Enol olefin metathesis

The synthesis in Scheme 13.49 features use of an enantioselective allylic boronate reagent derived from diisopropyl tartrate to establish the C(4) and C(5) stereochemistry. The ring is closed by an olefin metathesis reaction. The C(2) methyl group was introduced by alkylation of the lactone enolate. The alkylation is not stereoselective, but base-catalyzed epimerization favors the desired stereoisomer by 4 1. 

Tandem carbonyl olefmation—olefm metathesis utilizing the Tebbe reagent or dimethyl-titanocene is employed for the direct conversion of olefmic esters to six- and seven-mem-bered cyclic enol ethers. Titanocene-methylidene initially reacts with the ester carbonyl of 11 to form the vinyl ether 12. The ensuing productive olefm metathesis between titano-cene methylidene and the cis-1,2 -disubstituted double bond in the same molecule produces the alkylidene-titanocene 13. Ring-closing olefin metathesis (RCM) of the latter affords the cyclic vinyl ether 14 (Scheme 14.8) [18]. This sequence of reactions is useful for the construction of the complex cyclic polyether frameworks of maitotoxin [19]. 

Formation of cyclic enol ethers by carbonyl methylenation—olefin metathesis. 

As will be discussed more thoroughly in Section 3.2.5, transition metal carbene complexes can mediate olefin metathesis. Because heteroatom-substituted carbene complexes are usually less reactive towards olefins than the corresponding nonheteroatom-substituted complexes, it is, e.g., possible to use enol ethers to terminate living polymerization or other types of metathesis reaction catalyzed by a non-heteroatom-substituted carbene complex. Olefin metathesis can also be used to prepare new heteroatom-substituted carbene complexes (Figure 2.15, Table 2.11). 

In addition to reactions characteristic of carbonyl compounds, Fischer-type carbene complexes undergo a series of transformations which are unique to this class of compounds. These include olefin metathesis [206,265-267] (for the use as metathesis catalysts, see Section 3.2.5.3), alkyne insertion, benzannulation and other types of cyclization reaction. Generally, in most of these reactions electron-rich substrates (e.g. ynamines, enol ethers) react more readily than electron-poor compounds. Because many preparations with this type of complex take place under mild conditions, Fischer-type carbene complexes are being increasingly used for the synthesis [268-272] and modification [103,140,148,273] of sensitive natural products. 

The group of Samuel Danishefsky at the Sloan-Kettering Institute for Cancer Research in New York has also been active in the synthesis of the natural epothilones and biologically active analogs. One of these syntheses also uses the olefin metathesis reaction (not shown). The synthesis in Scheme 13.51 uses an alternative approach to create the macrocycle. One of the key steps is a Suzuki coupling carried out at step H-(l,2) between a vinylborane and vinyl iodide. The macrocyclization is an aldol addition reaction at step H-4. The enolate of the acetate adds to the aldehyde, creating the C(2)-C(3) bond of the macrolactone and also establishing the stereocenter at C-3. 

The synthetic strategies used for the preparation of pyrans on insoluble supports have mainly been hetero-Diels-Alder reactions of enones with enol ethers and ringclosing olefin metathesis (Table 15.33). Benzopyrans have been prepared by hetero-Diels-Alder reactions of polystyrene-bound o-quinodimethanes with aldehydes. The required quinodimethanes were generated by thermolysis of benzocyclobutanes, which were prepared in solution [308]. Other solid-phase procedures for the preparation of benzopyrans are the palladium-mediated reaction of support-bound 2-iodo-phenols with 1,4-dienes (Entry 5, Table 15.33) and the intramolecular Knoevenagel... 

Hong, F.-T., Paquette, L. A. Olefin metathesis in cyclic ether formation. Direct conversion of olefinic esters to cyclic enol ethers with Tebbe-type reagents. Copper(l)-promoted Stille cross-coupling of stannyl enol ethers with enol triflates construction of complex polyether frameworks. Chemtracts t997, 10,14-19. 

Formation of cydic enol ethers by carbonyl methylenation— olefin metathesis. 

Electron-rich olefins, such as alkyl enol ethers, react with pentacarbonyl[phenyl(methoxycar-bene)chromium(O) under carbon monoxide pressure to afford the corresponding 1,2-dialkoxy-cyclopropane derivatives 22 with moderate diastereoselectivity16. Without carbon monoxide pressure olefin metathesis occurs preferentially. 

Olefin metathesis. With catalyst (1) cycloalkenes including enol ethers and unsaturated heterocycles are effectively synthesized. Keto alkenes can also be used as substrates." ... 

The cyclopropanation of electron-rich alkenes requires modified reaction conditions. Warming a solution of a metal carbene and an enol ether at atmospheric pressure results in the formation of an alkene which apparently is formed in an olefin metathesis reaction. However, good yields of cyclopropanation products are obtained under CO pressure. Under these conditions the nucleophilic alkene is supposed to add to the carbene carbon to generate zwitterion 30 in which... 

Scheme 2.72 Domino olefin metathesis/carbonyl olefination to give the qfclic enol ether 206.

Scheme 2.73 Domino olefin metathesis/carbonyl olefination furnishing the cyclic enol ether 20S.

The addition of 1,4-benzoquinone was also found to prevent olefin isomerization in a number of ruthenium-catalyzed olefin metathesis reactions of allylic ethers (Scheme 12.32) [57]. When the siloxy ether 107, which bears a ds-olefin, was treated with Ru catalyst 3 (5 mol%) in CD2CI2 at 40 C for 24 h, a mixture of 107 and the corresponding tram isomer of 107 was observed in 19% yield, while 81% of the reaction mixture was the isomerized silyl enol ether product 108. The addition of 1,4-benzoquinone or acetic acid completely suppressed olefin migration, and mixtures of cis- and tram-105 were the major products (> 95%). Phenol, another common additive in olefin metathesis reactions, failed to inhibit olefin migration, and enol ether 108 was formed as the major product. 

Cossy s approach for the synthesis of leucascandrolide A involved an asymmetric allylmetalation to incorporate the stereogenic centers at C(5), C(7), C(9), C(ll) and C(12), and olefin metathesis. Construction of the 2,6-cis- and 2,6-trani-tetr-ahydropyrans was achieved by the Mukaiyama enol silane addition and oxa-conjugate addition reaction, respectively. The synthesis commenced with the... 

One important field of application of the NHC in transition metal-catalysed reactions is obviously the olefin metathesis. Among the various applications described, one can notice the nice use of complex (15) to affect the desymmetrization of oxabicyclic alkenes by a Z-diastereoselective and enantioselective ring opening/cross metathesis with enol... 

Scheme 17. Titanium-mediated metathesis strategy for the conversion of olefinic esters (118) to cyclic enol ethers (123) (Nicolaou et al.) [34]...

Scheme 19. Titanium-mediated metathesis strategy for the conversion of olefinic esters to 6- and 7-mem -bered cyclic enol ethers, (a) 4.0 equiv of Tebbe reagent (93), THF, 25°C, 20 min then reflux, 2-8 h, 64% (129), 45% (131a), 32% (131b), 45% (133) (Nicolaou etal.) [34a]...

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