Enantioselective allylic alkylations

Fig. 2.21 Chiral binap-based catalysts or catalyst precursors for the enantioselective allylic alkylation of aUylphosphates...

A Case History Enantioselective Allylic Alkylation Catalysed by Pd Nanoparticles... 

Scheme 7. The simplest type of enantioselective allylic alkylation which occurs on treatment of an allylic substrate with a metal derivative, together with a stabilized nucleophile (R = H, alkyl or aryl X" = leaving group [M] = metal catalyst Nu" = nucleophile L = coordinating atom).

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>. 

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. 

Use of some other diphosphines and monophosphines is also possible for this purpose. Osborn and his coworkers reported a highly enantioselective allylic alkylation of 2-cyclohexenyl acetate with malonates by using duthixantphospholane 18a (up to 93% ee) (Equation (21)).i d7a,i7b co-workers succeeded in obtaining... 

Highly enantioselective allylic alkylations by using solid-supported catalysts have been developed by several... 

Scheme 2.1.4.2 Pd-catalyzed enantioselective allylic alkylation of a sulfinate ion and kinetic resolution of a racemic allylic ester.

The Pd-catalyzed enantioselective allylic alkylation of thiols in the presence of BPA is limited to aryl and heteroaryl thiols [10]. However, allylic thioesters should... 

VII. ENANTIOSELECTIVE ALLYLIC ALKYLATION WITH GRIGNARD REAGENTS... 

Compared to the enantioselective allylic alkylation using soft nucleophiles, the reaction with Grignard reagents has received much less attention. The first enantioselective copper-catalyzed allylic alkylation with alkylmagnesium reagents was reported in 1995 by the groups of Backvall, van Koten and coworkers (Scheme 13). ... 

Similar to Hoveyda s work, which describes NHC ligands for the allylic alkylation with dialkyIzinc reagents , Okamoto and coworkers reported the enantioselective allylic alkylation with Grignard reagents using an a-methyl naphthylamine-based NHC complex (Scheme 14) . 

TABLE 12. Cu/Taniaphos-catalysed enantioselective allylic alkylation with Grignard reagents... 

The final modes of enantioselective allyl alkylations catalyzed by palladium involve the use of chiral nucleophiles447 and chiral leaving groups.448-449 Chiral enamines were found to undergo allylation in 100% optical yield in an intramolecular case and in up to 50% optical yield in intermolecular reactions (equation 358). 

Scheme 30 Application of 33 in the Cu-catalyzed enantioselective allylic alkylation...

The dendritic oxazoline ligand 197 <02JOC8197> was used for the formation of palladium complexes able to catalyse enantioselective allylic alkylation reactions. 

A series of chiral chelate phosphine ligands, mainly based on the ferrocene backbone (Figure 6.9), have been tested in [C4Ciim][PF6] as catalysts for enantioselective allylic alkylation reactions and results are listed in Table 6.9.[134]... 

Copper-catalyzed enantioselective allylic alkylation ring-opening reactions of oxiranes (and aziridines) with alkyl metals (e.g., dialkylzincs) has been reviewed by Pineschi <2004NJC657>. 

Enantioselective Allylic Alkylation. Reaction of l-(a-acet-oxyethyl)cyclopentene with the sodium salt of dimethyl mal-onate in refluxing 1,2-dimethoxyethane, when performed in the presence of tetrakis(triphenylphosphine)palladium and (R,S)-CAMPHOS catalyst, afforded the corresponding ct-alkylated malonic ester in 99% chemical yield (37% ee)(eq 3). Comparable results were obtained when this reaction was performed in THF solution by using Pd(PPh3)4-(S,S)-(+)-DIOP as catalyst. ... 

Enantioselective allylic substitutions catalyzed by transition-metal complexes are a powerful method for constructing complex organic molecules [4f,55]. Palladium-based catalysts have often given excellent results. To expand the scope of the reaction, a new enantioselective allylic alkylation catalyzed by planar-chiral ruthenium complexes was developed [56]. For example, the reaction of l,3-diphenyl-2-propenyl ethyl carbonate with sodium dimethyl malonate in the presence of 5 mol% of a planar chiral (S)-ruthenium complex (Figure 5.3) at 20 °C for 6 h in THE resulted in the formation of the corresponding chiral allylic alkylated product of dimethyl 2-((2 )(lS)-l,3-diphenylprop-2-enyl)propane-l,3-dioate in 99% yield vsdth 96% e.e. (Eq. 5.33). 

Another major contribution of polydentate ligands is the creation of a chiral pocket around the catalytic center providing, an appropriate chiral environment. The chiral pocket concept has been introduced by Trost for catalytic enantioselective allylic alkylation with the tetradentate aminophosphine ligand 33 [133]. The nucleophile fits into the chiral environment created by the chiral ligand and the allyl Pd intermediate. As a result, the enantiocontrol of the newly formed chiral center is very effective. In addition, the chiral control is likely to be efficient even at positions remote from the chiral ligand. That auxiliary has been widely... 

CHIRAL FERROCENYL-IMINO PHOSPHINES AS LIGANDS FOR PALLADIUM-CATALYSED ENANTIOSELECTIVE ALLYLIC ALKYLATIONS... 

Table 1. Enantioselective allylic alkylation of rac-4-R according to Eq. (a) [PdlCaHslClk (1 mol%)...

Figure 8.4 Optimized transition state structure of Pd fenchyl phosphinite, with diphenylallyacetate, leading to enantioselective allylic alkylation (83% ee, Senantiomer). The endo-trans structure shows better Pd-d-7l interaction and less steric repulsion. (Reproduced with permission from Ref [317].)...

Asymmetric Allylation Reactions. Enantioselective allylic alkylation is used extensively in asymmetric synthesis with chiral nonracemic phosphines often serving as the source of enantio-discrimination. A monodentate phosphabicyclononane derivative in conjunction with Pd(dba)2 was found to be effective in promoting the asymmetric allylation of 2-substituted cyclopen-tenyl and cyclohexenyl carbonates with malonate and sulfonamide nucleophiles with ee s ranging from 50 to 95% (eq 16). ... 

Chiral sulfoximine-palladium complexes catalyzed enantioselective allylic alkylation with moderate enantioselectivitiesJ The allylic alkylations of 1 with dimethyl malonate were carried out in dichloromethane at room temperature in the presence of [Pd(rr-allyl)Cl]2 (2 mol %), BSA (3 equiv), chiral ligands 45a-h (5 mol %), and AcOK, affording (5)-2 with 20-73% ee. 

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