Nucleophiles commercially available

Common Nucleophiles (Commercially Available or Readily Prepared)... 

Many saturated nitrogen heterocycles are commercially available from industrial processes, which involve, for example, nucleophilic substitution of hydroxyl groum by amino groups under conditions far from laboratory use, e.g. 

In stereoselective antitheses of chiral open-chain molecules transformations into cyclic precursors should be tried. The erythro-configurated acetylenic alcohol given below, for example, is disconnected into an acetylene monoanion and a symmetrical oxirane (M. A. Adams, 1979). Since nucleophilic substitution occurs with inversion of configuration this oxirane must be trens-conilgurated its precursor is commercially available trans-2-butene. 

Certain base adducts of borane, such as triethylamine borane [1722-26-5] (C2H )2N BH, dimethyl sulfide borane [13292-87-OJ, (CH2)2S BH, and tetrahydrofuran borane [14044-65-6] C HgO BH, are more easily and safely handled than B2H and are commercially available. These compounds find wide use as reducing agents and in hydroboration reactions (57). A wide variety of borane reducing agents and hydroborating agents is available from Aldrich Chemical Co., Milwaukee, Wisconsin. Base displacement reactions can be used to convert one adduct to another. The relative stabiUties of BH adducts as a function of Group 15 and 16 donor atoms are P > N and S > O. This order has sparked controversy because the trend opposes the normal order estabUshed by BF. In the case of anionic nucleophiles, base displacement leads to ionic hydroborate adducts (eqs. 20,21). 

Xenon difluoride [4, 5, 7, 8,10] is a white crystalline material obtained through the combination of fluorine and xenon m the presence of light The reagent is commercially available and possesses a relatively long shelf-life when stored cold (freezer) Xenon difluoride is very effective for small-scale fluormation of alkenes and activated nucleophilic substrates. The reactions are usually conducted between 0 °C and room temperature in chloroform or methylene chloride solutions Hydrogen fluoride catalysis is sometimes helpful Xenon difluoride reacts in a manner that usually involves some complexation between the substrate and reagent followed by the formation of radical and radical cation intermediates... 

The optically active iodide 153 (Scheme 43) can be conveniently prepared from commercially available methyl (S)-(+)-3-hydroxy-2-methylpropionate (154) (see Scheme 41). At this stage of the synthesis, our plan called for the conversion of 153 to a nucleophilic organometallic species, with the hope that the latter would combine with epoxide 152. As matters transpired, we found that the mixed higher order cuprate reagent derived from 153 reacts in the desired and expected way with epoxide 152, affording alcohol 180 in 88% yield this regioselective union creates the C12-C13 bond of rapamycin. 

Three types of synthases catalyze the addition of phosphoenolpyruvate (PEP) to aldoses or the corresponding terminal phosphate esters. By concurrent release of inorganic phosphate from the preformed enolate nucleophile, the additions are essentially irreversible. None of the enzymes are yet commercially available and little data are available oil the individual specificities for the aldehydic substrates. A bacterial NeuAc synthase (EC 4.1.3.19) has been used for the microscale synthesis of A -acetylncuraminic acid from Af-acetyl-D-mannosamine31 and its 9-azido analog from 2-acetamido-6-azido-2,6-dideoxy-D-mannose32. 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

In the present study the dimer (salen)CoAlX3 showed enhanced activity and enantioselectivity. The catalyst can be synthesized easily by readily commercially available precatalyst Co(salen) in both enantiomeric forms. Potentially, the catalyst may be used on an industrial scale and could be recycled. Currently we are looking for the applicability of the catalyst to asymmetric reaction of terminal and meso epoxides with other nucleophiles and related electrophile-nucleophile reactions. 

In addition to applications as nucleophiles, the lithium reagents have enormous importance in synthesis as bases and as lithiating reagents. The commercially available methyl, n-butyl, s-butyl, and f-butyl reagents are used frequently in this context. 

