Diynes catalysts

The metathesis of ene-ynamides has been investigated by Mori et al. and Hsung et al. [80]. Second-generation ruthenium catalysts and elevated temperatures were required to obtain preparatively useful yields. Witulski et al. published a highly regioselective cyclotrimerization of 1,6-diynes such as 98 and terminal alkynes using the first-generation ruthenium metathesis catalyst 9... 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

Haloalkynes (R—C=C—X) react with ArSnBu3 and Cul to give R—C= C—Ar. Acetylene reacts with two equivalents of iodobenzene, in the presence of a palladium catalyst and Cul, to give 1,2-diphenylethyne. 1-Trialkylsilyl alkynes react with 1-haloalkynes, in the presence of a CuCl catalyst, to give diynes and with aryl triflates to give 1-aryl alkynes. Alkynes couple with alkyl halides in the presence of Sml2/Sm. Alkynes react with hypervalent iodine compounds " and with reactive alkanes such as adamantane in the presence of AIBN. ... 

This type of alkyne dimerization is also catalyzed by certain nickel complexes, as well as other catalysts and has been carried out internally to convert diynes to large-ring cycloalkynes with an exocyclic double bond. ... 

Palladium salts are able to catalyse diyne carbonylation, so the reaction can be performed at room temperature under 1 atm of carbon monoxide. Thiourea (H2NCSNH2), which is added to stabilise the Pd catalyst (Scheme 34), is described as the best ligand for the efficiency of this reaction [124]. 

Pyridine compounds 45 can also be produced by the NHC-Ni catalysed cycloaddition between nitriles 43 and diynes 44 (Scheme 5.13) [16]. The SIPr carbene was found to be the best ligand for the nickel complex in this reaction. The reaction required mild reaction conditions and low catalyst loadings, as in the case of cycloaddition of carbon dioxide. In addition to tethered aUcynes (i.e. diynes), pyridines were prepared from a 3-component coupling reaction with 43 and 3-hexyne 23 (Scheme 5.13). The reaction of diynes 44 and nitriles 43 was also catalysed by a combination of [Ni(COD)J, NHC salts and "BuLi, which generates the NHC-Ni catalyst in situ. The pyridines 45 were obtained with comparable... 

A plausible mechanism for the [2+2+2] cycloaddition reactions between diynes and heterocumnlenes (or nitriles) is shown in Scheme 5.16. Initially [2+2] oxidative addition of one alkyne and the heterocnmnlene (or nitrile) forms the five-mem-bered intermediate 54 compound 55 is formed after the insertion of the second alkyne and finally the seven-membered compound 55 undergoes reductive elimination to afford the prodnct 56 and regenerate the Ni(0) catalyst. 

Asymmetric hydrosilylation can be extended to 1,3-diynes for the synthesis of optically active allenes, which are of great importance in organic synthesis, and few synthetic methods are known for their asymmetric synthesis with chiral catalysts. Catalytic asymmetric hydrosilylation of butadiynes provides a possible way to optically allenes, though the selectivity and scope of this reaction are relatively low. A chiral rhodium complex coordinated with (2S,4S)-PPM turned out to be the best catalyst for the asymmetric hydrosilylation of butadiyne to give an allene of 22% ee (Scheme 3-20) [59]. 

Diynes can be employed in intramolecular ring-closing metathesis. Several catalysts involving Mo and W have been investigated. These cyclizations can be combined with semihydrogenation to give macrocycles with Z-double bonds. 

Amatore et al. developed an aqueous cross-coupling reaction of terminal alkynes with 1-iodoalkynes using a water-soluble Pd(0) catalyst prepared in situ from Pd(OAc)2 and sulfonated triphenylphosphine P(C6H4 — m-SCENa (TPPTS) without Cu(I) promoter, giving diynes with moderate yields (43-65%)(Eq. 4.22) 42... 

Cationic palladium complex 121 reductively coupled enynes (Eq. 20) using trichlorosilane as the stoichiometric reductant [71]. This combination of catalyst and silane afforded silylated methylenecyclopentanes such as 122 in good yield from enynes such as 123. Attempts to develop an enantioselective version of this reaction were not successful [71]. When enediyne 124 was cyclized in the presence of trichlorosilane, the reaction favored enyne cycli-zation 126 by a 3 1 ratio over diyne cyclization to 125 (Eq. 21). In contrast, when the more electron-rich dichloromethylsilane was used as the reductant, diyne cyclization product 125 was preferred in a ratio of 4 1 [71]. Selectivities of up to 10 1 for enyne cyclization were observed, depending on the substrate employed [72],... 

