Will RequestReduce work on Sharepoint?

Technically, yes, RequestReduce can run and process Sharepoint content. However their is a potentially significant drawback to doing so on Sharepoint 2010. RequestReduce is not compatible with Sharepoint 2010 Output Caching. If you run RequestReduce with Sharepoint 2010, you must turn off output caching by adding <remove name="OutputCache" /> to <system.webServer> <modules> in your web.config.

You will need to weigh the amount of server side processing consumed by Sharepoint with the number of HTTP requests that Sharepoint produces on each page. If there are alot of sql queries involved in a page request, it may be best not to use RequestReduce in favor of Sharepoint output caching. However, if your pages are relatively static, you may indeed find that RequestReduce improves performance. Its best to use tools like webpagetest.org to measure and determine the true impact of this decision.