Markovnikov selectivity

Palladium(O) or readily reduced paUadium(II) complexes were the most efficient catalysts, giving higher yields than analogous Pt catalysts. The Markovnikov product was formed with high regioselectivity. In dialkynes, both C=C bonds could be hy-drophosphorylated, while the C=C double bond in a cyclohexenyl alkyne subshtuent did not react. With trimethylsilylacetylene, unusual anti-Markovnikov selectivity was observed. 

The anti-Markovnikov product was formed with >95% regioselectivity at 35°C. The examples in Scheme 5-21, Eq. (1) show that cyano and hydroxyl functional groups are tolerated by the catalyst, and diphenylphosphine oxide can be added to both C=C bonds in a di-alkyne. The reaction also worked for internal alkynes (Scheme 5-21, Eq. 2). Unusual Markovnikov selectivity was observed, however, for 1-ethynyl-cyclohexene (Scheme 5-21, Eq. 3) [17]. 

In an effort to apply the cooperative principles of metalloenzyme reactivity, involving a combination of metal-ligand and hydrogen bonding, we have reported a ruthenium catalyst incorporating imidazolyl phosphine ligands that efficiently and selectively hydrates terminal alkynes (5). We subsequently found that application of pyridyl phosphines to the reaction resulted in a >10-fold rate enhancement and complete anti-Markovnikov selectivity, even in the... 

Another approach toward C-O bond formation using alkynes that has been pursued involves the intermediacy of transition metal vinylidenes that can arise from the corresponding y2-alkyne complexes (Scheme 13). Due to the electrophilicity of the cr-carbon directly bound to the metal center, a nucleophilic addition can readily occur to form a vinyl metal species. Subsequent protonation of the resulting metal-carbon cr-bond yields the product with anti-Markovnikov selectivity and regenerates the catalyst. 

A remarkable feature of the structural work on the derivatives with unsaturated side chains is the method by which the double bonds were located. Thus a micromethod has been devised, based on the Markovnikov selectivity of olefin... 

The iridium(III)-complex, [Ir(p-acac-0,0,C )(acac-0,0)(acac-C )]2, mediates the activation of unactivated aromatic C—H bond with unactivated alkenes to form anti-Markovnikov products [57]. The reaction of benzene 131 with propene 132 (0.78 MPa of propylene, 1.96 MPa of N2) leads to the formation of n-propylbenzene 133 in 61% selectivities (turnover number (TON) = 13 turnover frequency (TOE) = 0.0110 s ) (Equation 10.34). The reaction of benzene with ethane at 180 °C for 3h gave ethylbenzene (TON = 455 TOE = 0.0421s ). The anti-Markovnikov selectivity was also proven for the reaction with 1-hexane and isobutene, giving 1-phenyUiexane (69% selectivity) and isobutylbenzene (82% selectivity), respectively. 

In the case of internal symmetric or terminal alkynes, reaction takes place according to Markovnikov selectivity, unlike the problem of regioselectivity that appears when internal asymmetric alkynes are used. Unfortunately, at that time only the gold(I) compound K[Au(CN)2] was tested, a compound that is now known not to be effective as a catalyst, unlike many other gold(I) compounds. 

The variety of C2-bridged PBs was further extended by Muhoro via hydroboration of diphenyl(vinyl)phosphine with catechol- and pinacol-boranes (Scheme 29).56 To compensate for the low Lewis acidity of these boronates, the hydroboration reactions were carried out in the presence of 5 mol% of titanocene bis(catecholborane) as catalyst. The desired products 40g and 40h were obtained with complete anti-Markovnikov selectivity. The spectroscopic data and the crystallographic study performed on 40h showed the expected monomeric open structure. 

The subsequent additions are more selective as the steric bulk increases, and a //-Markovnikov selectivity predominates in the end ... 

Electron-rich, electron-poor, and hindered styrenes (ArCH=CH2) undergo hydroamination with carboxamides (e.g. PhCONH2) in the presence of a 1 2 mixture of [PtCl2(H2C=CH2)]2 and (4-CF3CeH4)3P (5 mol%) in mesitylene at 140 °C for 24 h, to produce (PhCONH)CH(Me)Ar in moderate to good yields with excellent Markovnikov selectivity.90... 

PhsPAuOTf has been shown to catalyse the intermolecular addition of phenols and carboxylic acids to terminal alkenes, RCH2CH=CH2, at 85 °C in toluene with Markovnikov selectivity to produce RCH2CH(OR)Me.131 AUCI3 triggers the electrophilic 6(0)ir n-endo-dig cyclization of 2-(alk-l-ynyl)alk-2-en-l-ones to produce highly substituted furans in analogy with other electrophiles (see above Scheme 3).40... 

