Nucleophilicity, allylsilane

A plausible mechanism for the reaction is depicted in Scheme 13.73. Enol ether 200 reacts with the activated aldehyde to give the oxonium cation 204. This species is trapped intramolecularly by the allylsilane nucleophile and a new tetrahydro-pyran ring 202 is formed. 

Marshall et al. reported that more reactive allyltin analogs can be used instead of allylsilane nucleophiles in our CAB 1 catalyst system, and found that trifluoroacetic anhydride is an efficient promoter that retains stereoselectivity (Eq. 67) [50aj. 

The Nicholas and Pauson-Khand reactions, as well as the bond-angle effect, have been combined in a single synthetic scheme to make more efficient use of the cobalt. This has been done in a synthesis of epoxydictamine 7.90 (Scheme 7.24)." The Nicholas reaction was employed, in which a carbocation 7.87, generated from acetal 7.86, was trapped by an allylsilane nucleophile intramolecularly, to form the eight-membered ring... 

The most impressive use of a tandem strategy involving the Nicholas reaction in a total synthesis project is Schreiber s preparation of (+)-epoxydict5miene (61). Cobalt complexation of 58 followed by an endocyclic intramolecular Nicholas reaction with an allylsilane nucleophile yields Pauson-Khand precursor 59. Treatment of 59 with iV-methylmorpholine-iV-oxide (NMO) promotes the Pauson-Khand reaction to furnish tetracycle 60 which was ultimately converted to the target natural product 61. ... 

In the Sakurai reaction, the product-determining step should be the nucleophilic addition of the allylsilane to the Lewis acid coordinated enone28. 

Apparently the Lewis acid induced and the fluoride-induced reactions of allylsilanes with enones follow different pathways. The perpendicular approach of the nucleophilic allylsilane... 

A substrate containing an amine carboxylate moiety is converted in an electrolyte solution in the presence of a strong acid to a cationic intermediate, an N-acyliminium cation, by electrooxidative reaction. This species is immediately reacted with an allylsilane [66, 67]. By nucleophilic reachon, C-C bond formahon is achieved. 

Aubele et al. studied the aqueous Prins cyclization using cyclic unsaturated acetals as oxocarbenium ion progenitors and allylsilanes are used as nucleophiles. Cyclizations proceed efficiently inside Lewis acidic micelles (of cerium salt) in water. A variety of vinyl- and aryl-substituted tetrahydropyrans with excellent stereocontrol was obtained (Eq. 3.26).113... 

Treatment of a-(benzotriazol-l-yl)alkyl thioethers 831 with ZnBr2 weakens the bond with benzotriazole, and the obtained complex 832 may partially dissociate to thionium cation 835 that can be trapped by even mild nucleophiles. Thus, trimethylsilyl cyanide added to the reaction mixture causes substitution of the benzotriazole moiety by the CN group to give a-(phenylthio)carbonitrile 834. In a similar manner, treatment with allylsilane leads to y,S-unsaturated thioether 833. Addition of species 835 to the double bond of a trimethylsilyl ot-arylvinyl ether followed by hydrolysis of the silyloxy group furnishes (i-(phenylthio)alkyl aryl ketones 836 (Scheme 132) <1996TL6631>. 

In the second approach55 an allylsilane was employed as carbon nucleophile in the side chain. Allylsilanes have been frequently used as masked allyl carbanions, usually in reactions with a keto function57. Palladium-catalyzed reaction of allylsilane 57 with LiCl under similar conditions as used for the other intramolecular 1,4-oxidations afforded 58 (equation 22). Interestingly, the carbochlorination over the diene was highly 1,4-syn... 

This reaction has been extensively used for the synthesis of polyfunctionalized piperidines with a wide range of nucleophiles selected and representative examples are collected in Table 15. From these results, hydrides, Grignard reagents, aluminium derivatives, allylsilane, as well as aromatics can be used as nucleophiles to give the corresponding C-8a functionalized compounds in good yields and, in most cases, excellent selectivities. 

Various carbon nucleophiles, such as allylsilanes, allylstannanes, silyl enol ethers, ketene silyl acetals, organoaluminum compounds, and Grignard reagents were effective as carbon nucleophiles. 

