Inductive and Steric Effects in the Staudinger Reaction

Mechanisms and Substituent Effects of Metal-Free Bioorthogonal Reactions

“…The logarithm of the second order rate constant of the reaction of phenyl azide with variable trivalent phosphorus compounds correlated with Taft’s polar parameter σ* (see section ), which is in agreement with a buildup of positive charge on the phosphorus atom in the transition state. ,, For the reaction of phenyl azide with triarylphosphines, the slope of the rate constants to σ* was −2.43, which corresponds to a Hammett reaction parameter of ρ = −0.73 (benzene, 25 °C) . The same reactivity trend was observed for compounds with one or more oxygens linked to the phosphorus (instead of three carbon-based substituents); , however, the slope was offset by an increase in free energy of activation of 1.93 kcal mol –1 . Trialkylphosphines react several-fold faster than triphenylphosphine (PPh 3 ), possibly because of the lack of conjugation of the phosphorus atom …”

“…Trivalent phosphorus compounds with bulky substituents readily react with azides. For instance, replacing methyl in P­(OMe) 3 by adamantyl groups leaves the rate of the reaction nearly unchanged . The effect of steric crowding on the azide is more pronounced than for the phosphines.…”

“…The size of phosphine substituents strongly affects the cyclization step, contrasting the relative insensitivity of the bimolecular reaction of azides and phosphines to sterics . The dependency of the cyclization rate on the bulkiness of the substituents is intuitive in light of the crowded transition state .…”

“…248,360,361 For the reaction of phenyl azide with triarylphosphines, the slope of the rate constants to σ* was −2.43, which corresponds to a Hammett reaction parameter of ρ = −0.73 (benzene, 25 °C). 364 The same reactivity trend was observed for compounds with one or more oxygens linked to the phosphorus (instead of three carbon-based substituents); 364,365 however, the slope was offset by an increase in free energy of activation of 1.93 kcal mol −1 . Trialkylphosphines react several-fold faster than triphenylphosphine (PPh 3 ), possibly because of the lack of conjugation of the phosphorus atom.…”

“…For instance, replacing methyl in P(OMe) 3 by adamantyl groups leaves the rate of the reaction nearly unchanged. 365 The effect of steric crowding on the azide is more pronounced than for the phosphines. orthosubstituted phenyl azides react slower with PPh 3 than those substituted at the meta-and para-positions.…”