Alkynes enyne derivatives

AUylzirconium complexes are conveniently obtained by the regio- and stereoselective hydrozirconation of allene [127-133] and can be, for example, used subsequently for the MAO-catalyzed allylzirconation of alkynes to prepare enyne derivatives [132]. Alternatively, the preparation of (E)-l,3-dienes from aldehydes and the appropriate allylstannane zirconocene derivative (R = SnBu,) is accomplished (Scheme 8-17) [131], Note that addition of [Cp2Zr(H)Cl[n (1) on the aUenyl reagent with the... 

Pauson-Khand cyclization of vic-enyne derivatives of /3-lactams gave good yields of fused tricyclic compounds. The 1,4-disubstituted 2-azetidinone 391 and cobalt octacarbonyl gave the alkyne-cobalt carbonyl complex, which on thermolysis gave the tricycle 392 in 95% yield (Equation 54). When the complexes of 393 with cobalt octacarbonyl were treated with TMANO, a lower yield (65%) of 394 was obtained (Equation 55). A single diastereoisomer was formed in each case <1996TL6901>. 

Palladium-catalyzed alkynylation is an important method for the synthesis of alkynes [44]. Comasseto et al. described the efficient coupling of vinylic tellurides with alkynes using PdCl2/CuCl2 as the catalytic system to afford enyne derivatives. In order to further understand the mechanism of this reaction, a study using the ESI-MS/MS technique was performed by the authors [45]. The particular reaction studied by mass spectrometry is shown in Scheme 7.24. The coupling retains the doublebond geometry. 

KabaUca, G. W., Wu, Z., Ju, Y. 2004. A new halopropargylation of alkynes promoted by boron trihalides, highly stereo- and regioselective syntheses of substituted (Z)-l-halo-l,4-enyne derivatives. Org. Lett. 6 3929-3931. 

Pal et al. reported a facile and mild procedure for the regio- and stereospecific synthesis of novel enyne derivatives 131 via the copper-free palladium-catalyzed sequential coupling of 3-iodo(thio)flavone 130 with terminal alkynes [53] (Schane 6.34). 

C-C double bond cleavage of an enyne derivative using a metallocene derivative was reported by Takahashi and coworkers [34]. When an alkyne was treated with Cp2ZrEt2 and vinyl bromide or vinyl ether in this order after hydrolysis a 2,3-disubstituted diene derivative was obtained (Eqs. 22 and 23). Bis-silyl acetylene, aryl-substituted acetylene or cyclohexyl-substituted alkyne could be used as internal alkynes. 

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). 

Enynes 71 react with aldehydes 61 in the presence of the [Ni(COD)J/SIPr catalytic system to afford two distinct products 72 and 73 (Scheme 5.20) [20b], The enone 72 is derived from aldehyde addition with the alkyne moiety while the adduct 73 arises from the aldehyde addition with the alkene moiety. The product distribution is dependent on the substituent on either the alkyne or alkene moieties. The reaction between 71 and ketones 74 led to the unprecedented formation of pyrans 75 (Scheme 5.20). The reaction showed to be highly regioselective in aU the cases, the carbonyl carbon was bound to the olefin. 

Palladium complexes are effective catalysts for the reductive cydization of enyne substrates [53,54], The first report of catalytic cydization of 1,6- and 1,7-enynes 115a,b to cyclopentane 116a and cyclohexane 116b derivatives appeared in 1987 (Eq. 19) [70]. The authors proposed that the Pd(II) species 117 forms by oxidative addition of acetic acid to Pd(0) (Scheme 25). Complex 117 hydrometallates the alkyne to give 118, which cyclizes to provide... 

In a similar way as described for the hydroformylation, the rhodium-catalyzed silaformylation can also be used in a domino process. The elementary step is the formation of an alkenyl-rhodium species by insertion of an alkyne into a Rh-Si bond (silylrhodation), which provides the trigger for a carbocyclization, followed by an insertion of CO. Thus, when Matsuda and coworkers [216] treated a solution of the 1,6-enyne 6/2-87 in benzene with the dimethylphenylsilane under CO pressure (36 kg cm"2) in the presence of catalytic amounts of Rh4(CO)12, the cyclopentane derivative 6/2-88 was obtained in 85 % yield. The procedure is not restricted to the formation of carbocycles rather, heterocycles can also be synthesized using 1,6-enynes as 6/2-89 and 6/2-90 with a heteroatom in the tether (Scheme 6/2.19). Interestingly, 6/2-91 did not lead to the domino product neither could 1,7-enynes be used as substrates, while the Thorpe-Ingold effect (geminal substitution) seems important in achieving good yields. 

