Gold -catalyzed hydroalkoxylation

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

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. 

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

In a related study, Uemura and co-workers obtained planar-chiral isochromene chromium complexes by gold-catalyzed enantioselective cyclization of prochiral (l,3-dihydroxymethyl-2-alkynyl)benzene chromium complexes. " The highest selectivities in this 6-e <3to-dig-hydroalkoxylation were observed in the presence of a chiral cationic gold catalyst prepared in situ from (/ )-xylyl-BINAP(AuC1)2 and AgSbFs. With (/ )-SEGPHOS(AuCl)2 and AgBp4, the enantiomeric product was obtained, albeit with low enantioselectivity. 

Gold-catalyzed intermolecular hydroalkoxylations of allenes have received much less attention than their intramolecular counterpart. Nishina and Yamamoto performed the addition of primary or secondary alcohols using 5 mol% each of PhsPAuCl and AgOTf without any solvent and obtained the allylic ethers resulting from attack of the alcohol at the less substituted allenic terminus with moderate to high yield. The best results were obtained for aryl-substituted allenes. Unfortunately, enantiomerically enriched allenes provided only racemic addition products under these conditions. In the presence of a gold(I) catalyst and iV-iodosuccinimide, 2-iodoallylic ethers were obtained in a regioselective and stereoselective manner. 

Representative procedure for the gold-catalyzed intermolecular hydroalkoxylation of allenes. I-((E)-3-Isopropoxyprop-l-enyl)-4-methylbenzen ... 

Krause has reported the gold-catalyzed intramolecular endo-hydroalkoxylation of (3-hydroxyallenes to form dihydropyrans [103]. For example, treatment of a 70 30 diastereomeric mixture of (3-hydroxyallene 61 with a catalytic 1 1 mixture of AuCl and pyridine in dichloromethane led to isolation of dihydropyran 62 in 84% yield as a 70 30 mixture of diastereomers (Eq. (12.32)). This transformation was also catalyzed effectively by a 1 1 mixture of (PPh3)AuCl and AgBp4 in toluene. (3-Hydroxyallenes that possessed substitution at the internal allenyl carbon atom also underwent gold-catalyzed cycloisomerization with selective transfer of chirality from the allenyl... 

In 2006, Widenhoefer reported an effective gold(I)-catalyzed protocol for the exo-hydroalkoxylation of y- and 6-hydroxy allenes to form 2-vinyl tetrahydrofurans and 2-vinyl tetrahydropyrans, respectively [104]. For example, treatment of 1-phenyl-5,6-heptadienol with a catalytic 1 1 mixture of [P(f-Bu)20-biphenyl]AuCl and AgOTs in toluene at room temperature led to isolation of 2-phenyl-6-vinyltetrahydropyran in 96% yield as a 7.2 1 mixture of diastereomers (Eq. (12.33)). This gold(I)-catalyzed hydroalkoxylation protocol tolerated substitution at the terminal allenyl carbon atoms and along the alkyl chain that tethered the hydroxy group to the allenyl moiety and was also effective for the S-exo hydroalkoxylation of y-hydroxy allenes. Alcaide and Almendros have shown that gold(III) also catalyzes the S-exo hydroalkoxylation of y-allenyl alcohols in modest yields (Eq. (12.34)) [105]. 

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

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... 

Scheme 40 Aponick et al. s gold(I)-catalyzed hydroalkoxylation approach toward unsaturated spiroacetals [106]...

Nishina N, Yamamoto Y (2008) Gold-catalyzed intermolecular hydroalkoxylation of allenes difference in mechanism between hydroalkoxylation and hydroamination. Tetrahedron Lett 49 4908 911... 

Gold-Catalyzed Hydrofunctionalization of Ti-Bonds 2.1 Hydration and Hydroalkoxylation of Alkynes... 

Despite the successes of the gold-catalyzed addition of O-nucleophiles to alkynes, the corresponding catalyzed reactions involving nucleophilic addition to olefins are very limited. Mild, metal-catalyzed additions of O-H bonds across olefins have been studied for decades, and efforts to develop such processes have intensified in the last years. Results of the hydroalkoxylation of alkenes are collected in different reviews [1, 94-96, 161]. 

