Allyl metathesis

Only few examples of functionalized copper reagents have been prepared The perfluoroallyleopper reagent was prepared via metathesis of the corresponding perfluoroallylcadmium compound [146] (equation 159) Reaction of the allyl... 

In addition to the applications reported in detail above, a number of other transition metal-catalyzed reactions in ionic liquids have been carried out with some success in recent years, illustrating the broad versatility of the methodology. Butadiene telomerization [34], olefin metathesis [110], carbonylation [111], allylic alkylation [112] and substitution [113], and Trost-Tsuji-coupling [114] are other examples of high value for synthetic chemists. 

Metathesis of N-tosylated ene-amides and yne-amides has been less extensively investigated. An example of the RCM of ene-amides is a new indole synthesis developed by Nishida [79] metathesis precursor 96 (prepared by ruthenium-catalyzed isomerization of the corresponding allyl amide) is cy-clized to indole 97 in the presence of 56d (Eq. 13). 

Few reports describe the cross metathesis of allyl halides [88]. First-generation catalyst 9 does not seem to be sufficiently reactive to promote this reaction in preparatively useful yields and acceptable catalyst loadings, but second-generation catalyst 56d gives good results for allyl chloride. Cross-metathesis... 

Allylboronates are attractive reagents for the highly diastereoselective ally-lation of carbonyl compounds. A sequential cross-metathesis-allylation reaction has recently been developed by Grubbs et al. [88c] and by Miyaura et al. [103]. The sequence is illustrated in Scheme 23 for the formation of homoallylic alcohol 114 from allylboronate 112, acetal 113, and benzaldehyde [88c]. 

RCM was also used in Yamamoto s total synthesis of the marine neurotoxin gambierol (81) [62], to close the central seven-membered E ring, thereby completing the octacyclic polyether core 80 (Scheme 15). Following previously developed methodology [63], metathesis precursor 79 was produced as the major epimer, by boron trifluoride etherate-mediated intramolecular allylation of a-chloroacetoxy ether 78. Subsequent treatment of 79 with catalyst C produced the octacyclic ether 80 in 88% yield. 

An example of the efficient formation of an electron-deficient double bond by RCM was disclosed by a Japanese group in a novel total synthesis of the macrosphelides A (209) and B (208) (Scheme 41) [100]. When the PMB-pro-tected compound 204 was examined as a metathesis substrate, the ring closure did not proceed at all in dichloromethane using catalysts A or C. When the reaction was carried out using equimolar amounts of catalyst C in refluxing 1,2-dichloroethane, the cyclized product 205 was obtained in 65% yield after 5 days. On the other hand, the free allylic alcohol 206 reacted smoothly at room temperature leading to the desired macrocycle 207 in improved yield. 

Treatment of the 1,2-oxazines 52 with carbon monoxide at 1000 psi in the presence of cobalt carbonyl brings about insertion of carbon monoxide to form the 1,3-oxazepines S3 <96TL2713>. A convenient route to P-lactams fused to oxepines is made available by alkene metathesis. Thus reaction of 4-acetoxyazetidin-2-one with ally alcohol in the presence of zinc acetate, followed by iV-allylation of the nitrogen affords the derivative 54 which cyclises by RCM to form the oxazepinone 55 <96CC2231>. The same communication describes a similar synthesis of 1,3-dioxepines. 

A nice application of this reaction for the synthesis of cyclic a-sulfanylphos-phonates 63 has been reported [42]. It involves a Rh(II)-catalyzed [2,3]-sigmatropic rearrangement and a ring-closing metathesis of the resulting a-(S-allyl) y,d-unsaturated phosphonates 62 (Scheme 16). However, the last step occurs with a low yield (19%) when R = H. 

