Allylation enantio selective

It may be concluded from die different examples sliown here tiiat die enantio-selective copper-catalyzed allylic substitution reaction needs ftirdier improvemetiL High enantioselectivities can be obtained if diirality is present in tiie leaving group of die substrate, but widi external diiral ligands, enantioselectivities in excess of 9096 ee have only been obtained in one system, limited to die introduction of die sterically hindered neopeatyl group. 

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]. 

Enantioselective allylations of a-nitro ketones and a-nitro esters with allyl acetates are carried out in the presence of 2 equiv of alkali metal fluorides (KF, RbF, CsF) and 1 mol% palladium catalysts prepared in situ from Pd2(dba)3-CHC13 and chiral phosphine ligands. Moderate enantio-selectivity (ca 50% ee) is reported for allylation of cx-nitroketones (Eq. 5.60). The highest selectivity (80% ee) is observed for allylation of the reaction of tert-butyl ester (Eq. 5.61).93... 

An enantio-selective enzymatic hydrolysis of meso( )-2,5-diacetoxy-3-hexene gives (+)-( )-(25 ,5/ )-5-acetoxy-3-hexen-2-ol in 77% yield (92% ee).97 The monoacetate with its two allylic groups offers possibilities for stereo-controlled introduction of nucleophiles via Pd(0) catalysis. Synthesis of both enantiomers of the Carpenter bee pheromone based on this strategy is presented in Scheme 5.14.98... 

The aforementioned polymer-supported bis-pyridyl ligand has also been applied in microwave-assisted asymmetric allylic alkylation [140], a key step in the enantio-selective synthesis of (R)-baclofen (Scheme 7.118), as reported by Moberg and coworkers. The ( (-enantiomer is a useful agonist of the GABAb (y-aminobutyric acid) receptor, and the racemic form is used as a muscle relaxant (antispasmodic). Under microwave heating, the enantioselectivity could be improved to 89% when using toluene as solvent (see also Scheme 6.52) [140],... 

Zr-catalyzed enantio-selective intramolecular diene cyclizations with allylic alcohol and ether substrates afford carbocycles bearing quaternary carbon stereogenic centers the unexpected formation of the aldehyde product 19 is noteworthy. 

Scheme 26. Enantio-selective domino Heck-allyllation process...

Ruthenium complexes containing this phosphine ligand are able to reduce a variety of double bonds with enantiomeric excesses above 95%. In order to achieve high enantio-selectivity, the compound to be reduced must show a strong preference for a specific orientation when complexed with the catalyst. This ordinarily requires the presence of a fimctional group that can coordinate with the metal. The ruthenium binaphthyldiphosphine catalyst has been used successfully with unsaturated amides,11 allylic and homoallylic alcohols,12 and unsaturated carboxylic acids.13... 

In 2003, Lattanzi and coworkers reported on the use of the tertiary camphor-derived hydroperoxide 61 in the titanium-catalyzed asymmetric epoxidation of allylic alcohols (equation 39f. Yields were moderate and ranged between 30 and 59%. Also, the enantio-selectivities obtained were only moderate (24-46%). After the reaction, the enantiomeri-cally pure camphor-derived alcohol can be recovered in good yields by chromatography without loss of optical purity and can be reconverted into the corresponding hydroperoxide. 

Hallberg and his co-workers reported in 1999 the first microwave-promoted asymmetric palladium-catalyzed allylic alkylation of acyclic and cyclic allylic esters with dimethyl malonate, using some chiral ligands 57 and 118 (Equations (65) and (55))3 s,l6Sa,i6Sb both cases, microwave irradiation reduces reaction time without any loss of enantio-selectivity. The same group successfully applied this reaction system to the molybdenum-catalyzed allylic alkylation (Equation ((,7)) 60.160 -l60. 

Asymmetric allylation.n The chiral enamine 1, derived from the allyl ester of (S)-proline, when treated with this Pd(0) complex at 25° in various solvents provides (S)-( — )-2-allylcyclohexanone (2) in 80-100% ee, the highest enantio-selectivity being observed in CHC13. 

The means of entry into rr-allyl complexes, the elucidation o employed, a summary of the reaction types available for allylpall and enantio-selectivities of this reaction will be discussed in turn. 

