ROTf

ROTf, or alkyl/aryl triflate, refers to the triflate ester of an alcohol, written as R-O-Tf, where Tf denotes the trifluoromethanesulfonyl group (SO2–CF3). The triflate moiety is one of the best leaving groups available in organic synthesis, making ROTf species highly reactive in a range of substitution and cross-coupling reactions. Common examples include methyl triflate (MeOTf) and aryl triflates (ArOTf).

Preparation of ROTf typically involves converting an alcohol (ROH) with triflic anhydride (Tf2O) in the presence of a non-nucleophilic base such as 2,6-lutidine or DIPEA. The reaction is moisture-sensitive and typically conducted under dry, inert conditions to avoid hydrolysis to the corresponding alcohol and triflic acid (HOTf).

Properties and reactivity: ROTf compounds are generally highly reactive electrophiles due to the excellent leaving ability of the TfO− group. They readily undergo nucleophilic substitution (SN1 or SN2 depending on the substrate) and, for aryl and vinyl triflates, palladium- or nickel-catalyzed cross-coupling reactions to form new C–C or C–heteroatom bonds. Methyl triflate (MeOTf) is a particularly strong methylating agent and is used to methylate a wide range of nucleophiles, including amines and ethers. ROTf are typically moisture-sensitive and hydrolyze in the presence of water or base to yield the corresponding alcohol and triflic acid.

Applications and limitations: In synthesis, ROTf derivatives serve as versatile electrophiles for forming C–C and C–heteroatom bonds, enabling routes to complex molecules. However, their high reactivity can lead to side reactions, especially with sensitive substrates. Primary alkyl triflates are generally more stable than secondary or tertiary ones, which can undergo rearrangements or leading-by-elimination pathways under certain conditions.

Safety: ROTf compounds are moisture-sensitive and corrosive; handling often requires dry solvents, inert atmosphere, and appropriate protective equipment. Triflic acid generated in situ is a strong acid and must be managed carefully.