Tandem aldol/allylation reaction

In the presence of BF3-OEt2, allyldimethylsilyl enolates react with acetals to give allylated 1,3-diol monoethers.139 A similar tandem aldol-allylation reaction can be performed by strained allylsilyl enolates such as 26 without promoter (Equation (34)).140 Allylsilanes bearing a vinyl ether moiety at the /3-position give rise to another type of tandem aldol-allylation reaction in the presence of a Lewis acid.141... 

Silyl enol ethers containing a strained silacycle and an allylic group are designed to undergo tandem aldol-allylation reactions. The net transformation is understood by... 

Silyltitanation of 1,3-dienes with Cp2Ti(SiMe2Ph) selectively affords 4-silylated r 3-allyl-titanocenes, which can further react with carbonyl compounds, C02, or a proton source [26]. Hydrotitanation of acyclic and cyclic 1,3-dienes functionalized at C-2 with a silyloxy group has been achieved [27]. The complexes formed undergo highly stereoselective addition with aldehydes to produce, after basic work-up, anti diastereomeric (3-hydroxy enol silanes. These compounds have proved to be versatile building blocks for stereocontrolled polypropionate synthesis. Thus, the combination of allyltitanation and Mukayiama aldol or tandem aldol-Tishchenko reactions provides a short access to five- or six-carbon polypropionate stereosequences (Scheme 13.15) [28],... 

The tandem aldol-allylation strategy is also applicable to stereocontroDed poly-ketide/macrolide synthesis. ( )- and (Z)-Crotyl(enol)(pinacolato)silanes 49 and 51 react stereoselectively with cyclohexanecarbaldehyde to produce 1,3-diols 50 and 52, respectively, with high diastereoselectivities (Scheme 5.13) [20]. It is noteworthy that the reaction of ( , )-crotyl(enol)silane 53 is capable of constructing of... 

It has also been shown that dimethylsilyl enolates can be activated by diisopropylamine and water and exhibit a high reactivity toward iV-tosyl imines to give Mannich-type reaction products in the absence of a Fewis acid or a Bronsted acid.51 For example, the reaction of [(1-cyclohexen-l-yl)oxy]dimethylsilane with 4-methyl-A -(phenylmethylene)benzene sulfonamide gave re/-4-methyl-N- (f )-[(15)-(2-oxocyclohexyl)phenyl-methyl] benzenesulfonamide (anti-isomer) in 91% yield stereoselectively (99 1 anti syn) (Eq. 11.30). On the other hand, Fi and co-workers reported a ruthenium-catalyzed tandem olefin migration/aldol and Mannich-type reactions by reacting allyl alcohol and imine in protic solvents.52... 

Allylic alcohols react with aldehydes, in the presence of catalytic amounts of Fe(CO)s under photochemical activation conditions, to give mainly aldol products (Scheme 11).33 This novel tandem iosmerization-aldolization reaction is a process with a perfect atom economy, proceeding under neutral conditions. 

Recently, ruthenium-catalyzed tandem olefin migration/aldol-type or Mannich-type reactions have been developed with aldehydes or imines and allylic alcohols (Scheme 74). 

One of the important advantages of the intramolecular alkene silylformylation reaction as an aldol equivalent is that the products are masked 3,5-dihydroxyalkanals, and therefore that no manipulations are required prior to iteration of the process by aldehyde al-lylation to set up the next intramolecular silylformylation. Given that allylsilanes are well-known aldehyde allylation reagents, intramolecular silylformylation employing a diallylhydrosilane would, in principle, allow for the possibility of a tandem silylformyla-tion/allylsilylation reaction. This has been reduced to practice the diaUylsilyl ethers 60 were subjected to the previously developed silylformylation conditions and the unpuri-fied reaction mixtures were subjected to the Tamao oxidation ]36] to provide triols 61... 

The mechanism of the catalytic cycle is outlined in Scheme 1.37 [11]. It involves the formation of a reactive 16-electron tricarbonyliron species by coordination of allyl alcohol to pentacarbonyliron and sequential loss of two carbon monoxide ligands. Oxidative addition to a Jt-allyl hydride complex with iron in the oxidation state +2, followed by reductive elimination, affords an alkene-tricarbonyliron complex. As a result of the [1, 3]-hydride shift the allyl alcohol has been converted to an enol, which is released and the catalytically active tricarbonyliron species is regenerated. This example demonstrates that oxidation and reduction steps can be merged to a one-pot procedure by transferring them into oxidative addition and reductive elimination using the transition metal as a reversible switch. Recently, this reaction has been integrated into a tandem isomerization-aldolization reaction which was applied to the synthesis of indanones and indenones [81] and for the transformation of vinylic furanoses into cydopentenones [82]. 

A nickel hydride complex, NiHCl(diphenylphosphinoethane), catalyses the tandem isomerization-aldolization reaction of allylic alcohols with aldehydes.156 The atom- (g) efficient process proceeds at or below ambient temperature with low catalyst loading, and works well even for bulky aldehydes. Magnesium bromide acts as a co-catalyst, and mechanistic investigations suggest that a free enol is formed, which then adds to the aldehyde in a hydroxyl-carbonyl-ene -type reaction. 

The first step is of course the aza-Diels-Alder reaction 218 with no regioselectivity but lots of stereochemistry. The cis ring junction in 217 comes from the cis alkene in maleimide and the endo transition state gives the remaining centre. The next step is an allyl boronate reaction 219 with the aldehyde. Coordination of the aldehyde oxygen with the boron ensures that the aldehyde is delivered to the top face and the aldol stereochemistry comes from the six-membered cyclic transition state. Snieckus comments that the reaction works well as a tandem process because the 4 + 2 cycloaddition is slower than the allyl boronate reaction so the unstable intermediate does not accumulate. This comment has more general application. 

Branchadell, V., Crevisy, C., Gree, R., From Allylic Alcohols to Aldols by Using Iron Carbonyls as Catalysts Computational Study on a Novel Tandem Isomerization Aldolization Reaction, Chem. Eur. J. 2004, 10, 5795 5803. 

Krische and co-workers reported an intramolecular version of the tandem conjugate addition-aldol reaction. Enone-ketone 59 reacts with phenylboronic add (2m) in dioxane containing 5 equiv. of water [40] (Scheme 4.26). This cyclization probably proceeds through the (oxa-7t-allyl)rhodium intermediate. Because the intramolecular addition of the intermediate to the ketone is faster than protonolysis with water, the al-dol product is obtained in high yields. Binap is a ligand of choice, leading to the conjugate addition-aldol product in up to 95% ee. 

---