Three-component reaction vinyl ketone

One pot, three component reactions of a variety of arylaldehydes, dip-henylphosphinamide and methyl vinyl ketone catalysed by TiCU, PPhs and Et3N have been found to give the aza-Baylis-Hillman adducts (230) (Scheme 63). ... 

Furthermore, we have found that one-pot three-component reactions of aryl aldehydes, diphenylphosphinamide and methyl vinyl ketone, in the presence of TiCX, PPhs and EtsN, give the corresponding aza-MBH adducts 217 in moderate to good yields (Scheme 1.83). ... 

A highly chemo- and diastereoselective three-component reaction of an imine, alkyl vinyl ketone, and imide is catalysed by triphenylphosphine. The first two reactants are... 

Tietze reported a domino-Knoevenagel-hetero-Diels-Alder reaction involving a three-component reaction between an a-nitroketone, formaldehyde, and an alkyl vinyl ether. In one example, a Knoevenagel condensation between ketone 105 and formaldehyde (106) yields electron-poor hetero-diene 108 that undergoes an inverse electron demand Diels-Alder reaction with ethyl vinyl ether to furnish dihydropyran 109. Tietze subsequently converted 109 into the deoxysugar (+)-forosamin. ... 

Bis[(diphenylphosphinoyl)methyl] sulfide was converted to (diphenyl-phosphinoyl)methyl vinyl sulfides and to divinyl sulfides in Horner-Wittig type reactions with one or two equivalent(s) of oxo-compounds (ketones or aldehydes) (Schemes 60 and 61). The three-component reaction of lithium alkylselenolates/alkylthiolates, the diphenylphosphine oxide derivative of a bis(propargyl)ether and an aldehyde afforded 3-oxabicyclo[4.2.0]octa-1(8),5-dienes (Scheme 62). ... 

Recently, on the basis of the Markovnikov addition of water to alkynes, Trost et al. developed a three-component addition reaction of terminal alkynes, water, and methyl vinyl ketone, affording 1,5-diketones in DMF/water in the presence of ruthenium and indium catalysts (Eq. 4.38). 

Four-component annelation to alkenolides. Posner et al. have reported a one-pot three-step annelation of cycloalkenones to provide, after oxidation, four-atom enlarged macrolides. Thus Michael addition of tributyltinlithium to cyclo-hexenone (1) and Michael addition of the resulting enolate to ethyl vinyl ketone followed by an aldol reaction results in cyclization to a bicyclic hemiketal (2), which is oxidized by Pb(OAc)4 to an unsaturated 10-membered lactone (3). 

A similar three-component transformation can be achieved using triethylborane-induced radical reactions (Scheme 6.34) [53]. On exposure to air, triethylborane generates the ethyl radical, which abstracts iodine from alkyl iodides to generate the t-butyl radical. Addition of the resulting t-butyl radical to methyl vinyl ketone produces a radical a to the carbonyl group, which is trapped by triethylborane to form a boron enolate with the liberation of ethyl radical, thus creating a chain. 

As described in the section Reactions Involving Addition of Water to Alkynes, the reaction of terminal alkynes, water, and a-vinyl ketones afforded 1,5-diketones in DMF-H20 (Eq. 12). Under similar conditions, in the presence of halide, ruthenium-catalyzed three-component coupling of alkyne, an enone, and halide ion formed vinyl halide (Eq. 17) [35]. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

For example, the three-component domino inter-[4- -2]/inter-[3- -2] cycloaddition reaction of the D-galactose-derived heterodiene 538 with ethyl vinyl ether and methyl vinyl ketone took place with total chemo-, regio-, facial-, and stereoselectivity to give a single nitrosoacetal 539 in 70% yield (Equation 89) <1998CC459>. 

Treatment of a-iodo ketone and aldehyde with an equimolar amount of Et3B yielded the Reformatsky type adduct in the absence of PhaSnH (Scheme 21), unlike ot-bromo ketone as shown in Scheme 15 [22], Ethyl radical abstracts iodine to pro-duee carbonylmethyl radical, which would be trapped by EtsB to give the corresponding boron enolate and regenerate an ethyl radical. The boron enolate reacts with aldehyde to afford the adduct. The three-component coupling reaction of tert-butyl iodide, methyl vinyl ketone and benzaldehyde proceeded to give the corresponding adduct 38, with contamination by the ethyl radical addition product 39. The order of stability of carbon-centered radical is carbonylmethyl radical > Bu > Pr > Ef > Me . 

Ryu, Sonoda and coworkers reported that tris(trimethylsilyl)silane is a useful mediator for a three-component coupling reaction [45]. Table 4 summarizes examples of radical carbonylations mediated by (TMS)3SiH. The first example shows a three-component coupling reaction in which hexyl iodide, CO, and acrylonitrile combine to form a P-cymo ketone. The CO addition step is in competition with the addition to the alkene and the hydrogen abstraction from radical mediator. Thus, it is anticipated that a set of less efficient hydrogen donors, such as (TMS)3SiH, and the use of a smaller excess amount of an alkene is most favorable. Indeed, the reaction can be carried out at only 20 30 atm of CO pressure, substantially below the 80-90 atm which is used for carbonylative acyl radical reactions which are mediated by tin hydride, and a nearly stoichiometric amount (1.2 equiv) of acrylonitrile is sufficient. Some other examples, which include vinyl radical carbonylation, are also shown in Table 4. 

The Pd-catalyzed three-component connection reaction of vinyl iodides, vinylstannanes, and CO proceeds smoothly under mild, neutral conditions (40-50 °C) under moderate carbon monoxide pressures (3 atm) to provide the corresponding unsymmetrical divinyl ketones in good yields (Scheme 16). The reaction is highly catalytic and requires only 2% of PhCH2Pd(PPh3)2Cl or PdCl2(PPh3)2. 

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