Substitution Reactions of Alcohol, Enols, and Phenols

The first problem is the nature of the leaving group. If the leaving group, in the case of alcohols, enols, and phenols, is to be the hydroxyl (-OH), it will leave as hydroxide (OH ) anion and that ion is the conjugate base of the weak acid water (H-OH). Hydroxide (OH ) is a poor leaving group. 

Second, alcohols, enols, and phenols are, like water, protic (i.e., they are proton donors) and electron-rich nucleophiles would be expected to cause deprotonation at oxygen, resulting in alkoxide formation. The alkoxide anion itself is a nucleophile (as well as a base). 

Further, as noted below, substitution could mean (particularly for phenols) reaction elsewhere than at the oxygen or the carbon-bearing oxygen. 

When substitution occurs at oxygen, the alcohol, enol, or phenol is acting as the nucelophile and the proton on oxygen is replaced (e.g., C-O-H C-O-G [G H]) by the electrophile. These reactions are generally referred to as addition reactions (the alcohol having added to something). 

Some addition reactions (or substitutions at oxygen) involving replacement of the proton are temporary that is, the addition (or substitution) product is 

---

II. Substitution Reactions of Alcohols, Enols, and Phenols at Oxygen... 

Part I. The Reactions of Alcohols, Enols, and Phenols Oxidation, Reduction, Substitution, Addition, Elimination, and Rearrangement Part II. Ethers... 

All ethers react with Brpnsted and Lewis acids. Under forcing conditions, most ethers can be induced to fragment into an alkyl halide (or similar) component and alcohol, enol, or phenol. This is the formal reverse of a substitution reaction between... 

The Tsuji-Trost reaction is the palladinum-catalyzed substitution of allylic leaving groups by carbon nucleophiles. The nucleophile can be carbon-, nitrogen-, or oxygen- based compounds such as alcohols, enolates, phenols, and enamines, and the leaving group can be a halide or an acetate. This emerged as a powerful procedure for the formation of C—C, C—O and C—N bonds. The reaction, also known as Trost allylation or allylic alkylation, was named after Jiro Tsuij, who first reported the method in 1965 [42], and Barry Trost, who introduced an asymmetric version in 1973 [43]. 

---