Shimano's SD-300 2nd generation Di2 e-Tube wires are the lighter, thinner, and carry more data and power faster than than the SD50 models. The wire and connecting ends are both thinner, and NOT directly compatible with pre 12-speed Di2 systems and components. The SD300 wire is designed for internal and external use and is also compatible with the EP8/EP800 electric bike power units and Shimano's STePS systems.

With 12-speed road Di2 set-ups of Dura-Ace R9250 and Ultegra R8150 the SD300's are used individually from the internal battery to the Di2 front and rear derailleurs, while in the optimal set-up, the Di2 Shift/Brake Dual Control levers are used wirelessly. In such set-ups, no junction box of any kind is required as the rear derailleur effectively carries the interfaces need to communicate (formerly the D-Fly module), charge, asses, and adjust the wired Di2 components, while the shifters work wirelessly and are powered by coin cell batteries in each unit. Shimano does allow the Di2 R9250/R8150 levers to be wired into the system, bypassing the wireless option, though they believe the updated system works faster in the wireless mode. Some pro teams run the wired shifter option as a redundant back-up, to eliminate and cover for an extremely rare wireless failure during a race.

It is important to note that this second generation requires a battery interface with three SD300 ports, available as the BT-DN300 internal seatpost-type battery. Shimano does offer a bridging junction (AD-305 adapter) that converts the wiring for using existing 11-speed aerobar cockpit controls with the 12-speed Di2 battery and derailleurs, as there is no new version of these aerobar shift components. The AD-305 features an SD50 port and and SD300 port, but there are also firmware updates required for the 11-speed aerobar levers to work in this manner.