Alkynes hydride reduction

An illustration of the preparation of six-membered rings by enyne cycloisomerizations is found in Trost s total synthesis of (-t-)-cassiol (113) (Scheme 6-19) [44]. The key step of this synthesis involved conversion of enyne 111 to 1,4-diene 112. Although a mixture of diastereomers is produced, the offending stereocenter is not found in the natural product, allowing both diastereomers of 112 to be used. A reductive diyne cyclization (114 115) was recently described as the key step in a total synthesis of ( )-siccanin (116) [45]. Hydropalladation of the terminal alkyne, insertion of the internal alkyne, hydride transfer to palladium, and reductive elimination are proposed to account for the observed reaction. 

Semireduction of internal alkynes in the presence of a transition metal catalyst (e.g., Ni2B, Pd/C) provides disubstituted cw-alkenes. On the other hand, dissolving metal reduction of alkynes or reduction of propargylic alcohols with LiAlH4 or with Red-Al [sodium bis(2-methoxyethoxy)aluminum hydride] furnishes tran -disubstituted alkenes. ... 

The finely tuned reactivity of tri-n-butyltin hydride and of the resulting tin radical allows it to mediate radical additions to alkenes and alkynes in reductive carbon-carbon bond formation and for radical ring closures . It is a highly versatile and efficient reagent, but not a very green one delivering one useful atom (hydrogen, MW = 1) for every 40 atoms (MW = 290) lost as waste. 

The mechanism of the aluminium hydride reductions with LiAlff4 or RedAl involve a tram hydroalumination helped by coordination of A1 to the triple bond and external nucleophilic attack. The regioselectivity of the hydroalumination is again determined by silicon the electrophilic A1 attacks the alkyne on the carbon bearing the silyl group (the ipso carbon). 

Alternatively, hydride reduction of manganacycle 12 results in the incorporation of a second molecule of carbon mcmoxide and formation of butenolide 14. This unique transformation involves fcmnation of three carbon-carbon bonds, two molecules of CO being incorporated, and difunctionalization of an alkyne in a completely regioselective manner. 

The ( )-alkenylboronic acids are directly available from 1-alkynes by hydroboration-hydrolysis (eq4). The (2)-isomers are prepared from l-bromo-l-alk3Uies by hydroboration-hydride reduction (eq 5). ... 

To explain the preceding results, the authors proposed the mechanism depicted in Scheme 4.15. First, both the enoate and alkyne substrates coordinate to the Ni(0) catalyst, which bears the chiral N-heterocyclic carbene ligand. Next, the enantioselectivity-determining step of the process is the oxidative cyclisation, giving metallocyclic intermediate E. Then, cyclisation and subsequent (3-alkoxide elimination releases the enone. Transmetallation with BEtj, followed by p-hydride elimination, gives a nickel hydride. Reductive elimination then closes the catalytic cycle. 

The vinyl complexes are accessible by transmetallation, oxidative addition of a vinyl halide, addition of an acid on a neutral alkyne complex, insertion of an alkyne in a metal hydride, reduction of a vinylidene complex or nucleophilic attack of a... 

Stereoselective and chemoselective semihydrogenation of the internal alkyne 208 to the ew-alkene 210 is achieved by the Pd-catalyzed reaction of some hydride sources. Tetramethyldihydrosiloxane (TMDHS) (209) i.s used in the presence of AcOH[116]. (EtO)3SiH in aqueous THF is also effective for the reduction of alkynes to di-alkenes[l 17], Semihydrogenation to the d.v-alkene 211 is possible also with triethylammonium formate with Pd on carbon[118]. Good yields and high cis selectivity are obtained by catalysis with Pd2fdba)3-Bu3P[119],... 

It was found [99JCS(PI )3713] that, in all cases, the formation of the deiodinated products 38 and 39 was accompanied by formation of the diynes 40 which were isolated in 60-90% yield. The authors believed that the mechanism of deiodination may be represented as an interaction ofbis(triphenylphosphine)phenylethynyl-palladium(II) hydride with the 4-iodopyrazole, giving rise to the bisftriphenylphos-phine)phenylethynyl palladium(II) iodide complex which, due to the reductive elimination of 1 -iodoalkyne and subsequent addition of alk-1 -yne, converts into the initial palladium complex. Furthermore, the interaction of 1-iodoalkynes with the initial alkyne in the presence of Cul and EtsN (the Cadiot-Chodkiewicz reaction) results in the formation of the observed disubstituted butadiynes 40 (Scheme 51). 

