Markovnikov additions alkyne derivatives

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

Several ruthenium complexes are able to promote the classical Markovnikov addition of O nucleophiles to alkynes via Lewis-acid-type activation of triple bonds. Starting from terminal alkynes, the anti-Markovnikov addition to form vinyl derivatives of type 1 (Scheme 1) is less common and requires selected catalysts. This regioselectivity corresponding to the addition of the nucleophile at the less substituted carbon of the C=C triple bond is expected to result from the formation of a ruthenium vinylidene intermediate featuring a highly reactive electrophilic Ca atom. 

Hydroamination. Amides, lactams, carbamates and ureas add to 1-alkynes to give enamide derivatives. The stereoselectivity of this anti-Markovnikov addition is sensitive to phosphine ligands that are present. ... 

The enol esters obtained in this transformation can be further modified bearing in mind that they are protected aldehydes. Treatment of propargyl alcohols with benzoic acid in the presence of complex (dppe)Ru(2-methallyl)2 as catalyst affords the enol esters derived from the anti-Markovnikov addition of the acid to the alkyne (Scheme 6). Subsequent acid treatment gives rise to the conjugated enal, which is an isomer of the starting propargylic alcohol [80, 81]. 

The addition of water and methanol to terminal alkynes has also been studied by Laguna et al. by pentafluorophenyl and mesityl gold derivatives. Both acidic and non-acidic conditions led to high activity, even in the presence of as little as 0.5 mol% of catalyst. The use of pentafluorophenyl compounds allowed them to obtain additional spectroscopic information in the stoichiometric reaction of the complex [Au (C6F5)2C1]2 and phenylacetylene, which showed that gold(III) was the active species in the catalytic process. The reaction followed the Markovnikov rule, as shown in the proposed mechanism (Scheme 8.13), delivering the corresponding ketones or diacetal products [96]. 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

The cesium hydroxide-promoted addition of benzimidazole to phenylacetylene proceeded with exclusive anti-Markovnikov regioselectivity and complete stereoselectivity for the formation of the Z-isomer (Scheme 3.132) [142]. Similar reactivity was obtained for pyrrole and imidazole however, acyclic secondary amines such as diphenylamine or phenytmethylamine afforded mixtures of the stereoisomers. It should be noted that these additions were still regioselective for the anti-Markovnikov product. In related work, the base-assisted synthesis of enamines through the addition of indole derivatives to TMS-protected alkynes has been achieved using KOH as the promoter (Scheme 3.133) [143]. 

Cyclic five-membered H-phosphonates were found to be much more active in the addition reaction to the multiple carbon-carbon bonds compared to acyclic phosphorus derivatives [72] Rh-catalyzed addition of the five-membered H-phosphonate to alkynes was carried out under mild conditions at room temperature and results in high yield of the ) -isomer with -configuration (Scheme 8.8). It should be pointed out that Pd- and Rh-catalyzed reactions were complementary to each other providing the access to a-(Markovnikov) and trans-) -(anti-Markovnikov) isomers, respectively (cf. Schemes 8.5 and 8.8). 

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