Silicone-based nucleophiles

Several representative examples of nucleophilic hydroxymethylation of aldehydes, ketones, organic halides, tosylates, and epoxides are summarized in Table I. The oxidation conditions given in the original literature are not necessarily optimum, and results may be improved by use of the oxidation method employed here. These results, summarized in Table I, demonstrate the general applicability of the silicon-based nucleophilic hydroxymethylation. 

Agroclavine I Lewis acid assisted condensation reactions between a constituted 5-methoxy-isoxazolidine and silicon-based nucleophiles [20]... 

Scheme 1.29 Palladium-catalyzed arylation with silicon-based nucleophile 74 (Hiyama, 1989).

Siloxane bonds are opened readily with strong bases. Nucleophilic attack at the silicon atoms is involved in the reaction mechanism. Attempts at complete hydrolysis of the siloxane bonds on the surface of Aerosil by Boehm and Schneider 267) met with limited success. Partial hydrolysis was achieved with cold water over long periods, with boiling water in limited time, and by the action of ammoniacal pyrocatechol solutions. However, the number of silanol groups never exceeded 3.3OH/100A. Ashasbeenshownonpage228, avalueof ca. 5OH/100A would be expected from theoretical considerations. 

Silicon-based Lewis acids have been known for some time, and the related chemistry in catalysis has recently been reviewed [24]. Most examples in the literature are mainly based on achiral species and will be discussed only briefly in this section. In general, a broad variety of reactions can be catalyzed with compounds like MejSiOTf, MejSiNTf or MOjSiClO. One advantage over some metal Lewis acids is that they are compatible with many carbon nucleophiles like silyl enol ethers, allyl organometallic reagents and cuprates. 

Silicon-based protecting groups for alcohols are the best because they are the most versatile. They are removed by nucleophilic displacement with fluoride or oxygen nucleophiles and the rate of removal depends mostly on the steric bulk of the silyl group. The simplest is trimethylsilyl (Mt Si or often just TMS) which is also the most easily removed as it is the least hindered. Tn fact, it is removed so easily by water with a trace of base or acid that special handling is required to keep this labile group in place. 

Recently silicon-based protection has matured into a new Ix oad area of protecting group chemistry (see Section 3.1.3.2) and amines can also be conveniently blocked with appropriate silicon reagents. In organometallic syntheses, e.g. in the alkylation of amino acid enolates, the so-called stabase adducts (30) serve to temporarily protect the a-amino group (Scheme 21). In the absence of hard nucleophiles, in particular of 0-nucleophiles, the Si—N bonds are stable, but deprotection is readily effected in the presence of water and acids. 

Silicon-based Polymeric Materials Mechanistic Organosilicon Chemistry (a) Gas Phase and Photochemical Reactions (b) Hypervalent Silicon, Nucleophilic Substitution, and Biotransformations Structural Organosilicon Chemistry and New Organosilicon Compounds Organic Synthesis using Siiicon. 

Silanols are utilised for silicon-based polymeric materials and also find use as nucleophilic coupling partners in organic synthesis. Traditional synthetic methods utilise toxic reagents and are non-environmentally friendly, and other recently reported synthetic methods, in the absence of organic solvents, suffer the main drawback of the production of disiloxanes. Recent results by Kaneda et al. overcome this by using water as the solvent, with silver supported in hydroxyapatite with Mtde condensation to the disiloxanes. They show that the reaction can also be catalysed by homogeneous silver, although the supported nanoparticles were superior and reusable without any loss of activity or selectivity. 

Conjugate Addition. TBDMS triflate has been used to promote the conjugate addition of carbon- and heteroatom-based nucleophiles to a range of a./S-unsaturated carbonyl compounds, in both stoichiometric and catalytic quantities. In some cases, the silyl enol ether is isolated, in other cases, it is implied as an intermediate but hydrolyzed either in situ or by addition of an acid or a reagent known to cleave a carbon-silicon bond e.g., TBAF. Examples of carbon-based nucleophiles are shown in eqs 22-26. 

Applications in PET Imaging. Di-t-buylchlorosilane has been utilized in the synthesis of silicon-based building blocks for F-radiolabeling of peptides for application in PET imaging. Nucleophilic substitution of di-f-butylchlorosilane with 4-[2-(tetrahydro-2//-pyran-2-yloxy)ethyl]phenyl lithium proceeded in 74% yield (eq 13), the product of which was further modified to afford the F-radiolabeled compound. 

Nucleophilicity of the Fluoride. Although TASF has been valuable for the direct incorporation for fluoride into organic substrates, the nucleophilicity of the fluoride from TASF has not been exclusively exploited for silicon-based reactions. Recent examples of substitution reactions have been published since the previous article, mainly for sugar derivatives. Unfortunately, the reactions are t3q)ically low yielding and elimination byproducts are often observed. Despite these complications, TASF is often considered to be the mildest reagent for such reactions. In one case, the source of fluoride (DAST or TASF) gave stereo-complementary products (eqs 33 and 34). ... 

Hydrolysis of polyfluoroalkylsilicon di- or trihalides with water affords polyfluoroalkylsilicon polymers (66). However, even dilute aqueous alkali cleaves the silicon-carbon bonds of these polymers at room temperature when fluorine is in either the a- or the j8-positions. Fluorocarbon groups in nonpolymeric compounds like CHF2CF2SiCl3 or (CH3)2Si(C3F7)2 are also easily removed as fluoroalkanes with aqueous base. Nucleophilic attack on silicon is evidently favored by the electronegative polyfluoroalkyl groups. When fluorine is not in the a- or j8-positions, as in (CF3CH2CH2SiOt.s] , strong aqueous alkali fails to cleave silicon-carbon bonds even at elevated temperatures. 

In the last few years, the use of NHC-Cu complexes in catalysis has grown exponentially, particularly for the transfer of carbon and heteroatom-based nucleophiles to various electrophilic substrates. Copper-catalyzed boron and silicon transfers have recently been reported, thus expanding the scope of NHC-copper-catalyzed reactions. Notably, the design of new chiral NHC ligands has enabled the successful development of efficient C-C and C-H bond forming enantioselective reactions. 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

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