The basic Markovnikov selectivity pattern is partially or fully overrun in the presence of neighboring coordinating groups within the olefin substrate (Section 2.2.2). Known functionalities where inversed selectivity can occur include 3-alke-noylamides (e.g. 17 reacts to give a mixture of 18 and 19, Table 3) [43], homoallyl esters and alcohols, allyl ethers (but not necessarily allyl alcohols) [44], allyl amines, allyl amides, or carbamates (cf. 20 to 21) [45], allyl sulfides [46] or 1,5-dienes [47]. As a matter of fact, aldehyde by-products are quite normal in Wacker reactions, but tend to be overlooked. 

Very recently it was shown that sulfonyl oximes 359 are suitable reagents for the addition of oxime functions to olefins 355 (entry 22) [403]. This C-C bond-forming reaction proceeded for a wide range of terminal and 1,1-disubstituted substrates with formal Markovnikov selectivity using catalytic amounts of 357a. Branched oximes 360 were isolated in 33-95% yield. 

Silanes also add to alkenes under radical conditions (using AIBN) with high anti-Markovnikov selectivity. An alternative route to alkylsilanes reacted an alkene with lithium metal in the presence of 3 equivalents of chlorotrimethylsilane. 

When an alkene is treated with MesSiCN and AgC104, followed by aq. NaHCOs, the product is the isonitrile (RNC) formed with Markovnikov selectivity isos alternative reagent is the cyanohydrin of acetone, which adds to alkenes to give a nitrile in the presence of a nickel complex. 

Table 5.2. Enhanced Anti-Markovnikov Selectivity with Bulky Boranes...

Markovnikov or anti-Markovnikov selectivity in hydrophosphination of alkynes (Scheme 1) depends on the metal catalyst and reaction conditions it is thought to be controlled by the regioselectivity of insertion of an alkyne into an M-H or M-P bond. 

For example, Pd-catalyzed addition of PH(0R)2(0) to a terminal alkyne was branched-selective, while PHPh2(0) preferentially gave linear products. However, a Pd(dppe) catalyst resulted in Markovnikov selectivity both for diphenylphosphine oxide [8] and for the mixed substrate PH(Ph)(0Et)(0) (Scheme 2). For the latter, linear products were favored with the ligand P(f-Bu)3 and with PPha in a protic solvent, ethanol. However, the mechanistic basis for this selectivity was not elucidated [9]. 

Addition of diphenylphospholane oxide 6 to terminal alkynes was catalyzed by Pd(PPh3)4 with complete Markovnikov selectivity, while the precursor [Rh(cod) Cl]2 was anti-Markovnikov selective. With Rh, a sequence of P-H oxidative... 

Scheme 2 Markovnikov-selective Pd-catalyzed hydrophosphinylation of phenylacetylene...

Similarly, activation of a coordinated alkene was suggested in Markovnikov-selective addition of diphenylphosphine to alkyl vinyl ethers promoted by Ni(II) and Pd(II) precatalysts such as NiBr2(PPh3)2. Nucleophilic attack on bound alkene, followed by loss of HX to form chelate 26 and protonolysis of the M-C bond would form the product and regenerate the catalyst (Scheme 34). This mechanism was consistent with the observation that added EtsN shut down the reaction [55, 56]. 

Abstract Progress in the field of metal-catalyzed redox-neutral additions of oxygen nucleophiles (water, alcohols, carboxylic acids, and others) to alkenes, alkynes, and allenes between 2001 and 2009 is critically reviewed. Major advances in reaction chemistry include development of chiral Lewis acid catalyzed asymmetric oxa-Michael additions and Lewis-acid catalyzed hydro-alkoxylations of nonacti-vated olefins, as well as further development of Markovnikov-selective cationic gold complex-catalyzed additions of alcohols or water to alkynes and allenes. 

Rhenium A hydrocarboxylation with high selectivity for anti-Markovnikov addition and predominant (Z)-enol ester product is mediated by ReBr(CO)5 (1 mol%, 110°C, 15 h) [168]. The 7i-activation mechanism proposed by the authors does not fit to the observed anti-Markovnikov selectivity. Iridium The precursor complex [ IrCl(cod) 2] (1 mol%) combined with P(OMe)3 (4 mol%) and Na2C03 (2 mol%) produces a catalyst that adds carboxylic acids to terminal alkynes (toluene, 100°C, 15 h) to give a mixture isomers with variable selectivities, although the Markovnikov product is usually formed in excess (ca 5 1) [169]. The complex []IrCl(cod) 2] (1 mol%) in the presence of Na2C03 (0.6 equiv) is also a catalyst for the transvinylation of vinylacetate with diverse alcohols [170]. 

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. 

Kinetic analysis of the reaction between 60 and 110°C yields = +9.1(0.7) kcal/mol and AS - —45(2) eu, suggesting a highly ordered transition state and an intermolecular, turnover-limiting step. The hydrothiolation processes exhibits a high Markovnikov selectivity. This is presumably reflecting a four-membered transition state with the alkyne insertion regio-chemistry dictated by the transition state steric hindrance and the bond polarity orientation. 

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