Intermolecular with 1,3-enyne

The intermolecular ruthenium enyne Alder-ene reaction has been extended to the stereoselective preparation of enamines (Equation (26)).39 The yields obtained for this reaction were high with allylacetamides, -benzamides,... 

Intramolecular Pauson Khand reactions are synthetically more useful compared to their intermolecular counterparts. Enynes separated by either three or four atoms (1,6- or 1,7-enynes) cyclize in an intramolecular fashion upon complexa-tion with Co2(CO)s, and subsequent heating to form bicycUc enones. Angular tricyclic ring systems have been prepared in... 

AUyl propargyl ethers (oxygen-tethered 1,6-enynes) also react intermolecularly with alcohols or water to give six-membered ring acetals or hemiacetals (equation 52) AUyl silyl alkynes react somewhat similarly with Au(I) catalysts in the presence of alcohols to give cyclic or open alkenylsilanes (equation 59). Both types of products are the result of... 

Arenes from enynes and diynes. A novel synthesis of alkynylarenes by the intermolecular cycloaddition of enynes and diynes has been developed. With enynes alone the products are 2,6-disubstituted styrenes which are formed by cyclodimerization. Note that benzynes undergo trimerization to give triphenylenes in situ, e.g., by treatment of o-trimethylsilylphenyl triflate with CsF in the presence of (PhjPl.Pd. ... 

The precedent results shown in Scheme 2.3 suggested that aldehydes could react intermolecularly with 1,6-enynes possessing a terminal alkene moiety through cyclopropyl carbene 1-12 see (Scheme 2.4). Nevetheless, based on our observation of the intramolecular reaction of carbonyl compounds with 1,6-enynes I-l pos-... 

Even though not strictly speaking belonging to enyne cycloisomerization, an alkyne and an alkene can react intermolecularly with each other provided the alkyne is properly activated. Zhang and co-workers reported a number of such cycloadditions where a gold-mediated cascade was initiated by carbonyl addition to the alkyne moiety. The resulting 1,4- or 1,3-dipoles could then participate to formal [4 + 2] and [3 + 2] cycloadditions with an olefinic partner, giving access to... 

The benzene derivative 401 by the intermolecular insertion of acrylate[278], A formal [2 + 2+2] cycloaddition takes place by the reaction of 2-iodonitroben-zene with the 1,6-enyne 402. The neopentylpalladium intermediate 403 undergoes 6-endo-lrig cyclization on to the aromatic ring to give 404[279],... 

Intermolecular enyne metathesis has recently been developed using ethylene gas as the alkene [20]. The plan is shown in Scheme 10. In this reaction,benzyli-dene carbene complex 52b, which is commercially available [16b], reacts with ethylene to give ruthenacyclobutane 73. This then converts into methylene ruthenium complex 57, which is the real catalyst in this reaction. It reacts with the alkyne intermolecularly to produce ruthenacyclobutene 74, which is converted into vinyl ruthenium carbene complex 75. It must react with ethylene, not with the alkyne, to produce ruthenacyclobutane 76 via [2+2] cycloaddition. Then it gives diene 72, and methylene ruthenium complex 57 would be regenerated. If the methylene ruthenium complex 57 reacts with ethylene, ruthenacyclobutane 77 would be formed. However, this process is a so-called non-productive process, and it returns to ethylene and 57. The reaction was carried out in CH2Cl2 un-... 

In Section 9.2, intermolecular reactions of titanium—acetylene complexes with acetylenes, allenes, alkenes, and allylic compounds were discussed. This section describes the intramolecular coupling of bis-unsaturated compounds, including dienes, enynes, and diynes, as formulated in Eq. 9.49. As the titanium alkoxide is very inexpensive, the reactions in Eq. 9.49 represent one of the most economical methods for accomplishing the formation of metallacycles of this type [1,2]. Moreover, the titanium alkoxide based method enables several new synthetic transformations that are not viable by conventional metallocene-mediated methods. 

The rhodium A-heterocyclic carbine complex [Rh(IMes)(COD)] [IMes = A,A -bis(2,4,6-trimethylphenyl)imidazol-2-ylidine COD = cycloocta-1,5-diene] catalyses the 4 + 2 + 2-carbocyclization of 1,6-enynes (191) to carbocycles [(192) and (193)] (Scheme 54).226 Computational and experimental evidence of a new reaction pathway for the diastereospecific intermolecular rhodium-catalysed 4 + 2 + 2-carbocyclization (g) reactions of 1,6-enynes with r-components has been reported.227... 