Benzylic and allylic positions are hydroxylated by CPO in halide-dependent catalytic transformations. Toluene and p-xylene are oxidized to the respective aldehydes and carboxylic acids [247, 248]. Ethylbenzene and other substrates with longer alkyl chains form the respective benzylic/allylic alcohols with high enantio-selectivity. Straight-chain aliphatic and cyclic (Z)-alkenes are hydroxylated, favoring small unsubstituted substrates in which the double bond is not more than two carbon atoms from the terminus. Steric control is observed for benzylic hydroxylations. 

Platinum complexes, [PtCl2 (l ,l )-XantBino ] (2) and its S,S analogue, were treated with tin(II) chloride to form the pre-catalyst for chemo-, regio-, and enantio-selective hydroformylation of styrene, vinyl acetate and allyl acetate. Although the reaction showed good chemo- and regio-selectivities, only moderate ee was obtained.103... 

Palladium-catalysed chemo- and enantio-selective oxidation of allylic esters and carbonates has been achieved using nitronates as nucleophilic oxidants. The products, o /3-unsaturalcd carbonyl compounds, were obtained in excellent yields and ees. The mechanism in Scheme 5 has been suggested for the reaction.108... 

The products were obtained in satisfactory to good yields (up to 85%) and enantio-selectivity for the trans isomer was up to 90% ee. Diastereoselectivity was high for branched allyl halides, with d.r. (trans/cis) up to >50 1, whereas for unbranched allyl halides the diastereomeric ratio was only modest - 2.3 1 to 2.8 1. Selected examples are shown in Scheme 6.93. The methylallyl iodide or bromide was found to be the preferred allyl halide in terms of diastereoselectivity and enantioselectiv-... 

A regio- and enantio-selective palladium-catalysed allylic alkylation of ketones has been reported, using allyl enol carbonate chemistry in which a CO2 unit tethers the allylating agent to the nucleophile.198... 

In another study,4 the substituents on the phosphoramidite ligand on the [IrCODClh catalyst were altered from aryl groups to 1-naphthyl groups. This led to higher yields (>94%), and greater regio- and enantio-selectivities in the 5 2 reaction between several substituted allylic carbonates and amines or phenoxides. The S 2 /S 2 product ratios were >91 9 with the new catalyst. 

Similar to the reaction of allylamines, allyl alcohols also undergo enantioselective isomerization in the presence of [Rh(BINAP)(COD)]+ [10]. Yields and enantio-selectivity are usually moderate, however. Considerable improvement was recently achieved by application of Rh(I) catalysts bearing phosphaferrocenes, 27, as chiral ligands (Scheme 7) [11]. These air-stable complexes, which can be recovered after the reaction, afford chiral aldehydes with up to 93 % ee. 

Nagasawa and co-workers reported the use of a chiral bis-thiourea catalyst (108) for the asymmetric MBH reactions of cyclohexenone with aldehydes [95]. Since others had already shown that thioureas form hydrogen bonds with both aldehydes and enones, it was hypothesized that the inclusion of two thiourea moieties in close proximity on a chiral scaffold would organize the two partners of the MBH reaction and lead to enantiofacial selectivity. Initial studies showed that the achiral 3,5-bis-(trifluoromethyl)phenyl-substituted urea increased the rate of MBH reaction between benzaldehyde and cyclohexenone. These authors then showed that chiral 1,2-cyclohexyldiamine-linked bis-thiourea catalyst 108, used at 40 mol% loading in the presence of 40 mol% DMAP, promoted the MBH reactions of cyclohexenone with various aliphatic and aromatic aldehydes (40) to produce allylic alcohols in moderate to high yields (33-99%) and variable enantio-selectivities (19-90% ee Table 6.33). 

The first catalytic asymmetric allylation of imines has been reported using allyltri- -butyltin in the presence of a chiral 7r-allylpalladium complex.179 Zirconium is also demonstrated as a metal center for the design of chiral Lewis acid catalysts that are suitable for the activation of bidentate imino compounds.180 Jprgensen reports high enantio-selective allylation of ct-imino esters (Equation (52)).181... 

Silver salts or reagents have received much attention in preparative organic chemistry because they are useful catalysts for various transformations involving C-G and C-heteroatom bond formation.309 Especially, the silver(i)/ BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthalene) system is a very effective catalyst for a variety of enantio-selective reactions, including aldol, nitroso aldol, allylation, Mannich, and ene reactions. Moreover, silver salts are known to efficiently catalyze cycloisomerization and cycloaddition reactions of various unsaturated substrates. Recently, new directions in silver catalysis were opened by the development of unique silver complexes that catalyze aza-Diels-Alder reactions, as well as carbene insertions into C-H bonds. 

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