Alkynes subsequent transformation

Alkynes are much more reactive toward hydroalumination than alkenes. Hence, they readily react with both dialkylaluminum hydrides and LiAlH4 under mild conditions in the absence of a catalyst [1]. However, it is not always possible to avoid side reactions and subsequent transformation of the vinylalanes formed in this transformation [81, 82]. In addition, ds-trans-isomerization of the metallated C=C bond can take place, thereby reducing the stereoselectivity of the overall reaction [83]. 

Trost has prepared several alkynic ketones by direct acylation of A -methoxy-A -methylamides. Because of subsequent transformations on the product, the aspecifically activated towards nucleophilic addition, and the neighboring ester of the lactate system (25) was not disturbed during this transformation (equation IS). Prior coordination of the organolithium within the amide subunit and subsequent activated ad tion of Ae nucleophile serves as a reasonable explanation for the unusual selectivity of this pro-cess. ... 

The total synthesis of the marine toxin polycavemoside A was achieved by J.D. White and co-workers. In order to couple the central pyran moiety in a Nozaki-Hiyama-Kishi reaction, the aldehyde side chain had to be first homologated to the corresponding terminal alkyne and subsequently transformed into a vinyl bromide. The aldehyde substrate was treated under the Ohira-Bestmann protocol, and the desired alkyne product was obtained in high yield. 

The usefulness of nucleophile-promoted Iminium Ion-alkyne cyclizations derives from the ready availability of alkynylamines and the subsequent transformations of the cyclization products made possible because of their vinylic functionality (e.g., equations 1 and 2). Equation 2 illustrates use of this chemistry to elaborate an exocyclic tetrasubstituted double bond with complete stereooontrol. Net "reductive iminium ion alkyne cyclizations can be accomplished by dehalogenation of vinyl halide cyclization products. The conversion illustrated in equation 3 is a key step in an efficient, practical synthesis of the cardiotonic frog alkaloid pumiliotoxin A. ... 

AcOH followed by ring closure with potassium hydroxide in methanol, which afforded the epoxide. The other coupling unit was made from the reaction of 3-(2,4,10-trioxatricyclo[3.3.1.13 7]dec-3-yl)propanal with tetrabromomethane and triphenylphosphine, affording the terminal dibrominated alkene which was subsequently transformed into the terminal alkyne with n-BuLi [40]. Coupling of the lithiated alkyne with the epoxide proceeded stereoselectively to the alcohol with no racemization. The resulting alkyne was then hydrogenated under... 

Several reports have dealt with the reductive cyclization of enynes where the alkyne component undergoes addition to an adjacent carbonyl group. Typical of this is irradiation of 155, in the presence of the SET sensitizer trie thy lamine, which affords the bicyclic product 156, a piperidone, that was used in a synthesis of z o-oxyskyanthine. Unsaturated aldehydes such as 157 also undergo this photo-electron transfer-induced cyclization to afford a mixture of alcohols 158 (Scheme 6) . Pete and his coworkers have extended their study of this reductive cyclization of unsaturated ketones in a synthesis of hirsutene 159. The reaction involves the irradiation of the ketone 160 at 254 nm in the presence of triethylamine, whereby the tricyclic compound 161 is formed in 58% yield. This is subsequently transformed into hirsutene ... 

The products of standard hydrothiolation processes are capable of further undergoing subsequent transformations, such as Pt-catalyzed Heck reactions with appropriately tethered alkyne acceptors (23) [235]. Furthermore, Beletskaya demonstrated that following the organometallic intermediates formed in addition of disulfides to terminal alkynes may be intercepted these were found to undergo further carbon-carbon bond formation in the presence of a suitable ligand and excess alkyne (24) [158],... 

Solid-phase Cu(l) catalyzed azide-alkyne cycloadditions have also proven to be a rehable and highly robust procedure [6,25-27]. Both the azide and the alkyne functions have been incorporated into different resins. These functionaUzed supports have been appUed to the synthesis of triazole- and non-triazole-containing products by using, in the latter case, the triazole functionaUty as a hnker. The cycloadditions proceed easily on the solid phase showing more sensitivity to steric factors than in solution phase and little sensitivity to reaction conditions, resin type, or subsequent transformations. The Cu(II) reduction protocol, as well as the use of Cu(I) salts, work with equal efficiency in various organic solvents (THF, DMF, acetonitrile, DMSO). 

