1.3- Diphenyl-2-propenyl acetate

Catalytic reaction conditions [Pd/l]j.oii (ca. 2.35 x 10 mmols) and 1 (5.8 X 10 mmols) was dissolved in 2cm of CH2CI2. roc-1,3-diphenyl-2-propenyl acetate (252mg, 1 mmol), dissolved in 7 cm of CH2CI2, was added, followed by dimethyl malonate (396mg, 3mmols), BSA (610mg, 3 mmols), and a catalytic amoimt of KOAc. After each 24 h, 1 mmol of roc-I was added. 

Treatment of the (—)-menthone-derived 2/7-1,3-benzoxazin-4(3//)-one 202 with triflic anhydride gave the triflate 203 in quantitative yield. Palladium-catalyzed cross-coupling of 203 with 2-pyridylzinc halide resulted in formation of an approximately 3 1 mixture of the 4-(2-pyridyl)-2//-l,3-benzoxazine 204 and a 4-imino-l,3-benzodioxane derivative 205 (Scheme 36). Compound 205 was formed by the isomerization of 203, which occurred with complete retention of stereochemistry. The 4-(2-pyridyl)-l,3-benzoxazine derivative 204 was applied in enantioselective allylic alkylations of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate as a chiral ligand inducing a 62% ee in the product <2005JOM(690)2027>. 

Scheme 5.12 Pd(O)-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate.

In this way racemic starting materials 11 or the synthetically important cycloalkenyl derivatives 14 (Scheme 11) can be converted to enantiomerically enriched products. The most widely studied derivative is 1,3-diphenyl-2-propenyl acetate 11 (R=Ph, X=OAc) which has become the standard test substrate for evaluating enantioselective catalysts (see Sect. 9.1). 

It has been observed that the rate of palladium-catalyzed allylic alkylation in water is drastically enhanced when the reaction is performed in the presence of surfactant [14]. Enantioselectivity up to 92% is obtained in the reaction of dimethyl malonate with 1,3-diphenyl-2-propenyl acetate when a chiral ligand such as Binap is used in the presence of cetyltrimethylammonium hydrogen sulfate [15, 16],... 

Asymmetric palladium-catalyzed alkylation of various allylic acetates occurred in water or in an aqueous/organic biphasic medium, using as ligands phosphines derived from carbohydrates [29], amphiphilic resin-supported MOP and P,N-chelating ligands [30, 31], or BINAP in the presence of surfactants [32] enantio-selectivities up to 85%, 98%, and 92% have been obtained in the alkylation of 1,3-diphenyl-2-propenyl acetate, respectively. 

P-Menthylphosphetanes 77, in which an optical active dioxolane group is introduced at the a-position, have also provided asymmetric catalytic activity in the palladium-catalyzed allylic nucleophilic substitution of 1,3-diphenyl-propenyl acetate with the sodium salt of dimethyl malonate (Equation 12). 

Chiral phosphinous amides have been found to act as catalysts in enantio-selective allylic alkylation. Horoi has reported that the palladium-catalyzed reaction of ( )-l,3-diphenyl-2-propenyl acetate with the sodium enolate of dimethyl malonate in the presence of [PdCl(7i-allyl)]2 and the chiral ligands 45 gave 46 in 51-94% yields and up to 97% ee (Scheme 38). It is notorious that when the reaction is carried out with the chiral phosphinous amide (S)-45a, the product is also of (S) configuration, whereas by using (R)-45b the enantiomeric (R) product is obtained [165]. 

Diamine 108 led to 95% ee for the alkylation of l,3-diphenyl-2-propenyl acetate with 90% yield. By polycondensation with a diacid chloride or polyaddition with a diisocyanate, this ligand led, respectively, to an insoluble poly(amide) 109 or poly(urea) 110 with excellent yields. Poly(amide) 109 gave a better ee (80%) than poly(urea) 110 (38%), albeit with a lower conversion (respectively, 38 and 72%), when they were used as palladium hgands... 

Sulfoximines bearing a chiral sulfur atom have recently emerged as valuable ligands for metal-catalysed asymmetric synthesis.In particular, C2-symmetric bis(sulfoximines), such as those depicted in Scheme 1.51, were applied to the test reaction, achieving enantioselectivities of up to 93% ee. The most selective ligand (R = c-Pent, R = Ph) of the series was also applied to the nucleophilic substitution reaction of l,3-diphenyl-2-propenyl acetate with substituted malonates, such as acetamido-derived diethylmalonate, which provided the corresponding product in 89% yield and 98% ee. 

