The TS3USB221 is a great fit for I2C and USB 2.0 multiplexing applications since it is a bi-directional dual-channel single-pull double-throw (SPDT) switch. This switch has two signal paths to handle both handle the differential requirement for USB 2.0 and the data and clock signals (SDA and SCL) required for I2C. You may pass single ended signals as required by the I2C standard as well as differential signals for USB 2.0 over the TS3USB221 without any performance implications. The TS3USB221 1.1GHz bandwidth will easily meet the 480 Mbps USB 2.0 requirements as well as the 3.4 Mbps High-speed mode and the uni-directional 5.0 Mbps Ultra Fast-mode I2C data rates.
Thank you,
Adam
