Allylic alkylation reactions centers

In 2002, Trost and his co-workers reported a stereospecific ruthenium-catalyzed allylic alkylation reaction (Equation (58)). Treatment of an optically active allylic carbonate with carbon-centered nucleophiles in the presence of a ruthenium complex gives the corresponding allylic alkylated compounds with enantiomeric purity being completely maintained. Additionally, the regioselectivity is revealed not to be highly dependent on the nature of the starting carbonates. 

The preparation of 2-(3 p)-[(/ra r-(2/f,5/f)-2,5-dialkylpyrrolidinyl)methyl] ferrocenyldiphenylphosphines, 41, new ferrocenylphosphinamine ligands possessing one site of planar chirality and two stereogenic centers, has been described, and their application in palladium-catalyzed asymmetric allylic alkylation reaction has been investigated. ... 

The allylic alkylation products represent useful synthons, as exemplified by the reaction sequence outlined in Scheme 10.4. For example, reductive ozonolysis of the allylic alkylation product 15 afforded the y-lactone 16 as a single diastereoisomer. Sequential alkylation with methyl iodide, and reductive alkylation using lithium naphthalenide with allyl iodide furnished the ternary-quaternary substituted y-lactones 17a/17b in 72% overall yield, as a 10 1 mixture of diastereomers favoring 17a [18]. This method provides a versatile approach to the construction of a variety of a-quaternary-/9-ternary stereogenic centers. 

Strategies centered on reductive introduction of the fluoroolefin via a geminal difluoro allylic array have been reviewed [66]. In an introductory example to this synthetic approach, Okada et al. [67] developed a completely stereoselective synthesis of Z)-2,5-syn 2-alkyl-4-fluoro-5-hydroxy-3-alkenoic acids through the Cu(l)-mediated allylic substitution reaction of trialkylaluminum with the (E)-4,4-difluoro-5-hydroxyallylic alcohol derivative (61) (Scheme 21). Reaction... 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

Takemoto and his co-workers developed asymmetric allylic alkylation of allylic phosphates with (diphenyl-iminolglycinates as carbon-centered nucleophiles (Equation (56))/" " In this reaction system, use of optically active bidentate phosphites 142 bearing an (ethylthio)ethyl group as chiral ligands promotes the allylic alkylation, and chiral /3-substituted a-amino acids are obtained with an excellent enantioslectivity. 

There have been no quantitative kinetic studies of allyl alkyl ether eliminations however, a rather extensive study of relative reaction rates has been made . In all cases, the reactions of interest were the 6-center ene eliminations, viz. 

In general, the catalytic cycle for the transition-metal catalyzed allylic substitution reactions involves initial attack of the metal at the double bond followed by oxidative insertion into the antiperiplanar C-0 bond to afford the Ti-allyl system. At this point, depending on whether soft or hard nucleophiles are used, however, the alkylation reaction proceeds through distinctly different pathways (Scheme 10). With soft nucleophiles, where Pd is often the metal center of choice. 

Chen and coworkers employed the cinchona alkaloid-derived catalyst 26 to direct Mannich additions of 3-methyloxindole 24 to the A-tosylimine 25 to afford the all-carbon quaternary center of oxindole 27 with good enantioselectivity (84% ee) [22]. The outcome of this Mannich reaction is notable in that it provided very good selectivity for the anti diastereomer (anti/syn 94 6). The mechanism of asymmetric induction has been suggested to involve a hydrogen bonding network between the cinchona alkaloid 26, the oxindole enolate of 24, and the imine electrophile 25 (Scheme 7). Asymmetric allylic alkylation of oxindoles with Morita-Baylis-Hillman carbonates has been reported by the same group [23]. 

AUylic substitution reactions, such as allylic alkylations or allylic aminations, have recently attracted interest as suitable C-C and C-N bond-forming reactions in continuously operating membrane reactors. Oxidative addition of the starting material to a Pd center leads to an (ri -allyl)Pd(II) species, which, after attack of the nucleophile, forms the substituted product [Eq. (4)]. 

Chen et al. have found that commercially available modified cinchona alkaloids [(DHQD)2AQN] are outstanding catalysts for the asymmetric allylic alkylation (AAA) reaction of MBH carbonates with a,a-dicyanoolefins 268 or 3-substituted oxindoles 269. Enantioenriched compounds 270 and 271, respectively, with multifunctional frameworks bearing adjacent stereogenic centers were obtained in excellent stereoselectivities (Scheme 3.107). 

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