Dimethyl malonate/BSA

Fig. 3 List of sulfur- or selenium-containing ligands in Pd-catalyzed reactions of 1,3-diphenylpropenyl acetates with dimethyl malonate (BSA/CH2(C02Me)2)...

Evans showed that his P,S-ligand 36 was also efficient for the monoalkylation of cis- 1,4-diacetoxycyclopentene 76. Reaction of dimethyl malonate/BSA gave 77 in 85% yield and 96% ee (Eq. 6) [95]. The same reaction and the intramolecular cyclization of a biscarbamate has also been reported using a polymer-supported Trost-type catalyst with excellent results [166,167]. 

They appear to be more useful than bis(oxazolines) as ligands for palladium-catalyzed allylic alkylation with dimethyl malonate/BSA [N,0-bis(trimethylsilyl)acetamide]. 

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. 

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). 

Asymmetric nickel-catalyzed allylic alkylation with soft carbon-centered nucleophiles was reported in 1996 by Mortreux and his co-workers. Use of a catalytic amount of [Ni(cod)2] together with chiral diphosphines 138 promotes the allylic alkylation of a cyclic ester such as 2-cyclohexenyl acetate with dimethyl malonate in the presence of BSA and gives the corresponding alkylated compounds only with a moderate enantioselectivity (40% ee) (Equation (42)). 

The palladium-catalysed allylic alkylation of dimethylallyl acetate 35 with dimethyl malonate 36 in THF at 25°C was carried out using a combination of Pd2(dba)3 [fris(dibenzylideneacetone)dipalladium] and triphenylphosphine with 0,N-Ws(trimethylsilyl)acetamide (BSA) as a base.87... 

Allylic alkylation. In general, allylic alkviation catalyzed by transition metals results from attack at the less substituted carbon atom of the ir-allyl intermediate. Deviation from this pattern is observed with some nucleo[ihilcs when Mo(CO)h is used as catalyst. For example, the anion of dimethyl malonate genei ated with 0,N-bis(trimethylsilyl)acctamidc (BSA) reacts with the allylic acetate 1 mainly by attack at the tertiary center to give 2. 

Instead of an anionic nucleophile, the protonated neutral form can be used in combination with N,0-bis(trimethylsilyl)acetamide (BSA see Scheme 26) [65, 98, 99,100]. The reaction is initiated by catalytic amounts of acetate ions. Silyl transfer from BSA to the acetate generates the anion of N-(trimethylsilyl)aceta-mide which then deprotonates dimethyl malonate. In the subsequent allyhc substitution, one equivalent of acetate is generated which, as before, reacts with BSA. The use of BSA has the advantage that only catalytic amounts of a base are present in the reaction mixture and that the neutral protonated nucleophhe can... 

Because asymmetric catalysis enables access to several synthetically important compounds, microwave-assisted molybdenum-catalyzed allylic allylation has been studied using both free and polymer-supported bis-pyridylamide ligands [134]. The microwave-assisted catalytic reaction of 3-phenylprop-2-enyl methyl carbonate with dimethyl malonate in the presence of N,0-bis(trimethylsilyl)acetamide (BSA) and a polymer-bound bis-pyridyl ligand was rather slow, however. 

The reactions of 1 with dimethyl malonate were carried out in the presence of [Pd( 7T-allyl)Q]2,14a- BSA, and KOAc, affording (R)-2 with 82-94% ee. The i-propyl group on the backbone of the chelate ring can dictate the chirahty at the sulfur center up i coordination. 

Sulfur-containing chiral acetals derived from C2-symmetric diols have been developed. Ligands 17-20 in which the acetals are tethered to an auxiliary donor atom (sulfur) have afforded (S)-2 with <5%, 60%, 50%, or 82% ee, respectively, in the Pd-catalyzed aUylic substitution reactions of 1 with dimethyl malonate using [Pd(7r-allyl)Cl]2, BSA, and KOAc in dichloromethane at room temperature (Scheme 11). 

ProIine-derived phosphines bearing various sulfenyl substituents have been developed Use of 21a-g as chiral ligands provided (5)-2, except 21e [(/ )-2], with 31-88% ee in the Pd-catalyzed allylic alkylation of 1 with dimethyl malonate using [Pd(7r-allylX l]2, BSA, and AcONa in dichloromethane at room temperature. Increasing the steric bulk of the substituents of the sulfenyl groups results in enhanced enantiocontrol (21g. provides 88% ee). The thiophene ligand 22 provides (R)-2 with 30% ee (Scheme 12). 

Proline-derived phosphines 27a,b bearing chiral sulfinyl groups were used as chiral ligands in Pd-catalyzed allylic alkylations of 1 with dimethyl malonate using [Pd(7T-allyl)Cl]2, BSA, and AcONa, affording (5)-2 with 60% and 33% ee, respectively (Scheme 15). 

The structure of a palladium complex derived from 28 was determined as a C2-sym-metric five-membered chelate 29 by coordination of the sulfinyl sulfur atoms by the X-ray crystallographic analysis. The allylic alkylations of 1 with dimethyl malonate were carried out in dichloromethane at 25 C in the presence of [Pd( 7r-allyl)Cl]2, (S,S)-28, BSA, and AcONa, affording (5)-2 with 64% ee. The nucleophile attacks the aUyl terminus at position A in 30 to avoid the steric interaction between the phenyl group and a large substituent L (Scheme 16). 

The best results were obtained in apolar media using a mixture of dimethyl malonate and, 0-bis(trimethylsilyl)acetamide (BSA), according to a procedure... 

Palladium(II)-allyl complexes with these ligands were found to be effective catalysts for allylic alkylations with stabilized carbanions. Under standard conditions, using 2 mol% of catalyst and a mixture of BSA and catalytic amounts of KOAc as base, racemic l,3-diphenyl-2-propenyl acetate smoothly reacted with dimethyl malonate or acetylacetone to afford optically active substitution products (Table 1). The phosphinophenyl-oxazoline with a phenyl group at the stereogenic center proved to be the optimal ligand for this substrate. After a remarkably short reaction time, the desired substitution products were isolated in essentially quantitative yields with enantiomeric excess of 97-99%. These values exceed the selectivities previously obtained with other ligands [41-43]. 

Pfaltz and coworkers [29] had previously investigated the allylic alkylation of l,3-diphenylprop-2-enyl acetate with dimethyl malonate as nucleophile (in the presence of A/ ,0-bis(trimethylsilyl)acetamide, BSA) with the well-established BOX ligands as stereodirecting ligands, and this particular system therefore provided the point of reference for the catalytic study at hand (Table 15.3, entry 1) [28]. Under the reaction conditions displayed in Scheme 15.4, the trisoxazoline-based catalysts generally induce a better enantioselectivity compared to their BOX analogs, and this behavior appears to be independent of the substituent, as shown in Table 15.3. 

Scheme 15.4 Allylic alkylation of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate (in the presence of A/,0-bis(trimethylsilyl)acetamide - BSA).

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