I can see no reason why anyone who is signed off on the R22 can't transition onto the S300 with the required training. Yes, you will have the added workload of a manual throttle but operating the throttle manually should have been covered during your R22 training. The move from the R22 onto your second type will probably be the most difficult transition, depending on the type. If you go from the R22 to the R44, it should be achieved reasonably easily. Pretty much every type after the R22 is an improvement in terms of stability and that is the reasoning behind my comment that the R22 makes good pilots and allows you "to master every other machine" (with the proper training on that other machine).
All of this is largely dependent on one's level of talent and aptitude for piloting a helicopter and we are all different in that respect. I certainly can lay no claim to being a talented or natural pilot but I know the experience gained from flying the R22 has helped when flying the few other types I have been privileged to fly.
500 Fan.