As described in the previous section, when acyclic and symmetric allylic esters such as l,3-diphenyl-2-propenyl acetate and l,3-dialkyl-2-propenyl esters are used as substrates, high to excellent enantioselective allylic alkylation is performed by using a variety of chiral ligands. In contrast, the number of successful examples of the asymmetric allylic alkylation of acyclic and unsymmetric allylic esters is relatively limited. 

Recently, Majoral et al. described the synthesis of a third-generation phosphorus-containing dendrimer possessing 24 chiral iminophosphine end groups derived from (2S)-2-amino-l-(diphenylphosphinyl)-3-methylbutane (Fig. 11) [32]. The dendritic catalyst was tested in allylic substitution reactions, using rac-(.E)-diphenyl-2-propenyl acetate or pivalate as substrates. The observed enantioselectivities were good to excellent (max. 95% ee) in all reactions. After completion of the catalytic reaction, the catalyst could be reused at least twice after precipitation and filtration. A slight decrease... 

Allylic Alkylation. The palladium-catalyzed asymmetric alkylation of l,3-diphenyl-2-propenyl acetate with dimethyl... 

Transition Metal-Cataijrzed Reactions. Application of this ligand to the Pd-catalyzed ally lie alkylation of l,3-diphenyl-2-propenyl acetate with dimethyl malonate provides an alkylated product in >99.5% enantiomeric excess (eq 1). The enantiose-lectivity of the process is dependent on the ligand Pd ratio, the palladium precursor, and the nature of the nucleophile. Optimal conditions employed Pd(dba)s as the Pd precursor and 2 equiv of phosphine ligand, suggesting that two phosphines coordinate to the active Pd catalyst. Replacement of l,3-diphenyl-2-propenyl acetate with pent-3-en-2-yl acetate decreased the ee to 34% due to the reduced sterics of methyl relative to phenyl substituents. It is noteworthy that in contrast to this ligand, most monodentate ligands provide low enantioselectivity in this reaction. ... 

For this type of allylic alkylation, l,3-diphenyl-2-propenyl acetate 39a have been often used as allylic substrates. Although an enantioselectivity of ca. 90% ee has been reported in the reaction of 39 a with acetamidomalonate with usual chiral phosphines such as BINAP or chiraphos [46], the ferrocenylphosphines containing a hydroxyl functionality on the pendant side chain are more effective ligands for the reaction with sodium acetylacetate (Scheme 2-29) [5d, 47]. The enantioselectivity increases as the number of hydroxyl groups on the side chain increases. Thus, the ferrocenylphosphines 8a, 8b, and 8c give the alkylation product with 71, 90, and 96% ee, respectively. High enantioselectivity is also observed in the reaction of l,3-diaryl-2-propenyl acetates (Ar = 1-Np 39b 92% ee, 3-MeOCgH4 39c 86% ee) and ci5-3-acetoxy-5-carbomethoxycyclohexene 40 (72% ee) in the presence of the Pd/(E)-(S)-8b catalyst. 

Scheme 4.24 Cinchona alkaloid derived phenyl selenides in Pd-catalyzed alkylation of dimethyl malonate with l,3-diphenyl-2-propenyl acetate.

Sinou and co-workers [73] studied the influence of different surfactants on the palladium-catalyzed asymmetric alkylation of l,3-diphenyl-2-propenyl acetate with dimethyl malonate in presence of potassium carbonate as base and non-water-soluble chiral ligands. Best results in activity and enatioselectivity (> 90% ee) were observed with 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) as ligand and cetyltrimethylammonium hydrogen sulfate as surfactant in aqueous medium. Water-stable Lewis acids as catalysts for aldol reactions were developed by Kobayashi and co-workers [74]. An acceleration of the reaction was indicated in presence of SDS as anionic surfactants. An additional promotion could be observed by combination of Lewis acid and surfactant (LASCs = Lewis acid-surfactant-combined catalysts) as shown in Eq. (3). Surfactant the anion of dodecanesulfonic acid. 

Asymmetric allylic substitution of l,3-diphenyl-2-propenyl acetate in water or in an aqueous/organic biphasic medium was performed in the presence of the complex obtained from [Pd( 73-C3H5)C1]2 and a chiral amphiphilic phosphinite-oxazo-line derived from natural D-glucosamine. The enantioselectivity obtained was up to 85% ee [14] recycling of the catalyst was possible (Eq. 6). 

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