Anti 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. 

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. 

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. 

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. 

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. 

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. 

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... 

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. 

Catalysts for tfie additions of amines to vinylarenes have also been developed. These catalytic reactions include some of the first hydroaminations of unstrained olefins catalyzed by late transition metals, as well as examples catalyzed by lanthanide complexes. These additions occur with Markovrukov selectivity with one set of catalysts and with anti-Markovnikov selectivity with several others. These additions occur by several different mechanisms that are presented in Section 16.5.3.2. 

SCHEME 2.113 An anti-Markovnikov selective Wacker-type oxidation [169]. 

Need to generate a vinyl ether with anti-Markovnikov selectivity and E-stereochemistry... 

Need to make a vinyl ester with anti-Markovnikov selectivity... 

Nickel catalysts promoted the addition of nitrogen nucleophiles to internal alkynes [138] TMS-protected alkynes are excellent snbstrates for the base-assisted anti-Markovnikov selective hydroamination reaction [143]. No need to remove the protecting group prior to the hydroelementation reaction Tetrahydropyridines have been generated through the treatment of dihydropyrans with aniline precursors [149]... 

While the majority of the hydrophosphination reactions described previously led to the formation of products with almost complete anti-Markovnikov selectivity, devising an approach for the selective formation of the addition product with Markovnikov selectivity can be challenging [79]. To address this deficiency, Gaumont determined that a simple change to the catalyst structure switched the selectivity of the reaction (Scheme 4.29 and Example 4.23) [80]. The key observation was that using ferrous chloride as... 

SCHEME 4.29 Hydrophosphination with Markovnikov and anti-Markovnikov selectivity [80]. 

Treatment of benzyl halides with dihalomethane and NaHMDS affords vinyl halides with anti-Markovnikov selectivity and -stereochemistry [207] This conversion tends to work quite well following a Wittig-type process using CX or CHX [212,214, 215], Care must be exercised with this chemistry due to a propensity to generate the haloalkyne instead of the ge/n-dihalo species. Non-Wittig approaches have also been devised [210]... 

Contrary to simple aliphatic-substituted alkenes, the metal-catalyzed hydro-amination of vinyl arenes proceeds usually with high anti-Markovnikov selectivity to give p-phenethylamine derivatives (Fig. 12). This reversal of regioselectivity may be explained with the alkene insertion step proceeding through the sterically more encumbered transition state which is favored due to attractive metal-arene interactions and resonance stabilization of the benzyl carbanion. The same selectivity pattern is observed for alkali [40] and alkaline earth [154, 155] metal catalysts and is also explained by metal-aryl interactions as shown by DFT-calculations [40]. 

The intermolecular hydroamination reactions of alkynes and alkenes occur with Markovnikov or anti-Markovnikov selectivity. The nucleophilic addition to aUenes occurs at terminal carbon of allenes not at central one. 

Vinylarenes with electron donating or electron accepting substituents reacted with pinacol-H-phosphonate with excellent anti-Markovnikov selectivity >99% in dioxane at 100 °C using Wilkinson complex as catalyst precursor [78]. Changing the ligand in the RhCILa complex it was possible to find a catalytic system, which selectively reacts with the terminal double bond (L = PCya), while the addition reaction to the internal double bond did not take place [82]. 

---