Allyl carbon centers, nucleophilic substitution

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. 

Other kinds of propargylic-substituted products were prepared by this procedure. When Grignard reagents such as allylic and homoallylic magnesium bromides are used in place of lithium enolates as carbon-centered nucleophiles. 

Further examples of stabilized carbon-centered nucleophiles used in Pd-catalyzed allylic substitution are given in Scheme ii.wo]-[47] noteworthy that the dichloroben-zoate group of substrate 55 leaves selectively over the acetate, and that the (Z)-stereo-chemistry of the substrate becomes ( )-stereochemistry in the product 68. Nitromethane 66 is sufficiently acidic that there are no problems in the substitution reaction with acetate 59. Relative stereochemistry is preserved in the product 73. 

The reaction proceeds well with unhindered secondary amines as both nucleophiles and bases. The yield of allylic amine formed depends upon how easily palladium hydride elimination occurs from the intermediate. In cases such as the phenylation of 2,4-pentadienoic acid, elimination is very facile and no allylic amines are formed with secondary amine nucleophiles, while phenylation of isoprene in the presence of piperidine gives 29% phenylated diene and 69% phenylated allylic amine (equation 30).84 Arylation occurs at the least-substituted and least-hindered terminal diene carbon and the amine attacks the least-hindered terminal ir-allyl carbon. If one of the terminal ir-allyl carbons is substituted with two methyl groups, however, then amine substitution takes place at this carbon. The reasons for this unexpected result are not clear but perhaps the intermediate reacts in a a- rather than a ir-form and the tertiary center is more accessible to the nucleophile. Primary amines have been used in this reaction also, but yields are only low to moderate.85 A cyclic version occurs with o-iodoaniline and isoprene.85... 

Two types of palladium-catalyzed asymmetric reaction have been reported. One is the allylation of nucleophiles in which a new chiral carbon center is created in the nucleophile and the other is the allylic substitution reaction in which it is created in the allylic substrate (Scheme 2-24). Chiral ferrocenylbisphosphines designed and modified on the side chain have been successfully used for both of the two types of asymmetric reaction [5 c, d]. 

The nucleophilic substitution reactions of anilines at arylmethyl (ArCH2—), arylethyl (ArCH2CH2—), allyl (CH2=CHCH2—) and alkynylmethyl (CH=CCH2—) carbon centers take place by a direct displacement (SN2) mechanism with Bronsted coefficients, fix, in the range 0.3-0.8 as can be seen in Table 229-48... 

The presence of a stereogenic center on the aldehyde can strongly inlinence the diastereoselectivity in allylboration reactions, especially if this center is in the a-position. Predictive rules for nucleophilic addition on snch a-snbstitnted carbonyl substrates such as the Felkin model are not always snitable for closed transition structures.For a-substituted aldehydes devoid of a polar substituent, Roush has established that the minimization of ganche-ganche ( syn-pentane ) interactions can overrule the influence of stereoelectronic effects. This model is valid for any 3-monosubstituted allylic boron reagent. For example, althongh crotylboronate (E)-7 adds to aldehyde 39 to afford as the major prodnct the diastereomer predicted by the Felkin model (Scheme 2), " it is proposed that the dominant factor is rather the minimization of syn-pentane interactions between the Y-snbstitnents of the allyl unit and the a-carbon of the aldehyde. With this... 

The addition of Grignards and organolithium reagents proceeds by attack at the metal center in ir-allylpalladium complexes. The regiochemical selectivity exhibited by these hard carbon nucleophiles with ir-allyl complexes substituted at the termini with alkyl or aryl groups is comparable to the soft carbon nucleophiles (ligand attack) in most cases, with addition occurring predominantly at the less substituted terminus (equations 248 and 249).1591387... 

Allylic alkylation. In general, ally lie alkylation catalyzed by transition metals results from attack at the less substituted carbon atom of the TT-allyl intermediate. Deviation from this pattern is observed with some nucleophiles when Mo(CO)6 is used as catalyst. For example, the anion of dimethyl malonate generated with 0,N-bis(trimethylsilyl)acetamide (BSA) reacts with the allylic acetate 1 mainly by attack at the tertiary center to give 2. 

Recently, Stryker et al. have developed a new synthetic method that provides 3-sUbstituted metallacyclobutanes. Alkylation of the cationic allyl complex 23 with nucleophiles [74] and thermal reaction of the bis(allyl) complex 25 [75] result in the formation of metallacyclobutanes 24 and 26, respectively. Radical addition of RX to Ti(III)-ally complex 23 takes place exclusively at the center carbon atom, providing a metallacyclobutane [76]. 

The mechanism most often invoked for tliese reactions (Scheme 20.1) involves oxidative addition of the allylic electrophile to a low-valent metal center to generate an n -allylmetal intermediate. In most catalytic allylic substitutions, the acetate, halide, or carbonate leaving group is a counterion for a cationic allyl complex and is not directly bound to the metal. The resulting cationic n -allylmetal intermediate then reacts with the nucleophile, in most cases, by attack on Ihe opposite face of the allyl group to which ihe metal is bound. 

The [i-aUyl complexes can react with several types of nucleophiles, giving rise to the corresponding substitution products. O- and N-nucleophiles as well as soft carbon nucleophiles attack the t-allyl complex directly at the aUylic position, while hard C-nucleophiles react via transmetaUations [2c, 3]. If the nucleophihc attack occurs under an atmosphere of CO, insertion of CO can occur, yielding carbonyl compounds [4]. Alkenes and aUcynes can also insert into allyhnetal bonds, a protocol that is used preferentially for cycUzations [5]. Cyclizations can also occur, if the 7t-allylmetal complex contains an internal nucleophilic center. If the metalallyl complex acts as a nucleophile, direct coupling with aryl halides [6] or additions to electrophiles such as aldehydes, ketones, or imines are possible [7]. This review focuses on C-C coupling reactions via these tt-allyhnetal (or in some cases, a-allyhnetal) intermediates. 

Addition of an T -allyl-Fp complex to this compound affords an T -aIlyl-Fp-substituted cycloheptatriene system. Two double bonds are involved in an (T -diene)iron complex. The remaining free double bond of the silyl enol ether attacks as a nucleophile at the cationic r -alkene-Fp moiety to form an (Tj -diene)iron complexed cyclopentane annulated cycloheptadienone. Treatment with CAN in methanol under carbon monoxide atmosphere releases the methoxycarbonyl-substituted free ligand (Scheme 4-25). Reaction of the Ti -dienyliumiron intermediate of Scheme 4-25 with an ( , Z)-isomeric mixture of ri -crotyl-Fp proceeds with high diastereoselectivity. Four new stereogenic centers are formed in the course of this formal [3+2] cycloaddition. A hetero [3+2] cycloaddition is also feasible between T -ailyl-Fp complexes and aromatic aldehydes in the presence of zinc chloride or titanium(IV) chloride to provide tetrahydrofuran derivatives (Scheme 4-26). A 1,2-shift of the iron complex fragment occurs in the course of this reaction. Employment of imines affords the corresponding pyrrolidines. ... 

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