Octyne isomers

The hydrophosphorylation of internal alkynes is somewhat slow. For instance, the reaction of 4-octyne with diethyl phosphonate resulted in 82% yield only after heating for 65 h. Only c/s-isomer was observed in NMR spectroscopy. 

Cathodic reduction of disubstituted alkynes is possible but proceeds with relatively low current efficiency. Reduction of 4-octyne under similar conditions as used for 1-hexyne yields only 50% 4-octene after transfer of 8 F mol-1. It is interesting to note that the ratio trans/cis for the cathodically obtained 4-octene was 3/l. Other methods29 involving electron-transfer reductions yield the corresponding trans isomers almost exclusively. 

The successful result of Murai et al. [49] is shown in (Eq. 26). When 1-trimethylsilylpropyne is used, the desired coupling product is obtained in excellent yield and the regiochemical and stereochemical outcome is perfect [49]. The E isomer is the predominant product. This result indicates that the addition of C-H bonds to the C-C triple bond proceeds with syn selectivity. In the case of the reaction with 1-trimethylsilyl-l-octyne, stereoselectivity is slightly decreased. This suggests that the small difference in steric bulkiness between methyl and hexyl groups affects the stereoselectivity. 

This catalyst (1) is a selective catalyst for hydrogenation of 4-octyne to cw-4-octene (90% yield). If the product is left in contact with 1, it isomerizes to the trans-isomer. Since monoalkenes are hydrogenated slowly with this catalyst, cyclo-octene can be obtained from either 1,3- or 1,5-cyclooctadiene. Of more interest, benzene can be hydrogenated to cyclohexane (83% yield). One drawback is that the catalyst loses about 90% of its activity after one cycle. 

When 4-octyne (CH3CH2CH2-C=C-CH2CH2CH3) is added to n-propylamine (CH3CH2CH2NH2), two enamines result. This can be accounted for on the basis of Z-E geometric isomerism. The two isomers may be written as follows ... 

To resolve the situation, Harding and King prepared 6-octyn-2-one (56) and isomer-ized it with ethanolic HCl and (separately) with BF3 etherate. Both reactions yielded 55% of 57 and 45% of 58. The authors showed that the reaction did not involve oxygen exchange with -enriched solvent. 

Recently, Corey has rekindled interest in vinylstannanes as intermediates for alkenyl lithium reagents (79,80,81), and we (52,55) and others (53,56) have utilized this method to prepare various p-chain precursors (Scheme 17). We find hydrostanna-tion of terminal acetylenes to be a facile and high yield reaction, whereas iodovinylation is a capricious and tedious transformation. Thus, treatment of 3-triethylsilyloxy-l-octyne 91 with tributyl-stannane (TBS) in the presence of azobisisobutyronitrile (AIBN) gave stereospecifically an excellent yield of l-tributylstannyl-3-triethylsilyloxy-trans-l-octene (92), which when lithiated with butyllithium and treated with pentynylcopper provided the requisite lithio cuprate 93. The use of TBS to prepare homovinylic ethers such as 96 and 97 gave a 10 1 mixture of trans and cis isomers. 

Hydrothiolation of 1-alkynes with thiols gives vinyl sulfides with high regio- and stereoselectivities. Reaction of 1-octyne with benzenethiol catalyzed by Pd(OAc>2 gave the Markonikov-type product 110. Isomerization of the double bond occurred and the isomer 111 was obtained when PdCl2(PhCN)2 was used [34]. 

Wang s group achieved substitution at the 6- and 7-positions of the [2,1-c] core by reacting cyclopentadienone 162 with 4-octyne (163) in a Diels-Alder reaction to form terphenyl diester 164 (Scheme 45) [94]. Cyclization with concentrated sulfuric acid gave 6,7-di-n-propyl [2,l-c]IF dione 165 in 79% yield. These results stand in contrast to the observations in Scheme 11 where use of either phenylacetylene or diphenylacetylene gave the corresponding isomer in high yield. 

It was reported that the pyrazolyl-borate complex of rhodium (Tp Rh(PPh3)2, Tp =hydrotris(3,5-dimethylpyrazolyl)borate) is active not only in the hydrothiolation with ArS H, but also with AlkS H in good to high yields of Markovnikov isomer at room temperature (Scheme 3.91) [162,163]. However the reaction of 1-octyne gave a mixture of isomers in 70% yield. In addition to the double bond isomerization, a Markovnikov/anti-Markovnikov ratio of 12 1 was found in the case of 1-octyne. 

