1.3- Diphenylallyl acetate

Table 8. Reacemic 1,3-diphenylallyl acetate with dimethyl malonate under various...

Chiral nonracemic bidentate 2-[o-(diphenylphosphino)phenyl]-5,6-dihydro-4//-l,3-oxazine derivatives proved to be effective P,N-ligands in Pd-catalyzed asymmetric transformations. When used in the Pd-catalyzed allylic alkylations of 1,3-diphenylallyl acetate with dimethyl malonate, phosphino-oxazines 147 and 148 and the... 

The chiral nonracemic bis-benzothiazine ligand 75 has been screened for activity in asymmetric Pd-catalyzed allylic alkylation reactions (Scheme 42) <20010L3321>. The test system chosen for this ligand was the reaction of 1,3-diphenylallyl acetate 301 with dimethyl malonate 302. A stochiometric amount of bis(trimethylsilyl)acetamide (BSA) and a catalytic amount of KOAc were added to the reaction mixture. A catalytic amount of chiral ligand 75 along with a variety of Pd-sources afforded up to 90% yield and 82% ee s of diester 303. Since both enantiomers of the chiral ligand are available, both R- and -configurations of the alkylation product 303 can be obtained. The best results in terms of yield and stereoselectivity were obtained in nonpolar solvents, such as benzene. The allylic alkylation of racemic cyclohexenyl acetate with dimethyl malonate was performed but with lower yields (up to 53%) and only modest enantioselectivity (60% ee). 

TABLE 9.23. RNANTIOSF.I.F.CTIVF. SUBSTITUTION OF 1,3-DIPHENYLALLYL ACETATE WITH DIETHYLMALONATE... 

Also in 1999, Xiao reported the Pd(OAc)2/PPh3 catalyzed allylation of 1,3-diphenylallyl acetate with a wider range of stabilized carbanions in... 

Novel bicyclic (92) and tricyclic (93ab) hydrophosphoranes have been synthesized and shown to form complexes with PdCl2(COD), PdCl2(RCN)2, and Pd(allyl)Cl2 containing an open form of the phosphoranes. The Pd-catalyzed alkylation of 1,3-diphenylallyl acetate (94) with dimethyl malonate gave (95) in up to 74% ee using complexes of (92) or (93ab). " ... 

Subsequently, better ligands than 44 have been designed for the asymmetric palladium-catalyzed reaction of 1,3-diphenylallyl acetate with sodium mal-onate. Both the bis-(phosphaferrocene) 48 synthesized as shown in Eq. (32) [77] and the phosphaferrocene-oxazolines 49 [78] perform this condensation with much higher ees (79% in the first case and up to 82% in the second case). In the second case, the stereochemical outcome of the reaction is determined by the planar chirality at the phosphaferrocene, rather than the chirality of the oxazo-line [78] ... 

The following table compares the enantiomeric excesses obtained in the allylation of several nucleophiles with 1,3-diphenylallyl acetate catalyzed by different chiral ligands30-33 to show that trends are not deducible and that no reliable prediction can be made. 

Figure 1 gives an overview of chiral ligands which have been employed in the reaction of 1.3-diphenylallyl acetate with dimethyl malonatc. The examples shown are only representatives of a whole number of derivatives, but exhibited the best enantiomeric excesses for this class of ligand. 

Since the AAA in aqueous solution has been most studied with Pd(diphosphine)-bearing catalysts, we screened the library of biotinylated diphosphine ligands that were initially used in the hydrogenation study (Sect. 2.1). Our initial experiments focused on symmetric 1,3-diphenylallyl acetate and dimethytmalonate as soft nucleophiles (Scheme 3) [50]. It is widely accepted that the enantiodiscrimmation event occurs through the external attack of a soft nucleophile on a palladium allyl intermediate. The AAA thus bears resemblance to enzymatic reactions, in which a reactant need not necessarily bind to the active site of the enzyme for the reaction to proceed with high stereoselectivity [51]. The second coordination sphere may thus play an important role in ensuring selectivity. 

Scheme 3 Asymmetric allylic alkylation of symmetric 1,3-diphenylallyl acetate by malonic dimethylester...

In the field of C—C bond forming reactions, palladium occupies a privileged position. In this context, the asymmetric allylic alkylation attracted our interest due to its unique outersphere attack of the malonate on the 77 -coordinated 1,3-diphenylallyl moiety. Following the above-described chemogenetic optimization procedure, we screened twenty one biotinylated ligands in conjunction with twenty two (strept)avidin isoforms for the allylic alkylation of 1,3-diphenylallyl acetate. Addition of didodecyldimethylam-... 

Hybrid catalysts for the asymmetric allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate were obtained by incorporation of the biotinylated diphosphine Pd(II) complexes 8 or 9 (Figure 10.9) to wild-type SAV and mutants. The best combinations afforded the product with nearly quantitative yield and 90% ee (R) and 82% ee (S) [54], Supramolecular association between SAV and biotinylated Hoveyda-Gnibbs-type catalyst 10 catalyzed the ring-closing metathesis (RCM) of Af-tosyl diallylamine (Scheme 10.13) [55]. 

In order to assess the scope of Ugand-directed asymmetric allylations with chelated enolates, a representative set of substrates was investigated (Scheme 12.29) [50]. High levels of selectivity were achieved with 1,3-diphenylallyl acetate 58 as substrate especially with the PHOX Hgand LI, a diastereoselectivity of up to 95 5 in favor of the anti-isomer 60 and enantiomeric excess values of up to 94% could be achieved. AUyHc alkylations of cychc substrates such as cyclohexenyl acetate 57 led to the cydohexenyl-glydne derivative 59. With the chiral ligand L2, the syn product is formed preferentially. Enantiomeric excess values of up to 93% can be obtained with this Hgand, which is remarkable for such a cydic system. 

Successful asymmetric allylations have been carried out with high ee values using many kinds of chiral ligands. 1,3-Diphenylallyl acetate is used as a standard substrate to compare different chiral ligands based on desymmetrization of its meio-Tr-allylpalladium intermediate. Asymmetric allylation is treated in Sect. V.2.4. 

SCHEME 22.11 Palladium-catalyzed allylic amination of 1,3-diphenylallyl acetate. 

Allylic Amination of 1,3-Diphenylallyl Acetate with Pyrrolidine or Di-rr-Propylamine... 

Palladium-Catalyzed Allylic Alkylation of (f)-1,3-Diphenylallyl Acetate with Dimethyl Malonate... 

Palladium-Catalyzed Allylic Sulfonylation of (f)-1,3-diphenylallyl Acetate with Sodium para-Toluenes... 

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