Oxygen nucleophiles, addition

Addition of Carbon Nucleophiles The Wittig Reaction Addition of Oxygen Nucleophiles Addition of Nitrogen Nucleophiles Keto-Enol Tautomerism 16.10 Oxidation 6.11 Reduction... 

Thiolate-bridged dirutheniutn complexes catalyze the [3-f3] cycloaddition reaction between propargylic alcohols and cyclic 1,3-dicarbonyl compounds to afford 4,6,7,8-tetrahydrochromen-5-ones or 4//-cyclopenta[b]pyran-5-ones [193] and with 2-naphthols or phenols to afford l//-naphtho[2,l-b]pyrans and 4//-l-benzo-pyrans, respectively [194]. This cycloaddition is considered to proceed by stepwise propargylation and intramolecular cyclization (carbon and oxygen nucleophile additions) reactions, where ruthenium allenylidene and vinylidene complexes are the key intermediates (Scheme 57). Enantioselective mthenium-catalyzed [3-f3] cycloaddition of propargylic alcohols with 2-naphthols has also been described [195]. 

The mechanism for formation of benzaldehyde diethyl acetal which proceeds m two stages is presented m Figure 17 9 The first stage (steps 1-3) involves formation of a hemiacetal m the second stage (steps 4-7) the hemiacetal is converted to the acetal Nucleophilic addition to the carbonyl group characterizes the first stage carbocation chemistry the second The key carbocation intermediate is stabilized by electron release from oxygen... 

Under conditions of acid catalysis the nucleophilic addition step follows protonation of the carbonyl oxygen Protonation increases the carbocat ion character of a carbonyl group and makes it more electrophilic... 

FIGURE 18 7 Nucleophilic addition to a p unsaturated aldehydes and ketones may take place either in a 1 2 or 1 4 manner Direct addition (1 2) occurs faster than conjugate addition (1 4) but gives a less stable product The product of 1 4 addition retains the carbon-oxygen double bond which is in general stronger than a carbon-carbon double bond... 

Protonation of the carbonyl oxygen activates the carbonyl group toward nucleophilic addition Addition of an alcohol gives a tetrahedral inter mediate (shown m the box m the preceding equation) which has the capacity to revert to starting materials or to undergo dehydration to yield an ester... 

Step 1 The acid catalyst activates the anhydride toward nucleophilic addition by protonation of the carbonyl oxygen... 

The carbon-nitrogen triple bond of nitriles is much less reactive toward nucleophilic addition than is the carbon-oxygen double bond of aldehydes and ketones Strongly basic nucleophiles such as Gngnard reagents however do react with nitriles in a reaction that IS of synthetic value... 

Nucleophilic addition (Section 17 6) The charactenstic reac tion of an aldehyde or a ketone An atom possessing an un shared electron pair bonds to the carbon of the C=0 group and some other species (normally hydrogen) bonds to the oxygen... 

The reaction of a hydroperoxide with 2-methylaziridine [75-55-8] has been described (94). The reaction of ethyleneknine with phenols (95) and carboxyHc acids (96,97) produces ethylamine ethers and esters, respectively. However, these reactions frequentiy yield product mixtures which contain polyaminoalkylated oxygen nucleophiles and polymers, in addition to the desked products (1). The selectivity of the reaction can often be improved by using less than the stoichiometric amount of the aziridine component (98,99). 

The importance of steric effects in determining the oxidation state of the product can be illustrated by a thioether linkage, eg (57). If a methyl group is forced to be adjacent to the sulfur bond, the planarity required for efficient electron donation by unshared electrons is prevented and oxidation is not observed (48). Similar chemistry is observed in the addition of organic nitrogen and oxygen nucleophiles as well as inorganic anions. 

An especially interesting case of oxygen addition to quinonoid systems involves acidic treatment with acetic anhydride, which produces both addition and esterification (eq. 3). This Thiele-Winter acetoxylation has been used extensively for synthesis, stmcture proof, isolation, and purification (54). The kinetics and mechanism of acetoxylation have been described (55). Although the acetyhum ion is an electrophile, extensive studies of electronic effects show a definite relationship to nucleophilic addition chemistry (56). 

The reaction is induced by nucleophilic addition of the hydroxide anion to one of the two carbonyl groups. Then the respective substituent R migrates with the bonding electrons to the adjacent carbon atom (a 1,2-shift). Electron excess at that center is avoided by release of a pair of r-electrons from the carbonyl group to the oxygen ... 

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

The most common reaction of aldehydes and ketones is the nucleophilic addition reaction, in which a nucleophile, Nu , adds to the electrophilic carbon of the carbonyl group. Since the nucleophile uses an electron pair to form a new bond to carbon, two electrons from the carbon-oxygen double bond must move toward the electronegative oxygen atom to give an alkoxide anion. The carbonyl carbon rehybridizes from sp2 to sp3 during the reaction, and the alkoxide ion product therefore has tetrahedral geometry. 

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

As we saw in A Preview of Carbonyl Compounds, the most general reaction of aldehydes and ketones is the nucleophilic addition reaction. A nucleophile, Nu-, approaches along the C=0 bond from an angle of about 75° to the plane of the carbonyl group and adds to the electrophilic C=0 carbon atom. At the same time, rehybridization of the carbonyl carbon from sp2 to sp3 occurs, an electron pair from the C=0 bond moves toward the electronegative oxygen atom, and a tetrahedral alkoxide ion intermediate is produced (Figure 19.1). 

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