Hydroalkoxylation of Allenes In the year 2000, during their investigation of transition metal catalyzed reactions of allenyl ketones [29], Hashmi et al. discovered that gold(III) salts were able to lead the cydoisomerization and dimerization of these substrates (Equation 8.2) with a considerable improvement related to other assays with Ag (I) or Pd (II) catalysts [18]. 

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]. 

Krause and Belting studied a tandem catalyzed reaction, in this case intramolecular cyclization and intermolecular hydroalkoxylation. The substrates were various homo-propargylic alcohols in the presence of non-tertiary alcohols and a dual catalyst system consisting of Br( >nsted acids and a gold precatalyst (Equation 8.43). 

In 2001, Krause reported that gold(III) salts catalyzed the stereoselective endo-hydroalkoxylation of a-hydroxyallenes to form 2,5-dihydrofurans [94]. For example. 

In early 2007, Widenhoefer and Zhang reported the gold(I)-catalyzed intramolecular enantioselective hydroalkoxylation of y- and 6-hydroxyallenes [106]. For example, reaction of 2,2-diphenyl-4,5-hexadienol with a catalytic 1 2 mixture of [(S)-63]Au2Cl2 [(S)-63 = (S)-DTBM-MeObiphep] and AgOTs at 20 °C in toluene for 18h led to isolation of 4,4-diphenyl-2-vinyltetrahydrofuran in 67% yield with 93% ee (Eq. (12.35)). This protocol was also effective for the enantioselective 6-e%o-hydro-alkoxylation of 6-hydroxyallenes to form tetrahydropyrans. Gold(I)-catalyzed cycli-zation of y-hydroxyallenes that possessed an axially chiral 1,3-disubstituted allenyl moiety occurred with high enantioselectivity/low diastereoselectivity in a catalyst-... 

Toste and coworkers have developed effective gold(I)-catalyzed protocols for the intramolecular enantioselective hydroalkoxylation of y- and 8-hydroxy allenes employing chiral, enantiomerically pure silver salts [107]. For example, treatment of y-hydroxy allene 66 with a catalytic 1 2 mixture of the achiral bis(gold) complex (dppm)Au2Cl2 [dppm = bis(diphenylphosphino)methane] and chiral silver phos-phonate Ag-(J )-67 in benzene at room temperature led to isolation of 2-alkenyl tetrahydrofuran 68 in 90% yield with 97% ee (Eq. (12.36)). A combination of chiral bis(gold) complex with a chiral silver salt proved effective for terminally unsubstituted allenyl alcohols. For example, reaction of 5,6-heptadienol catalyzed by a mixture of [(S,S)-DIPAMP]Au2Cl2 [DIPAMP = l,2-ethanediylbis[(2-methoxyphenyl) phenylphosphine] and Ag-(J )-67 gave 2-vinyltetrahydropyran 69 in 96% yield with 92% ee (Eq. (12.37)). 

Nishina and Yamamoto have also reported the gold(I)allenes with alcohols [109]. As an example, treatment of a neat mixture of p-tolyl allene and isopropanol with a catalytic 1 1 mixture of (PPh3)AuCl and AgOTf at 30 °C led to isolation of isopropyl )-3-(4-tolyl)-2-propenyl ether in 98% yield (Eq. (12.39)). The protocol was most effective for monosubstituted and 1,3-disubstituted allenes and gave no transfer of chirality for the hydroalkoxylation of 1-phenyl-l,2-butadiene. Horino has reported the gold(I)-catalyzed intermolecular addition of alcohols to the allenyl moiety of 4-vinylidene-2-oxazolidinones [110]. 

Wang ZJ, et al. Hydroalkoxylation catalyzed by a gold complex encapsulated in a supramolecular host. J Am Chem Soc 2011 133 7358-60. 

Barluenga J, Fernandez A, Di6guez A, Rodriguez F, Fananas FJ (2009) Gold- or platinum-catalyzed cascade processes of alkynol derivatives involving hydroalkoxylation reactions followed by Prins-type cyclizations. Chem-Eur J 15 11660-11667. doi 10.1002/ chem.200900856... 

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