In an effort to identify a more stereoselective route to dihydroagarofuran (15), trimethylsilylated alkyne 17 was utilized as a substrate for radical cyclization (Scheme 2). Treatment of 17 with a catalytic amount of AIBN and tri-n-butyltin hydride (1.25 equiv) furnishes a mixture of stereoisomeric vinyl silanes 18 (72% combined yield) along with an uncyclized reduction product (13% yield). The production of stereoisomeric vinyl silanes in this cyclization is inconsequential because both are converted to the same alkene 19 upon protodesiiyiation. Finally, a diastereoselective di-imide reduction of the double bond in 19 furnishes dihydroagaro-... 

The tin hydrides find important applications as reducing agents. Many of their reactions (particularly the reduction of alkyl halides and the hydrostannation of simple alkenes and alkynes) arc known to proceed through RaSn- intermediates, and this aspect of their chemistry is referred to in Section II,G. 

The inertness of ordinary double bonds toward metallie hydrides is quite useful, since it permits reduction of, say, a carbonyl or nitro group, without disturbing a double bond in the same molecule (see Chapter 19 for a discussion of selectivity in reduction reactions). Sodium in liquid ammonia also does not reduce ordinary double bonds, although it does reduce alkynes, allenes, conjugated dienes, and aromatic rings (15-14). 

Iron porphyrins containing vinyl ligands have also been prepared by hydromet-allation of alkynes with Fe(TPP)CI and NaBH4 in toluene/methanol. Reactions with hex-2-yne and hex-3-yne are shown in Scheme 4. with the former giving two isomers. Insertion of an alkyne into an Fe(III) hydride intermediate, Fe(TPP)H, formed from Fe(TPP)Cl with NaBH4, has been proposed for these reactions. " In superficially similar chemistry, Fe(TPP)CI (present in 10 mol%) catalyzes the reduction of alkenes and alkynes with 200 mol% NaBH4 in anaerobic benzene/ethanol. For example, styrene is reduced to 2,3-diphenylbutane and ethylbenzene. Addition of a radical trap decreases the yield of the coupled product, 2,3-diphenylbutane. Both Fe(lll) and Fe(II) alkyls, Fe(TPP)CH(Me)Ph and [Fe(TPP)CH(Me)Ph] , were propo.sed as intermediates, but were not observed directly. ... 

Diyne 66, which possesses a three carbon linkage between the alkynes, also reacts with aldehyde 67 in presence of [Ni(COD)J/SIPr catalytic system (Scheme 5.19). However, the connectivity of the dienone 69 obtained from this diyne was different from those obtained from diyne 60. In the former case, adduct 69 was obtained from a )5-hydride elimination of the nickelacycle 68 instead of a reductive elimination. 

Since activation of the N-H bond of PhNHj by Ru3(CO)i2 has been reported to take place under similar conditions [306], it has been proposed that the reaction mechanism involves (i) generation of an anUido ruthenium hydride, (ii) coordination of the alkyne, (iii) intramolecular nucleophilic attack of the nitrogen lone pair on the coordinated triple bond, and (iv) reductive ehmination of the enamine with regeneration of the active Ru(0) center [305]. 

After formation of Pd(0) from the Pd(II) precursor, oxidative addition of the P-H bond could give a hydride complex. Insertion of the alkyne into either the Pd-P or Pd-H bond, followed by reductive eUmination, gives the product Consistent with this proposal, treatment of Pt(PEt3)3 with PH(0)(0Et)2 gave the P-H oxidative addition product 14, which reacted with phenylacetylene to give primarily (>99 1) the Markovnikov alkenylphosphonate (Scheme 5-18, Eq. 2). 

P-H oxidative addition followed by alkyne insertion into a Pd-P bond gives the re-gio-isomeric alkenyl hydrides 15 and 16. Protonolysis with diaUcyl phosphite regenerates hydride 17 and gives alkenylphosphonate products 18 and 19. Insertion of alkene 18 into the Pd-H bond of 17 followed by reductive eUmination gives the bis-products, but alkene 19 does not react, presumably for steric reasons. P-Hydride elimination from 16 was invoked to explain formation of trace product 20. 

Scheme 5.7 illustrates these and other applications of the hydride donors. Entries 1 and 2 are examples of reduction of alkyl halides, whereas Entry 3 shows removal of an aromatic halogen. Entries 4 to 6 are sulfonate displacements, with the last example using a copper hydride reagent. Entry 7 is an epoxide ring opening. Entries 8 and 9 illustrate the difference in ease of reduction of alkynes with and without hydroxy participation. 

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