The alkoxycarbenium ions generated by the cation pool method react with various carbon nucleophiles such as substituted allylsilanes and enol silyl ethers to give the corresponding coupling products in good yields. It should be noted that the reactions of alkoxycarbenium ion pools with such nucleophiles are much faster than the Lewis acid promoted reactions of acetals with similar nucleophiles. A higher concentration of the cationic species in the cation pool method seems to be responsible. 

Different nucleophiles such as methanol, allylsilanes, silyl enol ethers, trimethylsilyl-cyanide, and arenes can be used in this process [62]. When the sulfide itself contains an unsaturated or aromatic fragment and the process is carried out in the absence of a nucleophile, an intramolecular anodic sub-stitution/cyclization might occur [61-63]. Methyl esters of 2-benzothiazolyl-2-alkyl or aryl-acetic acid, oxidized in MeOH/Et4 NCIO4 or H2SO4 in the presence of CUCI2, form 2,2-dimethoxy products (Eq. 7) [64]. 

Lewis acid-mediated addition of allylsilanes to carbon nucleophiles. Also known as the Hosomi-Sakurai reaction. The allylsilane will add to the carbonyl compound directly if it is not part of an a,P-unsaturated system (Example 2), giving rise to an alcohol. 

The Lewis acid-catalyzed reaction of 4-acetoxy-l,3-dioxanes with nucleophiles has been reviewed <2001TCC(216)51>. The principles of the reaction are displayed in (Equation 44). The combination of boron trifluoride and organozinc compounds was found to be very efficient <1997JOC6460, 1999JOC2026> but allylsilanes react as well <19%SL536, 1998TL6811>. 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

In addition to allylsilanes, CM can also be applied to allylstannanes, which serve as valuable reagents for nucleophilic additions and radical reactions.To date, only eatalyst 1 has been shown to demonstrate CM reactivity in the preparation of 1,2-disubstituted allylstannanes, as ruthenium catalysts were found to be inactive in the presence of this substrate class.Poor stereoselectivities were generally observed, with the exeeption of one instance of >20 1 Z-selectivity in the reaction of allyltributylstannane with an acetyl-protected allyl gluco-side. 

Many newer methods for generating cyclohexane derivatives from carbohydrates still depend on the intramolecular attack of nucleophilic carbon species at electrophilic centers, and the range of options is now extensive. Thus, the nucleophiles may be carb-anions stabilized by carbonyl, phosphonate, nitro, or dithio groups, and they may bond to carbonyl carbon atoms, or to those that carry appropriate leaving groups or are contained in epoxide rings, or as jj-centers of a,p-unsaturated carbonyl systems. Otherwise, the nucleophilic activity at the 7-centers of allylsilanes or a-positions of vinyl silanes may be used to react with electrophilic carbon atoms. 

Epoxide rings may also be opened by intramolecular nucleophiles derived from allylsilane groups (see Scheme 9) to permit aldol-like closure onto aldehyde functions. Compound 63 (Scheme 15), derived by a multistep route from L-arabinose, when activated... 

The addition of an allyl metal to a-amino aldehydes has been used by Vara Prasad and Rich (Scheme 12)J23l After the addition step, the allyl group is oxidized to a carboxylic acid and lactonized. Then, the a-carbon of the lactone is alkylated stereoselectively. These investigators also systematically examined the addition reaction to determine its diastereo-selectivity. The highest diastereoselectivity was obtained when allyltrimethylsilane was used in the presence of tin(IV) chloride. An increase in the steric bulk of the protecting group and of the side chain also resulted in a better diastereoselection. Alternatively, Taddei and co-workers 24-26 used a 2-(halomethyl)allylsilane and the side chains were introduced by nucleophilic substitution of the halogen (Scheme 13). 

An analogous process, which provides a nucleophilic allylsilane, has been reported, employing (Me3Si)3Al etherate in conjunction with allyl acetates and Pd° (equation 113).225... 

The anion of cyclopentadiene has also been demonstrated to add via ligand addition (inversion).105 385-386 Indenyl nucleophiles derived from the corresponding allylsilane have been classified as adding via ligand addition,385 but the sodium salt of the indenyl anion has curiously been suggested to add via addition directly to the metal.386... 

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