The role of complexes 23-28 as catalyst precursors in the ring closing metathesis reactions was investigated. Three different diene substrates diethyldiallyl-malonate (29), diallyltosylamine (30). and dielhyldi(2-methylallyl)malonate (31) were added to the NMR tubes containing a solution of 5 mol% of catalyst precursor in an appropriate deuterated solvent. The NMR tubes were then kept at the temperatures reported in Table X. Product formation and diene disappearance were monitored by integrating the allylic methylene peaks in the H NMR spectra and the results are presented in Table X and the catalytic transformations are depicted in Scheme 3. 

The first cross metathesis to form a tetra-substituted olefin was achieved recently [146]. Howell and co-workers used lactams as substrates for CM with mono- and di-substituted olefins. The authors suggest that the limitations of the method are primarily due to steric reasons. Varying the electron density of the lactam showed no great influence on the reactivity while steric influences like a-branched allylic crosspartners or a methyl-group in the C4-position of the lactam both led to no reaction (Scheme 3.13). 

An interesting way to control the stereoselectivity of metathesis-reactions is by intramolecular H-bonding between the chlorine ligands at the Ru-centre and an OH-moiety in the substrate [167]. With this concept and enantiomerically enriched allylic alcohols as substrates, the use of an achiral Ru-NHC complex can result in high diastereoselectivities like in the ROCM of 111-112 (Scheme 3.18). If non-H-bonding substrates are used, the selectivity not only decreases but proceeds in the opposite sense (product 113 and 114). 

Asymmetric AUylic Alkylation acetylacetonate Asymmetric Cross-Metathesis Acyclic Diene Metathesis allyl ether... 

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. 

The synthesis and olefin metathesis activity in protic solvents of a phosphine-free ruthenium alkylidene bound to a hydrophilic solid support have been reported. This heterogeneous catalyst promotes relatively efficient ring-closing and cross-metathesis reactions in both methanol and water.200 The catalyst-catalyzed cross-metathesis of allyl alcohol in D20 gave 80% HOCH2CH=CHCH2OH. 

The homoallylation product 16a presumably stems from oxidative cycloaddition of a Ni(0) species across the diene and aldehyde moieties of 15, leading to an oxanickellacycle intermediate 17 (path A, Scheme 5), which undergoes 0-bond metathesis with triethylsilane giving rise to a o-allylnickel 19. On the other hand, formation of 16b may start with addition of a Ni - H species upon the diene followed by intramolecular nucleophilic allylation as described in Eqs. 4-6 (path B). Alternatively, allylic transposition of the NiH group providing 20 from 19 may be related to the formation of 16b. The different reactivity between cyclohexadiene and many other acyclic dienes is also observed for the reaction undertaken under typical homoallylation conditions (see Scheme 14). 

Molybdenum allyl complexes react with surface OH groups to produce catalysts active for olefin metathesis.34 35 Using silica as a support for the heterog-enization of Ti and Zr complexes for the polymerization of ethylene did not give clear results.36 In these cases, HY zeolite appeared to be a more suitable support. The comparable productivity of the zeolite-supported catalyst with... 

Grigg and coworkers developed bimetallic domino reactions such as the electro-chemically driven Pd/Cr Nozaki-Hiyama-Kishi reaction [69], the Pd/In Barbier-type allylation [70], Heck/Tsuji-Trost reaction/1,3 dipolar cycloaddition [71], the Heck reaction/metathesis [72], and several other processes [73-75]. A first example for an anion capture approach, which was performed on solid phase, is the reaction of 6/1-134 and 6/1-135 in the presence of CO and piperidine to give 6/1-136. Liberation from solid phase was achieved with HF, leading to 6/1-137 (Scheme 6/1.30) [76]. 

The most important ruthenium-catalyzed domino process is based on a metathesis reaction. Nonetheless, a few other ruthenium-catalyzed processes have been employed for the synthesis of substituted 3,y-unsaturated ketones, as well as unsaturated y-lactams and allylic amines. 

Scheme 6/4.20. Combination of a Cu-catalyzed allylic substitution with a metathesis.

A ruthenium-catalyzed metathesis of the allyl- and alkynyl-substituted pyridoindole 364 gives the canthine derivative 365 (Equation 131) <2005TL7267>. 

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