Alkene metathesis second-generation complexes

Isoxazolo[2,3-a]pyridin-7-ones were prepared by domino metathesis of the strained nitroso Diels-Alder adduct 87 and a terminal alkene in the presence of a catalytic amount of second generation Grubbs carbene or Hoveyda-Grabbs carbene complex. For example, 88 was obtained as the major product along with minor amounts of 89 starting from 87 and but-3-en-l-ol <07OL1485>. 

The catalysts that have played a dominant role in the development of this area of chemistry are those designed by Schrock (e.g. catalysts 27.1 and 27.2) and Grubbs (catalysts 27.3 and 27.4). Catalyst 27.3 is the traditional Grubbs catalyst , and related complexes are also used. The more recently developed second-generation catalyst 27.4 exhibits higher catalytic activities in alkene metathesis reactions. Catalysts 27.1, 27.3 and 27.4 are commercially available. 

The use of alkyne cross metathesis for the synthesis of unsymmetrical alkynes has potential utility in synthesis, although it has been studied less intensively than alkene cross metathesis. Mori published some of the first examples of alkyne cross metathesis to generate unsymmetrical alkynes. One example of this reaction conducted with the Montreux-type catalyst is shown in Equation 21.37. The selectivity for the cross-metathesis product was achieved by the use of an excess of the diphenylacetylene. A second example was conducted with the catalyst generated from Cummins trisamido complex. As shown in Equation 21.38, this cross metathesis was conducted in acceptable yields... 

The Grubbs pyridine solvates are the fastest initiators of alkene metathesis and are valuable as synthetic intermediates to prepare other ruthenium carbene complexes. In particular, the 18-electron pyridine solvates 4a,b are very fast initiators that were developed to catalyze difficult alkene metatheses (e.g., the cross metathesis of acrylonitrile) [6]. The rates of initiation for several complexes are provided in Table 9.9. The pyridine solvate 4a has been found to initiate about 105 times faster than the parent Grubbs complex 2 and at least 100 times faster than the second-generation triphenylphosphine variant 26. When compared with the Hoveyda-Blechert complex 3a, 4a initiated about 100 times faster (c entry 3 vs. entry 5). The bromopyridine solvate 4b exceeded all of these in its initiation rate it was at least 20 times more reactive than 4a. 

An efficient approach to a new family of highly functionalised phosphorus analogues of a-trifluoromethyl-substituted phenylalanine (492) and its homologues via Ru-catalysed intermolecular ene-yne metathesis has been developed. Thus, cross-metathesis of a-allynyl-a-trifluoromethyl-ot-aminophosphonates (489) with alkenes (490) catalysed by a second-generation Grubbs carbene complex (493) afforded corresponding aminophosphonates (491) with 1,3-diene backbone. Finally, one-pot Diels-Alder reaction-aromatisation step gave desired products (492) (Scheme 146). ... 

A very powerful cascade reaction had been developed by Cho and Lee in their approach to the total synthesis of (3I ,9i ,10/ )-Panaxytriol 179 (Scheme 7.37) [81], which was isolated from Panax ginseng in 1983 [82]. The cascade sequence was initiated by relay metathesis, which is then followed by metallotropic [l,3]-shift and cross-metathesis. This approach has become an efficient way for the synthesis of natural products with highly unsaturated carbon skeletons. Treatment of 174 with Grubbs second-generation catalyst in CH Clj at 40 °C in the presence of 2.0 equiv of alkene 175 generated the expected prodnet 178 in 61% yield as a mixture of Z E-isomers. Surprisingly, ruthenium alkylidene 176 was isolated in 10% yield and could be converted to 178 upon treatment with 175. This confirms that complex 176 is a catalytically viable intermediate in the catalytic cycle. 

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