Alkynes regiochemistry

Reactions of alkynes with electrophiles are generally similar to those of alkenes. Because the HOMO of alkynes (acetylenes) is also of n type, it is not surprising that there IS a good deal of similarity between alkenes and alkynes in their reactivity toward electrophilic reagents. The fundamental questions about additions to alkynes include the following. How reactive are alkynes in comparison with alkenes What is the stereochemistry of additions to alkynes And what is the regiochemistry of additions to alkynes The important role of halonium ions and mercurinium ions in addition reactions of alkenes raises the question of whether similar species can be involved with alkynes, where the ring would have to include a double bond ... 

Alkynes don t react directly with aqueous acid but will undergo hydration readily in the presence of mercury(II) sulfate as a Lewis acid catalyst. The reaction occurs with Markovnikov regiochemistry the -OH group adds to the more highly substituted carbon, and the — H attaches to the less highly substituted one. 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

An unexpected varying regiochemistry in intramolecular benzannulation has also been observed in the synthesis of cyclophanes. As mentioned above, there are only two possible regiochemical outcomes in the benzannulation reaction, which differ in the direction of alkyne incorporation. / -Tethered vinyl-carbene chromium complexes undergo an intramolecular benzannulation reaction with incorporation of the tethered alkyne with normal regioselectivity to give meta-cyclophanes [28]. 

The regiochemistry of Al-H addition to unsymmetrically substituted alkynes can be significantly altered by the presence of a catalyst. This was first shown by Eisch and Foxton in the nickel-catalyzed hydroalumination of several disubstituted acetylenes [26, 32]. For example, the product of the uncatalyzed reaction of 1-phenyl-propyne (75) with BujAlH was exclusively ds-[3-methylstyrene (76). Quenching the intermediate organoaluminum compounds with DjO revealed a regioselectivity of 82 18. In the nickel-catalyzed reaction, cis-P-methylstyrene was also the major product (66%), but it was accompanied by 22% of n-propylbenzene (78) and 6% of (E,E)-2,3-dimethyl-l,4-diphenyl-l,3-butadiene (77). The selectivity of Al-H addition was again studied by deuterolytic workup a ratio of 76a 76b = 56 44 was found in this case. Hydroalumination of other unsymmetrical alkynes also showed a decrease in the regioselectivity in the presence of a nickel catalyst (Scheme 2-22). 

This reaction exemplified that the regiochemistry of RS and H introduced by car-bonylahve addition differed from that of those by simple hydrothiolation. In the Rh-catalyzed hydrothiolation, the ArS group added to the terminal carbon and H to the internal carbon (Eq. 7.12). On the other hand, in the Rh-catalyzed thioformylation, RS was placed at internal carbon and formyl at the terminal carbon in spite of using the same catalyst precursor, [RhCljPPhsjs], which was also active for the thioformylation shown in Eq. (7.17). In 1997, the Pt-catalyzed hydrothiocarboxylation using RSH, alkyne and CO was reported to furnish 24 (Eq. 7.18), which showed the same regiochemistry as the Ni-catalyzed reaction shown in Eq. (7.1) [28]. 

The most synthetically valuable method for converting alkynes to ketones is by mercuric ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markovnikov rule. Internal alkynes give mixtures of ketones unless some structural feature promotes regioselectivity. Reactions with Hg(OAc)2 in other nucleophilic solvents such as acetic acid or methanol proceed to (3-acetoxy- or (3-methoxyalkenylmercury intermediates,152 which can be reduced or solvolyzed to ketones. The regiochemistry is indicative of a mercurinium ion intermediate that is opened by nucleophilic attack at the more positive carbon, that is, the additions follow the Markovnikov rule. Scheme 4.8 gives some examples of alkyne hydration reactions. 

CpRu(CH3CN)3PF6 catalyzes hydrosilylation of both terminal and internal alkynes. With this catalyst, addition exhibits the opposite regiochemistry. 

Rhodium complexes catalyze hydrosilylation-cyclization of 1,6-allenynes in the presence of (MeO SiH.77 To avoid complex product distributions, the use of substrates possessing fully substituted alkyne and allene termini is imperative. As shown in the cyclization of 1,6-allenyne 62a, the regiochemistry of silane incorporation differs from that observed in the rhodium-catalyzed hydrosilylation-cyclization of 1,6-enynes (see Section 10.10.2.3.2). For allenyne substrates, allene silylation occurs in preference to alkyne silylation (Scheme 40). 

The regiochemistry can be controlled by the nature of the substituents. With a tri-methylsilyl-substituted acetylene, the trimethylsilyl groups are placed in a positions of zirconacyclopentadienes with excellent selectivity (Eq. 2.8) [20]. With a phenyl-substituted alkyne, regioselective reactions are usually observed, although in some cases a mixture of two isomers may be formed. 

These results led to the proposal of the following mechanism. Decomplex-ation of the central C2 fragment allows coordination of the alkyne (intermediate 119), which then inserts to form the metallacycle 120. Deinsertion (reductive eliminate of the cobalt moiety allows ring closure to give the cyclohexadienone complex 121, which upon decomplexation yields the desired phenol. The regiochemistry of the alkyne insertion determines the ratio of 116 117 (for simplicity, only the sequence leading to 116 has been shown). 

Doyle et al. (39) expanded the rhodium-catalyzed generation of isomiinchnones from diazoacetacetamides and subsequent trapping with dipolarophiles (38). As shown in Scheme 10.12, in the case of diazoacetoacetyl urea (79) the derived isomtinchnone 80 reacts with methyl propiolate to give a 2 1 mixture of cycloadducts 81. The resulting regiochemistry is successfully rationalized using frontier molecular orbital (FMO) theory as being isomiinchnone-HOMO controlled. This result represents one of the few reactions in which the cycloadducts from isomiinchnones and alkynes are stable. 

---