Until recently, intermolecular enyne metathesis received scant attention. Competing CM homodimerisation of the alkene, alkyne metathesis and polymerisation were issues of concern which hampered the development of the enyne CM reaction. The first report of a selective ruthenium-catalysed enyne CM reaction came from our laboratories [106]. Reaction of various terminal alkynes 61 with terminal olefins 62 gave 1,3-substituted diene products 63 in good-to-excellent yields (Scheme 18). It is interesting that in these and all enyne CM reactions subsequently reported, terminal alkynes are more reactive than internal analogues, and 1,2-substituted diene products are never formed thus, in terms of reactivity and selectivity enyne CM is the antithesis of enyne RCM. The mechanism of enyne CM is not well understood. It would appear that initial attack is at the alkyne however, one report has demonstrated initial attack at the alkene (substrate-dependent) is also possible, see Ref. [107]. 

Enyne systems are also capable of impressive multiple RRM transformations. For the first such example see Ref. [119]. The reaction of a ruthenium alkyli-dene with an alkyne produces a new vinyl alkylidene, which can participate in further intramolecular or intermolecular metathesis reactions to form fused ring systems. This has led Grubbs to designate alkynes in such systems as relays . In a noteworthy example, Zuercher et al. [ 120] constructed the four fused rings of the steroid backbone 68 in one efficient step using tandem enyne re-... 

Later on, Schreiber used consecutively these two reactions in the key step for the synthesis of diterpene (-i-)-epoxydictimene (73), starting from natural (R)-pulegone [116,117]. This approach was built on their preliminary studies on Lewis acid mediated intermolecular Nicholas reactions [118]. They prepared functionalized enyne 70 bearing a mixed acetal. This compound was transformed into its dicobalt-hexacarbonyl complex and, in the presence of a carefully selected Lewis acid, it formed a stabilized carbocation by release of the more accessible ethyl moiety. This cation reacted intramolecularly with the allylsilane giving the central eight membered ring of the natural product... 

Some double-bond shifts and isomerizations have been observed previous to the PKR. Sometimes 1,6 enynes have reacted partially as 1,7 enynes, or 1,8-enynes have isomerized to 1,7-enynes prior to the PKR [59,60,133]. In some intermolecular examples strained alkenes have isomerized totally before the cyclization giving unexpected products. An example, in the synthesis of triquinanes like 120, depicted in Scheme 33, the starting alkene 118 was isomerized to 119 prior to the reaction with 117 [134,135]. 

Vinyl carbene intermediates can also be generated from the intermolecular addition of TMS diazomethane onto an alkyne component in the presence of Ni(cod)2 as a catalyst. If a diene moiety is also present, as in 1,6-enyne system 78, reaction of the intermediate nickel carbenoid with this partner gives birth to the fused 5,7-bicyclic system 79 in fair yields (Scheme 34). Several mechanistic scenarios are possible from generic precursor 78, including a metathesis-type sequence to generate a nickelacyclobutane 80, followed by... 

The intermolecular enyne cross metathesis, and consecutive RCM, between a terminal alkyne and 1,5-hexadiene produces cyclohexadienes, by cascade CM-RCM reaction, and trienes, formed during the sole CM step. Studies of various parameters of the reaction conditions did not show any improvement of the ratio of desired cyclohexadiene product [25] (Scheme 12). The reaction with cyclopentene instead of hexadiene as the alkene leads to 2-substituted-l,3-cycloheptadienes [26]. After the first cyclopentene ROM, the enyne metathesis is favored rather than ROMP by an appropriate balance between cycloalkene ring strain and reactivity of the alkyne. 

Diynes are also used to perform intermolecular enyne metathesis. With the objective of producing functionalized hetero- and carbocycles, a cascade diyne-alkene cross metathesis leading to five-membered cyclic products has recently been proposed [27] (Scheme 13). 

Formation of polycyclic ring systems via intermolecular reactions of Fischer carbenes with alkynes can be achieved. In a metathesis-type reaction, reactions of 1,6-enynes afford... 

The intramolecular amination of 1,5-enynes proceeds similarly to the intramolecular hydroxycyclizations of related substrates to give the products shown in equations (60) and (61). The intermolecular reaction of 1,6-enynes with a series of carbamates RO2CNH2 or anilines ArNH2 has also been reported. ... 

Similarly, the intermolecular reaction between enynes and alkenes proceeds with Au(I) catalysts (equation 69). ... 

Carbonyl compounds can also act as the nncleophtles in intermolecular processes with 1,6-enynes. Thus, the gold(I)-catalyzed reaction between enynes and aldehydes or acetone gives stereoselectively tricyclic compounds (equation 71). The transformation is mechanistically intriguing, as it proceeds by a rearrangement of the initially formed cyclopropyl gold carbene (the intermediate in the donble-cleavage mechanism), which is then trapped by the carbonyl compound to form the products. 

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