This study describes a new convenient method for the photocatalytic generation of glycosyl fluorides using sulfur(VI) hexafluoride as an inexpensive and safe fluorinating agent and 4,4′dimethoxybenzophenone as a readily available organic photocatalyst. This mild method was employed to generate 16 different glycosyl fluorides, including the substrates with acid and base labile functionalities, in yields of 43%−97%, and it was applied in continuous flow to accomplish fluorination on an 7.7 g scale and 93% yield.
Experimental and theoretical 13 C kinetic isotope effects (KIEs) are utilized to obtain atomistic insight into the catalytic mechanism of the Pd(PPh 3 ) 4 -catalyzed Suzuki-Miyaura reaction of aryl halides and aryl boronic acids. Under catalytic conditions, we establish that oxidative addition of aryl bromides occurs to a 12-electron monoligated palladium complex (Pd-(PPh 3 )). This is based on the congruence of the experimental KIE for the carbon attached to bromine (KIE C−Br = 1.020) and predicted KIE C−Br for the transition state for oxidative addition to the Pd(PPh 3 ) complex (1.021). For aryl iodides, the near-unity KIE C−I of ∼1.003 suggests that the first irreversible step in the catalytic cycle precedes oxidative addition and is likely the binding of the iodoarene to Pd(PPh 3 ). Our results suggest that the commonly proposed oxidative addition to the 14-electron Pd(PPh 3 ) 2 complex can occur only in the presence of excess added ligand or under stoichiometric conditions; in both cases, experimental KIE C−Br of 1.031 is measured, which is identical to the predicted KIE C−Br for the transition state for oxidative addition to the Pd(PPh 3 ) 2 complex (1.031). The transmetalation step, under catalytic conditions, is shown to proceed via a tetracoordinate boronate (8B4) intermediate with a Pd−O−B linkage based on the agreement between an experimental KIE for the carbon atom involved in transmetalation (KIE C-Boron = 1.035) and a predicted KIE C-Boron for the 8B4 transmetalation transition state (1.034).
This manuscript describes the electrochemical synthesis of 17 different glycosyl fluorides in 73−98% yields on up to a 5 g scale that relies on the use of SF 6 as an inexpensive and safe fluorinating agent. Cyclic voltammetry and related mechanistic studies carried out subsequently suggest that the active fluorinating species generated through the cathodic reduction of SF 6 are transient under these reductive conditions and that the sulfur and fluoride byproducts are effectively scavenged by Zn(II) to generate benign salts.
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