56-61], hydrosilylation [62], and hydroalkoxylation reactions [63] and has been employed in alkyne-alkyne and alkyne - alkene cyclizations and allylic substitution reactions [64-114]. In addition, Ir-catalyzed asymmetric 1,3-dipolar cycloaddition of a,P-unsaturated nitriles with nitrone was reported [115]. 

An intramolecular version of alkyne hydration was reported in 2006 by Belting and Krause [127] providing an efficient route to tetrahydrofuranyl ethers 32. This transformation consists in a tandem cycloisomerization-hydroalkoxylation of homopropargylic alcohols 31 in the presence of an alcohol in a dual catalyst system (a gold precatalyst and a Bronsted acid) under mild conditions (Scheme 13). The reaction proceeds satisfactorily with terminal and internal alkynes, with bis-homopropargylic alcohols and alkynyl phenols to provide cyclic acetal skeletons that occur in a variety of natural products. Substituted furanones can be obtained by gold(III)-catalyzed activation of alkynes by heterocyclization and subsequent 1,2-alkyl shift [128]. 

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