Anti-Markovnikov products from alkynes

New mechanistic studies with [Cp2Ti(CO)2] led to the observation that the tita-nocene bis(borane) complex [Cp2Ti(HBcat)2] (Hbcat = catecholborane) generated in situ is the active catalyst.603 It is highly active in the hydroboration of vinylarenes to afford anti-Markovnikov products exclusively, which is in contrast to that of most Rh(I)-catalyzed vinylarene hydroboration. Catecholborane and pinacolborane hydroborate various terminal alkynes in the presence of Rh(I) or Ir(I) complexes in situ generated from [Rh(COD)Cl2] or [Ir(COD)Cl2] and trialkylphosphines.604 The reaction yields (Z)-l-alkenylboron compounds [Eq. (6.107)] that is, anti addition of the B—H bond occurs, which is opposite to results found in catalyzed or uncatalyzed hydroboration of alkynes ... 

The authors proposed a mechanism based on a cage-mediated guest-to-host electron transfer (Fig. 9.30) in which the cage acted as a photosensitizing molecular flask. Excitement of the coordination cage, followed by electron transfer from alkyne to an electron-deficient cage and the reaction of a molecule of water (solvent) with the obtained phenyl alkyne radical cation, results in benzylic radicals and subsequently the anti-Markovnikov product. 

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. 

Hexyne has the triple bond in the middle of a carbon chain and is termed an internal alkyne. If, instead, an alkyne with the triple bond at the end of the carbon chain, a 1-alkyne or a terminal alkyne, were used in this reaction, then the reaction might be useful for the synthesis of aldehydes. The boron is expected to add to the terminal carbon of a 1-alkyne. Reaction with basic hydrogen peroxide would produce the enol resulting from anti-Markovnikov addition of water to the alkyne. Tautomerization of this enol would produce an aldehyde. Unfortunately, the vinylborane produced from a 1-alkyne reacts with a second equivalent of boron as shown in the following reaction. The product, with two borons bonded to the end carbon, does not produce an aldehyde when treated with basic hydrogen peroxide. 

Oxidation of the vinylborane (using basic hydrogen peroxide) gives a vinyl alcohol (end), resulting from anti-Markovnikov addition of water across the triple bond. This end quickly tautomerizes to its more stable carbonyl (keto) form. In the case of a terminal alkyne, the keto product is an aldehyde. This sequence is an excellent method for converting terminal alkynes to aldehydes. 

In addition to hydrogenation, alkynes can be hydrated into either a ketone or an aldehyde form. A (Markovnikov) ketone can be created from an alkyne using a solution of aqueous sulfuric acid (H2/H2SO4) and HgSO4, whereas the anti-Markovnikov aldehyde product requires different reagents and is a multi-step process. 

Anti-Markovnikov addition of H2O to olefins is of enormous importance in view of the production of linear alcohols directly from alkenes. It is a general phenomenon, however, that reaction of water with olefins and alkynes, as in the previous example, gives products of Markovnikov addition. The first anti-Markovnikov hydration of terminal alkynes (Scheme 42) with transition metal catalysis was reported in 1998 (227). A series of aliphatic and aromatic alkynes... 

Due to the electrophilic nature of the Ca in vinylidenes, their reactivity is dominated by the addition of nucleophiles to this position to afford Fischer-type carbenes (Scheme 2). Depending on the nature of the nucleophile and the subsequent evolution of the carbene a wide variety of compounds can be generated (aldehydes, dihydropyrans, furans, p,Y-unsaturated ketones, etc.) [55-65]. The regioselectivity of this process led to the product resulting from addition of the nucleophile to the less substituted carbon of the alkyne (anti-Markovnikov addition), which is the opposite result to that observed when the alkyne is activated by a Lewis acid (Markovnikov addition). 

L=AZARYPHOS, see Scheme 7) [86], to synthesize indoles from homo-propargylic amines/amides in good yields [105]. The use of doubly ethynylated substrates in the presence of water gave rise to the product derived from cyclization to the indole plus anti-Markovnikov hydration of the second terminal alkyne (Scheme 21). 

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