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. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

Subsequently, high chemoselectivity and enantioselectivity have been observed in the asymmetric epoxidation of a variety of conjugated enynes using fructose-derived chiral ketone as the catalyst and Oxone as the oxidant. Reported enantioselectivities range from 89% to 97%, and epoxidation occurs chemoselectively at the olefins. In contrast to certain isolated trisubstituted olefins, high enantioselectivity for trisubstituted enynes is noticeable. This may indicate that the alkyne group is beneficial for these substrates due to both electronic and steric effects. 

Wang s approach for the synthesis of enyne-allenes focused on ene-allenyl iodide 45 (Scheme 14.12) [24]. Palladium-catalyzed Sonogashira reaction of 45 with terminal alkynes 46 (R= Ph or CH2OH) proceeded smoothly under mild reaction conditions in the presence of the cocatalyst cuprous iodide and n-butylamine. The initially formed enyne-allene 47b with substituent R= CH2OH cyclized spontaneously to the corresponding a-methylstyrene derivative 48. 

The dimerization of alkynes is a useful method for forming compounds such as enynes from simple alkynes [13]. The iridium-catalyzed dimerizahon of 1-alkyries was first reported by Crabtree, and afforded (Zj-head-to-head enynes using [Ir(biph)(PMe3)Cl] (biph = biphenyl-2,2 -diyl) as a catalyst [14]. Thereafter, an iridium complex generated in situ from [Ir(cod)Cl]2 and a phosphine ligand catalyzed the dimerizahon of 1-alkynes 1 to give (Tj-head-to-head enyne 2, fZj-head-to-head enyne 3, or 1,2,3-butatriene derivatives 4 in the presence of hiethylamine... 

The Lee group originated rhodium alkenylidene-mediated catalysis by combining acetylide/alkenylidene interconversion with known metal vinylidene functionalization reactions [31], Thus, the first all-intramolecular three-component coupling between alkyl iodides, alkynes, and olefins was realized (Scheme 9.17). Prior to their work, such tandem reaction sequences required several distinct chemical operations. The optimized reaction conditions are identical to those of their original two-component cycloisomerization of enynes (see Section 9.2.2, Equation 9.1) except for the addition of an external base (Et3N). Various substituted [4.3.0]-bicyclononene derivatives were synthesized under mild conditions. Oxacycles and azacycles were also formed. The use of DMF as a solvent proved essential reactions in THF afforded only enyne cycloisomerization products, leaving the alkyl iodide moiety intact. 

Most of these catalytic systems are able to dimerize either aromatic alkynes, such as phenylacetylene derivatives, or aliphatic alkynes, such as trimethylsilylacetylene, tert-butylacetylene and benzylacetylene. The stereochemistry of the resulting enynes depends strongly on both the alkyne and the catalyst precursor. It is noteworthy that the vinylidene ruthenium complex RuCl(Cp )(PPh3)(=C=CHPh) catalyzes the dimerization of phenylacetylene and methylpropiolate with high stereoselectivity towards the ( )-enyne [65, 66], and that head-to-tail dimerization is scarcely favored with this catalyst. It was also shovm that the metathesis catalyst RuCl2(P-Cy3)2(=CHPh) reacted in refiuxing toluene with phenylacetylene to produce a... 

Blechert carried out a tandem reaction of enynes in the presence of olefins instead of ethylene (Scheme 21). Treatment of cyclopentenol derivative 58a with Ic in the presence of an alkene affords 59a. The five-membered ring in estrone 58b is cleaved by Ic to give 59 and an alkene part is introduced on the six-membered C ring. However, cycloalkenyl amine derivative 60 is treated in a similar manner in the presence of an allyl alcohol derivative to give pyrrolidine derivative 61, and in this case, an alkene part is introduced on the diene moiety. Presumably, ruthenium carbene complex XVI reacts with an alkyne part to produce the pyrrolidine ring with a regioselectivity opposite to the other cases. 

Another reaction is reductive cyclization. 1,6-Diynes and 1.6-enynes undergo reductive cyclization using hydrosilanes as a hydrogen source in AcOH. The 1,6-diynes 91 and 95 are converted into the 1,2-dialkylidenecyclopentane derivatives (1,3-dienes) 94 and 96. Triethylsilane is used as a hydrogen donor for the reaction[48]. The reaction involves the formation of a vinylpalladium bond in 92 via the insertion of an alkyne into the Pd—H bond, followed by the alkyne insertion to give 93, which is hydrogenolyzed with Si—H to give the 1,3-dienes 94 and 96. 

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