By employing H, and Ag NMR spectroscopy, the underlying mechanism and the involved intermediates were identified [125]. According to these findings, Ag(I) ions initially interact with the alkyne moiety to form an alkyne-Ag t-complex that is subsequently transformed into the corresponding silver acetylide, eventually promoting transmetallation to the Pd center. Hence, Ag as a cocatalyst basically acts in the same manner as Cu. 

Hydrazinediido complexes have been identified as active species in the titanium-catalyzed hydrohydrazination [12] and iminohydrazination of alkynes and the subsequent transformation of the hydrazones into indoles or tryptamine derivatives (Scheme 13.5) [13]. The postulated reaction mechanism of the group 4 metal-catalyzed reaction is based on the extensively studied mechanistic scheme for hydroaminations of alkynes, in which imido complexes are the key active species. 

Alkyne RCM reactions provide not only a useful macrocyc-Uzation technique but also a solution to avoid the issue on the unpredictable alkene geometry by olefin RCM macro-cycUzations. Thus, the Lindlar reduction of the formed cyclic alkynes leads to cyclic Z-alkenes, and the methodology has been widely employed in natural product syntheses.The hydrosilylation-protodesilylation of the cyclic alkynes " is the secured access to cyclic E-alkenes. As described below, the alkyne RCM-based strategies with the subsequent transformations indicated their usefiilness in target-oriented syntheses. 

Thus, carbonyl surrogate TIPS acylsilanes are resistant to 1,2-addition by Cp2Zr(H)Cl therefore allowing the hydrozirconation of the alkyne but can be further transmetallated into organocopper derivatives for subsequent transformations. 

Recently, Aumann et al. reported that rhodium catalysts enhance the reactivity of 3-dialkylamino-substituted Fischer carbene complexes 72 to undergo insertion with enynes 73 and subsequent formation of 4-alkenyl-substituted 5-dialkylamino-2-ethoxycyclopentadienes 75 via the transmetallated carbene intermediate 74 (Scheme 15, Table 2) [73]. It is not obvious whether this transformation is also applicable to complexes of type 72 with substituents other than phenyl in the 3-position. One alkyne 73, with a methoxymethyl group instead of the alkenyl or phenyl, i.e., propargyl methyl ether, was also successfully applied [73]. 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

A Cp2ZrCl2-catalyzed addition of Bu2AlH to terminal alkynes has been applied in the synthesis of (E)-vinyl phosphonates [84]. 1-Hexyne and 1-octyne were hydroalu-minated at 0°C and the resulting vinylalanes transformed into the respective alumi-nate complexes by treatment with methyllithium. Subsequent addition of oxaza-phospholidinone 79, derived from (-)-ephedrine, lead to the homochiral vinyl phosphonates in yields of ca. 75% (Scheme 2-23). 

Benzocyclobutenedione 57 is transformed to the phthaloylmetal complex 58 by treatment with Fe(CO)5, RhCl(PPh3)3, and CoCl(PPh3)3. The phthaloyliron complex 58 (M=Fe) reacts with alkynes, and subsequent acidification under air then gives the naphthoquinone 59. The cyclization of the phthaloyl-cobalt 58 (M=Co) with alkynes requires AgBF4-activation [32]. (Scheme 22)... 

Based on his previous work on the catalytic double addition of diazo compounds to alkynes173 using Cp RuCl(COD),174 Dixneuf has developed an efficient one-step synthesis of alkenyl bicyclo[3.1.0]-hexane derivatives of type 163 from enyne precursors 162 (Scheme 43). The catalytic cycle starts with the formation of an Ru=CHR species. It then adds to an alkyne to form ruthenacyclobutene 166, which evolves into vinylcarbene 167. [2 + 2]-Cycloaddition of 167 gives ruthenacyclobutane 168. The novelty in this transformation is the subsequent reductive elimination to give 170 without leading to the formation of diene 169. This can be attributed to the steric hindrance of the CsMes-Ru group. 

---