Alcohols oxygen nucleophiles

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

Reaction with Oxygen Nucleophiles. In the presence of strong acids, eg, H2SO4, HBF, or BF, aziridines react with alcohols to form P-amino ethers (93) ... 

S-Substituted thiiranium ions react with water and alcohols to give trans ring opening (Scheme 72). A report that oxygen nucleophiles attack sulfur as well as carbon has been shown to be incorrect (79ACR282). The intermediate thiiranium ion (57) in the presence of lithium perchlorate readily yields the carbenium ion which undergoes a transannular hydride... 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

Therefore, for the arylation of oxygenated nucleophiles, particularly of the alcohols, the investigations were focused on the nickel catalysts (Fig. 8). 

The oxygen nucleophiles that are of primary interest in synthesis are the hydroxide ion (or water), alkoxide ions, and carboxylate anions, which lead, respectively, to alcohols, ethers, and esters. Since each of these nucleophiles can also act as a base, reaction conditions are selected to favor substitution over elimination. Usually, a given alcohol is more easily obtained than the corresponding halide so the halide-to-alcohol transformation is not used extensively for synthesis. The hydrolysis of benzyl halides to the corresponding alcohols proceeds in good yield. This can be a useful synthetic transformation because benzyl halides are available either by side chain halogenation or by the chloromethylation reaction (Section 11.1.3). 

Although transition metal-catalyzed allylic alkylation has become one of the most powerful methods in chemical synthesis, the formation of ether bonds using this process has been slow to evolve.119-121 The main reasons for this disparity are the lower nucleophilicity and higher basicity of oxygen nucleophiles, particularly those derived from aliphatic alcohols, compared to their carbon or nitrogen analogs. However, this notion has rapidly been revised, as recent advances in the O-allylation area have largely addressed the issue of the reactivity mismatch between the hard alkoxide and the soft 7r-allylmetal species to provide a considerable body of literature. 

Rhodium catalysts have also been used with increasing frequency for the allylic etherification of aliphatic alcohols. The chiral 7r-allylrhodium complexes generated from asymmetric ring-opening (ARO) reactions have been shown to react with both aromatic and aliphatic alcohols (Equation (46)).185-188 Mechanistic studies have shown that the reaction proceeds by an oxidative addition of Rh(i) into the oxabicyclic alkene system with retention of configuration, as directed by coordination of the oxygen atom, and subsequent SN2 addition of the oxygen nucleophile. 

Aside from alcohols, other oxygen nucleophiles have also participated in hydroalkoxylation reactions with alkynes. The most common of these are 1,3-dicarbonyl compounds, whose enol oxygens are readily available to add to alkynes. Cyclization reactions of this type have been carried out under Pd(0) catalysis with various aryl or vinyl iodides or triflates, often in the presence of CO, affording the corresponding furan derivatives (Equation (95)).337-340 A similar approach employing cyclic 1,3-diketones has also been reported to prepare THFs and dihydropyrans under Pd, Pt, or W catalysis.341 Simple l-alkyn-5-ones have also been isomerized to furans under the influence of Hg(OTf)2.342... 

Both dienyl- and 7r-allylmetal complexes of Fe,492 Mo,493,494 and W374 have also been prepared and undergone similar reactions with oxygen nucleophiles. One pertinent example is the reaction of 7r-allylmolybdenum complexes with internal alcohols leading to THFs (Equation (128)) 493 additional examples of this chemistry have appeared in a... 

While in most reported cases the nucleophiles were amines, there were few examples involving heterocyclic nitrogens [40], alcoholic oxygens [27] or carbon nucleophiles [42, 43] too. Figure 4 shows a recent example of tandem Ugi-Dieckmann protocol [42]. Ugi convertible isocyanide 2, which requires a basic activation, was used, allowing a domino activation-cyclization of the intermediate 20 to give pyrrolidinediones (tetramic acids) 22. 

The oxygen nucleophiles that are of primary interest in synthesis are the hydroxide ion (or water), alkoxide ions, and carboxylate anions, which lead, respectively, to alcohols, ethers, and esters. Because each of these nucleophiles can also act as a base, reaction conditions must be selected to favor substitution over elimination. 

Substituents can play a part in the reaction of 1,2,4-trioxolanes with oxygen nucleophiles, for example 3-acyl or 3-aldehydic substituents can lead to fragmentation pathways via attack at the carbonyl (Section 4.16.6.2). Also, it is possible to displace suitable leaving groups in the 3-position with alcohol nucleophiles (Sections 4.16.6.3 and 4.16.9.4). 

In a general base catalysis, the pyridine forms a hydrogen bond to an alcohol function (56). This causes a polarization and increases the nucleophi-licity of the alcohol oxygen thus accelerating the reaction [46c]. The second mechanism postulates a betain intermediate 57 which is formed by a nucleophilic attack of the pyridine on the ketene 59 [46d]. 

Selectivity can be an overriding commodity in cases where reactivity is dictated by logic and accepted concepts. Such is the case with stannylene acetals of diols and trialkyl-stannyl ethers of alcohols. Enhanced nucleophilicity of oxygen attached to tin and well-documented stereoelectrorric effects associated with methine carbon atoms of trialkyhin ethers lead to remarkably selective reactions of (7-substitution and oxidation in polyhydroxy compounds. 

Cyclizations of substrates in which internal oxygen nucleophiles have been attached to unsaturated alcohols provide a method for stereoselective formation of acyclic 1,2- and 1,3-diol functionalities, as outlined in Scheme 2. 

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