Rhodium complexes facilitate the reductive cydization of diyne species in good yield, although the product olefin geometry depends on the catalysts used. Moderate yields of -dialkylideneclopentane 169 resulted if a mixture of diyne 146 and trialkylsilane was added to Wilkinson s catalyst ClRh[PPh3]3 (Eq. 33) [101]. If, however, the diyne followed by silane were added to the catalyst, a Diels-Alder derived indane 170 was produced (Eq. 34). Cationic Rh complex, (S-BINAP)Rh(cod) BF4, provides good yields of the Z-dialkylidenecyclopentane derivatives, although in this case, terminal alkynes are not tolerated (Eq. 35) [102]. 

Itoh and coworkers [223] have shown that fullerene derivatives as 6/2-113, which to date have been prepared in a stepwise procedure, can be obtained in a three-component domino process by treatment of diynes 6/2-109, dimethylphenylsilane 6/2-110 and fullerene (C60) in the presence of a Rh-catalyst [223]. Interestingly, using maleic anhydride as dienophile failed to give the desired cycloadduct, whereas Cso -in spite of its strong tendency to form complexes with various transition metals [224] - never suppressed the catalytic silylative cyclization step to give the diene 6/2-112 (Scheme 6/2.24). 

An interesting series of ring-closing alkyne metathesis reactions (RCAM) has recently been reported by Fiirstner and coworkers (Scheme 6.72) [152], Treatment of biaryl-derived diynes with 10 mol% of a catalyst prepared in situ from molybdenum hexacarbonyl and 4-(trifluoromethyl)phenol at 150 °C for 5 min led to a ca. 70% iso-... 

The rhodium-catalyzed cyclization/hydrosilylation of internal diyne proceeds efficiently with high stereoselectivity (Scheme 106). However, terminal diynes show low reactivity to rhodium cationic complexes. Tolerance of functionalities seems to be equivalent between the rhodium and platinum catalysts. The bulkiness of the hydrosilane used is very important for the regioselectivity of the rhodium-catalyzed cyclization/hydrosilylation. For example, less-hindered dimethylethylsilane gives disilylated diene without cyclization (resulting in the double hydrosilylation of the two alkynes), and /-butyldimethylsilane leads to the formation of cyclotrimerization compound. 

Ruthenium(ll)-catalyzed cycloadditions of diynes with bicycloalkenes illustrate the synthetic importance of ruthena-cyclopentatrienes as biscarbenoid intermediates.380 Reaction of 1,6-diyne 448 and biscyclic alkene 449 with ruthenium catalyst afforded a mixture of biscyclopropanation product 450 and cyclotrimerization product 451 (Scheme 113). 

Hydrative cyclization of diynes with ruthenium catalyst has been reported for the synthesis of sulfolenes or enones in aqueous medium.381 Reactions of unsymmetrical 1,6-diynes have been investigated, and some substrates are found to exhibit a directing effect of the ketone moiety in a pendant group. 

Beyond palladium, it has recently been shown that isoelectronic metal complexes based on nickel and platinum are active catalysts for diyne reductive cyclization. While the stoichiometric reaction of nickel(O) complexes with non-conjugated diynes represents a robust area of research,8 only one example of nickel-catalyzed diyne reductive cyclization, which involves the hydrosilylative cyclization of 1,7-diynes to afford 1,2-dialkylidenecyclohexanes appears in the literature.7 The reductive cyclization of unsubstituted 1,7-diyne 53a illustrates the ability of this catalyst system to deliver cyclic Z-vinylsilanes in good yield with excellent control of alkene geometry. Cationic platinum catalysts, generated in situ from (phen)Pt(Me)2 and B(C6F5)3, are also excellent catalysts for highly Z-selective reductive cyclization of 1,6-diynes, as demonstrated by the cyclization of 1,6-diyne 54a.72 The related platinum bis(imine) complex [PhN=C(Me)C(Me)N=Ph]2Pt(Me)2 also catalyzes diyne hydrosilylation-cyclization (Scheme 35).72a... 

The stoichiometric reaction of low-valent rhodium salts with l, -diynes to afford rhodacyclopentadiene complexes is well established and has been reviewed.73 733 The first rhodium-catalyzed reductive cyclization of a non-conjugated diyne has been reported only recently.74 743 The stereochemical outcome of the rhodium-catalyzed hydrosilylation-cyclization is dependent upon the choice of catalyst. Whereas reductive cyclization of 1,6-diyne 54a catalyzed by Rh4(CO)i2 provides modest yields of the Z-vinylsilane 54c, exposure of 54a to Wilkinson s catalyst... 

In the case of unsymmetrical alkynes, the carboxylation yielded a mixture of regioisomers. But the reaction in the carbon atom having an alkyl substituent in the alkyne unit seemed to be more preferred than the one with an aryl substituent (Scheme 24).30 The carboxylation of conjugated diynes by Ni/PTMDA under electrolytic conditions took place predominantly at an internal carbon atom of the diyne unit to give 74 as a major product (Scheme 25)38 When Ni(cod)2/DBU was used as a catalyst, however, the carboxylation occurred exclusively at the terminal carbon (Scheme 26).31... 

---