Towards Trisubstituted Olefins

When the number of substituents differs on the two carbons of the double bond, a correct choice of the coupling partners becomes essential for a successful Julia olefination. In the case of trisubstituted olefins, both disconnections suffer from some shortcomings. For example, addition of an aldehyde 63 to a secondary 

Although path a is more frequently encountered in the literature, ketones (path b) can also be successfully employed in these coupling reactions. However, due to the unfavorable equilibrium between 68 and 3/67, care must be taken in these cases, and the trapping protocols mentioned in Section 3.3.2 are highly recommended (Tables 3.3 [54] and 3.4 [53]). 

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An attempt to react trisubstituted double bonds with Schrock s tungsten and molybdenum catalysts produced the thermodynamically predicted mixture of products [61]. An attempt to polymerize 3,6-dimethyl-2,6-octadiene was unsuccessful. An attempt to react 2-ethylidenecyclohexane using [W]2 and [Mo]2 also confirmed the lack of activity toward trisubstituted olefins. This fact was... 

Phomactin A is the most challenging family member architecturally. The fragments that are most challenging are highlighted in Fig. 8.4. In Box-A, the highly sensitive hydrated furan is prone to dehydration under acidic or basic conditions, and any total synthesis almost certainly must save introduction of this fragment until the end game. Box-B relates to the strained and somewhat twisted electron-rich double bond. This trisubstituted olefin is extremely reactive toward electrophilic oxidants. 

The catalyst derived from ligand 9 perform well with several classes of olefins albeit with slightly lower enantioselectivities in reduction of trisubstituted olefins, but are remarkably reactive toward 1,3-dienes [11,33]. Further examples of the size... 

The availability of ketone 26 and its effectiveness toward a wide variety of tmns-and trisubstituted olefins make the epoxidation with this ketone a useful method. Other researchers have used ketone 26 in the synthesis of optically active complex molecules. Some of these studies will be highlighted in this section. 

The Mn(salen) complex 8 has also been appHed towards the synthesis of a-hydroxy carbonyl compounds from enol ethers and ketene acetals [87,88,89]. These substrates are a special class of trisubstituted olefins, previously demonstrated to be excellent substrates for AE. Indeed, the observed sense of stereoinduction in the oxidation of enol ether derivatives adheres to the skewed side-on approach model developed for trisubstituted olefins. In the presence of 7 mol % of 8, silyl enol ether 37 was oxidized under bleach conditions to afford the a-hy-droxy ketone in 87% ee (Scheme 14) [89]. 

Finally, Paterson and Schlapbach employed the Corey-Winter olefination to generate a trisubstituted olefin in their studies toward a total synthesis of discodermolide.19 In this example, diols 42 and 43 were treated with thiocarbonyldi-imidazole to give the corresponding thionocarbonates. Exposure of this mixture of thionocarbonates to phospholidine 21 at 50 °C generated olefin 44 in 81% yield. 

Co(II) and NaBH4 display an extremely high steric selectivity in the reduction of alkenes, trisubstituted olefins are virtually inert to these reducting conditions. Alkynes are readily reduced to alkenes [9]. However, the reaction is not catalytic in TM and the system is not selective towards ketones or aldehydes. Esters are unaffected under such conditions. (Ph3P)3CoCl is a selective reagent for reactions in which an alkyne is selectively reduced to an alkene (mixture of isomers) [10]. 

Epoxidations with peracids can exhibit high degree of chemoselectivity and these generally display preferences for reaction with more nucleophilic alkenes. This phenomenon is illustrated in Vandewalle s work directed towards the total synthesis of the sesquiterpene estafiatin (6, Equation 3) [52]. The final step included selective epoxidation of the trisubstituted olefin from its more accessible convex face (dr =97 3). 

The NHC-coordinated catalysts 2 and 5 also exhibit dramatically improved substrate scope relative to bis(phosphine) catalysts. For example, whereas catalyst 1 is unreactive toward sterically congested substrates and cannot form tetra-substituted RCM products, catalysts 2 and 5 readily form tetra-substituted olefins in five- and six-membered rings systems (Eq. 4.17 E = C02Et) [98,100]. They also mediate CM between terminal olefins and 2,2-disubstituted olefins to form new trisubstituted double bonds [102]. Previously, these transformations could only be accomplished using molybdenum-based catalysts. 

It has also been found that highly active catalysts can be prepared in situ by reducing a platinum, palladium, or rhodium salt with sodium borohydride in the presence of a carbon support. Similar reductions of nickel salts produce colloidal nickel-boron, which is highly selective toward olefins of different structural types. The normal order of reactivity—i.e., terminal > disubstituted > trisubstituted—is observed, but the reactivity spread is sufficiently large that selective hydrogenation of polyenes is possible, as illustrated by a step in a synthesis of the natural product... 

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