Synthesis and Applications of Sulfamates and Related Functionalities

Abstract

Sulfur-containing moieties play a crucial role in both medicinal and synthetic chemistry. Chapters 2 and 3 focus on two sulfonamide bioisosteres called sulfamates and sulfamides. Chapter 2 describes the development and scope of a practical new synthesis of sulfamates and sulfamides, which were previously challenging to prepare. This work employs a reagent called hexafluoroisopropyl sulfamate (HFIPS) to synthesize sulfamates and sulfamides from their corresponding alcohols and amines. Sulfamates and sulfamides are known to undergo numerous chemical transformations, primarily metal catalyzed. The most common transformations are CH aminations in which the NH2 reacts and inserts between a C-H bond. A lesser explored reaction is that of the NH2 with aryl bromides. As described in Chapter 3, this N-arylation of sulfamates and sulfamides through copper catalysis provides access to their arylated products that have previously been difficult or even impossible to synthesize. Sulfur-containing functionalities are often versatile intermediates in organic chemistry. The aryl trifluoromethylsulfonate (triflate; Ar-OSO2CF3) moiety is considered a “pseudohalide” as it is a useful alternative to aryl halides in the context of cross-coupling chemistry. Chapter 4 describes the development and scope of a practical substitution of alkyl amines by iodine salts via N-bistriflimide intermediates that act as N-leaving groups in substitution chemistry to yield their corresponding alkyl iodide product.