Hydroalkoxylation alkenes

The carbon-metal cr-bond emanating from the addition of an alcohol nucleophile to a 7t-alkene complex may undergo a protonolytic cleavage to effect overall hydroalkoxylation of the alkene. While this process is difficult to achieve due to the propensity of the cr-metal species to undergo f3-H elimination, some encouraging progress in this area has recently been forthcoming. 

A few examples of the intermolecular hydroalkoxylation of unactivated alkenes have also appeared in the literature. While limited results have been obtained with aliphatic alcohols using a Cp RuCl2(PPh3)/AgOTf... 

Hydroalkoxylation of Alkenes The first example was reported by Hashmi et al. when an intramolecular addition of a hydroxy group to an alkene was proposed as part of a tandem reaction [28] (Scheme 8.4). 

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... 

Mechanistic hypotheses play an important role in developing new catalytic and selective heterofunctionalizations of alkenes. Two basic reaction cycles for metal-catalyzed hydroalkoxylation (and hydration, for R = H) of alkenes can be postulated (Scheme 2). One pathway leads to Markovnikov products via activation of the nucleophile, oxy-metallation, and protonolysis (hydro-de-metallation) (Scheme 2a). Alternatively to the inner sphere syn-oxymetallation depicted in Scheme 2a, external anti-attack of the nucleophUe to coordinated olefin is plausible. The oxidation state of the metal remains constant in this cycle. The alternative hydrometallation pathway (Scheme 2b) proceeds via oxidative addition of the H-OR bond, hydrometallation of the olefin, and reductive elimination to the anti-Markovnikov addition product [3,4]. 

Synthesis of saturated heterocycles via metal-catalyzed formal cycloaddition reactions that generate a C—N or C—O bond 13THC(32)225. Synthesis of saturated heterocycles via metal-catalyzed alkene carboami-nation, carboalkoxylation diamination, aminoalkoxylation, dialkoxyla-tion hydroamination or hydroalkoxylation reactions 13THC(32)1, 13THC(32)39, 13THC(32)109. 

Several Au-ADC catalysts have been examined in intramolecular hydroamina-tion and hydroalkoxylation reactions of allenes, although no advantages over established systems were uncovered [27c,29a]. Notably, Hong and coworkers showed that highly bulky Au -ADC complex 32 and a comparably hindered acyclic aminooxycarbene complex provide catalytic activities comparable to those attained with equivalently bulky NHC-based catalyst 33 in a fairly challenging intramolecular alkene hydroamination reaction [15b,32]. By contrast, less bulky Au-ADC catalysts were ineffective. 

Hydroamination of 7i-bonds is one of the most straightforward methods for the construction of C N bonds and, as such, has attracted a lot of attention. NHC- Au catalysts, in line with results obtained in hydration and hydroalkoxylation reactions (vide supra), proved highly efficient in this field and the inter-and intramolecular hydroamination of various alkenes," allenes," and alkynes" were reported with a number of NHC- Au complexes. Among these reports, Widenhoefer published an elegant bis-hydroamination of allenes, leading... 

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]. 

R = CF3CH2, CF3CF2CH2, (CF3)3CH, Me, Et, Bn Scheme 43 Hydroalkoxylation of fluorinated alkene... 

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]. 

The pioneer experiments on the hydroalkoxylation of alkenes were carried out by Thomas et al. (1976, [162]) using HAUCI4 in MeOH, following the previous reported work on the oxidation of alkenes by mercury(ll), thalium(lll), and lead(lV) salts (1974-1975) [163, 164]. Mixtures of ketones, a-chloroketones, l-chloro-2-methoxyalkanes, and 1,2-dimethoxyalkanes were obtained in most of the cases (Scheme 22). 

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