Alkynes from vinyl halides

A similar approach was used by the Alcaide group [183] in the synthesis of tricyclic (3-lactams 6/1-391 from 6/1-390 (Scheme 6/1.99). In this domino process the primarily obtained it-allyl-Pd-complex reacts with the N-nucleophile of the urethane moiety to form a C-N-bond and a vinyl halide. The final step is then an intramolecular Heck-type reaction of the vinyl halide with the alkyne moiety and re-... 

The result of the retrosynthetic analysis of rac-lO is 2-hydroxyphenazine (9) and the terpenoid unit rac-23, which may be linked by ether formation [29]. The rac-23 component can be dissected into the alkyl halide rac-24 and the (E)-vinyl halide 25. A Pd(0)-catalyzed sp -sp coupling reaction is meant to ensure both the reaction of rac-24 and 25 and the ( )-geometry of the C-6, C-7 double bond. Following Negishi, 25 is accessible via carboalumination from alkyne 27, which might be traced back to (E,E)-farnesyl acetone (28). The idea was to produce 9 in accordance with one of the methods reported in the literature, and to obtain rac-24 in a few steps from symmetrical 3-methyl-pentane-1,5-diol (26) by selective functionalization of either of the two hydroxyl groups. 

Vinyl halides from alkynes + hydrogen halides (3.20)... 

New reports of organozirconium-organic halide cross-coupling reactions have almost completely stopped. Nevertheless, the palladium-catalyzed cross-coupling of vinyl zir-conocenes (from alkyne hydrozirconation) with vinyl halides has been employed in the synthesis of the lipid isobutylamide natural product anacyclin (equation 98). ... 

OxazoIones are alkylated at position 4 by alkyl halides, allyl halides and electrophilic alkynes, such as methyl propiolate (equation 36). In contrast, 2-phenyloxazolones react with methyl vinyl ketone at both C(4) and C(2) to yield a mixture of Michael adducts (equation 37). If the phenyl substituent is replaced by the bulky 2,4,6-trimethylphenyl group the addition is directed exclusively to C(4) (81CB2580). Alkylation of 5(4//)-oxazolones is a key step in the synthesis of ketones from a-amino acids (Scheme 16). The outcome of this sequence is the union of the electrophilic fragment R3 with the group R2CO the amino acid thus functions as the equivalent of an acyl anion (78AG(E)450). 

The authors point out that, unlike vinyl halides, the vinyl chloronium ion 23a could hardly show double bond character in the C-Cl bond because of unfavourable charge repulsion in 23b. The unreactivity of vinyl halides may therefore primarily be a consequence of the strength of the a bond to the sp2, carbon. However if opening of 23a is assumed to be due to nucleophilic attack of the solvent (or any other nucleophile) to either C5 or C2, the greater amount of shifted products obtained from alkynes than from alkenes is a direct consequence of the relative facility of nucleophilic attack at the sp3 carbon and sp% carbon (Rappoport, 1969 Modena, 1971). 

Vinyl bromides can themselves be made by elimination reactions of 1,2-dibromoalkanes. Watch what happens when 1,2-dibromopropane is treated with three equivalents of K NLi first, elimination to the vinyl halide then, elimination of the vinyl halide to the alkyne. The terminal alkyne is amply acidic enough to be deprotonated by R2NU, and this is the role of the third equivalent. Overall, the reaction makes a lithiated alkyne (ready for further reactions) from a fully saturated starting material. This may well be the first reaction you have met that makes an alkyne from a starling material that doesn t already contain a triple bond, making an alkyne from 1,2-dibromopropane... 

Terminal alkynes are weakly acidic. The alkyne hydrogen can he removed by s strong base 9uch ae Na NH.. to yield nn a<%tylide anipn An acetylide anion ads as a nucleophile and can displace a halide ion from a primary alkyl halide in a n alkylation reaction. Acetylide anions are more stable iJian either alkyl anions or vinylic anions because their m ative charge is in a hybrid orbital with 50% s character, allowing the charge to be doser to the nucleus. 