The competitive experiments were carried out with a series of terminal al-kynes characterized by similar electronic properties but differing in portions of the molecule remote from the reaction site. For aliphatic alkyne, the three substrates ethynyl cyclohexane, 1-octyne (which represents an acyclic isomer of the former substrate), and 1-dodecyne were tested, with the free catalyst compared to the encapsulated catalyst. In the former case, after a short induction time, the initial reaction rate for the three substrates showed similar behavior for 1-dodecyne and 1-octyne, while the cyclic isomer, being slightly more electron rich, reacted 1.5 times faster (Fig. 7.8a). Encapsulation of the catalyst led to a magnification of the favorable hydration of the cyclic substrate that reacted more than twice as rapidly as the longer substrate. It is likely that extended linear substrates, that in their extended conformation are approximately 1.4 and 2.1 times longer than ethynyl cyclohexane, have to fold to better complement the residual space left available within Ihe cavity occupied by the catalyst. 

PROBLEM 3.41 Draw and write the systematic names for all of the acyclic isomers of 1-octyne (CgH ) containing a triple bond. There are 32 isomers, including 1-octyne. 

Draw the structural formula for n-octyne. How many isomers are possible by moving only the position of the triple bond ... 

The palladium-catalyzed hydrothiolation of terminal alkynes has been achieved using a metallocycle catalyst that was generated through the treatment of palladium acetate with phosphinic acids (Scheme 5.53) [79], Using this catalyst system, benzenethiol was added to 1-octyne in moderate yield with high selectivity for the Markovnikov-isomer. While only a single hydrothiolation example was reported, this chemistry provides the foundation for the design of additional palladium-catalyzed reactions. 

What can we do if we want the tra s-alkene rather than the ds-isomer from alkyne reduction This can be accomplished using a dissolving metal reduction. When an alkali metal such as sodium is added to liquid ammonia, it is ionized to give solvated electrons (these are blue, but that s a story for the physical chemists...). One electron is added to the alkyne to give a radical anion (Figure 11.94). Because electrons repel each other, the orbitals containing the lone pair and the odd electron are on opposite sides of the triple bond. The lone pair is protonated by the solvent then a further electron and proton are added to complete the process. Thus, 4-octyne is cleanly reduced to fraKS-4-octene. 

The reaction of Pd(OAc)2 with 3 equiv of PhSH in THF-t/g immediately gave dark brown precipitates and ca. 2 equiv of AcOH. This precipitate scarcely exhibited the catalytic activities for the addition of PhSH to 1-octyne. On the other hand, the precipitates prepared in the presence of 1-octyne had a moderate catalytic activity. cw-Addition of PhSH to 1-octyne was confirmed by the reaction employing 1-octyne-i-J. The ( )-isomer, ( )- -C6Hi3(PhS)C=C(D)H, is the kinetic product and gradually isomerized to the (Z)-isomer. A mechanism similar to that shown in Scheme 6 was proposed [22]. 

According to the detailed results [7] on the nickel-catalyzed addition of //-phosphonate to terminal alkynes [8], the reaction of HP(0)(0Me)2 with 1-octyne run in ethanol at room temperature gives the linear isomer as major product (Scheme 2). As is anticipated in view of the influence of acidic additives found with palladium catalysts [9], the same reaction run with diphenylphosphinic acid added as an additive reverses the regioselectivity (branched/linear = 92/8). HP(0) Ph(OEt) and HP(0)Ph2 behave similarly. 

Even in the absence of catalyst, thiols add to alkynes under neutral conditions to afford a f -Markovnikov-type vinyhc sulfides with excellent regioselectivity usually as a stereoisomeric mixture. Indeed, the reaction of benzenethiol with 1-octyne in the absence of transition metal catalyst provides a t/-Markovnikov adduct 4a regioselectively with the E Z ratio of ca. 1 1. This hydrothiolation takes place, most probably via the radical process induced by trace amounts of oxygen existed in the reaction system. The radical addition of thiols to alkynes sometimes seems to proceed even in the presence of transition metal catalysts. Accordingly, when the a f -Markovnikov adducts are obtained with approximately equal amounts of E- and Z-isomers, the following possibility is present the anti-Markovnikov adducts are formed by the radical process, regardless of the presence of transition metal catalysts. 

To ascertain the stereochemistry of this Pd(OAc)2-catalyzed hydrothiolatiOTi of terminal alkynes, the reaction of PhSH with 1-octyne-l-d (containing 93% d) is monitored by H NMR spectroscopy. The E Z ratio of the thiolation products is 100 0 at the initial stage, and then -isomer as the kinetic product gradually isomerized to Z-isomer. These results clearly indicate that the hydrothiolation proceeds via yn-addition at least at the initial stage (Scheme 4). 

Stoichiometric reaction of the above mentioned Pd complex with 1-octyne gave a mixture of a- and j -isomers in 65% total yield. Different ratio of the a- and )S-isomers was observed in the stoichiometric reaction, which could be attributed to the changes in reaction conditions (temperature, concentration, etc.). It was proposed that catalytic cycle involves alkyne insertion into the Pd-H bond—i.e. hydropalladation [86]. 

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