Dienyne Metathesis

RCM of a dienyne was also a key step in Mori s recent total synthesis of the alkaloid erythrocarine (447) [183]. The tetracyclic framework of447 was elaborated in the penultimate step, by exposing the hydrochloride of metathesis precursor 445 (1 1 diastereomeric mixture at the carbinol center) to first-generation catalyst A. The tandem process occurred smoothly within 18 h at room temperature leading to tetracycles 446 (1 1 mixture) in quantitative yield. Deprotection of the a-acetoxy isomer 446a led to 447 (Scheme 88). 

Scheme 5.1 Tandem cyclopropanation/ring closing metathesis of dienyne using Gmbbs catalyst...

Scheme 6.71 Dienyne (reaction a) and triyne (reaction b) domino ring-closing metathesis reactions.

More recently, the bis-cyclopropanation of dienyne 325 has also been investigated by Fensterbank, Malacria, and Marco-Contelles to construct highly strained cyclopropyl-substituted diquinane frameworks 327 in a completely diastereoselective manner (Scheme 84). 3 It is noteworthy that the formal metathesis product was also observed in these reactions, albeit as a minor product, and that a simple introduction of a methyl group to one of the two ene moieties substantially affects the reaction. 

Diver has recently reported new entries for the assembly of tetracyclic compounds.304 Interestingly, ruthenium catalysts for metathesis have also yielded tricyclic products by incorporating a cyclopropane from dienynes, a process reminiscent of Dixneuf s work (see above). 

In turn, the propensity of 1 to respond to steric hindrance can be used to control the site of initiation of an RCM reaction in a polyene substrate (Scheme 9) [20]. Thus, dienyne 25 reacts with the catalyst regioselectively at the least substituted site the evolving ruthenium carbene 26 undergoes a subsequent enyne metathesis leading to a new carbene 27, which is finally trapped by the disubsti-tuted olefin to afford the bicyclo[4.4.0]decadiene product 28. By simply reversing the substitution pattern of the double bonds, the complementary bicyclo [5.3.0] compound 32 is formed exclusively, because the cyclization cascade is then triggered at the other end of the substrate. Note that in both examples tri-substituted olefins are obtained by means of a ruthenium based metathesis catalyst [20] ... 

The symmetrical dienyne 58a was converted to a fused bicyclo [4.3.0] ring in 95% yield [17] (Eq. 27). With substrate 58c containing an unsymmetrical diene tether, two different products, 59c and 59c, were obtained in a ratio of 1 to 1 (Eq. 28). The reaction course in the formation of the different bicyclic rings is shown in Scheme 8. This dienyne metathesis is also catalyzed by tungsten or molybdenum complex 62 or 63 (Fig. 1), and a dienyne bearing terminal alkyne 58b could be cyclized to give 59b in 97% yield. 

Group-selective enyne metathesis of dienyne 127f having a large substituent on the alkyne proceeds in the presence of aUcene 130 to give small ring compound 131... 

Dienyne metathesis has been further extended to the synthesis of polycyclic compounds 28 from poly ene-ynes 27 by one step (Scheme 9). 

Synthesis of a polyoxygenated bicyclic compound containing a medium-sized ring is achieved via tandem metathesis of the dienyne derived from D-ribose (Equation (11)). ... 

A concise total synthesis of dehydrohomoancepsenolide is achieved in an optically active form. The key steps are alkene metathesis and alkyne metathesis. A three-component coupling reaction affords dienyne 137, which undergoes ring-closing alkene metathesis in the presence of the first-generation ruthenium carbene complex to give 138,... 

Many natural products contain fused bicyclic structures and the dienyne metathesis reaction may well open up new and more efficient routes for their synthesis. 

Our group has used a combined metathesis-PKR for the synthesis of tricyclic compounds in one step. The process starts from pure cobalt complexed dienynes 52. The cobalt cluster acts first as a protecting group to avoid undesired enyne metathesis processes. The methodology allows the formation of tricyclic [6.5.5] (53) and [7.5.5] (54) structures including, in some examples, oxygen or nitrogen. Tricycles 53 are obtained in a total stereoselective manner, while compounds 54 are formed as mixtures of two diastereomers (Scheme 17) [110]. 

Illustrating the high potential of these reactions, cascade ring-closing metathesis of dienynes or trienynes have also provided access to fused 6,8,6-tricarbocyclic systems [14], and to a highly functionalized 5,7,6-tricyclic ring system related to the terpenoid guanacastepene A structure [15]. 

Recently, a catalytic system consisting of a second generation Grubbs catalyst or an in situ non-carbenic ruthenium complex have allowed a cascade catalytic reaction of cyclopropanation/ring closing metathesis of dienynes containing a malonate or bissulfone moiety. In this reaction, the interaction between the triple bond and one double bond gives a bicyclic product via cyclopropanation, and then the subsequent diene RCM produces the last cyclization step [16] (Scheme 6). 

A catalytic tandem cyclopropanation-ring-closing metathesis of dienyne 80 led to derivative 81 in good yield (Scheme 30 <2004JA9524>). For internal alkynes, carbene-mediated ring-closing enyne metathesis was observed. Less favorable alkyne binding leads to preferential reactions of the metal carbene with the 1-alkene moiety. 

A more complex mechanism via enyne cyclization and metathesis followed by metalladiene cycloaddition is discussed in the formation of bicyclo[3.1.0]hexanes from dienynes and dienes in the presence of a palladacyclopentadiene catalyst. ... 

The ruthenium carbene catalyst also effects the ring-closing metathesis of many acyclic dienynes to form fused bicyclic rings, containing five-, six-, and seven-... 

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