When we used asymmetric nucleophilic addition of malonate to the Mo tt-allyl complex in our first delivery, the Mo chemistry was not so clearly understood, and our application would be the first large scale example, to the best of our knowledge. Initially our contributions to Mo chemistry were two-fold (i) replacement of non-commercially available (EtCN)3Mo(CO)3 or (C7H8)Mo(CO)3 by more stable and inexpensive Mo(CO)6 by incorporation of proper pre-activating time (ii) simplified preparation of the chiral ligand. Even after we completed the project, we still had a strong interest in Mo chemistry. 

The behavior of the different amines depends on at least four factors basicity, nucleophilicity, steric hindrance and solvation. In the literature (16), 126 aliphatic and aromatic amines have been classified by a statistical analysis of the data for the following parameters molar mass (mm), refractive index (nD), density (d), boiling point (bp), molar volume, and pKa. On such a premise, a Cartesian co-ordinate graph places the amines in four quadrants (16). In our preliminary tests, amines representative of each quadrant have been investigated, and chosen by consideration of their toxicity, commercial availability and price (Table 1). 

All reactions of benzotriazole derivatives of the type Bt-CR RbS discussed above are based on electrophilic or nucleophilic substitutions at the ot-carbon, but radical reactions are also possible. Thus, the first report on unsubstituted carbon-centered (benzotriazol-l-yl)methyl radical 841 involves derivatives of (benzotriazol-l-yl)methyl mercaptan. 3 -(Benzotriazol-l-yl)methyl-0-ethyl xanthate 840 is readily prepared in a reaction of l-(chloromethyl)-benzotriazole with commercially available potassium 0-ethyl xanthate. Upon treatment with radical initiators (lauroyl peroxide), the C-S bond is cleaved to generate radical 841 that can be trapped by alkenes to generate new radicals 842. By taking the xanthate moiety from the starting material, radicals 842 are converted to final products 843 with regeneration of radicals 841 allowing repetition of the process (Scheme 134). Maleinimides are also satisfactorily used as radical traps in these reactions <2001H(54)301>. 

A wide variety of other heterocyclic ring systems can conceivably serve as the conjugated backbone in nonlinear organic molecules. We will give examples from preliminary work on two of these, the thiazole and pyrimidine heterocycle derivatives 65-72 in Table VIII. These two heterocycles were chosen because the appropriate haloderivatives are commercially available as starting materials for nucleophilic aromatic substitution. The pyrimidine derivatives are of particular interest since their absorption edges ( 400 nm) are shifted hypsochromically an additional 30 nm relative even to the pyridines. 

Organomagnesium reagents, which can serve as the nucleophiles in the Kumada coupling, are easy to make and many of them are commercially available. Even though some Kumada reactions can be run at room or lower temperature, many functional groups are not tolerant of Grignard reagents. Nonetheless, in the synthesis of thienylbenzoic acid 24, the carboxylic acid moiety did survive the reaction conditions [25],... 

A stronger base and notably weaker nucleophile is the anion of hexamethyl-disilazane (Mc3Si)2NH, (34H). The anion, (34) , is electrogenerated ex situ, similarly to (33) , as its magnesium salt in dimethoxyethane with 15% v/v HMPA [75]. The PB (34H) is commercially available, relatively cheap, and in many respects behaves very much Kke lithium diisopropylamide (LDA). Substitution of HMPA with Ai-methyl-2-pyrrolidone was not successful [75]. 

The asymmetric formation of industrially useful diaryl methanols can be realized through either the addition of aryl nucleophiles to aromatic aldehydes or the reduction of diaryl ketones. The latter route is frequently the more desirable, as the starting materials are often inexpensive and readily available and nonselective background reactions are not as common. For good enantioselectivity, chemical catalysts of diaryl ketone reductions require large steric or electronic differentiation between the two aryl components of the substrate and, as a result, have substantially limited applicability. In contrast, recent work has shown commercially available ketoreductase enzymes to have excellent results with a much broader range of substrates in reactions that are very easy to operate (Figure 9.6). ... 

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