As described above (Section 5.2), the Stephens-Castro reaction of alkynylcopper with aryl and vinyl halides in boiling pyridine is a useful route to aryl and vinyl acetylenes. Direct cross-coupling of organic halides, such as sp halides, with terminal alkynes is a more convenient procedure. Such a reaction is not so easy, but it can be done using a Pd-complex catalyst [41]. Especially facile Pd-catalyzed cross-coupling of aryl and alkenyl halides with terminal alkynes proceeds smoothly under mild conditions in the presence of a cocatalyst of cuprous iodide in amine solvents [Eq. (28)] [42]. This methodology is now used widely for the constiuction of conjugated arylalkyne or enyne systems [43], as described below. It is attractive from a synthetic point of view because mild reaction conditions and simplicity of the procedure are associated with recent developments in modem acetylene chemistry [44]. 

The base-induced dehydrohalogenation of vinyl halides and allyl halides often gives low yields of allenes because of the competing reaction to alkynes alkynes can either be formed by direct elimination from vinyl halides or by isomerization of the allene first formed to the isomeric alkyne. Since it has been established that anti elimination of hydrogen halide from vinyl halides to yield alkynes is much faster than syn elimination, the proper choice of the starting material is often important for a successful allene synthesis. When ( )-4-bromo-4-octene was treated with NaOMe, the sole product was 3,4-octadiene, whereas the conesponding Z-educt yielded 4-octyne (Scheme 66). ... 

Heck-type vinylations of alkynic halides proceed only under solid-liquid phase-transfer conditions. These mild conditions allow the reaction to be performed with thermily unstable substrates. Thus, methyl ( )-enynoates can be obtained from the reaction of 1-iodoalkynes with methyl 2-propenoate in DMF at room temperature in the presence of potassium carbonate, tetrabutylammonium chloride and a catalytic amount of palladium acetate (Scheme 36)." ... 

Some authors have described the generation of boronates and stannanes bound to a support starting from the corresponding aryl haHdes [372, 6]. Boranes, boronic esters, and stannanes can furthermore be readily obtained from vinyl halides or from alkenes or alkynes by means of hydroboration or hydrostannylation (see Section 4.2). Boronates and silanes or stannanes can act as carbanion equivalents. Thus, support-bound boronates can release aryl alkenyl groups upon transmetala-tion to Rh. The intermediately formed Rh species can act as nucleophiles, and react with aldehydes to give alcohols (618) or can perform Michael additions (621, 622) [437, 438, 439] (Scheme 129) (see also Sections 4.7.15 and 4.2). 

Halogenation of vinylboranes generates vinyl halides. Both cis and trans halides are available by modification of the reaction conditions. When trans-alkenyl boronic acid (73, derived from 1-octyne) was treated with iodine and sodium hydroxide, trans-1-iodo-l-octene (74) was formed in 90%. When the boronic acid was treated with iodine and then with base, the (Z)-alkenyl iodide (75) was produced.Vinylboranes derived from internal alkynes lead to cis-trans mixtures with both of these procedures. Boronic acids derived from alkynes and catecholborane give the (Z)-bromide on addition of bromine followed by sodium hydroxide. ... 

Oxidative addition of aryl (or vinyl) halide to Pd(0) precursor forms the monoarylpalladium complex that is the common intermediate in the catalytic cross-coupling reactions of haloarene with organometallic compounds of main group elements such as Mg, Si, and Sn. Alkynylcopper, formed from alkyne, Cu(I) salt and base in the reaction mixture, transfers the ligand to the above Pd complex, giving an intermediate complex with aryl (or vinyl) and alkynyl ligands bonded to Pd. Reductive elimination of arylacetylene (or enyne) occurs... 

Scheme 46) to both isomers of vinyl halides (X = Cl,Br, or I) from alkynes. Vinyl bromides can also be obtained from alkynes via hydroboration to vinyl boronic acids followed by treatment with ICl (Scheme 47)/ and a recent alternative approach to vinyl bromides by condensation of carbonyl compounds with dibromomethane is outlined in Scheme 48. ... 

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