Esterification and Alkylation Reactions Employing Isoureas

The synthetic applications of isoureas as alkylating agents are evaluated and reviewed. Esterifications employing isoureas were reported many years ago, but extended applications were inhibited by lack of isourea availability. A high-yield, mild synthesis of a major group of isoureas first appeared in 1955. This spurred numerous exploratory efforts which have extended alkylation reactions to a variety of carbon- and heteroatom-containing groups. These procedures are discussed in detail with respect to generality and selectivity. A discussion of the probable mechanism helps explain the observed selectivity and indicates potential developments of isoureas as general alkylating agents. A brief survey of the large number of available isoureas supports predictions as to their importance as reagents for analysis and organic synthesis. 1 . Introduction 2. Carboxylic Ester Formation 3. Phosphate Ester and Phenyl Ether Synthesis 4. Sulfur Alkylation 5. Nitrogen Alkylations 6. Active Carbon Alkylations 7. Isourea Rearrangements/Internal Alkylation 8.1 Mechanism of Alkylation 8.2 Heteroatom Selectivity in Alkylations 9. lsourea Availability