Phase allylic substitution

The supported aqueous phase methodology was applied to the system Pd(OAc)2/5 TPPTS, a catalytic precursor for the Trost-Tsuji reaction. The characterization of the solid by 31P MAS NMR confirms the presence of Pd°(TPPTS)3 as the main surface species. The catalytic properties of the solid were tested for the allylic substitution of E-cinnamylethylcarbonate by different nucleophiles such as ethyl acetoacetate, dimethyl malonate, morpholine, phenol, and 2-mercapto-pyridine. The absence of palladium leaching was demonstrated, and having solved the problem of water leaching from the solid to the organic phase, the SAP-Pd catalyst was successfully recycled several times without loss in its activity. It was used in a continuous flow experiment which... 

When chlorination or bromination of alkenes is carried out in the gas phase at high temperature, addition to the double bond becomes less significant and substitution at the allylic position becomes the dominant reaction.153-155 In chlorination studied more thoroughly a small amount of oxygen and a liquid film enhance substitution, which is a radical process in the transformation of linear alkenes. Branched alkenes such as isobutylene behave exceptionally, since they yield allyl-substituted product even at low temperature. This reaction, however, is an ionic reaction.156 Despite the possibility of significant resonance stabilization of the allylic radical, the reactivity of different hydrogens in alkenes in allylic chlorination is very similar to that of alkanes. This is in accordance with the reactivity of benzylic hydrogens in chlorination. 

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

It is well known that thermal decomposition of allyl-substituted silanes proceeds by retro-ene reaction with formation of transient species having a Si=C bond, such as silaben-zene, silatoluene and dimethylsilaethylene4b e. The kinetic data on the gas-phase pyrolysis of a similar allyloxysilane derivative, (l,l-dimethylallyloxy)dimethylsilane (16), and the results on thermolysis of allyloxydimethylsilane (17) in a flow system both indicate the participation of an intermediate silanone, (CH3)2Si=0 (10), as shown in Scheme 523. 

Liquid-phase halogenation of hexachlorobenzene with chlorine trifluoride appears to proceed by a series of additions and vinylic and allylic substitutions until all of the hexachlorobenzene is converted into chlorofluorocyclohexenes, C6F (Clio ) (n = mainly 4, 5 and 6), and conversion to cyclohexane derivatives occurs only upon the passage of quite a large excess of chlorine trifluoride [177] (Figure 2.29). The cyclohexene derivatives produced mainly retain the structure —CC1=CC1—. 

Reactions with Sulfur Nucleophiles. The use of sulfur nucleophiles in palladium-catalyzed allylic substitution reactions is less well documented than that of carbon, nitrogen and oxygen nucleophiles. The asymmetric synthesis of allylic sulfones utilizing a catalytic phase transfer system has been used to produce (35)-(phenylsulfonyl)cyclohex-l-ene on a 45 g scale (eq 10). In many cases, it has been reported that allylic carbonates are more reactive than allylic acetates in asymmetric allylic substitution... 

Peptide cleavage from the allyl-linker resin is achieved with morpholine in large excess in the presence of tetrakis(triphenylphosphine)palladium (10mol% based on the allylic substitution of the resin). (3-HYCRAM resin is a modification of HYCRAM containing a P-alanine residue as a spacer between the crotonoyl unit and the resin. It has been used for the solid-phase synthesis of glycopeptides by the Boc and Fmoc strategies.b 1 Difficulties may be... 

The Tsuji-Trost ally lie substitution catalyzed by Pd complexes using CH-acidic nucleophiles can be performed in an ionic liquid of type 1 alone [30] as well as in a biphasic system [31]. In the latter case the use of trisulfonated triphenylphosphine (TPPTS) prevents the catalyst from leaching into the organic phase. In comparison with water as the catalyst-supporting phase, the ionic liquid system exhibits higher activity and selectivity. The enantio-selective version of the allylic substitution with dimethyl malonate can also be performed in ionic liquids with a homochiral ferrocenylphosphine as the ligand [32]. 

Sinou, D. Allylic substitution. Aqueous-Phase Organometallic Catalysis 1998, 401-407. 

Dos Santos, S., Quignard, F., Sinou, D., Choplin, A. Allylic substitution catalyzed by silica-supported aqueous phase palladium(O) catalysts. Top. in Cat. 2000, 13, 311-318. 

Since polymers like 110 or 111 are phase-selectively soluble in the polar phase of a polar/nonpolar biphasic mixture cold and still soluble when the solvent mixture is heated to miscibility, polymers like 77 or 81 can be used as recoverable, recyclable allylic substitution, Heck, or hydrogenation catalysts in Eq. 48, Eq. 49, or 50, respectively. 

A supported aqueous phase system (SAPC see Section 2.6) has also been developed for allylic substitution. Alkylation of (Ej-cinnamyl ethyl carbonate by ethyl acetoacetate or morpholine occurs in acetonitrile or benzonitrile using Pd(OAc)2-TPPTS supported on mesoporous or nonporous silica no leaching of the catalyst has been observed, allowing proper recycling of the catalyst [22-26]. Polyhydroxylated supports such as cellulose and chitosan have also been used successfully in this approach [27-29]. 

Pd-catalyzed allylic substitution reactions can also be performed using water-soluble phosphine ligands, including TPPTS 132, as shown by the reaction of nitroester 48 with allyl acetate 133 to give the substitution product 134 (Scheme 24). The use of water-soluble palladium catalysts has been the subject of a review.t Water-soluble catalysts have also been applied to supported Uquid phase reactions. A silica bead supports a thin film of polar solvent in which the palladium complex resides.t The substrates and product reside in the bulk organic phase and can be decanted from the glass bead catalyst at the end of the reaction. 

Ally lie substitution (the Tsuji-Trost reaction) is among the most synthetically useful processes in palladium catalysis. As the catalytic efficiency of allylic substitution is often moderate (5-10 mol % of Pd catalyst are usually used), and phosphine-free systems are generally inefficient, the recycling of catalyst is the only feasible way to make the process more economical. Various phase-separation techniques have been tried for this reaction. In what concerns the rate of reaction and catalytic efficiency, such ligands as TPPTS are likely to be less effective compared to PhsP.f Thus, the main reason for the use of hydrophilic ligands in allylic substitution is the design of recyclable systems. 

A supported aqueous phase system has been developed for ally lie substitution. Coabsorption of Pd(OAc)2 and TPPTS onto both mesoporous and nonporous silicas gave catalysts active for the reaction of cinnamyl ethyl carbonate with ethyl acetoacetate. The activity of supported catalyst depends on the amount of water used to form a layer on the surface of silica. In the absence of water the catalyst is inactive. The supported catalyst possesses activity close to the activity of Pd(OAc)2-TPPTS catalyst in a biphasic systan, though it is more stable, as even on prolonged reaction times no tokens of catalyst decomposition leading to the formation of Pd-black was noted for the former. Still, the recycled SAPC catalyst possesses lower activity than the one freshly prepared. Another report on glass bead technology applied to allylic substitution has been published. " ... 

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